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Gong Z, Zhang L, Ma H, SiRi G. Effect of regional citrate anticoagulation vs. low molecular weight heparin anticoagulation in continuous renal replacement therapy for critically ill patients: A retrospective cohort study. Ther Apher Dial 2025; 29:447-458. [PMID: 40098363 DOI: 10.1111/1744-9987.70009] [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: 11/25/2024] [Revised: 02/18/2025] [Accepted: 03/10/2025] [Indexed: 03/19/2025]
Abstract
INTRODUCTION This study aimed to assess the efficacy and safety of regional citrate anticoagulation (RCA) and low molecular weight heparin anticoagulation (LMHA) in critically ill patients undergoing continuous renal replacement therapy (CRRT). METHODS The clinical data of patients who underwent CRRT at Inner Mongolia People's Hospital from January 2022 to March 2024 were collected. Patients were divided into the RCA group and the LMHA group. The primary outcomes were filter survival time and 28-day mortality. The secondary outcomes were adverse events of CRRT anticoagulation. RESULTS The filter lifespan of the RCA group was significantly extended (33.5 vs. 27.5 h, p ≤ 0.001), and the occurrence of filter coagulation events in the RCA group was markedly reduced (7.0% vs. 21.1%, p = 0.03). There were no statistically significant differences in bleeding and electrolyte disturbances between the two groups. The multivariate COX regression analysis demonstrated that the anticoagulation strategy was the singular factor influencing filter survival time (hazard ratio [HR] = 4.74, 95% CI 1.67-13.50, p = 0.004). CONCLUSIONS RCA demonstrated significantly prolonged filter lifespan and reduced instances of filter clotting compared to LMHA. RCA represents a safe and effective anticoagulation strategy for CRRT.
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Affiliation(s)
- Zhaotang Gong
- Department of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
- Department of Pharmacy, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China
| | - Lixin Zhang
- Department of Pharmacy, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China
| | - Hongling Ma
- Department of Pharmacy, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China
| | - Guleng SiRi
- Department of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
- Department of Pharmacy, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China
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Chen Y, Li W, Ni L, Mei Y, Zhou Y, Wan W. Case Report: Heparin-induced thrombocytopenia following double filtration plasmapheresis in a patient with anti-GAD65 autoimmune encephalitis. Front Cardiovasc Med 2025; 12:1574698. [PMID: 40276262 PMCID: PMC12018328 DOI: 10.3389/fcvm.2025.1574698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Accepted: 03/28/2025] [Indexed: 04/26/2025] Open
Abstract
Autoimmune encephalitis (AE) is a group of disorders characterized by antibodies targeting neuronal cell surface, intracellular structures and synapse antigens. Treatment for AE involves reducing antibody levels and suppressing immune-mediated inflammation using intravenous immunoglobulin, plasma exchange (PE), and immune-modulating agents. PE is commonly used in autoimmune neurological diseases, but the safety issues of PE are worth continuous attention. This case report describes a 28-year-old patient who was diagnosed with anti-GAD65 AE and underwent treatments including double filtration plasmapheresis (DFPP), steroids, and immunosuppressive agents. However, complications arose when the patient developed thrombosis and was diagnosed with type II heparin-induced thrombocytopenia (HIT). He was treated with an oral anticoagulant and eventually recovered. One month later, follow-up examinations showed no presence of emboli and his epilepsy remained well controlled. There is a risk of HIT, a potentially dangerous adverse reaction to heparin during treatment of PE. The current case highlights the importance of monitoring for HIT during PE and the need for alternative anticoagulants.
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Affiliation(s)
| | | | | | | | | | - Wenbin Wan
- Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Centre for Liver and Digestive Diseases (CIBERehd). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502208. [PMID: 39756832 DOI: 10.1016/j.gastrohep.2024.502208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 01/07/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:14-57. [PMID: 39350672 DOI: 10.17235/reed.2024.10805/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic. Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
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Mota L, Zhu M, Tomeo JN, Recarey M, Patel N, Pradhan-Nabzdyk L, LoGerfo FW, Liang P. The impact of heparin and direct thrombin inhibitors on cell-penetrating polymer siRNA transfection. Gene Ther 2024; 31:467-476. [PMID: 39013986 DOI: 10.1038/s41434-024-00460-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 06/18/2024] [Accepted: 06/25/2024] [Indexed: 07/18/2024]
Abstract
Gene therapy using siRNA has become a promising strategy to achieve targeted gene knockdown for treatment of cardiovascular pathologies. However, efficient siRNA transfection often relies on cationic delivery vectors such as synthetic cell-penetrating polymers which are susceptible to interference by negatively charged molecules. Anticoagulants such as heparin, which is negatively charged and widely used in cardiovascular applications, may pose a significant barrier to effective siRNA delivery. We therefore conducted in vitro studies utilizing human smooth muscle and endothelial cells transfected with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β2-microglobulin (B2M) siRNA in the presence of heparin, argatroban, and bivalirudin in order to determine which anticoagulant therapy is most compatible for siRNA delivery. We observed that while heparin, at clinical doses, decreases the efficiency of siRNA targeted mRNA knockdown, mRNA knockdown is not inhibited in the presence of either argatroban or bivalirudin. Our data suggests that heparin should be avoided during siRNA therapy with cationic transfection agents, and argatroban and bivalirudin should be used in its stead.
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Affiliation(s)
- Lucas Mota
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Max Zhu
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - John N Tomeo
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Melina Recarey
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Nyah Patel
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Leena Pradhan-Nabzdyk
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Frank W LoGerfo
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Patric Liang
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
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Ng JY, D’Souza M, Hutani F, Choi P. Management of Heparin-Induced Thrombocytopenia: A Contemporary Review. J Clin Med 2024; 13:4686. [PMID: 39200826 PMCID: PMC11355627 DOI: 10.3390/jcm13164686] [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: 06/11/2024] [Revised: 07/25/2024] [Accepted: 07/31/2024] [Indexed: 09/02/2024] Open
Abstract
Heparin-induced thrombocytopenia (HIT) is a life- and limb-threatening immune-mediated emergency classically associated with heparin therapy. This review focuses on type II HIT, characterized by the development of antibodies against platelet-factor 4 (PF4) bound to heparin after exposure, causing life-threatening thrombocytopenia, arterial thrombosis, and/or venous thrombosis. The high morbidity and mortality rates emphasize the need for early recognition and urgent intervention with discontinuation of heparin and initiation of non-heparin anticoagulation. We discuss the management of HIT with an emphasis on recent developments: (i) incorporating the phases of HIT (i.e., suspected, acute, subacute A and B, and remote) into its management, categorized according to platelet count, immunoassay, and functional assay results and (ii) direct-acting oral anticoagulants (DOACs), which are increasingly used in appropriate cases of acute HIT (off-label). In comparison to parenteral options (e.g., bivalirudin and danaparoid), they are easier to administer, are more cost-effective, and obviate the need for transition to an oral anticoagulant after platelet recovery. We also identify the knowledge gaps and suggest areas for future research.
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Affiliation(s)
- Jun Yen Ng
- Department of Hematology, Canberra Hospital, Canberra 2605, Australia (P.C.)
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Samimi MN, Hale A, Schults J, Fischer A, Roberts JA, Dhanani J. Clinical guidance for unfractionated heparin dosing and monitoring in critically ill patients. Expert Opin Pharmacother 2024; 25:985-997. [PMID: 38825778 DOI: 10.1080/14656566.2024.2364057] [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: 01/29/2024] [Accepted: 05/31/2024] [Indexed: 06/04/2024]
Abstract
INTRODUCTION Unfractionated heparin is a widely used anticoagulant in critically ill patients. It has a well-established safety profile and remains an attractive option for clinicians due to its short half-life and reversibility. Heparin has a unique pharmacokinetic profile, which contributes to significant inter-patient and intra-patient variability in effect. The variability in anticoagulant effect combined with heparin's short half-life mean close monitoring is required for clinical efficacy and preventing adverse effects. To optimize heparin use in critically ill patients, effective monitoring assays and dose adjustment strategies are needed. AREAS COVERED This paper explores the use of heparin as an anticoagulant and optimal approaches to monitoring in critically ill patients. EXPERT OPINION Conventional monitoring assays for heparin dosing have significant limitations. Emerging data appear to favor using anti-Xa assay monitoring for heparin anticoagulation, which many centers have successfully adopted as the standard. The anti-Xa assay appears have important benefits relative to the aPTT for heparin monitoring in critically ill patients, and should be considered for broader use.
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Affiliation(s)
- May N Samimi
- Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia
- Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Andrew Hale
- Discipline of Pharmacy, School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia
| | - Jessica Schults
- Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia
- School of Nursing, Midwifery and Social Work, University of Queensland, Brisbane, Australia
- Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia
| | - Andreas Fischer
- Pharmacy Department, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Jason A Roberts
- Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia
- Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia
- Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia
- Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia
- Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
| | - Jayesh Dhanani
- Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia
- Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia
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Larsen EL, Nilius H, Studt JD, Tsakiris DA, Greinacher A, Mendez A, Schmidt A, Wuillemin WA, Gerber B, Vishnu P, Graf L, Kremer Hovinga JA, Goetze JP, Bakchoul T, Nagler M. Accuracy of Diagnosing Heparin-Induced Thrombocytopenia. JAMA Netw Open 2024; 7:e243786. [PMID: 38530310 PMCID: PMC10966416 DOI: 10.1001/jamanetworkopen.2024.3786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 01/30/2024] [Indexed: 03/27/2024] Open
Abstract
Importance Heparin-induced thrombocytopenia (HIT) is a life-threatening condition that requires urgent diagnostic clarification. However, knowledge of the diagnostic utility of the recommended diagnostic tests is limited in clinical practice. Objective To evaluate the current diagnostic practice for managing the suspicion of HIT. Design, Setting, and Participants This prospective diagnostic study was conducted from January 2018 to May 2021 among consecutive patients with suspected HIT from 11 study centers in Switzerland, Germany, and the United States. Detailed clinical data and laboratory information were recorded. Platelet factor 4/heparin antibodies were quantified using an automated chemiluminescent immunoassay (CLIA). A washed-platelet heparin-induced platelet activation (HIPA) test was used as a reference standard to define HIT. Exposures Suspicion of HIT. Main Outcomes and Measures The primary outcome was the diagnostic accuracy of the 4Ts score, the CLIA, and the recommended algorithm serially combining both tests. Results Of 1448 patients included between 2018 and 2021, 1318 were available for the current analysis (median [IQR] age, 67 [57-75] years; 849 [64.6%] male). HIPA was positive in 111 patients (prevalence, 8.4%). The most frequent setting was intensive care unit (487 [37.0%]) or cardiovascular surgery (434 [33.0%]). The 4Ts score was low risk in 625 patients (46.8%). By 2 × 2 table, the numbers of patients with false-negative results were 10 (9.0%; 4Ts score), 5 (4.5%; CLIA), and 15 (13.5%; recommended diagnostic algorithm). The numbers of patients with false-positive results were 592 (49.0%; 4Ts score), 73 (6.0%; CLIA), and 50 (4.1%; recommended diagnostic algorithm), respectively. Conclusions and Relevance In this diagnostic study of patients suspected of having HIT, when the recommended diagnostic algorithm was used in clinical practice, antibody testing was required in half the patients. A substantial number of patients were, however, still misclassified, which could lead to delayed diagnosis or overtreatment. Development of improved diagnostic algorithms for HIT diagnosis should be pursued.
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Affiliation(s)
- Emil List Larsen
- Department of Clinical Biochemistry, Copenhagen University Hospital–Rigshospitalet, Copenhagen, Denmark
| | - Henning Nilius
- Department of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland
- Graduate School for Health Sciences, University of Bern, Bern, Switzerland
| | - Jan-Dirk Studt
- Division of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland
| | | | - Andreas Greinacher
- Department of Transfusion Medicine, Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Adriana Mendez
- Department of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland
| | - Adrian Schmidt
- Institute of Laboratory Medicine and Clinic of Medical Oncology and Hematology, Municipal Hospital Zurich Triemli, Zurich, Switzerland
| | - Walter A. Wuillemin
- Division of Hematology and Central Hematology Laboratory, Cantonal Hospital of Lucerne and University of Bern, Switzerland
| | - Bernhard Gerber
- Clinic of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Prakash Vishnu
- Fred Hutchinson Cancer Center, University of Washington, Seattle
| | - Lukas Graf
- Cantonal Hospital of St Gallen, St Gallen, Switzerland
| | - Johanna A. Kremer Hovinga
- Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
| | - Jens P. Goetze
- Department of Clinical Biochemistry, Copenhagen University Hospital–Rigshospitalet, Copenhagen, Denmark
- Department of Biomedical Sciences, Faculty of Health, Copenhagen University, Copenhagen, Denmark
| | - Tamam Bakchoul
- Centre for Clinical Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Michael Nagler
- Department of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland
- University of Bern, Bern, Switzerland
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Qiu Z, Pang X, Xiang Q, Cui Y. The Crosstalk between Nephropathy and Coagulation Disorder: Pathogenesis, Treatment, and Dilemmas. J Am Soc Nephrol 2023; 34:1793-1811. [PMID: 37487015 PMCID: PMC10631605 DOI: 10.1681/asn.0000000000000199] [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: 12/05/2022] [Accepted: 07/10/2023] [Indexed: 07/26/2023] Open
Abstract
ABSTRACT The interaction between the kidney and the coagulation system greatly affects each other because of the abundant vessel distribution and blood perfusion in the kidney. Clinically, the risks of complicated thrombosis and bleeding have become important concerns in the treatment of nephropathies, especially nephrotic syndrome, CKD, ESKD, and patients with nephropathy undergoing RRTs. Adverse effects of anticoagulant or procoagulant therapies in patients with nephropathy, especially anticoagulation-related nephropathy, heparin-induced thrombocytopenia, and bleeding, seriously worsen the prognosis of patients, which have become challenges for clinicians. Over the decades, the interaction between the kidney and the coagulation system has been widely studied. However, the effects of the kidney on the coagulation system have not been systematically investigated. Although some coagulation-related proteins and signaling pathways have been shown to improve coagulation abnormalities while avoiding additional kidney damage in certain kidney diseases, their potential as anticoagulation targets in nephropathy requires further investigation. Here, we review the progression of research on the crosstalk between the coagulation system and kidney diseases and systematically analyze the significance and shortcomings of previous studies to provide new sight into future research. In addition, we highlight the status of clinical treatment for coagulation disorder and nephropathy caused by each other, indicating guidance for the formulation of therapeutic strategies or drug development.
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Affiliation(s)
- Zhiwei Qiu
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China
| | - Xiaocong Pang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China
| | - Qian Xiang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China
| | - Yimin Cui
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China
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Skornova I, Simurda T, Stanciakova L, Lauko V, Holly P, Samos M, Bolek T, Schnierer M, Drotarova M, Belakova KM, Sokol J, Stasko J, Mokan M, Gumulec J, Chrastinova L. A Functional Assay for the Determination of Heparin-Induced Thrombocytopenia via Flow Cytometry. Diagnostics (Basel) 2023; 13:3019. [PMID: 37761386 PMCID: PMC10527925 DOI: 10.3390/diagnostics13183019] [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: 06/27/2023] [Revised: 09/18/2023] [Accepted: 09/19/2023] [Indexed: 09/29/2023] Open
Abstract
Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin therapy (both unfractionated heparin and low-molecular-weight heparin). In our study, we examined a group of 122 patients with suspected HIT. The samples of all patients were analyzed in the first step using an immunoassay (ID-PaGIA Heparin/PF4, Hemos1L-Acustar HIT IgG, ZYMUTEST HIA Monostrip IgG) to detect the presence of antibodies against heparin-PF4 complexes (platelet factor 4). When the immunoassay was positive, the sample was subsequently analyzed for HIT with a functional flow cytometry assay, the HITAlert kit, the purpose of which was to demonstrate the ability of the antibodies present to activate platelets. A diagnosis of HIT can be made only after a positive functional test result. In this article, we present an overview of our practical experience with the use of the new functional method of analysis, HIT, with flow cytometry. In this work, we compared the mutual sensitivity of two functional tests, SRA and the flow cytometry HITAlert kit, in patients perceived as being at risk for HIT. This work aims to delineate the principle, procedure, advantages, pitfalls, and possibilities of the application of the functional test HITAlert using flow cytometry.
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Affiliation(s)
- Ingrid Skornova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia; (I.S.); (P.H.); (M.D.); (K.M.B.); (J.S.); (J.S.)
| | - Tomas Simurda
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia; (I.S.); (P.H.); (M.D.); (K.M.B.); (J.S.); (J.S.)
| | - Lucia Stanciakova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia; (I.S.); (P.H.); (M.D.); (K.M.B.); (J.S.); (J.S.)
| | - Viliam Lauko
- National Institute of Cardiovascular Diseases, 83348 Bratislava, Slovakia
| | - Pavol Holly
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia; (I.S.); (P.H.); (M.D.); (K.M.B.); (J.S.); (J.S.)
| | - Matej Samos
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia; (M.S.); (T.B.); (M.M.)
| | - Tomas Bolek
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia; (M.S.); (T.B.); (M.M.)
| | - Martin Schnierer
- Department of Gastroenterology Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia;
| | - Miroslava Drotarova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia; (I.S.); (P.H.); (M.D.); (K.M.B.); (J.S.); (J.S.)
| | - Kristina Maria Belakova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia; (I.S.); (P.H.); (M.D.); (K.M.B.); (J.S.); (J.S.)
| | - Juraj Sokol
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia; (I.S.); (P.H.); (M.D.); (K.M.B.); (J.S.); (J.S.)
| | - Jan Stasko
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia; (I.S.); (P.H.); (M.D.); (K.M.B.); (J.S.); (J.S.)
| | - Marian Mokan
- Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia; (M.S.); (T.B.); (M.M.)
| | - Jaroslav Gumulec
- Clinic of Hemato-Oncology, Faculty Hospital in Ostrava, 708 00 Ostrava, Czech Republic;
| | - Leona Chrastinova
- Institute of Hematology and Blood Transfusion in Prague, 128 20 Nove Mesto, Czech Republic;
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Yang XD, Ju B, Xu J, Xiu NN, Sun XY, Zhao XC. Glucocorticoid-induced thrombotic microangiopathy in paroxysmal nocturnal hemoglobinuria: A case report and review of literature. World J Clin Cases 2023; 11:1799-1807. [PMID: 36970013 PMCID: PMC10037281 DOI: 10.12998/wjcc.v11.i8.1799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/02/2022] [Accepted: 02/08/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Thrombotic microangiopathy (TMA) is a group of disorders that converge on excessive platelet aggregation in the microvasculature, leading to consumptive thrombocytopenia, microangiopathic hemolysis and ischemic end-organ dysfunction. In predisposed patients, TMA can be triggered by many environmental factors. Glucocorticoids (GCs) can compromise the vascular endothelium. However, GC-associated TMA has rarely been reported, which may be due to the lack of awareness of clinicians. Given the high frequency of thrombocytopenia during GC treatment, particular attention should be given to this potentially fatal complication.
CASE SUMMARY An elderly Chinese man had a 12-year history of aplastic anemia (AA) and a 3-year history of paroxysmal nocturnal hemoglobinuria (PNH). Three months earlier, methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated hemolysis. Following GC treatment, his platelet counts and hemoglobin levels rapidly decreased. After admission to our hospital, the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect. However, increasing the GC dose did not alleviate hemolysis, and his cytopenia worsened. Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia. Cluster of differentiation (CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes. In the following days, platelet transfusion was required due to severe thrombocytopenia. Observation of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored proteins. We examined blood smears and found a small number of schistocytes, dacryocytes, acanthocytes and target cells. Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels. The patient’s platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation.
CONCLUSION GCs can drive TMA episodes. When thrombocytopenia occurs during GC treatment, TMA should be considered, and GCs should be discontinued.
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Affiliation(s)
- Xiao-Dong Yang
- Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
| | - Bo Ju
- Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
| | - Jia Xu
- Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
| | - Nuan-Nuan Xiu
- Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
| | - Xiao-Yun Sun
- Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
| | - Xi-Chen Zhao
- Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
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Tong Y, Rouzhahong J, Zhou W, Wang R, Wang Y, Ren Y, Guo J, Li Y, Wang Z, Song Y. Comparison of bivalirudin versus heparin in adult extracorporeal membrane oxygenation anticoagulant therapy: A retrospective case-control study. Int J Artif Organs 2023; 46:162-170. [PMID: 36600413 DOI: 10.1177/03913988221148763] [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: 01/06/2023]
Abstract
INTRODUCTION There were controversial opinions on the use of bivalirudin versus heparin for anticoagulant therapy in extracorporeal membrane oxygenation. The aim of our present study is to evaluate the efficacy and safety of bivalirudin versus heparin for the maintenance of systemic anticoagulation during adult veno-venous extracorporeal membrane oxygenation (V-V ECMO). METHODS Adult patients who received V-V ECMO support in our center between February 2018and February 2022 were retrospectively recruited. We analyzed their ECMO support time, platelet count, coagulation indicators, blood product infusion volume, the incidence of thrombosis and bleeding, probability of successful weaning of ECMO, and in-hospital mortality. RESULTS A total of 58 patients received V-V ECMO support. Thirty-four patients were finally included according to the exclusion and inclusion criteria, 14 and 20 accepted bivalirudin and heparin for anticoagulant therapy, respectively. The Minimum platelet value (98.50 × 109/L (85.50, 123.75) vs 49.50 × 109/L (31.25, 83.00), p = 0.002) and mean platelet value (149.90 × 109/L (127.40, 164.80) vs 74.55 × 109/L (62.45, 131.60), p = 0.03) and the ratio of successful weaning of ECMO (92.8% vs 60.0%, p = 0.033) in bivalirudin group were significantly higher than those in heparin group. The red blood cell infusion volume (7.00 U (3.00, 13.25) vs 13.75 U (7.25, 22.63), p = 0.039), platelet infusion volume (0.00 mL (0.00, 75.00) vs 300 mL (0.00, 825.00), p = 0.027), and the incidence of major bleeding (0.00% vs 30%, p = 0.024) in bivalirudin group were significantly lower than those in heparin group. CONCLUSIONS In V-V ECMO-supported adult patients, systemic anticoagulation with bivalirudin has achieved the same anticoagulation targets as heparin with less frequency of major bleeding events and lower requirement for blood products without significantly increased risk of thrombosis. Bivalirudin most likely is a safe and effective anticoagulation method for adult patients supported by V-V ECMO.
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Affiliation(s)
- Yaowei Tong
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Julaiti Rouzhahong
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Wangtao Zhou
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Rui Wang
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Yuqiang Wang
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Yucheng Ren
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Ju Guo
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Ying Li
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Zhengkai Wang
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
| | - Yunlin Song
- Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
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Favaloro EJ, Pasalic L. Heparin-Induced Thrombotic Thrombocytopenia (HITT) and Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Similar but Different. Methods Mol Biol 2023; 2663:405-415. [PMID: 37204726 DOI: 10.1007/978-1-0716-3175-1_26] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Heparin-induced thrombocytopenia (HIT) represents an autoimmune process whereby antibodies are formed against heparin in complex with platelet factor 4 (PF4) after heparin administration. These antibodies can be detected by a variety of immunological assays, including ELISA (enzyme-linked immunosorbent assay) and by chemiluminescence on the AcuStar instrument. However, pathological HIT antibodies are those that activate platelets in a platelet activation assay and cause thrombosis in vivo. We would tend to call this condition heparin-induced thrombotic thrombocytopenia (HITT), although some workers instead use the truncated abbreviation HIT. Vaccine-induced (immune) thrombotic thrombocytopenia (VITT) instead reflects an autoimmune process whereby antibodies are formed against PF4 after administration of a vaccine, most notably adenovirus-based vaccines directed against COVID-19 (coronavirus disease 2019). Although both VITT and HITT reflect similar pathological processes, they have different origins and are detected in different ways. Most notable is that anti-PF4 antibodies in VITT can only be detected immunologically by ELISA assays, tending to be negative in rapid assays such as that using the AcuStar. Moreover, functional platelet activation assays otherwise used for HITT may need to be modified to detect platelet activation in VITT.
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Affiliation(s)
- Emmanuel J Favaloro
- School of Medical Sciences, Faculty of Medicine and Health University of Sydney, Westmead Hospital, Westmead, NSW, Australia.
- School of Dentistry and Medical Sciences, Faculty of Science and Health, Charles Sturt University, Wagga, Wagga, NSW, Australia.
| | - Leonardo Pasalic
- Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia
- Sydney Centres for Thrombosis and Haemostasis, Westmead Hospital, Westmead, NSW, Australia
- Westmead Clinical School, University of Sydney, Westmead Hospital, Westmead, NSW, Australia
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Favaloro EJ, Pasalic L, Lippi G. How often are parenteral anticoagulants administered by parents? J Thromb Haemost 2022; 20:2746-2750. [PMID: 36129394 PMCID: PMC9828405 DOI: 10.1111/jth.15887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 09/17/2022] [Indexed: 01/13/2023]
Abstract
Parenteral anticoagulants are a class of anticoagulants that need to be administered non-orally, usually by injection or infusion. There are a variety of such agents, but heparin reflects the most frequently used. Being alerted to an error in a prior publication in which the word "parenteral" was inadvertently replaced by the word "parental," it became clear that even experienced authors make such errors, which could then remain undetected by reviewers and editors, thus leading to failure in correction of same before publication. Given this is likely to be a somewhat ongoing error, we undertook a PubMed search of the literature to identify that "parentally administered" anticoagulants, as well as "parental" administration of other compounds, seems to be evident throughout the literature. We hope this report acts to raise awareness and help avoid similar errors in the future.
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Affiliation(s)
- Emmanuel J. Favaloro
- Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health PathologyWestmead HospitalWestmeadNew South WalesAustralia
- Sydney Centres for Thrombosis and HaemostasisWestmeadNew South WalesAustralia
- School of Dentistry and Medical Sciences, Faculty of Science and HealthCharles Sturt UniversityWagga WaggaNew South WalesAustralia
- School of Medical Sciences, Faculty of Medicine and Health, University of SydneyWestmead HospitalWestmeadNew South WalesAustralia
| | - Leonardo Pasalic
- Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health PathologyWestmead HospitalWestmeadNew South WalesAustralia
- Sydney Centres for Thrombosis and HaemostasisWestmeadNew South WalesAustralia
- Westmead Clinical SchoolUniversity of SydneyWestmeadNew South WalesAustralia
| | - Giuseppe Lippi
- Section of Clinical BiochemistryUniversity of VeronaVeronaItaly
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15
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Favaloro EJ, Pasalic L, Lippi G. Autoimmune Diseases Affecting Hemostasis: A Narrative Review. Int J Mol Sci 2022; 23:ijms232314715. [PMID: 36499042 PMCID: PMC9738541 DOI: 10.3390/ijms232314715] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/20/2022] [Accepted: 11/24/2022] [Indexed: 11/26/2022] Open
Abstract
Hemostasis reflects a homeostatic mechanism that aims to balance out pro-coagulant and anti-coagulant forces to maintain blood flow within the circulation. Simplistically, a relative excess of procoagulant forces can lead to thrombosis, and a relative excess of anticoagulant forces can lead to bleeding. There are a wide variety of congenital disorders associated with bleeding or thrombosis. In addition, there exist a vast array of autoimmune diseases that can also lead to either bleeding or thrombosis. For example, autoantibodies generated against clotting factors can lead to bleeding, of which acquired hemophilia A is the most common. As another example, autoimmune-mediated antibodies against phospholipids can generate a prothrombotic milieu in a condition known as antiphospholipid (antibody) syndrome (APS). Moreover, there exist various autoimmunity promoting environments that can lead to a variety of antibodies that affect hemostasis. Coronavirus disease 2019 (COVID-19) represents perhaps the contemporary example of such a state, with potential development of a kaleidoscope of such antibodies that primarily drive thrombosis, but may also lead to bleeding on rarer occasions. We provide here a narrative review to discuss the interaction between various autoimmune diseases and hemostasis.
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Affiliation(s)
- Emmanuel J. Favaloro
- Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Sydney Centres for Thrombosis and Haemostasis, NSW Health Pathology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia
- School of Dentistry and Medical Sciences, Faculty of Science and Health, Charles Sturt University, Wagga Wagga, NSW 2678, Australia
- School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia
- Correspondence: ; Tel.: +61-2-8890-6618
| | - Leonardo Pasalic
- Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Sydney Centres for Thrombosis and Haemostasis, NSW Health Pathology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia
- Westmead Clinical School, University of Sydney, Westmead, Sydney, NSW 2006, Australia
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, 37129 Verona, Italy
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A case of severe COVID-19 with pulmonary thromboembolism related to heparin-induced thrombocytopenia during prophylactic anticoagulation therapy. J Infect Chemother 2022; 28:1208-1211. [PMID: 35570112 PMCID: PMC9091339 DOI: 10.1016/j.jiac.2022.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/29/2022] [Accepted: 05/06/2022] [Indexed: 12/22/2022]
Abstract
A 53-year-old male Japanese patient with COVID-19 was admitted to our hospital after his respiratory condition worsened on day 9 of the disease. With the diagnosis of severe COVID-19, treatment with remdesivir, dexamethasone, and unfractionated heparin was started for the prevention of thrombosis. Although the patient's respiratory status data improved after treatment, severe respiratory failure persisted. Thrombocytopenia and D-dimer elevation were observed on day 8 after heparin therapy initiation. Heparin-induced thrombocytopenia (HIT) antibody measured by immunological assay was positive, and contrast computed tomography showed pulmonary artery thrombus. The patient was diagnosed with HIT because the pre-test probability score (4Ts score) for HIT was 7 points. Heparin was changed to apixaban, a direct oral anticoagulant, which resulted in a reduction of the pulmonary thrombus and improvement of the respiratory failure. In patients with COVID-19, anticoagulant therapy with heparin requires careful monitoring of thrombocytopenia and elevated D-dimer as possible complications related to HIT. (151/250 words).
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Abstract
DISCLAIMER These guidelines for adult and pediatric anticoagulation for extracorporeal membrane oxygenation are intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing ECLS / ECMO and describe what are believed to be useful and safe practice for extracorporeal life support (ECLS, ECMO) but these are not necessarily consensus recommendations. The aim of clinical guidelines are to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of particular patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient in light of all the circumstances presented by the individual patient, and the known variability and biological behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.
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Favaloro EJ, Pasalic L, Henry B, Lippi G. Laboratory testing for platelet factor 4 antibodies: differential utility for diagnosis/exclusion of heparin induced thrombocytopenia versus suspected vaccine induced thrombotic thrombocytopenia. Pathology 2022; 54:254-261. [PMID: 35125202 DOI: 10.1016/j.pathol.2021.10.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/12/2021] [Accepted: 10/20/2021] [Indexed: 12/13/2022]
Abstract
Platelet factor 4 (PF4), a protein stored in the alpha-granules of platelets and released upon activation, forms cationic tetramers that bind with various polymeric anions, including heparin. Some individuals develop antibodies against PF4 in complex with heparin (PF4/H), which potentially lead to the onset of heparin induced thrombocytopenia (HIT). In some patients, this may cause activation and aggregation of platelets, promoting pathological thrombosis, in a process called heparin induced thrombocytopenia with thrombosis ('HITT'). Laboratories can assess for the presence of these antibodies using many PF4 antibody tests, including by enzyme linked immunosorbent assay (ELISA), latex immunoassay (LIA), chemiluminescence immunoassay (CLIA) and even rapid nanoparticle based lateral flow immunoassays. All these assays can identify such antibodies with high sensitivity, but methods may have variable specificity. For example, several studies have shown CLIA assays to have higher specificity to HITT than ELISA assays. Very recently, a new 'HITT-like' syndrome has been described in some individuals receiving adenovirus based COVID-19 (coronavirus disease 2019) vaccines. This condition has been given several names, including vaccine induced thrombotic thrombocytopenia (VITT) and thrombosis with thrombocytopenia syndrome (TTS), and also involves a mechanism mediated by antibodies formed against PF4. These antibodies can also be detected by PF4 antibody tests, but detection sensitivity appears to favour ELISA assays, with most other tests (including CLIA and LIA) not generally capable of detecting such antibodies. Additional functional assays assessing for PF4 mediated platelet activation may also be performed. The current review is focussed on laboratory testing for PF4 antibodies, in particular to distinguishing patterns in HITT versus VITT.
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Affiliation(s)
- Emmanuel J Favaloro
- Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, NSW, Australia; Sydney Centres for Thrombosis and Haemostasis, Westmead, NSW, Australia; Faculty of Science and Health, Charles Sturt University, Wagga Wagga, NSW, Australia.
| | - Leonardo Pasalic
- Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, NSW, Australia; Sydney Centres for Thrombosis and Haemostasis, Westmead, NSW, Australia
| | - Brandon Henry
- Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Ohio, USA; Host-Pathogens Interactions and Population Health Programs, Texas Biomedical Research Institute, San Antonio, TX, USA
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
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19
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Favaloro EJ, Pasalic L, Lippi G. Review and evolution of guidelines for diagnosis of COVID-19 vaccine induced thrombotic thrombocytopenia (VITT). Clin Chem Lab Med 2022; 60:7-17. [PMID: 34714985 DOI: 10.1515/cclm-2021-1039] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 10/17/2021] [Indexed: 11/15/2022]
Abstract
Coronavirus disease 2019 (COVID-19) is a life-threatening infectious disease caused by Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). In response to the still ongoing pandemic outbreak, a number of COVID-19 vaccines have been quickly developed and deployed. Although minor adverse events, either local (e.g., soreness, itch, redness) or systematic (fever, malaise, headache, etc.), are not uncommon following any COVID-19 vaccination, one rare vaccine-associated event can cause fatal consequences due to development of antibodies against platelet factor 4 (PF4), which trigger platelet activation, aggregation, and possible resultant thrombosis, often at unusual vascular sites. Termed thrombosis with thrombocytopenia syndrome (TTS) by reporting government agencies, the term vaccine-induced (immune) thrombotic thrombocytopenia (VITT) is more widely adopted by workers in the field. In response to increasing reports of VITT, several expert groups have formulated guidelines for diagnosis and/or management of VITT. Herein, we review some key guidelines related to diagnosis of VITT, and also provide some commentary on their development and evolution.
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Affiliation(s)
- Emmanuel J Favaloro
- Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia.,Sydney Centres for Thrombosis and Haemostasis, Westmead, NSW, Australia.,Faculty of Science and Health, Charles Sturt University, Wagga Wagga, NSW, Australia
| | - Leonardo Pasalic
- Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia.,Sydney Centres for Thrombosis and Haemostasis, Westmead, NSW, Australia.,Sydney University, Westmead, NSW, Australia
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
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