|
1
|
Stépanian A, Fischer F, Flaujac C, Eschwège V, Delassasseigne C, Leflem L, Loridon F, Voisin S, Lasne D. Light transmission aggregometry for platelet function testing: position paper on current recommendations and French proposals for accreditation. Platelets 2024; 35:2427745. [PMID: 39555668 DOI: 10.1080/09537104.2024.2427745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/17/2024] [Accepted: 11/05/2024] [Indexed: 11/19/2024]
Abstract
Light transmission aggregometry (LTA) is a method used to investigate platelet functions in platelet-rich plasma (PRP), notably when screening for platelet disorders. Various national guidelines and recommendations help in setting up the LTA test in specialized laboratories. However, due to the nature of the sample matrix and its subsequent specificities, more accurate positions are needed to achieve LTA accreditation according to the standard NF EN ISO 15 189. We reviewed guidelines and recommendations as they can be useful in the accreditation process, and we conducted a survey on LTA practice among members of the Société Française de Thrombose et d'Hémostase (SFTH) in 2021. We formulated 28 proposals, which have been approved by vote within the SFTH. All aspects to take into consideration for the proper conduct of LTA assays and their accreditation have been covered. Notably, preanalytical, analytical and postanalytical aspects are depicted, including blood sampling, PRP preparation, instruments, agonists, performance assessment, personnel training and data interpretation. This document, essentially representing a French position paper on the current recommendations and subsequent proposals for LTA accreditation, might prove useful also outside France for relevant laboratories and auditors involved in LTA accreditation.
Collapse
Affiliation(s)
- Alain Stépanian
- Service d'Hématologie Biologique, PhyMedExp UMR UM - CNRS 9214 - Inserm U1046, CHU de Montpellier, Université de Montpellier, Montpellier, France
| | | | - Claire Flaujac
- Laboratoire de biologie médicale, secteur hémostase, centre hospitalier de Versailles (André Mignot), Le Chesnay-Rocquencourt, France
| | | | | | - Léna Leflem
- Laboratoire Eurofins, Ivry-sur-Seine, France
| | | | - Sophie Voisin
- Laboratoire d'Hématologie, CHU de Toulouse, Toulouse, France
| | - Dominique Lasne
- Laboratoire d'Hématologie Générale, Hôpital Universitaire Necker-Enfants Malades, AP-HP, Paris, France
| |
Collapse
|
|
2
|
Gosselin RC, Castellone D, Dorgalaleh A, Hickey K, Lippi G, Moffat K, O'Toole R, Rigano J. International Council for Standardization in Haematology Guidance for New Lot Verification of Coagulation Reagents, Calibrators, and Controls. Semin Thromb Hemost 2024; 50:1091-1102. [PMID: 37967836 PMCID: PMC11469916 DOI: 10.1055/s-0043-1776405] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2023]
Abstract
The clinical laboratory uses commercial products with limited shelf life or certain expiry dates requiring frequent lot changes. Prior to implementation for clinical use, laboratories should determine the performance of the new reagent lot to ensure that there is no significant shift in reagent performance or reporting of patient data. This guideline has been written on behalf of the International Council for Standardization in Haematology (ICSH) to provide the framework and provisional guidance for clinical laboratories for evaluating and verifying the performance of new lot reagents used for coagulation testing. These ICSH Working Party consensus recommendations are based on good laboratory practice, regulatory recommendations, evidence emerged from scientific publications, and expert opinion and are meant to supplement regional standards, regulations, or requirements.
Collapse
Affiliation(s)
- Robert C. Gosselin
- CLS Hemostasis and Thrombosis Center, University of California, Davis Health System, Sacramento, California
| | | | | | - Kieron Hickey
- Sheffield Laboratory Medicine, Royal Hallamshire Hospital, Sheffield, United Kingdom
| | - Giuseppe Lippi
- Section of Clinical Biochemistry and School of Medicine, University of Verona, Verona, Italy
| | - Karen Moffat
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton Ontario, Canada
| | - Rebecca O'Toole
- Hematology Department, Wellington Hospital and Health Care, Wellington, New Zealand
| | - Joe Rigano
- CCS Northern Pathology Victoria, Melbourne, Australia
| |
Collapse
|
|
3
|
Casini A, Gebhart J. How to investigate mild to moderate bleeding disorders and bleeding disorder of unknown cause. Int J Lab Hematol 2024; 46 Suppl 1:27-33. [PMID: 38454298 DOI: 10.1111/ijlh.14266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 02/28/2024] [Indexed: 03/09/2024]
Abstract
A bleeding tendency is one of the most common complaints observed by hematologists. It is challenging to differentiate a clinically insignificant bleeding from a bleeding phenotype that requires hemostatic evaluation and medical intervention. A thorough review of personal and familial history, objective assessment of bleeding severity using a bleeding assessment tool, and a focused physical examination are critical to correctly identifying suspected patients with mild to moderate bleeding disorders (MBDs). A basic laboratory work-up should be performed in all patients referred for a bleeding tendency. If a hemostatic abnormality is found such as evidence of von Willebrand disease, a platelet function disorder, or a coagulation factor deficiency, more extensive testing should be performed to further characterize the bleeding disorder. Conversely, if all results are normal the patient is considered to have bleeding disorder of unknown cause (BDUC). For patients with BDUC, further evaluation may include non-routine testing to look for rare bleeding disorders not detected by routine hemostasis tests, such as thrombomodulin-associated coagulopathy, tissue factor pathway inhibitor-related bleeding disorder, hyperfibrinolytic-bleeding disorders or impaired tissue factor production. In this review, we summarize the stepwise diagnostic procedure in MBDs and provide some insights into the biological features of BDUC.
Collapse
Affiliation(s)
- Alessandro Casini
- Division of Angiology and Hemostasis, University Hospitals of Geneva, Geneva, Switzerland
| | - Johanna Gebhart
- Department of Medicine I, Division of Hematology and Hemostaseology, Medical University Vienna, Austria
| |
Collapse
|
|
4
|
Altahan RM, Mathews N, Bourguignon A, Tasneem S, Arnold DM, Lim W, Hayward CPM. Evaluation of a diagnostic platelet aggregation test strategy for platelet rich plasma samples with low platelet counts. Int J Lab Hematol 2024; 46:362-374. [PMID: 38148642 DOI: 10.1111/ijlh.14216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 11/25/2023] [Indexed: 12/28/2023]
Abstract
INTRODUCTION Light transmission aggregometry (LTA) is important for diagnosing platelet function disorders (PFD) and von Willebrand disease (VWD) affecting ristocetin-induced platelet aggregation (RIPA). Nonetheless, data is lacking on the utility of LTA for investigating thrombocytopenic patients and platelet rich plasma samples with low platelet counts (L-PRP). Previously, we developed a strategy for diagnostic LTA assessment of L-PRP that included: (1) acceptance of referrals/samples, regardless of thrombocytopenia severity, (2) tailored agonist selection, based on which are informative for L-PRP with mildly or severely low platelet counts, and (3) interpretation of maximal aggregation (MA) using regression-derived 95% confidence intervals, determined for diluted control L-PRP (C-L-PRP). METHODS To further evaluate the L-PRP LTA strategy, we evaluated findings for a subsequent patient cohort. RESULTS Between 2008 and 2021, the L-PRP strategy was applied to 211 samples (11.7% of all LTA samples) from 192 unique patients, whose platelet counts (median [range] × 109 /L) for blood and L-PRP were: 105 [13-282; 89% with thrombocytopenia] and 164 [17-249], respectively. Patient-L-PRP had more abnormal MA findings than simultaneously tested C-L-PRP (p-values <0.001). Among patients with accessible electronic medical records (n = 181), L-PRP LTA uncovered significant aggregation abnormalities in 45 (24.9%), including 18/30 (60%) with <80 × 109 platelets/L L-PRP, and ruled out PFD, and VWD affecting RIPA, in others. The L-PRP LTA strategy helped diagnose VWD affecting RIPA, Bernard Soulier syndrome, familial platelet disorder with myeloid malignancy, suspected ITGA2B/ITGB3-related thrombocytopenia, and acquired PFD. CONCLUSION Diagnostic LTA with L-PRP, using a strategy that considers thrombocytopenia severity, is feasible and informative.
Collapse
Affiliation(s)
- Rahaf Mahmoud Altahan
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
- Pathology and Clinical Laboratory Medicine Administration, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Natalie Mathews
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Alex Bourguignon
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Subia Tasneem
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Donald M Arnold
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Wendy Lim
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
| | - Catherine P M Hayward
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
| |
Collapse
|
|
5
|
Adamski P, Adamska U, Buszko K, Sikora J, Czajkowski R. Platelet Reactivity in the Exacerbation of Psoriasis. J Clin Med 2024; 13:965. [PMID: 38398278 PMCID: PMC10889129 DOI: 10.3390/jcm13040965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/27/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Background: Psoriasis is a chronic, inflammatory, immune-mediated disease with a specific cutaneous presentation. Increased platelet aggregation has been observed in patients with extensive psoriatic lesions. The aim of this study was to evaluate the clinical factors affecting platelet reactivity in patients with an exacerbation of psoriasis. Methods: This was a prospective, single-center, observational study, enrolling patients hospitalized for an aggravation of psoriasis. Enrolled patients underwent single platelet function testing with light transmission aggregometry on the first morning of hospitalization. Results: 120 patients were enrolled in the study. Of the compared subgroups, women had higher maximal platelet aggregation (MPA) than men (77% vs. 72%; p = 0.03), and those with BMIs < 25 kg/m2 showed higher platelet reactivity compared to subjects with BMIs ≥ 25 kg/m2 (75% vs. 73%; p = 0.02). There was a positive correlation between MPA and platelet count (r = 0.27; p < 0.01), as well as C-reactive protein concentration (r = 0.20; p = 0.03), while a negative correlation was observed with total cholesterol (r = -0.24; p = 0.01) and triglycerides (r = -0.30; p < 0.01). A two-step analysis based on multidimensional models with random effects revealed that every increase in the platelet count by 103/μL led to an increase in MPA by 0.07% (R2 = 0.07; p < 0.01), and an increase in triglycerides' concentration by 1 mg/dL was related to a reduction in MPA by 0.05% (R2 = 0.07; p < 0.01). Conclusions: The increased platelet reactivity observed in patients with psoriasis appears to be multifactorial and related to several clinical and laboratory features. Further research is warranted to put these findings into a clinical perspective.
Collapse
Affiliation(s)
- Piotr Adamski
- Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
| | - Urszula Adamska
- Department of Dermatology and Venerology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland; (U.A.); (R.C.)
| | - Katarzyna Buszko
- Department of Theoretical Foundations of Biomedical Science and Medical Informatics, Collegium Medicum, Nicolaus Copernicus University, 87-067 Bydgoszcz, Poland;
| | - Joanna Sikora
- Research and Education Unit for Experimental Biotechnology, Department of Transplantology and General Surgery, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland;
| | - Rafał Czajkowski
- Department of Dermatology and Venerology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland; (U.A.); (R.C.)
| |
Collapse
|
|
6
|
Babuty A, Debord C, Drillaud N, Eveillard M, Trossaert M, Ternisien C, Sigaud M, Cador E, Béné MC, Fouassier M. Prothrombin consumption as an indicator of hemorrhagic phenotype in mild platelet function disorders. Eur J Haematol 2023; 111:787-795. [PMID: 37553915 DOI: 10.1111/ejh.14079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 08/10/2023]
Abstract
BACKGROUND The bleeding risk of patients with mild platelet function disorders is difficult to assess and their phenotype remains ill-explored. AIM This study was designed to establish a comprehensive biological phenotype of patients with mild platelet function disorders. METHODS Twenty patients were included with persistent abnormal light transmission aggregometry (LTA). The ISTH bleeding assessment tool (ISTH-BAT) was assessed to identify laboratory analyses associated with an abnormal hemorrhagic score. RESULTS The majority of patients had defects that might affect Gαi protein signaling pathways or minor abnormalities. No LTA nor flow cytometry parameters were associated with an above-normal hemorrhagic score. However, prothrombin consumption, which corresponds to the ratio of serum residual factor II to plasma residual factor II, was significantly higher (p = .006) in the abnormal ISTH-BAT group (mean = 14%, SD = 6) compared with the normal ISTH-BAT group (mean = 8%, SD 4). Prothrombin consumption was significantly associated with ISTH-BAT score (r = .5287, IC 95% 0.0986-0.7924, p = .0165). CONCLUSION In this group of patients, there was an association between a pathological bleeding score and increased prothrombin consumption. This test could be used as an additional indicator of platelet function abnormality liable to be related to bleeding risk.
Collapse
Affiliation(s)
- Antoine Babuty
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
- Nantes Université, CHU Nantes, Centre de Ressource et de Compétence-Maladies Hémorragiques Constitutionnelles, Nantes, France
| | - Camille Debord
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
| | - Nicolas Drillaud
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
- Nantes Université, CHU Nantes, Centre de Ressource et de Compétence-Maladies Hémorragiques Constitutionnelles, Nantes, France
| | - Marion Eveillard
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
| | - Marc Trossaert
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
- Nantes Université, CHU Nantes, Centre de Ressource et de Compétence-Maladies Hémorragiques Constitutionnelles, Nantes, France
| | - Catherine Ternisien
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
- Nantes Université, CHU Nantes, Centre de Ressource et de Compétence-Maladies Hémorragiques Constitutionnelles, Nantes, France
| | - Marianne Sigaud
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
- Nantes Université, CHU Nantes, Centre de Ressource et de Compétence-Maladies Hémorragiques Constitutionnelles, Nantes, France
| | - Emmanuelle Cador
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
| | - Marie C Béné
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
| | - Marc Fouassier
- Nantes Université, CHU Nantes, Service d'Hématologie Biologique, Nantes, France
- Nantes Université, CHU Nantes, Centre de Ressource et de Compétence-Maladies Hémorragiques Constitutionnelles, Nantes, France
| |
Collapse
|
|
7
|
Chen Y, Zhou J, Liu Z, Wu T, Li S, Zhang Y, Yin X, Yang G, Zhang G. Tumor cell-induced platelet aggregation accelerates hematogenous metastasis of malignant melanoma by triggering macrophage recruitment. J Exp Clin Cancer Res 2023; 42:277. [PMID: 37872588 PMCID: PMC10591353 DOI: 10.1186/s13046-023-02856-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 10/09/2023] [Indexed: 10/25/2023] Open
Abstract
BACKGROUND Tumor cell-induced platelet aggregation (TCIPA) is not only a recognized mechanism for paraneoplastic thrombocytosis but also a potential breakthrough alternative for a low response to immune checkpoint inhibitors (ICIs) in hematogenous metastasis of malignant melanoma (MM). However, there is no TCIPA-specific model for further investigation of the relationship among TCIPA, the tumor immune microenvironment (TIME), and metastasis. METHODS We developed a TCIPA metastatic melanoma model with advanced hematogenous metastasis and enhanced TCIPA characteristics. We also investigated the pathway for TCIPA in the TIME. RESULTS We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1β. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis. CONCLUSIONS TCIPA accelerates MM lung metastasis via tumor-educated platelets (TEPs), triggering TAM recruitment, promoting TAM polarization (M2), and remodeling the suppressive TIME in lung metastases.
Collapse
Affiliation(s)
- Yuyi Chen
- Department of Oncology, Shunyi Hospital, Beijing Hospital of Traditional Chinese Medicine, Beijing, China
| | - Jie Zhou
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Zishen Liu
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Tongtong Wu
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Shumeng Li
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Yutong Zhang
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Xiaohui Yin
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Guowang Yang
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
| | - Ganlin Zhang
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
| |
Collapse
|
|
8
|
Jourdi G, Ramström S, Sharma R, Bakchoul T, Lordkipanidzé M. Consensus report on flow cytometry for platelet function testing in thrombocytopenic patients: communication from the SSC of the ISTH. J Thromb Haemost 2023; 21:2941-2952. [PMID: 37481072 DOI: 10.1016/j.jtha.2023.07.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 07/04/2023] [Accepted: 07/05/2023] [Indexed: 07/24/2023]
Abstract
BACKGROUND Platelet count alone does not reliably predict bleeding risk, suggesting platelet function is important to monitor in patients with thrombocytopenia. There is still an unmet need for improved platelet function diagnostics in patients with low platelet count in many clinical situations. Flow cytometry is a promising tool allowing reliable platelet function study in this setting. OBJECTIVES The goal of this joint project between the International Society on Thrombosis and Haemostasis (ISTH) Scientific Standardization Committee (SSC) Subcommittees on Platelet Physiology and Platelet Immunology is to provide expert consensus guidance on the use of flow cytometry for the evaluation of platelet function, particularly activation, in patients with low platelet counts. METHODS A literature review was performed to identify relevant questions and areas of interest. An electronic expression of interest form was thereafter announced on the ISTH webpage, followed by a survey encompassing 37 issues regarding preanalytical, analytical, postanalytical, and performance aspects. Areas of disagreement or uncertainty were identified and formed the basis for 2 focus group discussions. RESULTS Consensus recommendations relative to patient sample collection, preanalytical variables, sample type, platelet-count cutoff, any potential specific modification of the standard flow cytometry protocol, and results expression and reporting are proposed based on the current practices of experts in the field as well as on literature review. CONCLUSION The proposed consensus recommendations would allow standardization of protocols in upcoming clinical studies. The clinical utility of platelet function testing using flow cytometry to predict bleeding risk still needs rigorous multicenter outcome studies in patients with thrombocytopenia.
Collapse
Affiliation(s)
- Georges Jourdi
- Research Center, Montreal Heart Institute, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada; Université Paris Cité, INSERM, Innovative Therapies in Haemostasis, Paris, France; Service d'Hématologie Biologique, AP-HP, Hôpital Lariboisière, Paris, France
| | - Sofia Ramström
- Cardiovascular Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
| | - Ruchika Sharma
- Versiti Blood Center of Wisconsin Pediatric Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Division of Hematology/Oncology/BMT, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Tamam Bakchoul
- Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany
| | - Marie Lordkipanidzé
- Research Center, Montreal Heart Institute, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada
| |
Collapse
|
|
9
|
Alessi MC, Coxon C, Ibrahim-Kosta M, Bacci M, Voisin S, Rivera J, Greinacher A, Raster J, Pulcinelli F, Devreese KMJ, Mullier F, McCormick AN, Frontroth JP, Pouplard C, Sachs UJ, Diaz I, Bermejo N, Camera M, Fontana P, Bauters A, Stepanian A, Cozzi MR, Sveshnikova AN, Faille D, Hollon W, Chitlur M, Casonato A, Lasne D, Lavenu-Bombled C, Fiore M, Hamidou B, Hurtaud-Roux MF, Saultier P, Goumidi L, Gresele P, Lordkipanidzé M. Multicenter evaluation of light transmission platelet aggregation reagents: communication from the ISTH SSC Subcommittee on Platelet Physiology. J Thromb Haemost 2023; 21:2596-2610. [PMID: 37331519 DOI: 10.1016/j.jtha.2023.05.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 05/23/2023] [Accepted: 05/24/2023] [Indexed: 06/20/2023]
Abstract
BACKGROUND Light transmission aggregation (LTA) is used widely by the clinical and research communities. Although it is a gold standard, there is a lack of interlaboratory harmonization. OBJECTIVES The primary objective was to assess whether sources of activators (mainly adenosine diphosphate [ADP], collagen, arachidonic acid, epinephrine, and thrombin receptor activating peptide6) and ristocetin contribute to poor LTA reproducibility. The secondary objective was to evaluate interindividual variability of results to appreciate the distribution of normal values and consequently better interpret pathologic results. METHODS An international multicenter study involving 28 laboratories in which we compared LTA results obtained with center-specific activators and a comparator that we supplied. RESULTS We report variability in the potency (P) of activators in comparison with the comparator. Thrombin receptor activating peptide 6 (P, 1.32-2.68), arachidonic acid (P, 0.87-1.43), and epinephrine (P, 0.97-1.34) showed the greatest variability. ADP (P, 1.04-1.20) and ristocetin (P, 0.98-1.07) were the most consistent. The data highlighted clear interindividual variability, notably for ADP and epinephrine. Four profiles of responses were observed with ADP from high-responders, intermediate-responders, and low-responders. A fifth profile corresponding to nonresponders (5% of the individuals) was observed with epinephrine. CONCLUSION Based on these data, the establishment and adoption of simple standardization principles should mitigate variability due to activator sources. The observation of huge interindividual variability for certain concentrations of activators should lead to a cautious interpretation before reporting a result as abnormal. Confidence can be taken from the fact that difference between sources is not exacerbated in patients treated with antiplatelet agents.
Collapse
Affiliation(s)
- Marie-Christine Alessi
- Laboratory of Hematology, Centre de référence des pathologies plaquettaires, C2VN, INRAE, INSERM, Aix Marseille Université, Marseille, France.
| | - Carmen Coxon
- National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, United Kingdom
| | - Manal Ibrahim-Kosta
- Laboratory of Hematology, Centre de référence des pathologies plaquettaires, C2VN, INRAE, INSERM, Aix Marseille Université, Marseille, France
| | - Monica Bacci
- Center for Thrombosis and Hemorrhagic Diseases, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Sophie Voisin
- Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
| | - José Rivera
- Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, Instituto Murciano De Investigación Biosanitaria, IMIB-Arrixaca, Murcia, Spain
| | - Andreas Greinacher
- Institut für Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
| | - Johannes Raster
- Institut für Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
| | - Fabio Pulcinelli
- Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy
| | - Katrien M J Devreese
- Department of Diagnostic Sciences, Coagulation Laboratory, Ghent University Hospital, Ghent University, Ghent, Belgium
| | - Francois Mullier
- Namur Thrombosis and Hemostasis Center, CHU UCLouvain Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - Aine N McCormick
- Haemostasis and Thrombosis Laboratory, Viapath Analytics, St Thomas' Hospital, London, United Kingdom
| | - Juan Pablo Frontroth
- Laboratorio de Hemostasia y Trombosis, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," Buenos Aires, Argentina
| | - Claire Pouplard
- Department of Hemostasis, University Hospital of Tours, University of Tours, Tours, France
| | - Ulrich J Sachs
- Department of Thrombosis and Haemostasis, Giessen University Hospital, Giessen, Germany
| | - Isabelle Diaz
- Laboratory of Hematology, University Hospital of Montpellier, Montpellier, France
| | - Nuria Bermejo
- Servicio de Hematología, Hospital San Pedro de Alcántara, Complejo Hospitalario Universitario de Cáceres, Cáceres, Spain
| | - Marina Camera
- Centro Cardiologico Monzino, Istituto di Ricerca e Cura a Carattere Scientifico, Milan, Italy
| | - Pierre Fontana
- Division of Angiology and Haemostasis, Geneva University Hospitals, and Geneva Platelet Group, Faculty of Medicine, Geneva, Switzerland
| | - Anne Bauters
- Hemostasis Unit, Hospital University Center Lille, Lille, France
| | - Alain Stepanian
- Hematology Laboratory and Thrombosis Unit, Université Paris Cité, Hospital Group Lariboisière-Fernand Widal, Assistance Publique-Hôpitaux de Paris AP-HP, Paris, France
| | - Maria R Cozzi
- Immunopathology and Cancer Biomarkers Unit Centro di Riferimento Oncologico di Aviano, Aviano, Italy
| | - Anastasia N Sveshnikova
- Hemostasis Research Department, Dmitry Rogachev Pediatric Hematology and Immunology Hospital, Moscow, Russia
| | - Dorothée Faille
- Département d'Hématologie Biologique, Assistance Publique-Hôpitaux de Paris AP-HP, Centre Hospitalo-Universitaire CHU Bichat-Claude Bernard, Paris, France
| | - Wendy Hollon
- Jeanne M. Lusher Special Coagulation Laboratory, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan, USA
| | - Meera Chitlur
- Central Michigan University, Jeanne M. Lusher Special Coagulation Laboratory, Children's Hospital of Michigan, Detroit, Michigan, USA
| | - Alessandra Casonato
- Department of Medicine, University of Padua Medical School, First chair of Internal Medicine, Padua, Italy
| | - Dominique Lasne
- Laboratoire d'Hématologie, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants malades, Paris, France
| | - Cécile Lavenu-Bombled
- Service Hématologie Biologique, Centre de ressources et compétences de la filière de santé des maladies Hémorragiques constitutionnelles MHEMO, Centre Hospitalo-Universitaire CHU Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de médecine Paris Saclay, Le Kremlin-Bicêtre, France
| | - Mathieu Fiore
- Bordeaux University Hospital, Laboratory of Hematology, Centre de Reference des Pathologies Plaquettaires Pessac, France
| | - Bello Hamidou
- Laboratory of Hematology, Centre de référence des pathologies plaquettaires, C2VN, INRAE, INSERM, Aix Marseille Université, Marseille, France
| | - Marie-Francoise Hurtaud-Roux
- Assistance Publique-Hôpitaux de Paris, Centre de Reference des Pathologies Plaquettaires, Hôpital Robert Debré, Paris, France
| | - Paul Saultier
- Laboratory of Hematology, Centre de référence des pathologies plaquettaires, C2VN, INRAE, INSERM, Aix Marseille Université, Marseille, France
| | - Louisa Goumidi
- Laboratory of Hematology, Centre de référence des pathologies plaquettaires, C2VN, INRAE, INSERM, Aix Marseille Université, Marseille, France
| | - Paolo Gresele
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Marie Lordkipanidzé
- Faculté de Pharmacie, Research Center and The Montreal Heart Institute, Université de Montréal, Montréal, Quebec, Canada
| |
Collapse
|
|
10
|
Pruthi RK. Testing strategies used in the diagnosis of rare inherited bleeding disorders. Expert Rev Hematol 2023:1-15. [PMID: 37144355 DOI: 10.1080/17474086.2023.2211257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
INTRODUCTION Rare Bleeding Disorders have a low population prevalence and may not be recognized by most clinicians. In addition, knowledge gaps of the indicated laboratory tests and their availability add to the potential for delayed diagnosis or misdiagnosis. The lack of widely available commercial, regulatory body approved esoteric tests limit them to reference laboratories, thus limiting easy access for patients. AREAS COVERED A literature search of Pubmed, Medline, Embase and review of international society guidelines was performed. Additional references from published articles were reviewed. A patient-centered approach to recognition and evaluation of RBD is discussed. EXPERT OPINION Recognition of RBD relies on obtaining a detailed patient personal and family hemostatic history. Inquiry into a history of involvement of other organ systems is important and if present should lead to suspicion of an inherited platelet disorder or a variant of Ehlers Danlos Syndrome. Multiple factors contribute to the complexity of development of efficient algorithms for diagnostic testing. Limitations in diagnostic sensitivity and specificity of screening tests, diagnostic tests, and esoteric tests further compound the complexity of establishing a diagnosis. Educational efforts focusing on clinician awareness of RBDs and available testing options are vital for optimal management of such patients.
Collapse
Affiliation(s)
- Rajiv K Pruthi
- Mayo Comprehensive Hemophilia Center, Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
| |
Collapse
|
|
11
|
Sidonio RF, Bryant PC, Di Paola J, Hale S, Heiman M, Horowitz GS, Humphrey C, Jaffray J, Joyner LC, Kasthuri R, Konkle BA, Kouides PA, Montgomery R, Neeves K, Randi AM, Scappe N, Tarango C, Tickle K, Trapane P, Wang M, Waters B, Flood VH. Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities for mucocutaneous bleeding disorders. Expert Rev Hematol 2023; 16:39-54. [PMID: 36920856 DOI: 10.1080/17474086.2023.2171983] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
BACKGROUND Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research. RESEARCH DESIGN AND METHODS National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them. They recruited multidisciplinary expert working groups (WG) to distill community-identified priorities into concrete research questions and score their feasibility, impact, and risk. RESULTS WG2 detailed 38 high priority research questions concerning the biology of MCB, VWD, inherited qualitative platelet function defects, HDS/EDS, HHT, bleeding disorder of unknown cause, novel therapeutics, and aging. CONCLUSIONS Improving our understanding of the basic biology of MCB, large cohort longitudinal natural history studies, collaboration, and creative approaches to novel therapeutics will be important in maximizing the benefit of future research for the entire MCB community.
Collapse
Affiliation(s)
- Robert F Sidonio
- Department of Pediatrics, Aflac Cancer and Blood Disorders, Atlanta, Georgia, USA.,Hemophilia of Georgia Center for Bleeding and Clotting Disorders, Atlanta, Georgia, USA
| | - Paulette C Bryant
- Pediatric Hematology Oncology, St. Jude Affiliate Clinic at Novant Health Hemby Children's Hospital, Charlotte, North Carolina, USA.,National Hemophilia Foundation, New York, New York, USA
| | - Jorge Di Paola
- Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, USA.,Hematology/Oncology Department, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Sarah Hale
- Takeda Pharmaceuticals U.S.A, Lexington, Massachusetts, USA
| | - Meadow Heiman
- Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA
| | | | | | - Julie Jaffray
- Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.,Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Lora C Joyner
- East Carolina University Hemophilia Treatment Center, Greenville, North Carolina, USA
| | - Raj Kasthuri
- Division of Hematology, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Barbara A Konkle
- Washington Center for Bleeding Disorders, Seattle, Washington, USA
| | | | - Robert Montgomery
- Blood Center of Wisconsin, Versiti, Milwaukee, Wisconsin, USA.,Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Keith Neeves
- Hemophilia and Thrombosis Center, University of Colorado Denver, Denver, Colorado, USA.,Department of Bioengineering, University of Colorado Denver, Denver, Colorado, USA.,Department of Pediatrics, University of Colorado Denver, Denver, Colorado, USA.,Department of pediatrics, Anschutz Medical Campus, Aurora, Colorado, USA
| | - Anna M Randi
- National Heart and Lung Institute, Imperial College, London, UK
| | - Nikole Scappe
- National Hemophilia Foundation, New York, New York, USA
| | - Cristina Tarango
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Kelly Tickle
- Department of Pediatrics, Aflac Cancer and Blood Disorders, Atlanta, Georgia, USA.,Hemophilia of Georgia Center for Bleeding and Clotting Disorders, Atlanta, Georgia, USA.,Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Pamela Trapane
- Division of Pediatric Genetics, Department of Pediatrics, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
| | - Michael Wang
- Department of pediatrics, Anschutz Medical Campus, Aurora, Colorado, USA
| | | | - Veronica H Flood
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| |
Collapse
|
|
12
|
Sharma R, Flood V, Jobe S, Punzalan R, Simpson P, Conway C, Malec L. Utilization and optimization of an electronic self-administered bleeding assessment tool (E-Self BAT) for the screening of pediatric bleeding disorders in the hematology clinic. Haemophilia 2023; 29:685-688. [PMID: 36580378 DOI: 10.1111/hae.14717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 10/21/2022] [Accepted: 11/09/2022] [Indexed: 12/30/2022]
Affiliation(s)
- Ruchika Sharma
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA.,Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Veronica Flood
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA.,Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Shawn Jobe
- Department of Pediatrics and Human Development, Michigan State University College of Human Medicine, East Lansing, Michigan, USA
| | - Rowena Punzalan
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA.,Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Pippa Simpson
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | | | - Lynn Malec
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA.,Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| |
Collapse
|
|
13
|
Bruno L, Lenberg J, Le D, Dimmock D, Thornburg CD, Briggs B. Novel Approach to Improve the Identification of the Bleeding Phenotype in Noonan Syndrome and Related RASopathies. J Pediatr 2023:S0022-3476(23)00019-7. [PMID: 36646249 DOI: 10.1016/j.jpeds.2022.12.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 11/10/2022] [Accepted: 12/01/2022] [Indexed: 01/14/2023]
Abstract
OBJECTIVES To characterize bleeding phenotype in Noonan Syndrome, to test the utility of following national guidelines in detecting this phenotype, to evaluate thromboelastography (TEG) as a diagnostic tool and to evaluate the cohort for genotype-phenotype correlations. STUDY DESIGN Participants with a clinical diagnosis NS or related RASopathy were enrolled in a cohort study. Study procedures included clinical bleeding assessment, coagulation testing per guidelines and hematology consultation. TEG was completed in a subset and genetic testing was conducted for those without a molecular diagnosis. International Society of Haemostasis and Thrombosis Bleeding Assessment Tool (ISTH-BAT) scores were calculated with hematology consultation. Bleeding phenotype was defined as abnormal bleeding score. RESULTS Twenty participants enrolled; 12completed clinical and laboratory evaluation, five of whom met the definition for bleeding phenotype. Four of the five participants with a bleeding phenotype had platelet aggregation defects and at least one additional coagulation defect. TEG was performed in nine participants, four with bleeding phenotype and five without, and results were normal in all cases. No genotype-phenotype correlation was found. CONCLUSION Five of 20 participants had a bleeding phenotype identified. Based on available data we do not recommend incorporating TEG into clinical practice for NS patients. Platelet aggregation defects were the most common abnormalities, which would not be detected on Tier 1 testing of current guidelines, therefore we propose a new algorithm.
Collapse
Affiliation(s)
- Leah Bruno
- Department of Pediatrics, Division of Hematology and Oncology, University of California San Diego, La Jolla, California; Rady Children's Institute of Genomic Medicine, San Diego, California
| | - Jerica Lenberg
- Rady Children's Institute of Genomic Medicine, San Diego, California
| | - Dzung Le
- Department of Pathology, University of California San Diego, La Jolla, California
| | - David Dimmock
- Rady Children's Institute of Genomic Medicine, San Diego, California
| | - Courtney D Thornburg
- Department of Pediatrics, Division of Hematology and Oncology, University of California San Diego, La Jolla, California; Hemophilia and Thrombosis Treatment Center, Rady Children's Hospital San Diego, San Diego, California
| | - Benjamin Briggs
- Rady Children's Institute of Genomic Medicine, San Diego, California.
| |
Collapse
|
|
14
|
Gosselin RC. Preparing Surrogate Abnormal Quality Control Samples for Platelet Function Studies and Viscoelastic Testing. Methods Mol Biol 2023; 2663:637-645. [PMID: 37204742 DOI: 10.1007/978-1-0716-3175-1_42] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
In the United States, published options for clinical laboratories to perform quality control (QC) procedures less stringent than the regulatory requirements (Clinical and Laboratory Improvement Act, CLIA) based on risk assessment, although the laboratory must perform to manufacturer's minimum requirements. The US requirements for internal quality control requires at least two levels of control material every 24 h of patient testing. For some coagulation testing, the recommended quality control may be a normal sample or commercial controls that do not address all reporting components of the test. Additional circumstances and difficulties in achieving this minimum QC requirement can be due to either (1) nature of the sample type (i.e., whole blood sample requirements), (2) lack of commercial or suitable control material, or (3) unusual or rare samples. The purpose of this chapter is to provide provisional guidance for laboratory sites to prepared samples to verify the performance of reagents and testing performance of platelet function studies and viscoelastic measurements.
Collapse
Affiliation(s)
- Robert C Gosselin
- Thrombosis & Hemostasis Center, University of California, Davis Health System, Sacramento, CA, USA
| |
Collapse
|
|
15
|
Batçıoğlu K, Küçükbay FZ, Alagöz MA, Günal S, Yilmaztekin Y. Antioxidant and antithrombotic properties of fruit, leaf, and seed extracts of the Halhalı olive (Olea europaea L.) native to the Hatay region in Turkey. FOODS AND RAW MATERIALS 2022. [DOI: 10.21603/2308-4057-2023-1-557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
The olive (Olea europaea L.) is one of the most important plants grown in many Mediterranean countries that has a high economic value. Olives, which are specific to each region, have different bioactive components. In this study, we investigated the phenolic/flavonoid contents, as well as antioxidant, antimicrobial, and antithrombotic activities of the fruit, leaf, and seed extracts obtained from the Halhalı olive grown in Arsuz district of Hatay, Turkey.
Antioxidant activities of the phenolic compounds found in the olive fruit, seed, and leaf extracts were determined by employing established in vitro systems. Total phenolics were determined as gallic acid equivalents, while total flavonoids were determined as quercetin equivalents. Also, we evaluated a possible interaction between oleuropein and aggregation-related glycoproteins of the platelet surface via docking studies.
The extracts showed effective antioxidant activity. The seed extract had the highest phenolic content of 317.24 μg GAE, while the fruit extract had the highest flavonoid content of 4.43 μg. The highest potential for metal chelating activity was found in the leaf extract, with an IC50 value of 13.33 mg/mL. Also, the leaf extract showed higher levels of antioxidant, antithrombotic, and antimicrobial activity, compared to the fruit and seed extracts. The docking scores of oleuropein against the target molecules GPVI, α2β1, and GPIbα were calculated as –3.798, –4.315, and –6.464 kcal/mol, respectively.
The olive fruit, leaf, and seed extracts used as experimental material in our study have remarkable antioxidant, antimicrobial, and antithrombotic potential.
Collapse
|
|
16
|
Schriner JB, George MJ, Cardenas JC, Olson SD, Mankiewicz KA, Cox CS, Gill BS, Wade CE. PLATELET FUNCTION IN TRAUMA: IS CURRENT TECHNOLOGY IN FUNCTION TESTING MISSING THE MARK IN INJURED PATIENTS? Shock 2022; 58:1-13. [PMID: 35984758 PMCID: PMC9395128 DOI: 10.1097/shk.0000000000001948] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
ABSTRACT Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. After injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure one or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays have revealed that platelet dysfunction is strongly associated with poor clinical outcomes. However, to date, the mechanism(s) causing clinically significant platelet dysfunction remain poorly understood. We review the pros, cons, and evidence for use of many of the popular assays in trauma, discuss limitations of their use in this patient population, and present approaches that can be taken to develop improved functional assays capable of elucidating mechanisms of trauma-induced platelet dysfunction. Platelet dysfunction in trauma has been associated with need for transfusions and mortality; however, most of the current platelet function assays were not designed for evaluating trauma patients, and there are limited data regarding their use in this population. New or improved functional assays will help define the mechanisms by which platelet dysfunction occurs, as well as help optimize future treatment.
Collapse
Affiliation(s)
- Jacob B. Schriner
- Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Mitchell J. George
- Department of Cardiothoracic and Vascular Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Jessica C. Cardenas
- Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Scott D. Olson
- Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Kimberly A. Mankiewicz
- Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Charles S. Cox
- Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
- Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
- Program in Pediatric Regenerative Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Brijesh S. Gill
- Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
- Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Charles E. Wade
- Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA
| |
Collapse
|
|
17
|
Hsu H, Chan MV, Armstrong PC, Crescente M, Donikian D, Kondo M, Brighton T, Chen V, Chen Q, Connor D, Joseph J, Morel-Kopp MC, Stevenson WS, Ward C, Warner TD, Rabbolini DJ. A pilot study assessing the implementation of 96-well plate-based aggregometry (Optimul) in Australia. Pathology 2022; 54:746-754. [PMID: 35750510 DOI: 10.1016/j.pathol.2022.03.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 03/09/2022] [Accepted: 03/21/2022] [Indexed: 11/19/2022]
Abstract
Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function. We evaluated the Optimul assay at two centres in Australia, one regional and one tertiary metropolitan, to assess its feasibility as a screening test applicable to remote regional centres. Concentration-response curves were established from 45 healthy volunteers at the participating regional hospital and from 31 healthy volunteers at the tertiary institution. Optimul successfully detected anti-platelet effects in individuals taking aspirin (n=4), NSAID (n=2), clopidogrel (n=2) and dual therapy with aspirin and clopidogrel (n=1). When tested in parallel to LTA in individuals referred for the evaluation of abnormal bleeding symptoms there was overall a very good level of agreement between Optimul and LTA [Cohen's kappa (k2)=0.84], supporting its role as a useful screening tool in the assessment of platelet function. Optimul assay performance was quick and the methodology simple, requiring no specialised training or resources to be implemented at either the regional or metropolitan laboratory. Widespread implementation, particularly in regional laboratories within Australia where specialised platelet function testing is unavailable, has the potential to drastically improve the inequity of access to such services.
Collapse
Affiliation(s)
- Hannah Hsu
- Prince of Wales Hospital, Sydney, NSW, Australia
| | - Melissa V Chan
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; National Heart, Blood and Lung Institute, Population Sciences Branch, Framingham, MA, USA
| | - Paul C Armstrong
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Marilena Crescente
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Dea Donikian
- Haematology NSW Health Pathology Randwick, Sydney, NSW, Australia
| | - Mayuko Kondo
- Haematology NSW Health Pathology Randwick, Sydney, NSW, Australia
| | - Timothy Brighton
- Haematology NSW Health Pathology Randwick, Sydney, NSW, Australia; Prince of Wales Hospital, Sydney, NSW, Australia
| | - Vivien Chen
- Haematology, Concord Repatriation General Hospital and NSW Health Pathology, Sydney, NSW, Australia; ANZAC Research Institute and University of Sydney, Sydney, NSW, Australia
| | - Qiang Chen
- Northern Blood Research Centre, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
| | - David Connor
- St Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia
| | - Joanne Joseph
- St Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia; St Vincent's Hospital, Sydney, NSW, Australia
| | - Marie-Christine Morel-Kopp
- Northern Blood Research Centre, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
| | - William S Stevenson
- Northern Blood Research Centre, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
| | - Christopher Ward
- Northern Blood Research Centre, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
| | - Timothy D Warner
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - David J Rabbolini
- Northern Blood Research Centre, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Northern Clinical School and the Rural Clinical School (Northern Rivers), Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Lismore Base Hospital, Lismore, NSW, Australia.
| |
Collapse
|
|
18
|
Loganathan J, Cohen AC, Kaloupis GM, Harris C, Chronopoulos A, James V, Hamilton J, Green S, Wallis A, Morgan S, Dauer R, Gilfillan C, Dear AE. A pilot clinical study to Evaluate Liraglutide-mediated Anti-platelet activity in patients with type-2 Diabetes (ELAID study). J Diabetes Complications 2022; 36:108188. [PMID: 35382966 DOI: 10.1016/j.jdiacomp.2022.108188] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/24/2022] [Accepted: 03/26/2022] [Indexed: 11/20/2022]
Abstract
BACKGROUND Liraglutide is an effective treatment for the management of type 2 diabetes mellitus (T2DM). In addition to glycemic control and potential cardioprotective effects, recent studies suggest a possible role for liraglutide in the inhibition of platelet reactivity, further attenuating atherothrombotic risk in patients with T2DM. We evaluated the in-vivo antiplatelet effect of liraglutide in T2DM patients without macrovascular disease or concurrent anti-platelet therapy. METHODS A double-blind, placebo-controlled pilot study of 16 T2DM patients, 51-69 y/o, (mean age 60.4 y/o, 63.0% male) randomised to receive liraglutide (1.8 mg/day) or placebo (saline) for 6 months was conducted. Platelet aggregation studies at baseline and after initiation of the study intervention: days 1, 7, and 14 and months 1, 3 and 6 were performed. RESULTS Liraglutide (n = 7) and placebo (n = 9) treated patients demonstrated normal platelet aggregation responses although transient and significant attenuation in maximum slope of platelet aggregation in response to collagen (p ≤ 0.05), arachidonic acid (p ≤ 0.05) and ADP (p ≤ 0.02) was observed in liraglutide compared to placebo treated patients in the first week. CONCLUSIONS In this pilot study of patients with T2DM liraglutide treatment was associated with a significant, early and transient decrease in maximum slope of platelet aggregation. The clinical significance of this effect is currently unknown and may warrant further investigation. CLINICAL TRIAL REGISTRATION NUMBER UTN 1111-1181-9567.
Collapse
Affiliation(s)
- Jayasree Loganathan
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Adam C Cohen
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Georgia M Kaloupis
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Carolyn Harris
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | | | - Vanessa James
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Justin Hamilton
- Australian Centre for Blood Diseases, Monash University, Prahran, Melbourne, Victoria, Australia
| | - Sarah Green
- Alfred Pathology Service, Alfred Health, Alfred Hospital, Melbourne, Victoria, Australia
| | - Andrew Wallis
- Alfred Pathology Service, Alfred Health, Alfred Hospital, Melbourne, Victoria, Australia
| | - Susan Morgan
- Alfred Pathology Service, Alfred Health, Alfred Hospital, Melbourne, Victoria, Australia
| | - Raymond Dauer
- Department of Pathology, Eastern Health, Box Hill Hospital, Melbourne, Australia
| | - Christopher Gilfillan
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia; Department of Endocrinology, Eastern Health, Box Hill Hospital, Melbourne, Victoria, Australia
| | - Anthony E Dear
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia.
| |
Collapse
|
|
19
|
Kaiser T, Liebscher K, Scholz U, Pfrepper C, Netto J, Drogies T, Tiebel O, Knöfler R, Krause M. Influencing factors and differences in Born aggregometry in specialized hemostaseological centers – results of a multi-center laboratory comparison. TH OPEN 2022; 6:e213-e220. [PMID: 36046201 PMCID: PMC9395241 DOI: 10.1055/a-1827-7025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 02/14/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction
Light transmission aggregometry (LTA) is regarded as the gold standard in platelet function diagnostics. However, there is a relevant degree of interlaboratory variability in practical applications.
Objective
The aim of the present study was to develop a practicable laboratory comparison on LTA and to analyze differences and influencing factors in regard to standardization in five specialized hemostaseological centers.
Methods
The study was performed on 30 patients in total. Each center performed LTA on blood samples from six healthy volunteers (three men and three women) using the inductors collagen (Col), adenosine diphosphate (ADP), arachidonic acid (ARA), and ristocetin. The LTA was performed three times using different methods as follows: (1) International Society on Thrombosis and Haemostasis recommendations with identical reagents, (2) in-house protocols and the identical reagents; and (3) in-house protocols and in-house reagents.
Results
A total of 396 measurements of 30 probands were performed. Even after standardization of the protocol and using identical reagents, there were significant differences between the centers regarding the final and maximum aggregation (
p
= 0.002 and <0.001) and further significant differences in the maximum and final aggregation according to the wavelength of the device used to measure the LTA (PAP-8: 430 nm, APACT 4004: 740 nm [
p
< 0.001 each]). Using identical reagents but individual inductor concentrations and laboratory protocols also resulted in different maximum and final aggregation. The largest differences were seen with Col and ristocetin; there were significant influences from the reagents' manufacturers in the results of aggregometry for the inductor Col (
p
< 0.01) but not for ADP, ARA, and ristocetin.
Conclusion
In this study, we proved that there are significant influences from the used aggregometers, inductors concentrations, and manufacturers. These results illustrate the challenges and importance of standardization of LTA.
Collapse
Affiliation(s)
- Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany, Leipzig, Germany
| | - Karin Liebscher
- Institute of Transfusion Medicine and Clinical Hemostaseology, Klinikum St. Georg gGmbH, Leipzig, Germany
| | | | | | - Jeffrey Netto
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany, Leipzig, Germany
| | - Tim Drogies
- Medical Central Laboratory Altenburg, Altenburg, Germany
| | - Oliver Tiebel
- Institute of Clinical Chemistry and Laboratory Medicine, Universitätsklinikum Carl Gustav Carus, Dresden, Germany
| | - Ralf Knöfler
- 10. Department of Pediatric Hemostaseology, Univ. Children Hospital, Dresden, Germany
| | - Michael Krause
- MVZ Laboratory Reising-Ackermann MD and Colleagues, Leipzig, Germany
| |
Collapse
|
|
20
|
Bourguignon A, Tasneem S, Hayward CP. Screening and diagnosis of inherited platelet disorders. Crit Rev Clin Lab Sci 2022; 59:405-444. [PMID: 35341454 DOI: 10.1080/10408363.2022.2049199] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Inherited platelet disorders are important conditions that often manifest with bleeding. These disorders have heterogeneous underlying pathologies. Some are syndromic disorders with non-blood phenotypic features, and others are associated with an increased predisposition to developing myelodysplasia and leukemia. Platelet disorders can present with thrombocytopenia, defects in platelet function, or both. As the underlying pathogenesis of inherited thrombocytopenias and platelet function disorders are quite diverse, their evaluation requires a thorough clinical assessment and specialized diagnostic tests, that often challenge diagnostic laboratories. At present, many of the commonly encountered, non-syndromic platelet disorders do not have a defined molecular cause. Nonetheless, significant progress has been made over the past few decades to improve the diagnostic evaluation of inherited platelet disorders, from the assessment of the bleeding history to improved standardization of light transmission aggregometry, which remains a "gold standard" test of platelet function. Some platelet disorder test findings are highly predictive of a bleeding disorder and some show association to symptoms of prolonged bleeding, surgical bleeding, and wound healing problems. Multiple assays can be required to diagnose common and rare platelet disorders, each requiring control of preanalytical, analytical, and post-analytical variables. The laboratory investigations of platelet disorders include evaluations of platelet counts, size, and morphology by light microscopy; assessments for aggregation defects; tests for dense granule deficiency; analyses of granule constituents and their release; platelet protein analysis by immunofluorescent staining or flow cytometry; tests of platelet procoagulant function; evaluations of platelet ultrastructure; high-throughput sequencing and other molecular diagnostic tests. The focus of this article is to review current methods for the diagnostic assessment of platelet function, with a focus on contemporary, best diagnostic laboratory practices, and relationships between clinical and laboratory findings.
Collapse
Affiliation(s)
- Alex Bourguignon
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
| | - Subia Tasneem
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
| | - Catherine P Hayward
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.,Department of Medicine, McMaster University, Hamilton, Canada
| |
Collapse
|
|
21
|
Dave RG, Geevar T, Chellaiya GK, Mammen JJ, Vijayan R, Samuel A, Gowri M, Nair SC. Stability and utility of flow cytometric platelet activation tests: A modality to bridge the gap between diagnostic demand and supply. Platelets 2022; 33:1043-1051. [DOI: 10.1080/09537104.2022.2042232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Rutvi Gautam Dave
- Department of Transfusion Medicine and Immunohematology, Christian Medical College Vellore, Vellore, India
| | - Tulasi Geevar
- Department of Transfusion Medicine and Immunohematology, Christian Medical College Vellore, Vellore, India
| | | | - Joy John Mammen
- Department of Transfusion Medicine and Immunohematology, Christian Medical College Vellore, Vellore, India
| | - Ramya Vijayan
- Department of Transfusion Medicine and Immunohematology, Christian Medical College Vellore, Vellore, India
| | - Ashok Samuel
- Department of Transfusion Medicine and Immunohematology, Christian Medical College Vellore, Vellore, India
| | - Mahasampath Gowri
- Department of Biostatistics, Christian Medical College Vellore, Vellore, India
| | - Sukesh Chandran Nair
- Department of Transfusion Medicine and Immunohematology, Christian Medical College Vellore, Vellore, India
| |
Collapse
|
|
22
|
Wagner M, Uzun G, Bakchoul T, Althaus K. Diagnosis of Platelet Function Disorders: A Challenge for Laboratories. Hamostaseologie 2022; 42:36-45. [PMID: 35196730 DOI: 10.1055/a-1700-7036] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
In patients with normal plasmatic coagulation and bleeding tendency, platelet function defect can be assumed. Congenital platelet function defects are rare. Much more commonly they are acquired. The clinical bleeding tendency of platelet function defects is heterogeneous, which makes diagnostic approaches difficult. During the years, a large variety of tests for morphological phenotyping and functional analysis have been developed. The diagnosis of platelet function defects is based on standardized bleeding assessment tools followed by a profound morphological evaluation of the platelets. Platelet function assays like light transmission aggregation, luminoaggregometry, and impedance aggregometry followed by flow cytometry are commonly used to establish the diagnosis in these patients. Nevertheless, despite great efforts, standardization of these tests is poor and in most cases, quality control is lacking. In addition, these tests are still limited to specialized laboratories. This review summarizes the approaches to morphologic phenotyping and platelet testing in patients with suspected platelet dysfunction, beginning with a standardized bleeding score and ending with flow cytometry testing. The diagnosis of a functional defect requires a good collaboration between the laboratory and the clinician.
Collapse
Affiliation(s)
- Miriam Wagner
- Transfusion Medicine, Faculty of Medicine, University of Tübingen, Tübingen, Germany
| | - Günalp Uzun
- Centre for Clinical Transfusion Medicine, Tübingen ZKT gGmbH, Tübingen, Germany
| | - Tamam Bakchoul
- Transfusion Medicine, Faculty of Medicine, University of Tübingen, Tübingen, Germany.,Centre for Clinical Transfusion Medicine, Tübingen ZKT gGmbH, Tübingen, Germany
| | - Karina Althaus
- Transfusion Medicine, Faculty of Medicine, University of Tübingen, Tübingen, Germany.,Centre for Clinical Transfusion Medicine, Tübingen ZKT gGmbH, Tübingen, Germany
| |
Collapse
|
|
23
|
Stasko J, Holly P, Kubisz P. A new decade awaits sticky platelet syndrome: where are we now, how do we manage and what are the complications? Expert Rev Hematol 2022; 15:53-63. [PMID: 35034520 DOI: 10.1080/17474086.2022.2030217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Sticky platelet syndrome is a less known platelet function disorder with a familiar occurrence and likely genetic background. Clinically, it is characterized by an increased risk of venous and arterial thromboembolic events and obstetric placenta-mediated complications. The increased aggregation after low-dose ADP and/or epinephrine is its distinctive laboratory feature. Though described for almost 40 years, several issues regarding its etiology, involved pathomechanisms, genetic background, optimal diagnostic and treatment approach remain controversial. AREAS COVERED The work aims to summarize published studies, the actual definition of the syndrome, and point out its drawbacks. A literature search on Medline, Embase, and archives from EHA congresses was performed (terms: 'sticky platelet syndrome' - 'platelet hyperreactivity' - 'platelet hyperaggregability'). The authors added in their unpublished data. The introductory overview of the present understanding is followed by the discussion of the pathophysiologic, diagnostic, and therapeutic problems. EXPERT OPINION Despite the growing evidence provided by case reports and series, the lack of robust studies limits the decision-making on diagnostics and management. The diagnostic issues, particularly the standardization of light transmission aggregometry, represent the crucial problem for the broader acceptance of the syndrome.
Collapse
Affiliation(s)
- Jan Stasko
- Department of Hematology and Transfusion Medicine, National Center of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin of the Comenius University in Bratislava, University Hospital in Martin, Martin, Slovakia
| | - Pavol Holly
- Department of Hematology and Transfusion Medicine, National Center of Hemostasis and Thrombosis, University Hospital in Martin, Martin, Slovakia
| | - Peter Kubisz
- Department of Hematology and Transfusion Medicine, National Center of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin of the Comenius University in Bratislava, University Hospital in Martin, Martin, Slovakia
| |
Collapse
|
|
24
|
Clauser JC, Maas J, Mager I, Halfwerk FR, Arens J. The porcine abattoir blood model-Evaluation of platelet function for in-vitro hemocompatibility investigations. Artif Organs 2021; 46:922-931. [PMID: 34904246 DOI: 10.1111/aor.14146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 10/21/2021] [Accepted: 12/07/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The major obstacle of blood-contacting medical devices is insufficient hemocompatibility, particularly thrombogenicity and platelet activation. Pre-clinical in-vitro testing allows for the evaluation of adverse thrombogenicity-related events, but is limited, among others, by the availability and quantity of human blood donations. The use of animal blood is an accepted alternative for several tests; however, animal and particularly abattoir blood might present species-specific differences to human blood as well as elevated blood values, and pre-activated platelets due to stressed animals and non-standardized blood collection. MATERIAL & METHODS To this end, we investigated porcine abattoir blood in comparison to human donor blood with the focus on platelet pre-activation and remaining activation potential. By means of light transmission aggregometry, aggregation kinetics of platelet rich plasma after stimulation with three different concentrations of each adenosine diphosphate (ADP) (5 µM, 10 µM, 20 µM) and collagen (2.5 µg/ml, 5 µg/ml, 10 µg/ml) were monitored. RESULTS The activation with collagen revealed no significant differences in platelet behavior of the two species. In contrast, stimulation with ADP resulted in a lower maximum aggregation and a high disaggregation for porcine abattoir blood. The latter is a species-specific phenomenon of porcine platelets. Variations within each study cohort were comparable for human and abattoir pig. CONCLUSION The similarities in platelet activation following collagen stimulation and the preservation of the porcine-specific reaction to ADP prove a general functionality of the abattoir blood. This finding provides a first step towards the complete validation of the porcine abattoir blood model.
Collapse
Affiliation(s)
- Johanna C Clauser
- Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Judith Maas
- Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Ilona Mager
- Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Frank R Halfwerk
- Chair of Engineering Organ Support Technologies, Department of Biomechanical Engineering, Faculty of Engineering Technology, University of Twente, Enschede, The Netherlands.,Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Jutta Arens
- Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Chair of Engineering Organ Support Technologies, Department of Biomechanical Engineering, Faculty of Engineering Technology, University of Twente, Enschede, The Netherlands
| |
Collapse
|
|
25
|
Kim CJ, Kim J, Sabaté Del Río J, Ki DY, Kim J, Cho YK. Fully automated light transmission aggregometry on a disc for platelet function tests. LAB ON A CHIP 2021; 21:4707-4715. [PMID: 34752594 DOI: 10.1039/d1lc00708d] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Platelet function tests, a group of assays that measure the ability of platelets to aggregate and promote clotting in a sample of blood, are performed in various medical fields to assess inherited platelet function disorders and monitor antiplatelet therapies. Light transmission aggregometry (LTA) is considered the gold standard for platelet function assessment. However, the lack of a standardized protocol is a major drawback when applied at the point of care. Moreover, it is a time-consuming and labor-intensive assay that requires a large volume of blood. Here, we describe the design, fabrication, and operation of a centrifugal microfluidic disc that can perform a fully automated LTA assay from a small volume of a whole blood sample (<1 mL), achieving highly reproducible results (3.2% coefficient of variation) within a short period (<25 min). The assays performed with this device yield more precise and accurate results than traditional LTA because of the automation of the reaction steps, minimal human operation, robust detection strategy via the distinctive structure of the microfluidic chamber, and quick analysis that minimizes the adverse effects of platelet instability.
Collapse
Affiliation(s)
- Chi-Ju Kim
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
- Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea
| | - Jungmin Kim
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
- Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea
| | - Jonathan Sabaté Del Río
- Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea
| | - Dong Yeob Ki
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
- Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea
| | - Junyoung Kim
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
- Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea
| | - Yoon-Kyoung Cho
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
- Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea
| |
Collapse
|
|
26
|
Li L, Huskens D, Florin L, de Laat B, Roest M, Devreese KMJ. Flow cytometric analysis of platelet function to detect high on-treatment residual platelet reactivity in patients on dual antiplatelet therapy. Int J Lab Hematol 2021; 44:e100-e102. [PMID: 34672087 DOI: 10.1111/ijlh.13744] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/04/2021] [Accepted: 10/06/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Li Li
- Synapse Research Institute, Maastricht, The Netherlands.,Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Dana Huskens
- Synapse Research Institute, Maastricht, The Netherlands
| | - Lisa Florin
- Coagulation Laboratory, Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - Bas de Laat
- Synapse Research Institute, Maastricht, The Netherlands.,Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Mark Roest
- Synapse Research Institute, Maastricht, The Netherlands
| | - Katrien M J Devreese
- Coagulation Laboratory, Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.,Department of Diagnostic Sciences, Ghent University, Ghent, Belgium
| |
Collapse
|
|
27
|
Gomez K, Anderson J, Baker P, Biss T, Jennings I, Lowe G, Platton S. Clinical and laboratory diagnosis of heritable platelet disorders in adults and children: a British Society for Haematology Guideline. Br J Haematol 2021; 195:46-72. [PMID: 34435350 DOI: 10.1111/bjh.17690] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Keith Gomez
- Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London
| | - Julia Anderson
- Haemophilia Thrombosis and Immunology Centre, Royal Infirmary, NHS Lothian, Edinburgh
| | - Peter Baker
- Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Foundation Trust, Oxford
| | - Tina Biss
- Haemophilia Comprehensive Care Centre, Royal Victoria Infirmary, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne
| | - Ian Jennings
- UK NEQAS for Blood Coagulation, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield
| | - Gillian Lowe
- Haemophilia Comprehensive Care Centre, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Sean Platton
- Haemophilia Centre, The Royal London Hospital, Barts Health NHS Trust, London, UK
| |
Collapse
|
|
28
|
Approach to the Patient with Bleeding. Hematol Oncol Clin North Am 2021; 35:1039-1049. [PMID: 34535288 DOI: 10.1016/j.hoc.2021.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Approach to the patient with bleeding begins with a thorough bleeding, medical, and family history to determine the nature of bleeding and severity of bleeding symptoms. Use of a Bleeding Assessment Tool allows the clinician to obtain a comprehensive bleeding history and ultimately determine the individual bleeding score that reflects bleeding severity and is classifiable as either normal or abnormal. In the absence of significant findings within patient history or presenting symptoms clearly pointing to a specific bleeding pathology, an approach to laboratory investigation is presented that proceeds through first-line, second-line, and third-line testing.
Collapse
|
|
29
|
Racine-Brzostek SE, Asmis LM. Assessment of platelet function utilizing viscoelastic testing. Transfusion 2021; 60 Suppl 6:S10-S20. [PMID: 33089932 DOI: 10.1111/trf.16081] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 08/29/2020] [Accepted: 08/29/2020] [Indexed: 12/19/2022]
Affiliation(s)
- Sabrina E Racine-Brzostek
- Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, New York, USA
| | - Lars M Asmis
- Centre for Perioperative Thrombosis and Haemostasis, Zurich, Switzerland
| |
Collapse
|
|
30
|
Monteyne T, Heireman L, Hemelsoet D, van Schaik RHN, Devreese KMJ. Is monitoring of antiplatelet therapy by light transmission aggregometry dependent on instrument and reagent used? Int J Lab Hematol 2021; 43:786-794. [PMID: 34129280 DOI: 10.1111/ijlh.13579] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 04/15/2021] [Accepted: 04/22/2021] [Indexed: 01/22/2023]
Abstract
INTRODUCTION Light transmission aggregometry (LTA), used to detect clopidogrel resistance in patients under antiplatelet therapy, is prone to multiple variables potentially influencing results and interpretation. Currently, no attention is given to type of aggregometer or reagent used. The aim of this study was to evaluate the interassay variability between two aggregometers (Chronolog700 and TA-8V), using two different ADP reagents (Chrono-Par® and Agro-Bio ADP) in patients under clopidogrel therapy. Additionally, LTA results were correlated to CYP2C19-polymorphism. METHODS Light transmission aggregometry was performed in 20 healthy individuals and 30 patients using both aggregometers, and applying two different reagents (2.5 and 5 µmol/L). The maximum platelet aggregation (ADPmax ), the platelet aggregation at 6 minutes (ADP6min ), and the percentage of disaggregation at 6 min (ADP%disaggr ) were compared between four applied combinations. Additionally, 23 clopidogrel-resistant patients according to Chronolog700-Chrono-par® ADP reagent analysis were tested for CYP2C19*2 polymorphism. RESULTS Comparison of the LTA of healthy individuals revealed a significant lower ADPmax , lower ADP6min , and higher ADP%disaggr with the TA-8V aggregometer compared to Chronolog700, regardless of the reagent. In contrast, LTA results in patients are depending on the reagent, with significant higher ADPmax and ADP6min and lower ADP%disaggr using Chrono-Par® compared to Agro-Bio ADP reagent. All intermediate clopidogrel metabolizers (CYP2C19*2 carriers) were correctly classified as clopidogrel resistant using Chrono-Par® , in contrast to the Agro-Bio ADP reagent. CONCLUSION Light transmission aggregometry in clopidogrel-treated patients is mainly depending on the type of ADP reagent. Comparison of LTA with genotype reveals that the choice of instrument seems less influencing. In contrast, in the healthy individuals, differences could be attributed to the instrument.
Collapse
Affiliation(s)
- Tinne Monteyne
- Coagulation Laboratory, Department of Laboratory Medicine, University Hospital Ghent, Ghent, Belgium
| | - Laura Heireman
- Coagulation Laboratory, Department of Laboratory Medicine, University Hospital Ghent, Ghent, Belgium
| | | | - Ron H N van Schaik
- Department of Clinical Chemistry, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Katrien M J Devreese
- Coagulation Laboratory, Department of Laboratory Medicine, University Hospital Ghent, Ghent, Belgium.,Department of Diagnostic Sciences, Ghent University, Ghent, Belgium
| |
Collapse
|
|
31
|
Jurk K, Shiravand Y. Platelet Phenotyping and Function Testing in Thrombocytopenia. J Clin Med 2021; 10:jcm10051114. [PMID: 33800006 PMCID: PMC7962106 DOI: 10.3390/jcm10051114] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 02/21/2021] [Accepted: 03/02/2021] [Indexed: 01/19/2023] Open
Abstract
Patients who suffer from inherited or acquired thrombocytopenia can be also affected by platelet function defects, which potentially increase the risk of severe and life-threatening bleeding complications. A plethora of tests and assays for platelet phenotyping and function analysis are available, which are, in part, feasible in clinical practice due to adequate point-of-care qualities. However, most of them are time-consuming, require experienced and skilled personnel for platelet handling and processing, and are therefore well-established only in specialized laboratories. This review summarizes major indications, methods/assays for platelet phenotyping, and in vitro function testing in blood samples with reduced platelet count in relation to their clinical practicability. In addition, the diagnostic significance, difficulties, and challenges of selected tests to evaluate the hemostatic capacity and specific defects of platelets with reduced number are addressed.
Collapse
Affiliation(s)
- Kerstin Jurk
- Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
- Correspondence: ; Tel.: +49-6131-178278
| | - Yavar Shiravand
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy;
| |
Collapse
|
|
32
|
Hayward CPM, George TI, Van Cott EM, Smock KJ. Patient advocacy and its importance to laboratory medicine practice. Int J Lab Hematol 2021; 42 Suppl 1:21-22. [PMID: 32543067 DOI: 10.1111/ijlh.13193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 02/18/2020] [Accepted: 03/11/2020] [Indexed: 11/27/2022]
Affiliation(s)
- Catherine P M Hayward
- Departments of Pathology and Molecular Medicine, and Medicine, McMaster University and The Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada
| | - Tracy I George
- Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT, USA
| | - Elizabeth M Van Cott
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kristi J Smock
- Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT, USA
| |
Collapse
|
|
33
|
Kaufmann J, Adler M, Alberio L, Nagler M. Utility of the Platelet Function Analyzer in Patients with Suspected Platelet Function Disorders: Diagnostic Accuracy Study. TH OPEN 2020; 4:e427-e436. [PMID: 33376942 PMCID: PMC7755505 DOI: 10.1055/s-0040-1721502] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 10/28/2020] [Indexed: 11/30/2022] Open
Abstract
Introduction
The platelet function analyzer (PFA) is widely used as a screening tool for bleeding disorders in various settings. The diagnostic performance regarding platelet function disorders (PFDs), which are among the most common inherited bleeding disorders, is however still elusive. We aimed to assess the diagnostic value of PFA for PFD in clinical practice.
Methods
Comprehensive clinical and laboratory data of all consecutive patients referred to a specialized outpatient between January 2012 and March 2017 with a suspected bleeding disorder were prospectively recorded. The diagnostic work-up was performed according to a prespecified protocol following current guidelines and platelet function was tested using light transmission aggregometry as well as flow cytometry.
Results
Five hundred and fifty-five patients were included (median age 43.7 years; interquartile range [IQR] 29.3, 61.7; 66.9% female). Possible PFD was diagnosed in 64 patients (11.5%) and confirmed PFD in 54 patients (9.7%). In patients with confirmed PFD, median closure times were 107 seconds (ADP or adenosine diphosphate; IQR 89, 130) and 169 seconds (EPI; IQR 121, 211). In patients without bleeding disorders, PFA closure times were 96 seconds (ADP; IQR 83, 109) and 137 seconds (EPI; IQR 116, 158). The sensitivity was 19.5% in case of PFA ADP (95%CI 12.6, 30.0; specificity 86.4%; 95% CI 82.4, 89.8), and 44.3% in case of PFA EPI (95% CI 34.9, 53.9; specificity 75.6%; 95% CI 70.8, 79.9).
Conclusion
The diagnostic performance of PFA for PFD was moderate to poor. Our results do not support the utilization of PFA for screening of PFD in clinical practice.
Collapse
Affiliation(s)
- Jonas Kaufmann
- Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland
| | - Marcel Adler
- Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.,Division of Hematology and Central Hematology Laboratory, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Lorenzo Alberio
- Division of Hematology and Central Hematology Laboratory, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.,Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Michael Nagler
- Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.,University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| |
Collapse
|
|
34
|
Trampuš-Bakija A, Jazbec J, Faganel-Kotnik B. Platelet lumiaggregation testing: Reference intervals and the effect of acetylsalicylic acid in healthy adults. J Med Biochem 2020; 39:422-427. [PMID: 33312057 DOI: 10.5937/jomb0-24690] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 11/21/2019] [Indexed: 11/02/2022] Open
Abstract
Background Light transmission aggregometry with lumiaggregometry are methods commonly recommended as a first-line test in platelet dysfunction diagnostic work-up. They are poorly standardized and usually performed in specialized laboratories. For proper interpretation, each laboratory should establish its own diagnostic approach in order to recognize abnormal aggregation patterns. The aim of this study was to measure plasma lumiaggregometry with basic agonists to establish the analyzer-reagent reference intervals (RI) for adults and to test the method response to aspirin. Methods The Chrono-Log Model 700 lumiaggregometer using Chrono-Par and Chrono-lume reagents (Chrono-Log Corp., Havertown, PA, USA) was used to measure the maximal aggregation and adenosine triphosphate release using adenosine diphosphate (2 μmol/L), collagen (2 μg/mL), arachidonic acid (1 μmol/L), epinephrine (5.5 μmol/L) and ristocetin (1.25 mg/mL), and thrombin (1 U/mL). The effect of aspirin on platelet aggregation and granule release was inspected. Results RIs derived from 40 healthy adults were calculated using the non-parametric approach. Wider intervals and low lower limits were determined for weak agonist as well as absence or impaired aggregation in up to one of 7 healthy controls. The response of platelets to aspirin shows response comparable to previously reported study. Conclusions Locally established RI in our study enable us to investigate platelet function in patients with a high probability of bleeding disorders. Values are agonist and equipment specific. The variability of the method can be reduced by considering standardized preanalytical and analytical variables. Pathological results must be interpreted in the context of other hemostasis test results and clinical findings.
Collapse
Affiliation(s)
- Alenka Trampuš-Bakija
- University Medical Centre Ljubljana (UMC), University Children's Hospital, Institute of Special Laboratory Diagnostic, Ljubljana, Slovenia
| | - Janez Jazbec
- University Medical Centre Ljubljana (UMC), University Children's Hospital, Department of Haematology and Oncology, Ljubljana, Slovenia
| | - Barbara Faganel-Kotnik
- University Medical Centre Ljubljana (UMC), University Children's Hospital, Department of Haematology and Oncology, Ljubljana, Slovenia
| |
Collapse
|
|
35
|
Abstract
: Platelets play a pivotal role in controlling hemorrhaging from vessels of the human body. The impairment of platelets may lead to the development of bleeding manifestations. Unraveling the precise defects of platelets by means of suitable laboratory methods paves the way for the effective control and management of platelet disorders. Choosing the most appropriate approach for the detection of platelet disorders may be difficult for a researcher or clinical internist when faced with ordering a platelet-function test. The aim of the current study was to provide a user-friendly overview of the advantages and disadvantages of the available detection systems. To reach this goal, 11 commonly used methods of studying platelet activity were evaluated and compared in detail. A literature search, with no time or language limitations, was conducted in Google Scholar and Medline. All publications published before June 2019 were analyzed. The following laboratory methods were compared: number and size of platelets, bleeding time, clot retraction time, platelet function assay 100 & 200, Rapid platelet function assay, flow cytometry, light transmission aggregometry, multiple electrode aggregometry, 96-well plate aggregometry, cone and plate(let) analyzer (Impact-R), and Plateletworks (single platelet counting system). This article provides the reader with a rapid comparison of the different systems used to study platelets activities.
Collapse
|
|
36
|
Huskens D, Li L, Florin L, de Kesel P, de Laat B, Roest M, Devreese KMJ. Flow cytometric analysis of platelet function to improve the recognition of thrombocytopathy. Thromb Res 2020; 194:183-189. [PMID: 32788114 DOI: 10.1016/j.thromres.2020.06.037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/02/2020] [Accepted: 06/22/2020] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Light transmission aggregometry (LTA) is the gold standard for diagnosing bleeding disorders. Although LTA is laborious, requires large volumes of blood and is relatively insensitive to small changes in platelet function, there is still no competing alternative approach to replace LTA for the diagnosis of platelet bleeding disorders. MATERIALS AND METHODS This study investigates the correlation between flow cytometry-based whole blood platelet activation test (WB-PACT) and LTA and whether WB-PACT is of additional value for the identification of bleeding disorders. In total, 161 patients with suspected bleeding diathesis were tested. RESULTS A correlation of 0.41 between LTA and WB-PACT was found, and there was agreement between tests in 62% of cases (κ = 0.23). The WB-PACT is of additional value to LTA to detect platelet function disorders (PFD) as 10 patients with elevated bleeding score (BS) were detected with WB-PACT, 4 with LTA and 7 patients were positive with both tests. Interestingly, in contrast to LTA, WB-PACT has an additional option to detect VWF disfunctions. CONCLUSION WB-PACT may have added value for the routine diagnostic work-up in patients who need to have platelet function tested.
Collapse
Affiliation(s)
- Dana Huskens
- Synapse Research Institute, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, the Netherlands.
| | - Li Li
- Synapse Research Institute, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Lisa Florin
- Coagulation Laboratory, Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - Pieter de Kesel
- Coagulation Laboratory, Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - Bas de Laat
- Synapse Research Institute, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Mark Roest
- Synapse Research Institute, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Katrien M J Devreese
- Coagulation Laboratory, Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium
| |
Collapse
|
|
37
|
Le Blanc J, Mullier F, Vayne C, Lordkipanidzé M. Advances in Platelet Function Testing-Light Transmission Aggregometry and Beyond. J Clin Med 2020; 9:jcm9082636. [PMID: 32823782 PMCID: PMC7464122 DOI: 10.3390/jcm9082636] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/07/2020] [Accepted: 08/10/2020] [Indexed: 01/19/2023] Open
Abstract
Platelet function testing is essential for the diagnosis of hemostasis disorders. While there are many methods used to test platelet function for research purposes, standardization is often lacking, limiting their use in clinical practice. Light transmission aggregometry has been the gold standard for over 60 years, with inherent challenges of working with live dynamic cells in specialized laboratories with independent protocols. In recent years, standardization efforts have brought forward fully automated systems that could lead to more widespread use. Additionally, new technical approaches appear promising for the future of specialized hematology laboratories. This review presents developments in platelet function testing for clinical applications.
Collapse
Affiliation(s)
- Jessica Le Blanc
- Montreal Heart Institute Research Center, Montréal, QC H1T 1C8, Canada;
- Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada
| | - François Mullier
- Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Hematology Laboratory, 5530 Yvoir, Belgium;
| | - Caroline Vayne
- Department of Hemostasis, University Hospital of Tours, 37044 Tours, France;
- EA 7501 GICC, University of Tours, 37000 Tours, France
| | - Marie Lordkipanidzé
- Montreal Heart Institute Research Center, Montréal, QC H1T 1C8, Canada;
- Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada
- Correspondence: ; Tel.: +1-514-376-3330 (ext. 2694); Fax: +1-514-376-0173
| |
Collapse
|
|
38
|
Munnix ICA, Van Oerle R, Verhezen P, Kuijper P, Hackeng CM, Hopman-Kerkhoff HIJ, Hudig F, Van De Kerkhof D, Leyte A, De Maat MPM, Oude Elferink RFM, Ruinemans-Koerts J, Schoorl M, Slomp J, Soons H, Stroobants A, Van Wijk E, Henskens YMC. Harmonizing light transmission aggregometry in the Netherlands by implementation of the SSC-ISTH guideline. Platelets 2020; 32:516-523. [PMID: 32522065 DOI: 10.1080/09537104.2020.1771549] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Light transmission aggregometry (LTA) is considered the gold standard method for evaluation of platelet function. However, there are a lot of variation in protocols (pre-analytical procedures and agonist concentrations) and results. The aim of our study was to establish a national LTA protocol, to investigate the effect of standardization and to define national reference values for LTA. The SSC guideline was used as base for a national procedure. Almost all recommendations of the SSC were followed e.g. no adjustment of PRP, citrate concentration of 109 mM, 21 needle gauge, fasting, resting time for whole blood and PRP, centrifugation time, speed and agonists concentrations. LTA of healthy volunteers was measured in a total of 16 hospitals with 5 hospitals before and after standardization. Results of more than 120 healthy volunteers (maximum aggregation %) were collected, with participating laboratories using 4 different analyzers with different reagents. Use of low agonist concentrations showed high variation before and after standardization, with the exception of collagen. For most high agonist concentrations (ADP, collagen, ristocetin, epinephrine and arachidonic acid) variability in healthy subjects decreased after standardization. We can conclude that a standardized Dutch protocol for LTA, based on the SSC guideline, does not result in smaller variability in healthy volunteers for all agonist concentrations.
Collapse
Affiliation(s)
- I C A Munnix
- Department of Clinical Chemistry, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
| | - R Van Oerle
- Central Diagnostic Laboratory, Maastricht University Medical Centre +, Maastricht, The Netherlands
| | - P Verhezen
- Central Diagnostic Laboratory, Maastricht University Medical Centre +, Maastricht, The Netherlands
| | - P Kuijper
- Clinical Laboratory, Maxima Medical Centre, Veldhoven, The Netherlands
| | - C M Hackeng
- Department of Clinical Chemistry, St. Antonius Hospital, Nieuwegein, The Netherlands
| | | | - F Hudig
- LabWest, Haga Teaching Hospital, The Hague, The Netherlands
| | - D Van De Kerkhof
- Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands
| | - A Leyte
- Department of Clinical Chemistry, OLVG Laboratoria BV, Amsterdam, The Netherlands
| | - M P M De Maat
- Department of Hematology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | | | - J Ruinemans-Koerts
- Department of Clinical Chemistry and Haematology, Rijnstate Hospital, Arnhem, The Netherlands
| | - M Schoorl
- Department of Clinical Chemistry, Haematology & Immunology,Northwest Clinics, Alkmaar, The Netherlands
| | - J Slomp
- Department of Clinical Chemistry, Medlon, Location Medisch Spectrum Twente, Enschede, The Netherlands
| | - H Soons
- Department of Clinical Chemistry, St. Anna Hospital, Geldrop, The Netherlands
| | - A Stroobants
- Department of Clinical Chemistry, AmsterdamUMC Location AMC, Amsterdam, The Netherlands
| | - E Van Wijk
- Department of Clinical Chemistry, St. Elisabeth Hospital, Tilburg, The Netherlands
| | - Y M C Henskens
- Central Diagnostic Laboratory, Maastricht University Medical Centre +, Maastricht, The Netherlands
| |
Collapse
|
|
39
|
Fouassier M, Babuty A, Debord C, Béné MC. Platelet immunophenotyping in health and inherited bleeding disorders, a review and practical hints. CYTOMETRY PART B-CLINICAL CYTOMETRY 2020; 98:464-475. [PMID: 32516490 DOI: 10.1002/cyto.b.21892] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 04/16/2020] [Accepted: 05/13/2020] [Indexed: 12/15/2022]
Abstract
Inherited platelet function disorders are rare hemorrhagic diseases. The gold standard for their exploration is optical aggregometry; however, investigations by flow cytometry (FCM) are being increasingly used. In this review, the physiology of platelets is first recalled, setting the stage for the compartments of platelets that can be apprehended by specific and appropriate labeling. As this requires some pre-analytical precautions and specific analytical settings, a second part focuses on these characteristic aspects, based on literature and on the authors' experience in the field, for qualitative or quantitative explorations. Membrane labeling with antibodies to CD42a or CD41, respectively, useful to assess the genetic-related defects of Glanzmann thrombocytopenia and Bernard Soulier syndrome are then described. Platelet degranulation disorders are detailed in the next section, as they can be explored, upon platelet activation, by measuring the expression of surface P-Selectin (CD62P) or CD63. Mepacrin uptake and release after activation is another test allowing to explore the function of dense granules. Finally, the flip-flop anomaly related to Scott syndrome is depicted. Tables summarizing possible FCM assays, and characteristic histograms are provided as reference for flow laboratories interested in developing platelet exploration.
Collapse
Affiliation(s)
- Marc Fouassier
- Hematology Biology Department, Nantes University Hospital and CRCINA, Nantes, France
| | - Antoine Babuty
- Hematology Biology Department, Nantes University Hospital and CRCINA, Nantes, France
| | - Camille Debord
- Hematology Biology Department, Nantes University Hospital and CRCINA, Nantes, France
| | - Marie C Béné
- Hematology Biology Department, Nantes University Hospital and CRCINA, Nantes, France
| |
Collapse
|
|
40
|
Heireman L, Monteyne T, Hemelsoet D, van Schaik RHN, Devreese KMJ. Search for a practical approach for detection of clopidogrel resistance: Comparison of light transmission aggregometry and INNOVANCE® PFA P2Y cartridge and correlation with CYP2C19 variants. Int J Lab Hematol 2020; 42:e189-e191. [PMID: 32427413 DOI: 10.1111/ijlh.13240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/07/2020] [Accepted: 04/27/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Laura Heireman
- Coagulation Laboratory, Department of Laboratory Medicine, University Hospital Ghent, Ghent, Belgium
| | - Tinne Monteyne
- Coagulation Laboratory, Department of Laboratory Medicine, University Hospital Ghent, Ghent, Belgium
| | | | - Ron H N van Schaik
- Department of Clinical Chemistry, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Katrien M J Devreese
- Coagulation Laboratory, Department of Laboratory Medicine, University Hospital Ghent, Ghent, Belgium.,Department of Diagnostic Sciences, Ghent University, Ghent, Belgium
| |
Collapse
|
|
41
|
Stratmann J, Karmal L, Zwinge B, Miesbach W. Platelet Aggregation Testing on a Routine Coagulation Analyzer: A Method Comparison Study. Clin Appl Thromb Hemost 2020; 25:1076029619885184. [PMID: 31773967 PMCID: PMC7019398 DOI: 10.1177/1076029619885184] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Platelet function (PF) plays a pivotal role in both hemostasis and thrombosis, and manual
light transmission aggregometry (LTA) is considered the standard of care for platelet
function testing but is an error-prone and time-consuming procedure. We aimed to test the
agreement regarding maximum aggregation (MA), velocity (VEL), and lag-phase (LagP) of
platelet aggregation of the automated Sysmex CS-2100i analyzer (Siemens,
Germany) against the APACT 4004 (Elitech, France) in samples derived from healthy
participants and patients with hemostaseologic disorders. In total, 123 patient-derived
samples were investigated, including 42 patients with acetylsalicylic acid and/or
clopidogrel intake and 20 patients with other hemostaseologic disorders. Both MA and VEL
showed good or excellent intermethod correlation. Agreement between the testing methods
was only partially achieved, and values were indicative for a systematic bias to lower
measurements below a threshold of 50% MA with the CS-2100i compared to
the APACT 4004. All patients with impaired PF in the APACT 4004 were successfully
identified with the CS-2100i, and reference values for automated LTA are
provided. Conclusively, automated LTA with the CS-2100i is a highly
standardized and reliable PF testing method and represents a decisive step in the
simplification of platelet function testing in clinical routine.
Collapse
Affiliation(s)
- Jan Stratmann
- Department of Haemostaseology and Haemophilia Centre, Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany
| | - Lida Karmal
- Department of Haemostaseology and Haemophilia Centre, Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany
| | - Birga Zwinge
- Department of Haemostaseology and Haemophilia Centre, Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany
| | - Wolfgang Miesbach
- Department of Haemostaseology and Haemophilia Centre, Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany.,Institute of Transfusion Medicine, University Hospital Frankfurt, Frankfurt, Germany
| |
Collapse
|
|
42
|
Alessi MC, Sié P, Payrastre B. Strengths and Weaknesses of Light Transmission Aggregometry in Diagnosing Hereditary Platelet Function Disorders. J Clin Med 2020; 9:jcm9030763. [PMID: 32178287 PMCID: PMC7141357 DOI: 10.3390/jcm9030763] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 02/17/2020] [Accepted: 03/03/2020] [Indexed: 12/15/2022] Open
Abstract
Hereditary defects in platelet function are responsible for sometimes severe mucocutaneous hemorrhages. They are a heterogeneous group of abnormalities whose first-line diagnosis typically involves interpreting the results of in vitro light transmission aggregometry (LTA) traces. Interpretation of LTA is challenging. LTA is usually performed in specialized laboratories with expertise in platelet pathophysiology. This review updates knowledge on LTA, describing the various platelet aggregation profiles typical of hereditary platelet disorders to guide the physician in the diagnosis of functional platelet disorders.
Collapse
Affiliation(s)
- Marie-Christine Alessi
- Aix Marseille Univ, Inserm, Inrae, C2VN, 13385 Marseille CEDEX, France
- Correspondence: ; Tel.: +33-4-91-32-45-06
| | - Pierre Sié
- CHU de Toulouse, Laboratoire d’Hématologie, 31059 Toulouse CEDEX, France;
| | - Bernard Payrastre
- Inserm U1048, I2MC et Université Paul Sabatier, 31024 Toulouse CEDEX, France;
| |
Collapse
|
|
43
|
Barale C, Russo I. Influence of Cardiometabolic Risk Factors on Platelet Function. Int J Mol Sci 2020; 21:ijms21020623. [PMID: 31963572 PMCID: PMC7014042 DOI: 10.3390/ijms21020623] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 01/15/2020] [Accepted: 01/16/2020] [Indexed: 12/16/2022] Open
Abstract
Platelets are key players in the thrombotic processes. The alterations of platelet function due to the occurrence of metabolic disorders contribute to an increased trend to thrombus formation and arterial occlusion, thus playing a major role in the increased risk of atherothrombotic events in patients with cardiometabolic risk factors. Several lines of evidence strongly correlate metabolic disorders such as obesity, a classical condition of insulin resistance, dyslipidemia, and impaired glucose homeostasis with cardiovascular diseases. The presence of these clinical features together with hypertension and disturbed microhemorrheology are responsible for the prothrombotic tendency due, at least partially, to platelet hyperaggregability and hyperactivation. A number of clinical platelet markers are elevated in obese and type 2 diabetes (T2DM) patients, including the mean platelet volume, circulating levels of platelet microparticles, oxidation products, platelet-derived soluble P-selectin and CD40L, thus contributing to an intersection between obesity, inflammation, and thrombosis. In subjects with insulin resistance and T2DM some defects depend on a reduced sensitivity to mediators—such as nitric oxide and prostacyclin—playing a physiological role in the control of platelet aggregability. Furthermore, other alterations occur only in relation to hyperglycemia. In this review, the main cardiometabolic risk factors, all components of metabolic syndrome involved in the prothrombotic tendency, will be taken into account considering some of the mechanisms involved in the alterations of platelet function resulting in platelet hyperactivation.
Collapse
|
|
44
|
De Kesel PM, Vantilborgh A, Dierick J, Luyckx A, Debussche S, Freson K, Devreese KMJ. Autosomal dominant macrothrombocytopenia caused by a rare GPIBB variant: The importance of DNA sequencing. Int J Lab Hematol 2019; 42:e98-e100. [PMID: 31793234 DOI: 10.1111/ijlh.13136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 11/05/2019] [Accepted: 11/11/2019] [Indexed: 11/27/2022]
Affiliation(s)
- Pieter M De Kesel
- Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - Anna Vantilborgh
- Department of Hematology, Ghent University Hospital, Ghent, Belgium
| | - Jan Dierick
- Department of Laboratory Medicine, AZ Maria Middelares, Ghent, Belgium
| | - Ariane Luyckx
- Department of Laboratory Medicine, AZ Maria Middelares, Ghent, Belgium
| | - Sarah Debussche
- Department of Hematology, AZ Maria Middelares, Ghent, Belgium
| | - Kathleen Freson
- Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
| | | |
Collapse
|
|
45
|
Lomakin NV, Buryachkovskaya LI, Sumarokov AB, Gabbasov ZA, Gerasimov AN. [Relation of Functional Activity of Platelets to Prognosis of Unfavorable Cardiovascular Events in Patients with Acute Coronary Syndrome. Results of a Registry Study]. ACTA ACUST UNITED AC 2019; 59:5-13. [PMID: 31615383 DOI: 10.18087/cardio.2019.10.n678] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 07/16/2019] [Accepted: 09/17/2019] [Indexed: 11/18/2022]
Abstract
AIM to assess relation ofhigh functional activity ofplatelets to prognosis ofunfavorable cardiovascular events in patients with Acute Coronary Syndrome (ACS). MATERIALS The study was based on the data of a single center ACS registry conducted in the Central Clinical Hospital of the Presidential Affairs Department of Russian Federation. Of 529 included patients in 425 without contraindications to double antiplatelet therapy we carried out analysis of dependence of 30 days level of unfavorable events on parameters of functional activity of platelets. RESULTS High on-treatment platelet reactivity (HTPR) was found to be associated with 3.5 increase of mortality in the group of patients with high cardiovascular risk. Logistic model of prognosis of unfavorable events based on multifactorial analysis of data from patients with measured platelet aggregation included chronic kidney disease, type of myocardial infarction, and degree ofplatelet aggregation >45%. C -statistic was equal to 0.77. We also present in this paper discussion of problems related to studying approaches to individualization of anti-aggregation therapy in real clinical practice and problems of organization ofsimilar studies. CONCLUSION The study showed that patients with ACS increased platelet aggregation, as well as chronic kidney disease and type 2 MI are associated with a 30 day prognosis of adverse events.
Collapse
Affiliation(s)
- N V Lomakin
- Central Clinical Hospital of the Management Affair of President RF
| | | | | | | | - A N Gerasimov
- Sechenov First Moscow State Medical University (Sechenov University)
| |
Collapse
|
|
46
|
Riley R, Khan A, Pai S, Warmke L, Winkler M, Gunning W. A Case of Chronic Thrombocytopenia in a 17-Year-Old Female. Lab Med 2019; 50:406-420. [PMID: 31228350 DOI: 10.1093/labmed/lmz013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Storage pool deficiency (SPD) is a group of rare platelet disorders that result from deficiencies in α-granules, δ-granules, or both. One type of α-SPD is gray platelet syndrome (GPS), caused by mutations in the neurobeachin-like 2 (NBEAL2) gene that results in a bleeding diathesis, thrombocytopenia, splenomegaly, and progressive myelofibrosis. Due to the lack of α-granules, platelets have a gray and degranulated appearance by light microscopy. However, definitive diagnosis of GPS requires confirmation of α-granule deficiency by electron microscopy. Treatment is nonspecific, with the conservative utilization of platelet transfusions being the most important form of therapy. We present a case of a 17-year-old female with a past medical history of thrombocytopenia, first identified at the age of five. Her clinical symptomatology included chronic fatigue, gingival bleeding, bruising, menorrhagia, and leg pain. This report will discuss both the clinical and the pathophysiologic aspects of this rare platelet disorder.
Collapse
Affiliation(s)
- Roger Riley
- Departments of Pathology, Virginia Commonwealth University (VCU) School of Medicine, Richmond
| | - Asad Khan
- Departments of Pediatrics, Virginia Commonwealth University (VCU) School of Medicine, Richmond
| | - Shella Pai
- Departments of Pathology, Virginia Commonwealth University (VCU) School of Medicine, Richmond
| | - Laura Warmke
- Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston
| | | | - William Gunning
- Department of Pathology, University of Toledo College of Medicine, Toledo, Ohio
| |
Collapse
|
|
47
|
High Prevalence of Sticky Platelet Syndrome in Patients with Infertility and Pregnancy Loss. J Clin Med 2019; 8:jcm8091328. [PMID: 31466364 PMCID: PMC6780264 DOI: 10.3390/jcm8091328] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 08/23/2019] [Accepted: 08/26/2019] [Indexed: 11/16/2022] Open
Abstract
Platelet hyperaggregability, known as sticky platelet syndrome (SPS), is a prothrombotic disorder that has been increasingly associated with pregnancy loss. In this retrospective study, we aimed to investigate the clinical and diagnostic relevance of SPS in 208 patients with infertility and unexplained pregnancy loss history. We studied 208 patients that had been referred to undergo a dose-dependent platelet aggregation response to adenosine diphosphate and epinephrine using light transmission aggregometry modified by Mammen during an 11-year period. Patients’ platelet aggregation response was compared with platelet function in 29 female healthy controls of fertile age with no previous history of pregnancy loss. We found a prevalence of SPS type II (33.2%) in 208 female patients with infertility and pregnancy loss. ∆-epinephrine-induced platelet aggregation in patients with SPS was significantly decreased (median 7% and range −21 to 43%) compared to patients without SPS (median 59%, range 7–88% and p < 0.0001) and healthy controls (median 57%, range 8–106% and p < 0.0001). The optimum SPS-diagnostic cutoff value for ∆-epinephrine aggregation was ≤32% (sensitivity 95.7%, specificity 95.2%). SPS patients with low-dose acetylsalicylic acid (ASA) therapy (n = 56) showed improved pregnancy outcome (32 pregnancies; live births n = 18 (56%)) compared to SPS patients without low-dose ASA (n = 13) (3 pregnancies; live births n = 1 (33%)). Our study demonstrates the clinical and diagnostic relevance of platelet hyperaggregation in women with infertility and pregnancy loss history. Further studies should investigate the potential of SPS as a novel decisional tool with both diagnostic and clinical implications in infertility and pregnancy loss.
Collapse
|
|
48
|
Adler M, Kaufmann J, Alberio L, Nagler M. Diagnostic utility of the ISTH bleeding assessment tool in patients with suspected platelet function disorders. J Thromb Haemost 2019; 17:1104-1112. [PMID: 31021046 PMCID: PMC6852182 DOI: 10.1111/jth.14454] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 04/11/2019] [Indexed: 01/09/2023]
Abstract
Essentials The utility of bleeding assessment tools regarding platelet function disorders is still elusive. We studied consecutive patients in a prospective cohort study in a tertiary hospital. Substantially higher scorings were observed in patients with platelet function disorders. Bleeding assessment tools might provide a useful screening tool. BACKGROUND Bleeding assessment tools (BATs) have been widely implemented in the evaluation of patients with suspected bleeding disorders. However, diagnostic BAT utility regarding platelet function disorders is still elusive. AIM We aimed to assess the diagnostic value of the International Society on Thrombosis and Haemostasis BAT (ISTH-BAT) for platelet function disorders in clinical practice. METHODS The clinical characteristics and laboratory data of all consecutive patients with a suspected bleeding disorder referred between January 2012 and March 2017 to an outpatient unit of a university hospital were prospectively collected. The diagnostic evaluation was performed according to current recommendations following a prespecified protocol and platelet function was tested using light transmission aggregometry as well as flow cytometry. RESULTS Five hundred and fifty-five patients were assessed; 66.9% were female, median age was 43.7 years (interquartile range [IQR] 29.3, 61.7). Confirmed platelet function disorder was diagnosed in 54 patients (9.7%), possible platelet function disorder in 64 patients (11.5%), and other disorders in 170 patients (30.6%). Median scoring of the ISTH-BAT was 2 in patients without a bleeding disorder (IQR 1, 3), 4 in patients with a possible platelet function disorder (2, 7), and 7 in patients with confirmed platelet function disorder (5, 9). Area under the receiver operating characteristic curve (the area under the curve [AUC]) was 0.75 (95% CI 0.70, 0.80). CONCLUSIONS Presence of a platelet function disorder was associated with substantially higher BAT scorings compared to patients without. Our data suggest that the ISTH-BAT provides a useful screening tool for patients with suspected platelet function disorders.
Collapse
Affiliation(s)
- Marcel Adler
- Department of Haematology and Central Haematology Laboratory, InselspitalBern University Hospital and University of BernBernSwitzerland
- Division of Haematology and Central Hematology LaboratoryCHUVLausanne University Hospital and University of LausanneLausanneSwitzerland
| | - Jonas Kaufmann
- Department of Haematology and Central Haematology Laboratory, InselspitalBern University Hospital and University of BernBernSwitzerland
| | - Lorenzo Alberio
- Division of Haematology and Central Hematology LaboratoryCHUVLausanne University Hospital and University of LausanneLausanneSwitzerland
- Faculty of Biology and MedicineUniversity of LausanneLausanneSwitzerland
| | - Michael Nagler
- Department of Haematology and Central Haematology Laboratory, InselspitalBern University Hospital and University of BernBernSwitzerland
- University Institute of Clinical ChemistryUniversity of BernBernSwitzerland
| |
Collapse
|
|
49
|
Hayward CPM, Moffat KA, Brunet J, Carlino SA, Plumhoff E, Meijer P, Zehnder JL. Update on diagnostic testing for platelet function disorders: What is practical and useful? Int J Lab Hematol 2019; 41 Suppl 1:26-32. [PMID: 31069975 DOI: 10.1111/ijlh.12995] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 02/07/2019] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Platelet function disorders (PFD) are an important group of bleeding disorders that require validated and practical laboratory strategies for diagnosis. METHODS This review summarizes the authors' experiences, current literature, and an international survey to evaluate the practices of diagnostic laboratories that offer tests for PFD. RESULTS Blood counts, blood film review, and aggregation tests are the most commonly performed investigations for PFD and help determine whether there is thrombocytopenia and/or defective platelet function due to a variety of causes. The performance characteristics of tests for PFD, and the level of evidence that these tests detect bleeding problems, are important issues to determine where tests are useful for diagnostic or correlative purposes, or research only uses. Platelet aggregation assays, and quantitative analysis of platelet dense granule numbers, are tests with good performance characteristics that detect abnormalities associated with increased bleeding in a significant proportion of individuals referred for PFD investigations. Lumiaggregometry estimates of platelet adenosine triphosphate release show greater variability which limits the diagnostic usefulness. Diagnostic laboratories report that fiscal and other constraints, including a lack of high-quality evidence, limit their ability to offer an expanded test menu for PFD. CONCLUSION PFD are clinically important bleeding disorders that remain challenging for diagnostic laboratories to investigate. While some PFD tests are well validated for diagnostic purposes, gaps in scientific evidence and resource limitations influence diagnostic laboratory decisions on which PFD tests to offer.
Collapse
Affiliation(s)
- Catherine P M Hayward
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Medicine, McMaster University, Hamilton, Ontario, Canada.,Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
| | - Karen A Moffat
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada.,Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
| | - Justin Brunet
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Stephen A Carlino
- Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
| | | | - Piet Meijer
- ECAT Foundation, Voorschoten, The Netherlands
| | - James L Zehnder
- Departments of Pathology and Medicine, Stanford University, Stanford, California
| |
Collapse
|
|
50
|
Acquired platelet function disorders. Thromb Res 2019; 196:561-568. [PMID: 31229273 DOI: 10.1016/j.thromres.2019.06.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 06/08/2019] [Accepted: 06/14/2019] [Indexed: 12/16/2022]
Abstract
The possibility of an acquired platelet function disorder should be considered in patients who present with recent onset muco-cutaneous bleeding. Despite the availability of newer and faster platelet function assays, light transmission aggregometry (LTA) remains the preferred diagnostic test. This review examines and discusses the causes of acquired platelet dysfunction; most commonly drugs, dietary factors, medical disorders and procedures. In addition to well-known antiplatelet therapies, clinicians should be alert for newer drugs which can affect platelets, such as ibrutinib. There is little clinical trial evidence to guide the management of acquired platelet function defects, but we summarise commonly employed strategies, which include addressing the underlying cause, antifibrinolytic agents, desmopressin infusions, and in selected patients, platelet transfusions.
Collapse
|