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Koami H, Sakamoto Y, Hirota Y, Sasaki A, Ogawa H, Furukawa Y, Matsuoka A, Shinada K, Nakayama K, Sakurai R, Iwanaga S, Onohara T, Narumi S, Koba M. Effect of hypofibrinolysis on clinical outcomes of patients with septic disseminated intravascular coagulation. Thromb Res 2025; 245:109235. [PMID: 39644620 DOI: 10.1016/j.thromres.2024.109235] [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: 09/07/2024] [Revised: 11/26/2024] [Accepted: 12/03/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND This study investigated the utility of thromboelastometry (ROTEM) in assessing hypofibrinolysis among septic patients, specifically the association of hypofibrinolysis, as determined by ROTEM, with septic disseminated intravascular coagulation (DIC), organ dysfunction, and clinical outcomes. METHODS This single-center, retrospective analysis included adult septic patients admitted to Saga University Hospital from 2013 to 2017, with available ROTEM data. Hypofibrinolysis was assessed using the lysis index at 60 min (LI60) in extrinsic thromboelastometry (EXTEM). Based on their LI60 values, patients were classified into three groups: Hyper (LI60 ≤ 85), Normal (LI60 86-96), and Hypo (LI60 ≥ 97). RESULTS Among the 63 cases analyzed, the Hypo group showed significantly higher APACHEII and SOFA scores than the Normal group, indicating greater disease severity. Similarly, DIC and sepsis-induced coagulopathy (SIC) scores were notably higher in the Hypo group. The diagnostic performance of LI60 for ISTH-overt DIC showed an area under the curve (AUC) of 0.954, with an optimal cutoff value of 97 %, achieving 100 % sensitivity and 83.3 % specificity. The odds ratio for ISTH-overt DIC was 2.894, indicating a strong association between elevated LI60 and occurrence of DIC. Hypofibrinolysis predicted 28-day mortality and high SOFA scores (≥ 10) with high specificity and negative predictive value (NPV). A Kaplan-Meier curve revealed that the Hypo Group showed significantly worse clinical outcomes than the Normal and Hyper groups. CONCLUSION For septic patients, fibrinolysis suppression presenting as "hypofibrinolysis" (elevated LI60) is associated with poor prognosis and risk of higher organ dysfunction. Moreover, it is a significant predictor of adverse clinical outcomes in sepsis.
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Affiliation(s)
- Hiroyuki Koami
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Yuichiro Sakamoto
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Yuri Hirota
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Akira Sasaki
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Hirotaka Ogawa
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Yutaro Furukawa
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Ayaka Matsuoka
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Kota Shinada
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Kento Nakayama
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Ryota Sakurai
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Sachiko Iwanaga
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Takayuki Onohara
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Shogo Narumi
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
| | - Mayuko Koba
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga City, Saga 849-8501, Japan.
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Tsaousi M, Sokou R, Pouliakis A, Politou M, Iacovidou N, Boutsikou T, Sulaj A, Karapati E, Tsantes AG, Tsantes AE, Valsami S, Iliodromiti Z. Hemostatic Status of Neonates with Perinatal Hypoxia, Studied via NATEM in Cord Blood Samples. CHILDREN (BASEL, SWITZERLAND) 2024; 11:799. [PMID: 39062248 PMCID: PMC11276384 DOI: 10.3390/children11070799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 06/25/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Perinatal hypoxia may result in coagulation dysfunction. Diminished blood flow or oxygen to the fetus/neonate during the perinatal period can cause bone marrow and liver function impairment, leading to thrombocytopenia, impaired synthesis of clotting and fibrinolytic factors, and increased destruction of platelets in the small blood vessels. The goal of the present study was to evaluate the hemostatic status of newborns with perinatal hypoxia via the non-activated thromboelastometry (NATEM) assay in cord blood samples. METHODS 134 hypoxic neonates born in our maternity unit over a 1.5-year period were enrolled in this observational cohort study, and 189 healthy neonates served as the control group. Participation in the study was voluntary and parents signed informed consent prior to recruitment. Demographic and clinical data were recorded on admission, and the NATEM method was performed on cord blood samples. The following NATEM values were evaluated: clotting time (CT), alpha angle (α-angle), clot formation time (CFT), clot amplitude at 5 and 10 min. (A5, A10), maximum clot firmness (MCF), clot lysis index at 60 min. after CT (LI60), and maximum clot elasticity (MCE). Statistical analysis was conducted utilizing the SAS for Windows 9.4 software platform. RESULTS Neonates with perinatal hypoxia exhibited decreased fibrinolytic potential in comparison to healthy neonates, as indicated by increased LI60, and this difference was statistically significant (LΙ60: 94 (92-96) Vs 93 (91-95), p value = 0.0001). There were no statistically significant differences noted among the remaining NATEM variables. CONCLUSION Our findings indicate decreased fibrinolytic potential in hypoxic neonates in comparison to healthy neonates, suggesting that NATEM could serve as an effective tool for promptly identifying hemostasis dysfunction in this group of neonates.
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Affiliation(s)
- Marina Tsaousi
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.T.); (R.S.); (T.B.); (A.S.); (E.K.); (Z.I.)
| | - Rozeta Sokou
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.T.); (R.S.); (T.B.); (A.S.); (E.K.); (Z.I.)
| | - Abraham Pouliakis
- 2nd Department of Pathology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Marianna Politou
- Hematology Laboratory Blood Bank, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.P.); (S.V.)
| | - Nicoletta Iacovidou
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.T.); (R.S.); (T.B.); (A.S.); (E.K.); (Z.I.)
| | - Theodora Boutsikou
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.T.); (R.S.); (T.B.); (A.S.); (E.K.); (Z.I.)
| | - Alma Sulaj
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.T.); (R.S.); (T.B.); (A.S.); (E.K.); (Z.I.)
| | - Eleni Karapati
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.T.); (R.S.); (T.B.); (A.S.); (E.K.); (Z.I.)
| | - Andreas G. Tsantes
- Laboratory of Haematology and Blood Bank Unit, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.G.T.); (A.E.T.)
| | - Argirios E. Tsantes
- Laboratory of Haematology and Blood Bank Unit, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.G.T.); (A.E.T.)
| | - Serena Valsami
- Hematology Laboratory Blood Bank, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.P.); (S.V.)
| | - Zoi Iliodromiti
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (M.T.); (R.S.); (T.B.); (A.S.); (E.K.); (Z.I.)
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Adamik B, Frostell C, Dragan B, Paslawska U, Zielinski S, Paslawski R, Janiszewski A, Zielinska M, Ryniak S, Albert J, Gozdzik W. Abnormalities of Coagulation and Fibrinolysis Assessed by Thromboelastometry in an Endotoxic Shock Model in Piglets Treated with Nitric Oxide and Hydrocortisone. Arch Immunol Ther Exp (Warsz) 2024; 72:aite-2024-0011. [PMID: 38847555 DOI: 10.2478/aite-2024-0011] [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: 09/05/2023] [Accepted: 04/18/2024] [Indexed: 06/24/2024]
Abstract
This is an animal model study to investigate changes in hemostasis during endotoxemic shock and to determine whether the combination of inhaled nitric oxide (iNO) + intravenous hydrocortisone had an effect on clot formation and fibrinolysis. iNO selectively decreases pulmonary artery pressure, without affecting cardiac index or systemic vascular resistance; however, the results of studies on the possible consequences of iNO administration on coagulation are inconsistent and require further research. Thirty-four piglets were included. Administering endotoxin caused severe hypodynamic shock. Half of the animals received iNO (30 ppm) + hydrocortisone, starting 3 h after endotoxin infusion and continuing to the end of the study. All animals developed coagulation disorders, manifested by a tendency to hypocoagulation; at the same time, fibrinolysis was impaired. Coagulation and fibrinolysis disorders persisted after endotoxin infusion was discontinued, with worse severity in the animals that died before the study was terminated. Administering iNO + hydrocortisone did not cause further changes in coagulation and fibrinolysis parameters, either during or after the endotoxin challenge, suggesting that potential therapeutic interventions with iNO to lower pulmonary arterial pressure will not affect hemostasis.
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Affiliation(s)
- Barbara Adamik
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland
| | - Claes Frostell
- Department of Anesthesia and Intensive Care, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden
| | - Barbara Dragan
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland
| | - Urszula Paslawska
- Nicolaus Copernicus University, Institute of Veterinary Medicine, Faculty of Biological and Veterinary Sciences, Torun, Poland
- Department of Internal Medicine and Clinic of Horses, Dogs and Cats, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - Stanislaw Zielinski
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland
| | - Robert Paslawski
- Nicolaus Copernicus University, Institute of Veterinary Medicine, Faculty of Biological and Veterinary Sciences, Torun, Poland
| | - Adrian Janiszewski
- Department of Internal Disease and Diagnostics, Poznan University of Life Sciences, Faculty of Veterinary Medicine and Animal Sciences, Poznan, Poland
| | - Marzena Zielinska
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland
| | - Stanislaw Ryniak
- Department of Anesthesia and Intensive Care, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden
| | - Johanna Albert
- Department of Anesthesia and Intensive Care, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden
| | - Waldemar Gozdzik
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland
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Cralley AL, Moore EE, Coleman JR, Vigneshwar N, Bartley M, Kissau D, Eitel A, Hom P, Mitra S, Ghasabyan A, Fragoso M, Guo Z, Deguchi H, Griffin JH, Cohen MJ, Silliman CC, Banerjee A, Hansen K, Sauaia A. Hemorrhagic shock and tissue injury provoke distinct components of trauma-induced coagulopathy in a swine model. Eur J Trauma Emerg Surg 2023; 49:1079-1089. [PMID: 36319860 PMCID: PMC10802987 DOI: 10.1007/s00068-022-02148-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 10/14/2022] [Indexed: 03/02/2023]
Abstract
INTRODUCTION Tissue injury (TI) and hemorrhagic shock (HS) are the major contributors to trauma-induced coagulopathy (TIC). However, the individual contributions of these insults are difficult to discern clinically because they typically coexist. TI has been reported to release procoagulants, while HS has been associated with bleeding. We developed a large animal model to isolate TI and HS and characterize their individual mechanistic pathways. We hypothesized that while TI and HS are both drivers of TIC, they provoke different pathways; specifically, TI reduces time to clotting, whereas, HS decreases clot strength stimulates hyperfibrinolysis. METHODS After induction of general anesthesia, 50 kg male, Yorkshire swine underwent isolated TI (bilateral muscle cutdown of quadriceps, bilateral femur fractures) or isolated HS (controlled bleeding to a base excess target of - 5 mmol/l) and observed for 240 min. Thrombelastography (TEG), calcium levels, thrombin activatable fibrinolysis inhibitor (TAFI), protein C, plasminogen activator inhibitor 1 (PAI-1), and plasminogen activator inhibitor 1/tissue-type plasminogen activator complex (PAI-1-tPA) were analyzed at pre-selected timepoints. Linear mixed models for repeated measures were used to compare results throughout the model. RESULTS TI resulted in elevated histone release which peaked at 120 min (p = 0.02), and this was associated with reduced time to clot formation (R time) by 240 min (p = 0.006). HS decreased clot strength at time 30 min (p = 0.003), with a significant decline in calcium (p = 0.001). At study completion, HS animals had elevated PAI-1 (p = 0.01) and PAI-1-tPA (p = 0.04), showing a trend toward hyperfibrinolysis, while TI animals had suppressed fibrinolysis. Protein C, TAFI and skeletal myosin were not different among the groups. CONCLUSION Isolated injury in animal models can help elucidate the mechanistic pathways leading to TIC. Our results suggest that isolated TI leads to early histone release and a hypercoagulable state, with suppressed fibrinolysis. In contrast, HS promotes poor clot strength and hyperfibrinolysis resulting in hypocoagulability.
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Affiliation(s)
| | - Ernest E Moore
- Department of Surgery, University of Colorado, Aurora, CO, USA
- Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health, Denver, CO, USA
| | - Julia R Coleman
- Department of Surgery, University of Colorado, Aurora, CO, USA
| | | | - Matt Bartley
- Department of Surgery, University of Colorado, Aurora, CO, USA
| | - Daniel Kissau
- Department of Surgery, University of Colorado, Aurora, CO, USA
| | - Andrew Eitel
- Department of Surgery, University of Colorado, Aurora, CO, USA
| | - Patrick Hom
- Department of Surgery, University of Colorado, Aurora, CO, USA
| | | | - Arsen Ghasabyan
- Department of Surgery, University of Colorado, Aurora, CO, USA
| | - Miguel Fragoso
- Department of Surgery, University of Colorado, Aurora, CO, USA
| | - Zihan Guo
- Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA
| | - Hiroshi Deguchi
- Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA
| | - John H Griffin
- Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA
- Department of Medicine, University of California, San Diego, CA, USA
| | | | - Christopher C Silliman
- Vitalant Research Institute, Denver, CO, USA
- Department of Pediatrics, University of Colorado, Aurora, CO, USA
| | | | - Kirk Hansen
- Department of Proteomics and Metabolomics, University of Colorado, Aurora, CO, USA
| | - Angela Sauaia
- Department of Health Systems, Management and Policy, School of Public Health, University of Colorado Denver, Aurora, CO, USA
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Which Septic Shock Patients With Non-Overt DIC Progress to DIC After Admission? Point-of-Care Thromboelastography Testing. Shock 2022; 57:168-174. [PMID: 35025842 DOI: 10.1097/shk.0000000000001847] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Disseminated intravascular coagulation (DIC) is a life-threatening complication of septic shock; however, risk factors for its development after admission are unknown. Thromboelastography (TEG) can reflect coagulation disturbances in early non-overt DIC that are not detected by standard coagulation tests. This study investigated the risk factors including TEG findings as early predictors for DIC development after admission in septic shock patients with non-overt DIC. METHODS This retrospective observation study included 295 consecutive septic shock patients with non-overt DIC at admission between January 2016 and December 2019. DIC was defined as an International Society on Thrombosis and Hemostasis (ISTH) score ≥ 5. The primary outcome was non-overt DIC at admission that met the ISTH DIC criteria within 3 days after admission. RESULTS Of the 295 patients with non-overt DIC, 89 (30.2%) developed DIC after admission. The DIC group showed a higher ISTH score and 28-day mortality rate than the non-DIC group (2 vs. 3, P < 0.001; 13.6% vs. 27.0%, P = 0.008, respectively). The DIC rate increased with the ISTH score (7.7%, 13.3%, 15.8%, 36.5%, and 61.4% for scores of 0, 1, 2, 3, and 4, respectively). Among TEG values, the maximum amplitude (MA) was higher in the non-DIC group (P < 0.001). On multivariate analysis, an MA < 64 mm was independently associated with DIC development (odds ratio, 2.311; 95% confidence interval, 1.298-4.115). CONCLUSIONS DIC more often developed among those with admission ISTH scores ≥ 3 and was associated with higher mortality rates. An MA < 64 mm was independently associated with DIC development in septic shock patients.
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Suga Y, Akita F, Yamada S, Morishita E, Asakura H. Recombinant human erythropoietin attenuates hepatic dysfunction by suppressing hepatocellular apoptosis in lipopolysaccharide-induced disseminated intravascular coagulation in rats. Biomed Rep 2021; 16:5. [PMID: 34900254 PMCID: PMC8652644 DOI: 10.3892/br.2021.1488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 10/25/2021] [Indexed: 11/19/2022] Open
Abstract
The aim of the present study was to clarify the effect of recombinant human erythropoietin (EPO) and low molecular weight heparin (LMWH) on a rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC). Experimental DIC was induced by sustained infusion of 5 mg/kg LPS for 4 h. EPO or LMWH was then administered to the LPS-induced DIC model. LPS-induced consumption coagulopathy, hemostatic activation and plasma TNF elevation remained unaltered in the LPS+EPO group, except for the D-dimer levels, and these abnormalities were significantly improved in the LPS+LMWH group. Plasma alanine aminotransferase (ALT) levels were markedly reduced in the LPS+EPO group, accompanied by a significant suppression of hepatocellular apoptosis. In the LPS+LMWH group, plasma creatinine levels and glomerular fibrin deposition were significantly attenuated, along with plasma ALT levels and hepatocellular apoptosis. Thus, a single administration of EPO may improve hepatic dysfunction by primarily exerting an anti-apoptotic, not anticoagulant, effect in the LPS-induced DIC model.
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Affiliation(s)
- Yukio Suga
- Department of Clinical Pharmacy and Healthcare Science, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Fumio Akita
- Department of Clinical Pharmacy and Healthcare Science, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Shinya Yamada
- Department of Hematology, Kanazawa University Hospital, Takaramachi, Kanazawa, Ishikawa 920-8641, Japan
| | - Eriko Morishita
- Department of Hematology, Kanazawa University Hospital, Takaramachi, Kanazawa, Ishikawa 920-8641, Japan
| | - Hidesaku Asakura
- Department of Hematology, Kanazawa University Hospital, Takaramachi, Kanazawa, Ishikawa 920-8641, Japan
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Buliarca A, Horhat A, Mocan T, Craciun R, Procopet B, Sparchez Z. Viscoelastic tests in liver disease: where do we stand now? World J Gastroenterol 2021; 27:3290-3302. [PMID: 34163112 PMCID: PMC8218367 DOI: 10.3748/wjg.v27.i23.3290] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/17/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests [INR (international normalized ratio), platelet count and fibrinogen] only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.
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Affiliation(s)
- Alina Buliarca
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Adelina Horhat
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Tudor Mocan
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Rares Craciun
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Bogdan Procopet
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Zeno Sparchez
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
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Role of thromboelastography in the evaluation of septic shock patients with normal prothrombin time and activated partial thromboplastin time. Sci Rep 2021; 11:11833. [PMID: 34088928 PMCID: PMC8178375 DOI: 10.1038/s41598-021-91221-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 05/24/2021] [Indexed: 02/06/2023] Open
Abstract
Coagulopathy is frequent in septic shock and plays a key role in multiple organ dysfunction. The aim of this study is to investigate application values of thromboelastography (TEG) for outcome in septic shock patients with a normal value of prothrombin time (PT) and active partial thromboplastin time (aPTT). Prospective observational study using 1298 consecutive septic shock patients with TEG at admission was conducted at the emergency department (ED) of a tertiary care hospital in South Korea between 2016 and 2019. After excluding overt-disseminated intravascular coagulation (DIC) defined by scoring system, we included patients with a normal value of international normalized ratio ≤ 1.3 and aPTT ≤ 34 s. The primary outcome was 28-day mortality. 893 patients were included and 129 patients with overt DIC were excluded. Of the 764 remaining patients, 414 (54.2%) patients showed normal PT and aPTT (28-day mortality rate, 11.4%). TEG values such as reaction time, kinetic time (K), alpha angle (α), maximum amplitude (MA) and lysis index (LY 30) showed no significant mean difference between the survivor and non-survivor groups. However, hypocoagulable TEG values such as α < 53° (12.0% vs. 23.4%; p = 0.039), and MA < 50 mm (6.3% vs. 21.3%; p = 0.002) were significantly higher in the non-survived group. In multivariate analysis, hypocoagulable state (defined as K > 3 and α < 53 and MA < 50) was independent factors associated with increased risk of death (OR 4.882 [95% CI, 1.698–14.035]; p = 0.003). In conclusion, septic shock patients with normal PT and aPTT can be associated with impaired TEG profile, such as hypocoagulability, associated with increased mortality.
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Detailed exploration of pathophysiology involving inflammatory status and bleeding symptoms between lipopolysaccharide- and tissue factor-induced disseminated intravascular coagulation in rats. Int J Hematol 2021; 114:172-178. [PMID: 33907978 DOI: 10.1007/s12185-021-03158-y] [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: 02/16/2021] [Revised: 04/22/2021] [Accepted: 04/22/2021] [Indexed: 10/21/2022]
Abstract
Lipopolysaccharide (LPS) and tissue factor (TF) have frequently been used to induce disseminated intravascular coagulation (DIC) in experimental animal models. We have previously reported that the pathophysiology of DIC differs according to the inducing agents. However, inflammatory status and bleeding symptoms have not been fully compared between rat models of the two forms of DIC. We attempted to evaluate detailed characteristic features of LPS- and TF-induced DIC models, especially in regard to inflammatory status and bleeding symptoms, in addition to selected hemostatic parameters and pathologic findings in the kidneys. The degree of hemostatic activation in both types of experimental DIC was identical, based on the results of thrombin-antithrombin complex levels. Markedly elevated tumor necrosis factor, interleukin-6, and high-mobility group box-1 concentrations were observed with severe organ dysfunction and marked fibrin deposition in the kidney on administration of LPS, whereas markedly elevated D-dimer concentration and bleeding symptoms were observed with TF administration. Pathophysiology such as fibrinolytic activity, organ dysfunction, inflammation status, and bleeding symptom differed markedly between LPS- and TF-induced DIC models in rats. We, therefore, recommend that these disease models be assessed carefully as distinct entities to determine the implications of their experimental and clinical use.
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10
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Standard and derived rotational thromboelastometry parameters for prediction of disseminated intravascular coagulation in septic patients. Blood Coagul Fibrinolysis 2021; 31:317-323. [PMID: 32398464 DOI: 10.1097/mbc.0000000000000919] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
: Waiting for lab tests results for the calculation of disseminated intravascular coagulation (DIC) scores leads to unwanted delays in diagnosis. The use of rotational thromboelastometry (ROTEM) for this purpose would allow for a more rapid DIC diagnosis at the bedside. The aim of this study was to assess the ability of standard ROTEM parameters and calculated parameters from the ROTEM velocity curve to predict DIC. The retrospective observational study included 97 septic patients. Japanese Association for Acute Medicine score was used for DIC diagnosis and whole-blood ROTEM was performed at study inclusion. Univariate analysis revealed delayed coagulation initiation and propagation and reduced clot firmness and maximum elasticity in DIC patients compared with patients without DIC. To adjust for confounders, multivariable logistic regression models were created and fibrinogen levels, prothrombin time and ROTEM parameters such as maximum clot firmness, maximum clot elasticity (MCE) and total thrombus formation [area under the curve (AUC)] were identified as significant predictors of DIC. According to receiver operating characteristics analysis, MCE and total thrombus formation (AUC) were the most useful ROTEM parameters for DIC prediction. MCE less than 158 (73% sensitive, 80% specific) and AUC less than 6175 mm × 100 (73% sensitive, 76% specific) predicted DIC in septic patients. Both standard and derived ROTEM parameters are useful for rapid DIC prediction in septic patients, allowing the timely identification of patients with higher mortality risk which might benefit from additional therapies. Further studies are needed to assess the clinical relevance of these findings.
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11
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Coagulopathy Characterized by Rotational Thromboelastometry in a Porcine Pediatric ECMO Model. THE JOURNAL OF EXTRA-CORPOREAL TECHNOLOGY 2020; 52:203-211. [PMID: 32981958 DOI: 10.1182/ject-2000011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 07/16/2020] [Indexed: 11/20/2022]
Abstract
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to support patients with reversible cardiopulmonary insufficiency. Although it is a lifesaving technology, bleeding, inflammation, and thrombosis are well-described complications of ECMO. Adult porcine models of ECMO have been used to recapitulate the physiology and hemostatic consequences of ECMO cannulation in adults. However, these models lack the unique physiology and persistence of fetal forms of coagulation factors and fibrinogen as in human infants. We aimed to describe physiologic and coagulation parameters of piglets cannulated and supported with VA-ECMO. Four healthy piglets (5.7-6.4 kg) were cannulated via jugular vein and carotid artery by cutdown and supported for a maximum of 20 hours. Heparin was used with a goal activated clotting time of 180-220 seconds. Arterial blood gas (ABG) was performed hourly, and blood was transfused from an adult donor to maintain hematocrit (Hct) > 24%. Rotational thromboelastometry (ROTEM) was performed at seven time points. All animals achieved adequate flow with a patent circuit throughout the run (pre- and post-oxygenator pressure gradient <10 mmHg). There was slow but significant hemorrhage at cannulation, arterial line, and bladder catheter sites. All animals required the maximum blood transfusion volume available. All animals became anemic after exhaustion of blood for transfusion. ABG showed progressively declining Hct and adequate oxygenation. ROTEM demonstrated decreasing fibrin-only ROTEM (FIBTEM) clot firmness. Histology was overall unremarkable. Pediatric swine are an important model for the study of pediatric ECMO. We have demonstrated the feasibility of such a model while providing descriptions of physiologic, hematologic, and coagulation parameters throughout. Weak whole-blood clot firmness by ROTEM suggested defects in fibrinogen, and there was a clinical bleeding tendency in all animals studied. This model serves as an important means to study the complex derangements in hemostasis during ECMO.
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12
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Application of Piezo-Based Measuring System for Evaluation of Nucleic Acid-Based Drugs Influencing the Coagulation. SENSORS 2019; 20:s20010152. [PMID: 31881749 PMCID: PMC6982813 DOI: 10.3390/s20010152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 12/15/2019] [Accepted: 12/21/2019] [Indexed: 11/16/2022]
Abstract
During open-heart surgery, the status of hemostasis has to be constantly monitored to quickly and reliably detect bleeding or coagulation disorders. In this study, a novel optimized piezo-based measuring system (PIEZ) for rheological monitoring of hemostasis was established. The applicability of the PIEZ for the evaluation of nucleic acid-based drugs influencing coagulation was analyzed. Thrombin aptamers such as NU172 might be used during extracorporeal circulation (ECC) in combination with a reduced heparin concentration or for patients with heparin-induced thrombocytopenia (HIT). Therefore, the effect of the coagulation inhibiting thrombin aptamer NU172 and the abrogation by its complementary antidote sequence (AD) were investigated by this rheological PIEZ system. After the addition of different NU172 concentrations, the coagulation of fresh human blood was analyzed under static conditions and using an in vitro rotation model under dynamic conditions (simulating ECC). The clotting times (CTs) detected by PIEZ were compared to those obtained with a medical reference device, a ball coagulometer. Additionally, after the circulation of blood samples for 30 min at 37 °C, blood cell numbers, thrombin markers (thrombin-antithrombin III (TAT) and fibrinopeptide A (FPA)) and a platelet activation marker (β-thromboglobulin (β-TG)) were analyzed by enzyme-linked immunosorbent assays (ELISAs). The increase of NU172 concentration resulted in prolonged CTs, which were comparable between the reference ball coagulometer and the PIEZ, demonstrating the reliability of the new measuring system. Moreover, by looking at the slope of the linear regression of the viscous and elastic components, PIEZ also could provide information on the kinetics of the coagulation reaction. The shear viscosity at the end of the measurements (after 300 s) was indicative of clot firmness. Furthermore, the PIEZ was able to detect the abrogation of coagulation inhibition after the equimolar addition of NU172 aptamer´s AD. The obtained results showed that the established PIEZ is capable to dynamically measure the hemostasis status in whole blood and can be applied to analyze nucleic acid-based drugs influencing the coagulation.
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13
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Krogh AKH, Brunse A, Thymann T, Bochsen L, Kristensen AT. Staphylococcus epidermidis sepsis induces hypercoagulability in preterm pigs. Res Vet Sci 2019; 127:122-129. [PMID: 31704497 DOI: 10.1016/j.rvsc.2019.10.019] [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: 08/30/2018] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 11/30/2022]
Abstract
Gram positive bacteria are a cause of sepsis in human preterm infants, and associates with high mortality and hemostatic dysfunction. It is unknown whether bovine colostrum may protect against sepsis and prevent hemostatic dysfunction. The current study was part of an overall sepsis study investigating Staphylococcus epidermidis (SE) induced sepsis in premature pigs including investigation of the effect of feeding bovine colostrum. The specific hypothesis of this study was that the hemostatic response would be hypercoagulable in septic pigs compared to non-infected controls, and that feeding bovine colostrum would increase the hypercoagulant response. Thromboelastography, activated partial thromboplastin time, prothrombin time and fibrinogen concentration were characterized in SE infected pigs, SE infected pigs fed bovine colostrum, and uninfected controls. All pigs were followed for 24 h. In addition, the same parameters were evaluated in a group of premature pigs and a group of full born pigs all followed for 11 days. SE septic premature pigs were characterized by increased clot strength and decreased fibrinolysis, significantly low platelet count and high fibrinogen concentration. Feeding bovine colostrum did not affect the hemostatic response. Compared to full born pigs, preterm newborn pigs demonstrated reduced clot strength, prolonged prothrombin time and low fibrinogen concentration. In all pigs, the fibrinogen concentration increased 11 days post-partum. To conclude, SE induced sepsis in premature pigs resulted in hypercoagulability. Bovine colostrum did not mitigate the hemostatic response. A hypocoagulable hemostatic response was present in healthy preterm pigs compared to full born pigs, similar to previous reports in infants.
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Affiliation(s)
- Anne Kirstine Havnsøe Krogh
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
| | - Anders Brunse
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
| | - Thomas Thymann
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
| | - Louise Bochsen
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
| | - Annemarie T Kristensen
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
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14
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Scarlatescu E, Juffermans NP, Thachil J. The current status of viscoelastic testing in septic coagulopathy. Thromb Res 2019; 183:146-152. [PMID: 31678709 DOI: 10.1016/j.thromres.2019.09.029] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Revised: 08/11/2019] [Accepted: 09/16/2019] [Indexed: 12/26/2022]
Abstract
Sepsis can be associated with different degrees of coagulopathy, ranging from a mild activation of the coagulation system to disseminated intravascular coagulation (DIC). The evaluation of haemostasis in the context of sepsis is important since it has been shown that anticoagulant therapies were beneficial mainly in patients with sepsis-induced DIC, but not in the general population of septic patients. Sepsis-induced haemostatic disturbances are not adequately reflected by standard coagulation tests (SCTs) which only consider the plasmatic components of the haemostatic system and not the cellular components. In addition, SCTs only assess the initiation phase of coagulation and reflect the activity of pro-coagulant factors, but lack sensitivity for the anticoagulant drive and the fibrinolytic activity. Viscoelastic tests (VET) are whole-blood tests which can assess clot formation and dissociation, and the contribution of both plasmatic and cellular components with a shorter turnaround time compared to SCTs. The use of VET in septic patients has proved useful for the assessment of the fibrinolytic activity, detecting hypercoagulable status and for the diagnosis of DIC and mortality risk prediction. While having relevant advantages over SCTs, the VET also present some blind spots or limitations leaving space for future improvement by the development of new reagents or new viscoelastic parameters.
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Affiliation(s)
- Ecaterina Scarlatescu
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, Bucharest, Romania.
| | - Nicole P Juffermans
- Department of Intensive Care, Amsterdam University Medical Center, location AMC, Amsterdam, the Netherlands
| | - Jecko Thachil
- Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom
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15
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Schmitt FCF, Manolov V, Morgenstern J, Fleming T, Heitmeier S, Uhle F, Al-Saeedi M, Hackert T, Bruckner T, Schöchl H, Weigand MA, Hofer S, Brenner T. Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 2019; 9:19. [PMID: 30701381 PMCID: PMC6353981 DOI: 10.1186/s13613-019-0499-6] [Citation(s) in RCA: 169] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 01/22/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Septic coagulopathy represents a very dynamic disease entity, tilting from initial hypercoagulability towards a subsequent hypocoagulable disease state, entitled overt disseminated intravascular coagulation. Acute fibrinolysis shutdown has recently been described to be a crucial component of initial hypercoagulability in critically ill patients, although the underlying pathomechanisms, the specific temporal kinetics and its outcome relevance in patients with sepsis remain to be determined. METHODS In total, 90 patients (30 with septic shock, 30 surgical controls and 30 healthy volunteers) were enrolled. Blood samples were collected at sepsis onset or prior and immediately after the surgical procedure as well as 3 h, 6 h, 12 h, 24 h, 48 h and 7 d later, whereas blood samples from healthy volunteers were collected once. Besides viscoelastic and aggregometric point-of-care testing (POCT), enzyme-linked immunosorbent and thrombin generation assays and liquid chromatography-mass spectrometry-based measurements were performed. RESULTS As assessed by viscoelastic POCT, fibrinolysis shutdown occurred early in sepsis. Significant increases in tissue plasminogen activator had no effect on thromboelastometrical lysis indices (LIs). Contrariwise, plasminogen activator inhibitor-1 was already significantly increased at sepsis onset, which was paralleled by significantly increased LIs in patients suffering from septic shock in comparison with both control groups. This effect persisted throughout the 7-day observation period and was most pronounced in severely ill as well as non-surviving septic patients. Thromboelastometrical LI, therefore, proved to be suitable for early diagnosis [e.g. LI 45 min: area under the curve (AUC) up to 0.933] as well as prognosis (e.g. LI 60 min: AUC up to 1.000) of septic shock. CONCLUSIONS Early inhibition of plasminogen activation leads to acute fibrinolysis shutdown with improved clot stability and is associated with increased morbidity and mortality in septic patients. Trial registration This study was approved by the local ethics committee (Ethics Committee of the Medical Faculty of Heidelberg; Trial-Code No. S247-2014/German Clinical Trials Register (DRKS)-ID: DRKS00008090; retrospectively registered: 07.05.2015). All study patients or their legal representatives signed written informed consent.
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Affiliation(s)
- Felix Carl Fabian Schmitt
- Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, 69120, Heidelberg, Germany
| | - Vasil Manolov
- Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, 69120, Heidelberg, Germany
| | - Jakob Morgenstern
- Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany
| | - Thomas Fleming
- Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany.,German Centre for Diabetes Research (DZD), Neuherberg, Germany
| | | | - Florian Uhle
- Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, 69120, Heidelberg, Germany
| | - Mohammed Al-Saeedi
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Thomas Bruckner
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Herbert Schöchl
- Department of Anesthesiology and Intensive Care Medicine, AUVA Trauma Centre Salzburg, Academic Teaching Hospital of the Paracelsus Medical University, Salzburg, Austria.,Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria
| | - Markus Alexander Weigand
- Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, 69120, Heidelberg, Germany
| | - Stefan Hofer
- Clinic for Anesthesiology, Intensive Care and Emergency Medicine I, Westpfalz Hospital, Kaiserslautern, Germany
| | - Thorsten Brenner
- Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, 69120, Heidelberg, Germany.
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16
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Sokou R, Giallouros G, Konstantinidi A, Pantavou K, Nikolopoulos G, Bonovas S, Lytras T, Kyriakou E, Lambadaridis I, Gounaris A, Douramani P, Valsami S, Kapsimali V, Iacovidou N, Tsantes AE. Thromboelastometry for diagnosis of neonatal sepsis-associated coagulopathy: an observational study. Eur J Pediatr 2018; 177:355-362. [PMID: 29255948 DOI: 10.1007/s00431-017-3072-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 12/01/2017] [Accepted: 12/08/2017] [Indexed: 01/01/2023]
Abstract
UNLABELLED Our aim was to evaluate the potential role of standard extrinsically activated thromboelastometry (EXTEM) assay in the early detection of neonatal sepsis. We studied 91 hospitalized neonates categorized in two groups: group A included 35 neonates with confirmed sepsis, while group B included 56 neonates with suspected sepsis; 274 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM assay was performed, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE) and Tοllner score were calculated, and clinical findings and laboratory results were recorded. Septic neonates had significantly prolonged clotting time (CT) and clot formation time (CFT), and reduced maximum clot firmness (MCF), compared to neonates with suspected sepsis (p values 0.001, 0.001, and 0.009, respectively) or healthy neonates (p values 0.001, 0.001, and 0.021, respectively). EXTEM parameters (CT, CFT, MCF) demonstrated a more intense hypocoagulable profile in septic neonates with hemorrhagic diathesis than those without (p values 0.021, 0.007, and 0.033, respectively). In septic neonates, CFT was correlated with platelet count, SNAPPE, Tollner score, and day of full enteral feeding (p values 0.01, 0.02, 0.05, and 0.03, respectively). CONCLUSIONS A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity. What is Known: • The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated. • Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis. What is New: • ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis. • ROTEM could be a useful tool in the early detection of sepsis in neonates.
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Affiliation(s)
- Rozeta Sokou
- Neonatal Intensive Care Unit, "Agios Panteleimon" General Hospital of Nikaia, Piraeus, Greece
| | | | | | | | | | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Humanitas Clinical and Research Center, Milan, Italy
| | - Theodore Lytras
- Hellenic Center for Disease Control and Prevention, Athens, Greece
| | - Elias Kyriakou
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" University Hospital, National and Kapodistrian University of Athens, 1 Rimini Str, 12462, Athens, Greece
| | - Ioannis Lambadaridis
- Neonatal Intensive Care Unit, "Agios Panteleimon" General Hospital of Nikaia, Piraeus, Greece
| | - Antonis Gounaris
- Neonatal Intensive Care Unit, University Hospital of Larissa, Larissa, Greece
| | - Panagiota Douramani
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" University Hospital, National and Kapodistrian University of Athens, 1 Rimini Str, 12462, Athens, Greece
| | - Serena Valsami
- Department of Blood Transfusion, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Violetta Kapsimali
- Department of Microbiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Nicoletta Iacovidou
- Neonatal Department, Aretaeio Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Argirios E Tsantes
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" University Hospital, National and Kapodistrian University of Athens, 1 Rimini Str, 12462, Athens, Greece.
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17
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Voelckel W, Maegele M, Solomon C, Schöchl H. Trauma-associated hyperfibrinolysis. Hamostaseologie 2017; 32:22-7. [DOI: 10.5482/ha-1178] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2011] [Accepted: 09/29/2011] [Indexed: 12/17/2022] Open
Abstract
SummaryTrauma-induced coagulopathy (TIC) has been considered for a long time as being due to depletion of coagulation factors secondary to blood loss, dilution and consumption. Dysfunction of the remaining coagulation factors due to hypothermia and acidosis is assumed to additionally contribute to TIC. Recent data suggest that hyperfibrinolysis (HF) represents an additional important confounder to the disturbed coagulation process. Severe shock and major tissue trauma are the main drivers of this HF. The incidence of HF is still speculative. According to visco-elastic testing of trauma patients upon emergency room admission, HF is present in approximately 2.5–7% of all trauma patients. However, visco-elastic tests provide information on severe forms of HF only. Occult HF seems to be much more common but diagnosis is still challenging. Results from a recent randomized, placebo-controlled trial suggest that the early treatment of trauma patients with tranexamic acid may result in a significant reduction of trauma-associated mortality.
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18
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Lee KCL, Baker L, Mallett S, Riddell A, Chowdary P, Alibhai H, Chang YM, Priestnall S, Stanzani G, Davies N, Mookerjee R, Jalan R, Agarwal B. Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs. Sci Rep 2017; 7:9347. [PMID: 28839178 PMCID: PMC5571150 DOI: 10.1038/s41598-017-09508-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 07/26/2017] [Indexed: 02/06/2023] Open
Abstract
Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability.
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Affiliation(s)
- Karla Chui Luan Lee
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, Hertfordshire, UK. .,Liver Failure Group, Institute of Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK.
| | - Luisa Baker
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Susan Mallett
- Department of Anaesthesia, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | - Anne Riddell
- Katherine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | - Pratima Chowdary
- Katherine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | - Hatim Alibhai
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Yu-Mei Chang
- Department of Research Support, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Simon Priestnall
- Department of Pathobiology and Population Sciences, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Giacomo Stanzani
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, Hertfordshire, UK
| | - Nathan Davies
- Liver Failure Group, Institute of Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK
| | - Rajeshwar Mookerjee
- Liver Failure Group, Institute of Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK
| | - Rajiv Jalan
- Liver Failure Group, Institute of Liver and Digestive Health, University College London Medical School Royal Free Campus, London, UK
| | - Banwari Agarwal
- Department of Intensive Care Medicine, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
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19
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Tóth J, Debreceni IB, Deák Á, Pető K, Berhés M, Hajdú E, Szabó J, Németh N, Fülesdi B, Kappelmayer J. Characteristics of thrombin generation in a fulminant porcine sepsis model. Thromb Res 2017; 158:25-34. [PMID: 28802974 DOI: 10.1016/j.thromres.2017.07.030] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 07/06/2017] [Accepted: 07/31/2017] [Indexed: 12/14/2022]
Abstract
INTRODUCTION The activation of blood coagulation has been demonstrated in most cases of sepsis, however previous studies in humans could not detect hypercoagulability with global hemostasis assays. In a fulminant porcine sepsis model we analysed coagulation screening tests and thrombin generation to evaluate hemostatic alterations. MATERIALS AND METHODS Live Escherichia coli bacteria were inoculated to female pigs and prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen were measured by coagulometry. Platelet counts, platelet aggregates and platelet phosphatidyl serine (PS) expression were studied, furthermore in in vitro experiments the PS-inducing ability of septic and control plasmas was investigated by flow cytometry. Thrombin generation was carried out by the Ascent Fluoroscan reader and results were evaluated by the Thrombinoscope software. RESULTS Clotting assays showed a large variability, but no systematic changes during the 4-hour observation period. Platelet count significantly decreased and the number of platelet aggregates increased already by 2h compared to baseline values and to control animals. Although the increase in platelet PS expression was non-significant in the septic group, the septic plasma elicited PS expression on normal human red blood cells. Thrombin generation became significantly faster, but the quantity of formed thrombin demonstrated both hypo- and hypercoagulability depending on the setting of the assay. CONCLUSIONS Enhanced thrombin generation without activators and the PS-inducing capacity of septic plasma are signs of hemostatic activation during fulminant sepsis while the decreased amount of generated thrombin upon tissue factor and phospholipid induced activation demonstrates attenuated thrombin forming ability.
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Affiliation(s)
- Judit Tóth
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Ildikó Beke Debreceni
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Ádám Deák
- Department of Operative Techniques and Surgical Research, Institute of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Katalin Pető
- Department of Operative Techniques and Surgical Research, Institute of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Mariann Berhés
- Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Endre Hajdú
- Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Judit Szabó
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Norbert Németh
- Department of Operative Techniques and Surgical Research, Institute of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Béla Fülesdi
- Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - János Kappelmayer
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
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Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry. Sci Rep 2017. [PMID: 28623360 PMCID: PMC5473891 DOI: 10.1038/s41598-017-03159-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Endothelial cells (ECs) are major modulators of hemostasis by expressing and releasing pro- and anticoagulant mediators into the circulation. Previous studies showed that cultured ECs release procoagulant mediators into cell culture supernatants as evidenced by the reduction of viscoelastic clotting time. This effect was reversed with an anti-tissue factor antibody. Here, we aimed to investigate whether tissue factor (TF) was released by endothelial-derived extracellular vesicles (EVs) and which portion of the released vesicles displays the most prominent procoagulant properties. After stimulation of ECs with tumor-necrosis factor-α (TNF-α) the supernatants of EC cultures were subjected to differential centrifugation steps to collect larger and smaller EVs which were then characterised by nanoparticle tracking analysis (NTA) and flow cytometry. Mixed with fresh human blood and analysed by thromboelastometry EVs exerted a significant procoagulant stimulus, which could be partly reversed by addition of an anti-TF antibody. Moreover, TF activity was confirmed in the centrifuged fractions. In summary, our results provide evidence of the procoagulant potential of smaller and larger endothelial-derived EV fractions detected by thromboelastometry. The observed effect is most likely due to the release of TF-bearing EVs of different dimensions, which are released upon TNF-α stimulation of endothelial cell cultures.
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Novel Function of Isoamylamine Improves Survival in Endotoxemic Mice by Ameliorating Coagulopathy and Attenuating MMP-9 Expression Through p-ERK/p-p38 Signaling at Early Stage. Shock 2017; 47:772-779. [DOI: 10.1097/shk.0000000000000786] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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22
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Lansink MO, Görlinger K, Hartmann M, de Groot H, Effenberger-Neidnicht K. Melatonin does not affect disseminated intravascular coagulation but diminishes decreases in platelet count during subacute endotoxaemia in rats. Thromb Res 2016; 139:38-43. [DOI: 10.1016/j.thromres.2015.10.025] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 09/30/2015] [Accepted: 10/13/2015] [Indexed: 12/15/2022]
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Jain A, Graveline A, Waterhouse A, Vernet A, Flaumenhaft R, Ingber DE. A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function. Nat Commun 2016; 7:10176. [PMID: 26733371 PMCID: PMC4729824 DOI: 10.1038/ncomms10176] [Citation(s) in RCA: 129] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 11/11/2015] [Indexed: 12/15/2022] Open
Abstract
Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic. The current hemostasis assays are unable to predict thrombotic or bleeding risk in clinics. Here, Jain et al. present a novel microfluidic device mimicking stenosed arterioles that determines clotting times in vitro and in extracorporeal circuits, offering a simple and reliable monitoring of blood homeostasis and platelet function.
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Affiliation(s)
- Abhishek Jain
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.,Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.,Vascular Biology Program, Departments of Pathology and Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
| | - Amanda Graveline
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA
| | - Anna Waterhouse
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA
| | - Andyna Vernet
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA
| | - Robert Flaumenhaft
- Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
| | - Donald E Ingber
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.,Vascular Biology Program, Departments of Pathology and Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.,Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA
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Meesters MI, Koch A, Kuiper G, Zacharowski K, Boer C. Instability of the non-activated rotational thromboelastometry assay (NATEM) in citrate stored blood. Thromb Res 2015; 136:481-3. [DOI: 10.1016/j.thromres.2015.05.026] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 05/21/2015] [Accepted: 05/22/2015] [Indexed: 11/16/2022]
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Nates JL, Cattano D, Chelly JE, Doursout MF. Study of acute hemocoagulation changes in a porcine endotoxemic shock model using thrombelastography. Transl Res 2015; 165:549-57. [PMID: 25262937 DOI: 10.1016/j.trsl.2014.09.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Revised: 08/29/2014] [Accepted: 09/04/2014] [Indexed: 11/19/2022]
Abstract
Disseminated intravascular coagulation and fibrinolysis have been associated with lipopolysaccharide (LPS)-induced endotoxemic sepsis. It has been well established by point-of-care (POC) thrombelastography (TEG) that pigs have a hemocoagulation pathophysiology that resembles humans. We evaluated the use of TEG during the development of coagulation abnormalities in a porcine model of endotoxemia. After approval by the Animal Welfare Committee, pigs were instrumented to record hemodynamic variables. Ten days after surgical instrumentation, LPS (50 μg/kg) was infused intravenously over a period of 45 minutes in conscious animals. Hemodynamic parameters were recorded before and for 6 hours after LPS infusion was completed. Simultaneously, blood samples were analyzed using TEG to measure reaction time (R), clotting time (K), alpha angle (α), maximum amplitude (MA), coagulation index (CI), percent lysis at 30 minutes, and percent lysis at 60 minutes. LPS induced profound hemodynamic changes associated with the induced endotoxemia. Concomitantly, a progressive consumption coagulopathy characterized by significant increases in R and K and decreases in α, MA, and CI developed. The overall hemocoagulation profile of the 3 nonsurviving animals (27%) was significantly different than that of the survivors. Fibrinolysis was not detected during the 6-hour evaluation period. All stages of clot formation were affected as demonstrated by TEG (increased R and K, decreased α and MA). Our results suggest that TEG is a rapid method for assessing coagulation abnormalities in early stages of endotoxemia in pigs. TEG could have significant clinical applications as a rapid POC method in human patients with sepsis.
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Affiliation(s)
- Joseph L Nates
- Division of Anesthesiology and Critical Care, Department of Critical Care Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
| | - Davide Cattano
- Department of Anesthesiology, The University of Texas Medical School at Houston, Houston, TX
| | - Jacques E Chelly
- Department of Anesthesiology, The University of Pittsburgh School of Medicine, Pittsburgh, PA
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Zarogiannis SG, Wagener BM, Basappa S, Doran S, Rodriguez CA, Jurkuvenaite A, Pittet JF, Matalon S. Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice. Am J Physiol Lung Cell Mol Physiol 2014; 307:L347-54. [PMID: 25038191 DOI: 10.1152/ajplung.00152.2014] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Chlorine (Cl2) is a highly reactive oxidant gas that, when inhaled, may cause acute lung injury culminating in death from respiratory failure. In this study, we tested the hypothesis that exposure of mice to Cl2 causes intra-alveolar and systemic activation of the coagulation cascade that plays an important role in development of lung injury. C57Bl/6 mice were exposed to Cl2 (400 for 30 min or 600 ppm for 45 min) in environmental chambers and then returned to room air for 1 or 6 h. Native coagulation (NATEM) parameters such as blood clotting time and clot formation time were measured in whole blood by the viscoelastic technique. D-dimers and thrombin-anti-thrombin complexes were measured in both plasma and bronchoalveolar lavage fluid (BALF) by ELISA. Our results indicate that mice exposed to Cl2 gas had significantly increased clotting time, clot formation time, and D-dimers compared with controls. The thrombin-anti-thrombin complexes were also increased in the BALF of Cl2 exposed animals. To test whether increased coagulation contributed to the development of acute lung injury, mice exposed to Cl2 and returned to room air were treated with aerosolized heparin or vehicle for 20 min. Aerosolized heparin significantly reduced protein levels and the number of inflammatory cells in the BALF at 6 h postexposure. These findings highlight the importance of coagulation abnormities in the development of Cl2-induced lung injury.
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Affiliation(s)
- Sotirios G Zarogiannis
- Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Center for Pulmonary Injury and Repair, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Brant M Wagener
- Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and
| | - Susanna Basappa
- Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and
| | - Stephen Doran
- Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and
| | - Cilina A Rodriguez
- Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and
| | - Asta Jurkuvenaite
- Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Center for Pulmonary Injury and Repair, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Jean Francois Pittet
- Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Center for Pulmonary Injury and Repair, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Sadis Matalon
- Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Center for Pulmonary Injury and Repair, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
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27
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Kundu B, Schlimp CJ, Nürnberger S, Redl H, Kundu SC. Thromboelastometric and platelet responses to silk biomaterials. Sci Rep 2014; 4:4945. [PMID: 24824624 PMCID: PMC4018936 DOI: 10.1038/srep04945] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2013] [Accepted: 04/17/2014] [Indexed: 12/02/2022] Open
Abstract
Silkworm's silk is natural biopolymer with unique properties including mechanical robustness, all aqueous base processing and ease in fabrication into different multifunctional templates. Additionally, the nonmulberry silks have cell adhesion promoting tri-peptide (RGD) sequences, which make it an immensely potential platform for regenerative medicine. The compatibility of nonmulberry silk with human blood is still elusive; thereby, restricts its further application as implants. The present study, therefore, evaluate the haematocompatibility of silk biomaterials in terms of platelet interaction after exposure to nonmulberry silk of Antheraea mylitta using thromboelastometry (ROTEM). The mulberry silk of Bombyx mori and clinically used Uni-Graft W biomaterial serve as references. Shortened clotting time, clot formation times as well as enhanced clot strength indicate the platelet mediated activation of blood coagulation cascade by tested biomaterials; which is comparable to controls.
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Affiliation(s)
- Banani Kundu
- Department of Biotechnology, Indian Institute of Technology, Kharagpur-721302, India
- These authors contributed equally to this work
| | - Christoph J. Schlimp
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria
- These authors contributed equally to this work
| | - Sylvia Nürnberger
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Heinz Redl
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - S. C. Kundu
- Department of Biotechnology, Indian Institute of Technology, Kharagpur-721302, India
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Müller MC, Meijers JCM, Vroom MB, Juffermans NP. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2014; 18:R30. [PMID: 24512650 PMCID: PMC4056353 DOI: 10.1186/cc13721] [Citation(s) in RCA: 152] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Accepted: 01/29/2014] [Indexed: 12/12/2022]
Abstract
Introduction Coagulation abnormalities are frequent in sepsis. Conventional coagulation assays, however, have several limitations. A surge of interest exists in the use of point-of-care tests to diagnose hypo- and hypercoagulability in sepsis. We performed a systematic review of available literature to establish the value of rotational thromboelastography (TEG) and thromboelastometry (ROTEM) compared with standard coagulation tests to detect hyper- or hypocoagulability in sepsis patients. Furthermore, we assessed the value of TEG/ROTEM to identify sepsis patients likely to benefit from therapies that interfere with the coagulation system. Methods MEDLINE, EMBASE, and the Cochrane Library were searched from 1 January 1980 to 31 December 2012. The search was limited to adults, and language was limited to English. Reference lists of retrieved articles were hand-searched for additional studies. Ongoing trials were searched on http://www.controlled-trials.com and http://www.clinicaltrials.gov. Studies addressing TEG/ROTEM measurements in adult patients with sepsis admitted to the ICU were considered eligible. Results Of 680 screened articles, 18 studies were included, of which two were randomized controlled trials, and 16 were observational cohort studies. In patients with sepsis, results show both hyper- and hypocoagulability, as well as TEG/ROTEM values that fell within reference values. Both hyper- and hypocoagulability were to some extent associated with diffuse intravascular coagulation. Compared with conventional coagulation tests, TEG/ROTEM can detect impaired fibrinolysis, which can possibly help to discriminate between sepsis and systemic inflammatory response syndrome (SIRS). A hypocoagulable profile is associated with increased mortality. The value of TEG/ROTEM to identify patients with sepsis who could possibly benefit from therapies interfering with the coagulation system could not be assessed, because studies addressing this topic were limited. Conclusion TEG/ROTEM could be a promising tool in diagnosing alterations in coagulation in sepsis. Further research on the value of TEG/ROTEM in these patients is warranted. Given that coagulopathy is a dynamic process, sequential measurements are needed to understand the coagulation patterns in sepsis, as can be detected by TEG/ROTEM.
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Abstract
OBJECTIVES Accidental hypothermia increases mortality and morbidity after hemorrhage, but controversial data are available on the effects of therapeutic hypothermia. Therefore, we tested the hypothesis whether moderate pretreatment hypothermia would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation. DESIGN Prospective, controlled, randomized study. SETTING University animal research laboratory. SUBJECTS Twenty domestic pigs of either gender. INTERVENTIONS Using an extracorporeal heat exchanger, anesthetized and instrumented animals were maintained at 38°C, 35°C, or 32°C core temperature and underwent 4 hours of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Resuscitation comprised of hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at preshock values. MEASUREMENTS AND MAIN RESULTS Before, immediately at the end of, and 12 and 22 hours after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, and nitric oxide and cytokine production. Hemostasis was assessed by rotation thromboelastometry. Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and markers of apoptosis (kidney Bcl-xL and caspase-3 expression). Hypothermia at 32°C attenuated the shock-related lactic acidosis but caused metabolic acidosis, most likely resulting from reduced carbohydrate oxidation. Although hypothermia did not further aggravate shock-related coagulopathy, it caused a transitory attenuation of kidney and liver dysfunction, which was ultimately associated with reduced histological damage and more pronounced apoptosis. CONCLUSIONS During long-term porcine hemorrhage and resuscitation, moderate pretreatment hypothermia was associated with a transitory attenuation of organ dysfunction and less severe histological tissue damage despite more pronounced metabolic acidosis. This effect is possibly due to a switch from necrotic to apoptotic cell death, ultimately resulting from reduced tissue energy deprivation during the shock phase.
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Krzanicki D, Sugavanam A, Mallett S. Intraoperative hypercoagulability during liver transplantation as demonstrated by thromboelastography. Liver Transpl 2013; 19:852-61. [PMID: 23696318 DOI: 10.1002/lt.23668] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2013] [Accepted: 04/23/2013] [Indexed: 12/13/2022]
Abstract
Thrombotic complications are more common in liver disease than might be expected because of the coagulopathy described by conventional coagulation tests. Some of these complications may be life-threatening. The phenomenon of hypercoagulation is associated with complications in many populations, but the incidence in liver transplant recipients is unclear. We performed a retrospective database review of intraoperative thromboelastography (TEG) for 124 liver transplant recipients. We assessed the prevalence of hypercoagulation in this group and investigated the relative frequency of both shortened TEG reaction times (R times) and increased net clot strength (G) values. These findings were correlated with thrombotic complications. At the baseline, the prevalence of high G values was 15.53% on native TEG, and the prevalence of shortened R times was 6.80% on native-heparinase TEG. Patients with cholestatic pathologies had particularly high rates of hypercoagulation (42.9% with primary biliary cirrhosis and 85.7% with primary sclerosing cholangitis), but hypercoagulation was also common in patients with fulminant hepatic failure (50%) and nonalcoholic steatohepatitis (37.5%). There was a poor correlation between the TEG R time and the international normalized (INR), with 37.7% of TEG analyses demonstrating a short R time with an INR > 2. Six of the patients developed early hepatic artery thrombosis (5%); 3 of these patients had TEG evidence of high G values (P = 0.25), and 4 had short R times (not significant). In conclusion, intraoperative TEG evidence of high G values and short R times is relatively common in liver transplantation. It is unclear what bearing this condition has on thrombotic complications. Conventional coagulation tests have no ability to diagnose this condition. It is conceivable that such patients may come to harm if hypercoagulability is unrecognized and, therefore, inappropriately managed.
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Affiliation(s)
- Dominik Krzanicki
- Department of Anaesthesia, Royal Free Hospital, London, United Kingdom.
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31
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Gando S, Wada H, Thachil J. Differentiating disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype from coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS). J Thromb Haemost 2013; 11:826-35. [PMID: 23522358 DOI: 10.1111/jth.12190] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Accepted: 02/25/2013] [Indexed: 11/28/2022]
Abstract
Two concepts have been proposed for the hemostatic changes occurring early after trauma. Disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype is characterized by activation of the coagulation pathways, insufficient anticoagulant mechanisms and increased fibrinolysis. Coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS) occurs as a result of increased activation of the thrombomodulin and protein C pathways, leading to the suppression of coagulation and activation of fibrinolysis. Despite the differences between these two conditions, independent consideration of COT/ACOTS from DIC with the fibrinolytic phenotype is probably incorrect. Robust diagnostic criteria based on its pathophysiology are required to establish COT/ACOTS as a new independent disease concept. In addition, the independency of its characteristics, laboratory data, time courses and prognosis from DIC should be confirmed. Confusion between two concepts may be based on studies of trauma lacking the following: (i) a clear distinction of the properties of blood between the inside and outside of vessels, (ii) a clear distinction between physiologic and pathologic hemostatic changes, (iii) attention to the time courses of the changes in hemostatic parameters, (iv) unification of the study population, and (v) recognition that massive bleeding is not synonymous with coagulation disorders. More information is needed to elucidate the pathogenesis of these two entities, DIC with the fibrinolytic phenotype and COT/ACOTS after trauma. However, available data suggest that COT/ACOTS is not a new concept but a disease entity similar to or the same as DIC with the fibrinolytic phenotype.
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Affiliation(s)
- S Gando
- Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
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Zipperle J, Schlimp CJ, Holnthoner W, Husa AM, Nürnberger S, Redl H, Schöchl H. A novel coagulation assay incorporating adherent endothelial cells in thromboelastometry. Thromb Haemost 2013; 109:869-77. [PMID: 23494019 DOI: 10.1160/th12-10-0767] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Accepted: 02/05/2013] [Indexed: 12/30/2022]
Abstract
Following vascular injury or activation, endothelial cells (ECs) participate in the modulation of haemostasis and fibrinolysis. Viscoelastic tests (VETs) are a potent bedside monitoring tool that reports haemostatic parameters in real time. However, VETs neglect the influence of the surrounding endothelium. Our aim was therefore to establish an assay that incorporates ECs in a whole blood VET and to assess the impact of ECs on coagulation parameters. Outgrowth endothelial cells (OECs) and human umbilical vein endothelial cells (HUVECs) were seeded onto microbeads to create transferable EC-microcarriers. Microbeads were then added to citrated whole blood in the measurement cup of a thromboelastometry device (ROTEM). After the addition of CaCl2 (star-TEM®) to the blood sample (NATEM assay), standard ROTEM parameters were analysed. Scanning electron microscopy (SEM) was carried out to visualise the interactions of the beads, whole blood components and the ROTEM pin after clotting. SEM showed that the added microbeads were effectively incorporated into the final blood clot. In the presence of activated ECs, the clotting time (CT) of the blood was shortened fourfold compared to that in uncoated control beads. A significant reduction in CT was also observed in the presence of unstimulated ECs. Interestingly, CT was also reduced by the addition of purified EC culture supernatant. CT shortening was prevented by incubating the supernatant with an inhibiting antibody against tissue factor (TF). Our findings demonstrate that ECs can be incorporated into a ROTEM assay via coated microbeads, and whole blood clotting initiation is accelerated by non-activated and activated ECs.
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Affiliation(s)
- J Zipperle
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Donaueschingenstrasse 13, Vienna, Austria
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Görlinger K, Bergmann L, Dirkmann D. Coagulation management in patients undergoing mechanical circulatory support. Best Pract Res Clin Anaesthesiol 2013; 26:179-98. [PMID: 22910089 DOI: 10.1016/j.bpa.2012.04.003] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2012] [Revised: 03/25/2012] [Accepted: 04/20/2012] [Indexed: 12/28/2022]
Abstract
The incidence of bleeding and thrombo-embolic complications in patients undergoing mechanical circulatory support therapy remains high and is associated with bad outcomes and increased costs. The need for anticoagulation and anti-platelet therapy varies widely between different pulsatile and non-pulsatile ventricular-assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) systems. Therefore, a unique anticoagulation protocol cannot be recommended. Notably, most thrombo-embolic complications occur despite values of conventional coagulation tests being within the targeted range. This is due to the fact that conventional coagulation tests such as international normalised ratio (INR), activated partial thromboplastin time (aPTT) and platelet count cannot detect hyper- or hypofibrinolysis, hypercoagulability due to tissue factor expression on circulating cells or increased clot firmness, and platelet aggregation as well as response to anti-platelet drugs. By contrast, point-of-care (POC) whole blood viscoelastic tests (thromboelastometry/-graphy) and platelet function tests (impedance or turbidimetric aggregometry) reflect in detail the haemostatic status of patients undergoing mechanical circulatory support therapy and the efficacy of their anticoagulation and antiaggregation therapy. Therefore, monitoring of haemostasis using POC thromboelastometry/-graphy and platelet function analysis is recommended during mechanical circulatory support therapy to reduce the risk of bleeding and thrombo-embolic complications. Notably, these haemostatic tests should be performed repeatedly during mechanical circulatory support therapy since thrombin generation, clot firmness and platelet response may change significantly over time with a high inter- and intra-individual variability. Furthermore, coagulation management can be hampered in non-pulsatile VADs by acquired von Willebrand syndrome, and in general by acquired factor XIII deficiency as well as by heparin-induced thrombocytopenia. In addition, POC testing can be used in bleeding patients to guide calculated goal-directed therapy with allogeneic blood products, haemostatic drugs and coagulation factor concentrates to optimise the haemostasis and to minimise transfusion requirements, transfusion-associated adverse events and to avoid thrombo-embolic complications, as well. However, coagulation management in patients undergoing mechanical circulatory support therapy is somehow like navigating between Scylla and Charybdis, and development of protocols based on POC testing seems to be beneficial.
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Affiliation(s)
- Klaus Görlinger
- Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinkum Essen, Universität Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
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BRENNER T, SCHMIDT K, DELANG M, MEHRABI A, BRUCKNER T, LICHTENSTERN C, MARTIN E, WEIGAND MA, HOFER S. Viscoelastic and aggregometric point-of-care testing in patients with septic shock - cross-links between inflammation and haemostasis. Acta Anaesthesiol Scand 2012; 56:1277-90. [PMID: 22897591 DOI: 10.1111/j.1399-6576.2012.02750.x] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2012] [Indexed: 12/16/2022]
Abstract
BACKGROUND In the pathogenesis of sepsis, inflammation-induced changes in coagulation play a pivotal role. METHODS In total, 90 patients (30 patients with septic shock, 30 surgical patients following major abdominal surgery and 30 healthy volunteers) were enrolled. Blood samples from patients with septic shock were collected at the time of sepsis diagnosis as well as 24 h, 4 days, 7 days, 14 days and 28 days later. Samples from surgical patients with a post-surgical inflammatory response were collected three times (before surgery, immediately after surgery and 24 h after surgery) and once from healthy volunteers. Thromboelastometry (ROTEM (®) ), as well as whole blood impedance aggregometry (Multiplate(®) ) were performed. Additionally, plasma concentrations of interleukin-6 and tumour necrosis factor-alpha were measured using enzyme-linked immunosorbent assay kits. RESULTS Thromboelastometry lysis index was shown to be a reliable biomarker for septic shock. Furthermore, in septic patients with overt disseminated intravascular coagulation, thromboelastometry revealed signs indicating a hypocoagulable status, whereas patients without overt disseminated intravascular coagulation were found to be hypercoagulable. Platelet aggregation capability, as assessed by whole blood impedance aggregometry, was significantly reduced in septic patients with overt disseminated intravascular coagulation, whereas it was comparable with healthy volunteers and in septic patients without overt disseminated intravascular coagulation. CONCLUSION Viscoelastic and aggregometric point-of-care testing was shown to be potentially useful for bedside diagnosis of sepsis. Moreover, viscoelastic and aggregometric point-of-care testing was able to determine the phase of septic coagulopathy (hypercoagulability vs. hypocoagulability) and therefore identified patients at high risk for overt disseminated intravascular coagulation.
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Affiliation(s)
- T. BRENNER
- Department of Anaesthesiology; University of Heidelberg; Heidelberg; Germany
| | - K. SCHMIDT
- Department of Anaesthesiology; University of Heidelberg; Heidelberg; Germany
| | - M. DELANG
- Department of Anaesthesiology; University of Heidelberg; Heidelberg; Germany
| | - A. MEHRABI
- Department of General and Transplant Surgery; University of Heidelberg; Heidelberg; Germany
| | - T. BRUCKNER
- Institute of Medical Biometry and Informatics; University of Heidelberg; Heidelberg; Germany
| | - C. LICHTENSTERN
- Department of Anaesthesiology and Intensive Care Medicine; University of Gießen; Gießen; Germany
| | - E. MARTIN
- Department of Anaesthesiology; University of Heidelberg; Heidelberg; Germany
| | - M. A. WEIGAND
- Department of Anaesthesiology and Intensive Care Medicine; University of Gießen; Gießen; Germany
| | - S. HOFER
- Department of Anaesthesiology; University of Heidelberg; Heidelberg; Germany
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Scharbert G, Thaler U, Weilnböck C, Wetzel L, Kozek-Langenecker S. Heparin-induced effects of prothrombin complex concentrates in thromboelastometry. Wien Klin Wochenschr 2012; 124:320-5. [PMID: 22576961 DOI: 10.1007/s00508-012-0171-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2011] [Accepted: 04/15/2012] [Indexed: 11/30/2022]
Abstract
BACKGROUND Prothrombin complex concentrates (PCC) are currently used to treat congenital or acquired coagulation factor deficiency. In case of serious bleeding caused by new oral anticoagulant agents, reversing treatment with PCC is under debate. PCC preparations mostly contain heparin to prevent thromboembolic events. In factor VIII and IX deficient plasma, Takeyama et al. observed in vitro a heparin effect at appropriate concentrations of PCCs. The aim of the present experiment was to investigate the heparin effect of four factor-PCC at clinically relevant concentrations in whole blood. In an in vitro experiment, we compared the PCC preparation used in the experiments of Takeyama with a high heparin content to a new heparin-free PCC preparation. METHOD After ethics committee approval and written informed consent, the citrated whole blood was obtained from ten healthy volunteers. We tested heparin-containing Prothromplex(®) and heparin-free Cofact(®) at concentrations of 0.31, 0.63, and 1.25 IU/ml. Protamine was added to another set of samples (1:1 heparin:protamine). We used the NATEM test in the rotational thromboelastometer ROTEM(®). RESULTS In the heparin PCC preparation, we observed a significant (p < 0.001) concentration-dependent prolongation in CT and CFT, even at the lowest concentration. MCF was also significantly reduced. The heparin effect was reversible by protamine. The heparin-free PCC did not affect the onset of coagulation. The interpretation of the alpha-angle showed no increased thrombus formation in heparin-free PCC preparation. CONCLUSION Our results extend the report of Takeyama et al. At clinically relevant PCC concentrations, the heparin effect was significant in thromboelastometry. The heparin content of PCCs should be considered in clinical routine.
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Affiliation(s)
- Gisela Scharbert
- Department of Special Anesthesiology and Pain Management, General Intensive Care and Pain Control, Vienna Medical University, 1090, Vienna, Waehringer Guertel 18-20, Austria.
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Raeven P, Feichtinger GA, Weixelbaumer KM, Atzenhofer S, Redl H, Van Griensven M, Bahrami S, Osuchowski MF. Compartment-specific expression of plasminogen activator inhibitor-1 correlates with severity/outcome of murine polymicrobial sepsis. Thromb Res 2012; 129:e238-45. [DOI: 10.1016/j.thromres.2012.02.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 01/24/2012] [Accepted: 02/05/2012] [Indexed: 01/28/2023]
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Similarities in thromboelastometric (ROTEM®) findings between humans and baboons. Thromb Res 2012; 130:e107-12. [PMID: 22482831 DOI: 10.1016/j.thromres.2012.03.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2011] [Revised: 03/05/2012] [Accepted: 03/12/2012] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Interest in visco-elastic testing in different clinical scenarios has increased but few data are available on thromboelastometric findings in primates. MATERIALS AND METHODS Blood cell count (hemoglobin, hematocrit, platelet count), coagulation parameters (prothrombin time, International Normalized Ratio, fibrinogen), and ROTEM® (Tem International GmbH, Munich, Germany) variables were analyzed using blood from 25 anesthetized male baboons and 21 non-anesthetized healthy volunteers. The platelet component of the clot was calculated as the difference in maximum clot elasticity (MCE) between the whole blood clot (EXTEM test) and the fibrin-based clot (FIBTEM test). In subgroups of each species, 10 μg abciximab was added to the regular FIBTEM reagent (cytochalasin D) for additional platelet inhibition. RESULTS Blood cell count was comparable between humans and primates. Both fibrinogen concentration (p<0.0001) and maximum clot firmness (MCF) in FIBTEM assays were significantly lower in baboons (p>0.0001, and p=0.006, respectively). PT, INR, and clotting time in NATEM assays were significantly prolonged in humans compared with baboons. MCF in NATEM, EXTEM and INTEM assays was not different between baboons and humans. Clot lysis in NATEM, EXTEM and INTEM assays was significantly higher in humans (p<0.0001). In contrast FIBTEM clot lysis was significantly higher in baboons (p=0.01). Addition of abciximab into the FIBTEM assay resulted in a significant reduction in MCF and MCE (p<0.001) and, consequently, the platelet component increased similar in both humans and baboons (p<0.001). CONCLUSION Activated ROTEM® tests revealed broad similarities between humans and baboons. ROTEM® assays developed for use in humans can also be used in baboons.
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