Abstract
Background: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. Methods: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables. Results: Among all 79 patients, 12 (15.2%) had bleeding events, and 20 (25.3%) had thrombosis. Multivariate logistic regression analysis identified a prediction model for bleeding (adjusted R2 = 0.787, p < 0.001) comprised of increased reaction time (p = 0.016), decreased fibrinogen (p = 0.006), decreased D-dimer (p = 0.063), and increased activated partial thromboplastin time (p = 0.084). Multivariate analysis of thrombosis identified a weak prediction model (adjusted R2 = 0.348, p < 0.001) comprised of increased D-dimer (p < 0.001), decreased reaction time (p = 0.002), increased maximum amplitude (p < 0.001), and decreased alpha angle (p = 0.014). Adjunctive thromboelastography decreased the use of packed red cells (p = 0.031) and fresh frozen plasma (p < 0.001). Conclusions: Significantly, this study demonstrates the need for a precision-based titration strategy of anticoagulation for hospitalized COVID-19 patients. Since severely ill COVID-19 patients may switch between thrombotic or hemorrhagic phenotypes or express both simultaneously, institutions may reduce these complications by developing their own titration strategy using daily conventional coagulation tests with adjunctive thromboelastography.
Highlights
Diagnosis of COVID-19 was confirmed by reverse transcriptase-polymerase chain reaction assay based on the World Health Organization (WHO) standard, that targets the SARS-CoV2 E gene and RdRp gene, or by positive SARS-CoV-2 IgM antibody
This single center, retrospective study corroborates existing literature regarding the high incidence of thrombohemorrhagic complications in severely ill COVID-19 patients [2,9,12,14,15,25,30,31,41,42]
This study includes patients treated at a time in the pandemic when evidence was actively evolving, and empiric escalation of the anticoagulant dose was recommended for those patients with elevated D-dimer at admission and without macrovascular thrombosis [15]
Summary
Despite the frequent hypercoagulable state of hospitalized COVID-19 patients and the attractive therapeutic hypothesis of heparinoids, anticoagulation is often complicated by the rapid evolution from heparinoid resistance to heparinoid hypersensitivity, which may result in major hemorrhage [9,12,13,14,15,16]. With little evidence early in the pandemic, institutions offered conflicting guidelines for the empiric escalation of prophylactic anticoagulation to intermediate or therapeutic doses for hospitalized patients with COVID-19 pneumonitis and without macrovascular thrombosis [17,18,19,20,21]. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. Methods: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables
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