Assessment and determinants of whole blood and plasma fibrinolysis in patients with mild bleeding symptoms

Vries, Minka J A; Macrae, Fraser L.; Nelemans, Patricia J.; Kuiper, Gerhardus J.A.J.M.; Wetzels, Rick; Bowman, Polly; Verhezen, Paul W M; Cate, Hugo Ten; Ariëns, Robert A. S.; Henskens, Yvonne

doi:10.1016/j.thromres.2018.12.004

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…Also, no evidence was found supporting a systemic hyperfibrinolytic capacity in BUC patients. In contrast, we found that clot lysis time was significantly prolonged in BUC patients compared to healthy controls, in line with previously published data, 30,31 hereby carefully rejecting hyperfibrinolysis as underlying pathophysiological mechanism for BUC.…”

Section: Discussionsupporting

confidence: 92%

Evaluation of thromboelastometry, thrombin generation and plasma clot lysis time in patients with bleeding of unknown cause: A prospective cohort study

et al. 2020

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Introduction: Diagnostic evaluation of patients with a bleeding tendency remains challenging, as no disorder is identified in approximately 50% of patients. An impaired interplay of several haemostatic factors might explain bleeding phenotype in these patients. Objective: To investigate whether global haemostasis assays are able to identify haemostatic abnormalities in patients with a bleeding tendency unexplained by current diagnostic laboratory tests. Materials and methods: Patients of ≥12 years with a bleeding tendency were included from a tertiary outpatient clinic. Bleeding phenotype was assessed with the ISTH-BAT. Patients were classified as having bleeding of unknown cause (BUC) or a mild bleeding disorder (MBD) based on abnormalities assessed by routine haemostatic tests. Global haemostasis tests (rotational thromboelastometry (ROTEM), thrombin generation test (TG) and plasma clot lysis time (CLT)) were measured in all patients. The results were compared with 76 controls. Results: One hundred and eighty-one patients were included, and 60% (109/181) was classified as having BUC. BUC patients demonstrated a significantly prolonged lag time in TG (median 7.7 minutes, IQR 6.7-8.7) and a significantly prolonged CLT (median 60.5 minutes, IQR 54.7-66.1) compared to controls. No differences in ROTEM variables were found. Patients with MBD showed an impaired thrombin generation with a significantly decreased ETP (median 1024 nmol/L*min, IQR 776-1355) and peak height (median 95 nmol/L, IQR 76-138), compared to BUC patients and controls. Conclusion: No major differences were found in ROTEM and TG variables in BUC patients compared to controls. BUC patients did have a significantly prolonged clot lysis time. The underlying mechanism for this finding is unknown. K E Y W O R D S bleeding, bleeding of unknown cause, fibrinolysis, haemostasis, mild bleeding disorder, thrombin generation, thromboelastometry | e107 VEEN Et al.

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Section: Discussionsupporting

confidence: 92%

Evaluation of thromboelastometry, thrombin generation and plasma clot lysis time in patients with bleeding of unknown cause: A prospective cohort study

et al. 2020

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“…Viscoelastic testing might better represent coagulation in vivo than routine hemostatic assays due to its whole blood dynamic assessment. Assessment of the complete fibrinolytic system remains notoriously difficult, but tissue plasminogen activator rotational thromboelastometry (tPA ROTEM) is thought to be more sensitive to hypofibrinolysis than other clinically used assays (19,20).…”

Section: Introductionmentioning

confidence: 99%

Serial EXTEM, FIBTEM, and tPA Rotational Thromboelastometry Observations in the Maastricht Intensive Care COVID Cohort—Persistence of Hypercoagulability and Hypofibrinolysis Despite Anticoagulation

Hulshof

Brüggemann

Mulder

et al. 2021

Front. Cardiovasc. Med.

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Background: Coronavirus Disease 2019 (COVID-19) patients often present with thromboembolic events. In COVID-19 patients, routine hemostatic assays cannot correctly identify patients at risk for thromboembolic events. Viscoelastic testing with rotational thromboelastometry (ROTEM) might improve the characterization of COVID-19-associated coagulopathy.Objective: To unravel underlying coagulopathy and fibrinolysis over time as measured by serial assessment heparin-independent (FIBTEM and EXTEM) and fibrinolysis illustrating (tissue plasminogen activator; tPA) ROTEM assays.Patients/Methods: Between April 23 and June 12, consecutive adult patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included, and a comprehensive set of clinical, physiological, pharmaceutical, and laboratory variables were collected daily. Twice per week, EXTEM, FIBTEM, and tPA ROTEM were performed. Clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT) were determined to assess clot development and breakdown and were compared to routine hemostatic assays.Results: In 36 patients, 96 EXTEM/FIBTEM and 87 tPA ROTEM tests were performed during a 6-week follow-up. CT prolongation was present in 54% of EXTEM measurements, which were not matched by prothrombin time (PT) in 37%. Respectively, 81 and 99% of all EXTEM and FIBTEM MCF values were above the reference range, and median MCF remained elevated during follow-up. The ROTEM fibrinolysis parameters remained prolonged with median LOT consequently >49 min and unmeasurable LT in 56% of measurements, suggesting a severe hypofibrinolytic phenotype.Conclusion: ROTEM tests in COVID-19 ICU patients show hypercoagulability and severe hypofibrinolysis persisting over at least 6 weeks.

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“…Finally, another Dutch group, Vries et al, 48 recently did not identify significant differences in clot formation nor clot strength using ROTEM nor differences in a turbidity assay between 240 patients with self‐reported bleeding and 95 patients without bleeding symptoms who were scheduled for an elective surgery. The discrepancies between these studies may be partially explained by the smaller samples sizes in some cohorts, 4,47,48 the heterogeneity of investigated patients, and interlaboratory variations 49 . More specifically, Hofer et al 47 included adult patients with a MBD, who were screened by a hemostasis expert, Veen et al included subjects >12 years old while Vries et al compared patients >18 years old who had one or more self‐reported bleeding symptom before an elective surgery with patients without a self‐reported bleeding manifestation.…”

Section: Hyperfibrinolysis In Bleeding Cohorts and Patients With Bucmentioning

confidence: 98%

“…In contrast, Veen et al 4 recently reported a prolonged clot lysis time in a smaller cohort of 109 patients with BUC compared to healthy controls, and no difference in ROTEM parameters was found. Finally, another Dutch group, Vries et al, 48 recently did not identify significant differences in clot formation nor clot strength using ROTEM nor differences in a turbidity assay between 240 patients with self‐reported bleeding and 95 patients without bleeding symptoms who were scheduled for an elective surgery. The discrepancies between these studies may be partially explained by the smaller samples sizes in some cohorts, 4,47,48 the heterogeneity of investigated patients, and interlaboratory variations 49 .…”

Section: Hyperfibrinolysis In Bleeding Cohorts and Patients With Bucmentioning

confidence: 98%

Fibrinolysis and bleeding of unknown cause

Mehic

Pabinger

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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Assessment and determinants of whole blood and plasma fibrinolysis in patients with mild bleeding symptoms

Abstract: This is a repository copy of Assessment and determinants of whole blood and plasma fibrinolysis in patients with mild bleeding symptoms.

Cited by 7 publications

References 30 publications

Evaluation of thromboelastometry, thrombin generation and plasma clot lysis time in patients with bleeding of unknown cause: A prospective cohort study

Evaluation of thromboelastometry, thrombin generation and plasma clot lysis time in patients with bleeding of unknown cause: A prospective cohort study

Serial EXTEM, FIBTEM, and tPA Rotational Thromboelastometry Observations in the Maastricht Intensive Care COVID Cohort—Persistence of Hypercoagulability and Hypofibrinolysis Despite Anticoagulation

Fibrinolysis and bleeding of unknown cause

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