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Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding-A Systematic Review and a Cohort Study
Hvas CL, Larsen JB, Adelborg K, Christensen S, Hvas AM
Seminars in thrombosis and hemostasis. 2021
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Editor's Choice
Abstract
Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3-4, and 7-8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin-antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis (n = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.
PICO Summary
Population
Patients admitted to intensive care unit with COVID-19 (18 studies).
Intervention
Systematic review examining the haemostasis with a wide range of dynamic haemostasis assays including platelet aggregation, global whole blood coagulation, thrombin generation assays, and fibrinolysis assays.
Comparison
Outcome
The included studies revealed normal or slightly reduced primary haemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome.
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The Role of Platelets in Premature Neonates with Intraventricular Hemorrhage: A Systematic Review and Meta-Analysis
Grevsen AK, Hviid CVB, Hansen AK, Hvas AM
Seminars in thrombosis and hemostasis. 2019
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Editor's Choice
Abstract
Intraventricular hemorrhage (IVH) affects up to 22% of extremely low birth weight neonates. Impaired coagulation might contribute to the pathogenesis of IVH. The aims of this study were to summarize the current knowledge on the role of platelet indices in premature neonates with IVH and to provide an overview of secondary hemostasis parameters as well as fibrinolysis in premature neonates with IVH. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, Scopus, and Web of Science were searched on March 7, 2019, without time restrictions. In total, 30 studies were included. Most studies investigated the significance of platelet counts and/or mean platelet volume (MPV). The meta-analysis showed that at day 1 of life, neither platelet count nor MPV differed significantly between neonates with or without IVH (standardized mean difference [SMD]: -0.15 x 10(9)/L, 95% confidence interval [CI]: -0.37 to 0.07 and SMD: 0.22 fl, 95% CI: -0.07 to 0.51, respectively). However, platelet counts < 100 x 10(9)/L were associated with an increased risk of IVH. Secondary hemostasis parameters did not differ between neonates with and without IVH. Fibrinolysis was only sparsely investigated. In conclusion, platelet counts < 100 x 10(9)/L were associated with an increased risk of IVH in premature neonates. The impact of secondary hemostasis was only sparsely investigated but seemed to be minor, and the role of fibrinolysis in IVH in premature neonates needs further research. Whether reduced platelet function is associated with an increased risk of IVH in premature neonates remains to be investigated.
PICO Summary
Population
Extremely low birth weight neonates (30 studies).
Intervention
Platelet indices in neonates with IVH.
Comparison
Platelet indices in neonates without IVH.
Outcome
The meta-analysis showed that at day 1 of life, neither platelet count nor MPV differed significantly between neonates with or without IVH. However, platelet counts < 100 x 10(9)/L were associated with an increased risk of IVH. Secondary hemostasis parameters did not differ between neonates with and without IVH. Fibrinolysis was only sparsely investigated.