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Published on: November 5, 2021
COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection
Hanny Al-Samkari1,2, Rebecca S Karp Leaf1,2, Walter H Dzik1,2
1Division of Hematology Oncology, Massachusetts General Hospital, Boston, MA.
Insights
Elevated D-dimer in COVID-19 patients predicts thrombosis and bleeding. Standard anticoagulation showed moderate VTE and bleeding rates, suggesting a need for trials on intensified prophylaxis.
Area of Science:
- Internal Medicine
- Hematology
- Critical Care Medicine
Background:
- Coronavirus disease 2019 (COVID-19) is associated with elevated D-dimer levels.
- Early reports suggest high rates of venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) in COVID-19 patients, but data are limited.
Purpose of the Study:
- To describe the incidence and severity of hemostatic and thrombotic complications in hospitalized COVID-19 patients.
- To identify predictors of coagulation-associated complications, critical illness, and death.
Main Methods:
- Multicenter retrospective study of 400 hospitalized COVID-19 patients, including 144 critically ill.
- Analysis of coagulation and inflammatory parameters, comparing patients with and without complications.
- Multivariable logistic regression to assess predictive utility of markers.
Main Results:
- The radiographically confirmed VTE rate was 4.8%, and the overall thrombotic complication rate was 9.5%. Overall and major bleeding rates were 4.8% and 2.3%, respectively.
- Elevated D-dimer (>2500 ng/mL) predicted thrombosis, bleeding, critical illness, and death.
- Higher platelet count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) also predicted thrombosis.
Conclusions:
- Elevated D-dimer is a significant predictor of thrombotic and bleeding complications in COVID-19 patients.
- Standard-dose prophylactic anticoagulation resulted in moderate VTE and bleeding rates.
- Randomized trials are necessary to evaluate the efficacy of intensified anticoagulation strategies.
Abstract:
Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels. Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited. This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation. Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications. Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death. The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8). The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively. In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively. Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death. Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]). ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without. DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations. Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.
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