Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding—A Systematic Review and a Cohort Study

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.

Hypercoagulability in critically ill patients with COVID 19, an observational prospective study

“…Despite HDPA and even CDA, hypercoagulability was more pronounced on day 4 than on day 1. These results are in close agreement with those of previous studies [ 32 , 71 ]. Our data support the results of REMAP-CAP demonstrating the absence of benefit of CDA in COVID ICU patients [ 43 ].…”

“…Similarly, Roh et al suggested that the significant increase in fibrinogen plasma concentrations and FIBTEM MCF indicates the severity of COVID-19 and can be used for risk stratification for thrombosis, respiratory failure, and mortality [ 66 ]. The relationship between Li60 values and mortality remains debatable [ 32 ]: it has been reported in septic patients, but never to our knowledge in COVID-19 ICU patients [ 36 ].…”

SARS-CoV-2 Spike Protein and Neutralizing Anti-Spike Protein Antibodies Modulate Blood Platelet Function

“…However, the greater platelet number and fibrin crosslinking have the overall effect of increasing fibrin density and reducing clot permeability and pore size, which affects fibrinolysis. Increased thrombin generation and decreased fibrinolysis were reported in COVID-19 patients in vivo [ 39 ]. In another study of COVID-19 patients, pronounced significant inhibition of all stages of blood clot contraction was observed.…”

2023 Eberhard F. Mammen Award Announcements: Part I—Most Popular Articles

“…Consequently, the most popular articles from each category are identified separately. Tables 3 and 4 , respectively, list the top 15 downloaded articles from STH in 2022 (from 2021 and 2022 inclusive), as eligible for either the “free access” ( Table 3 ) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 or the “General Category” ( Table 4 ) 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 awards. As expected, the majority of the “Free Access” articles were related to COVID-19.…”