Fibrinolysis Shutdown Correlation with Thromboembolic Events in Severe COVID-19 Infection

Abstract

BACKGROUND: COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement. The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events. STUDY DESIGN: Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied. Conventional coagulation assays, D-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure. RESULTS:Forty-four patients with COVID-19 were included in the analysis. Derangements in coagulation laboratory values, including elevated D-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes. A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p ¼ 0.021). A D-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p ¼ 0.005). Overall, patients with no lysis of clot at 30 minutes and a D-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p ¼ 0.008), and had a hemodialysis rate of 80% compared with 14% (p ¼ 0.004). CONCLUSIONS: Fibrinolysis shutdown, as evidenced by elevated D-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19. Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.

COVID-19 and Venous Thromboembolism: A Meta-analysis of Literature Studies

“…The number of patients varied from 11 to 328, with mean age of 64.3 years (from 51.7 to 80.5 years). Eleven studies 18,19,21,24,25,28,30,[32][33][34]36 specifically enrolled patients admitted to ICU. A total of 66.8% of patients were males (range: 45.7-90.9%) and the mean BMI was 28.2 kg/m 2 (range: 23.6-31.3 kg/m 2 ).…”

A Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for COVID-19

“…The thrombotic complications observed in COVID-19 include several unusual features that differ from disseminated intravascular coagulation (DIC), e.g. elevated fibrinogen and fibrin D-dimer, hyperreactive platelets, and formation of microthrombi in multiple organs, but without the consumption of coagulation factors that typically accompany other severe inflammatory conditions such as sepsis [6][7][8][9][10][11][12][13][14][15][16][17] .…”

Clinical characteristics and outcome of critically ill COVID-19 patients with Acute Kidney Injury: A single centre cohort study

“…The contribution of microthrombi formation in AKI has been found in postmortem ndings, where there is erythrocyte stagnation with clot formation in the glomerular and peri-tubular capillaries in COVID-19 patients [6]. Moreover, one study demonstrated that elevated D-Dimer level and complete failure of lysis at 30 minutes on a thromboelastogram are predictive of signi cant increase in the incidence of thromboembolism and a need for haemodialysis in critically ill COVID-19 patients [21]. In our report, the development of AKI was associated with raised admission D-dimer levels and these abnormalities persisted in patients with AKI even after a week of ICU admission.…”