Abstract
A hypercoagulable state has been described in coronavirus disease 2019 (COVID-19) patients. Others have reported a survival advantage with prophylactic anticoagulation (pAC) and therapeutic anticoagulation (tAC), but these retrospective analyses have important limitations such as confounding by indication. We studied the impact of tAC and pAC compared with no anticoagulation (AC) on time to death in COVID-19. We performed a cross-sectional analysis of 127 deceased COVID-19 patients and compared time to death in those who received tAC ( n = 67), pAC ( n = 47), and no AC ( n = 13). Median time to death was longer with higher doses of AC (11 days for tAC, 8 days for pAC, and 4 days for no AC, p < 0.001). In multivariate analysis, AC was associated with longer time to death, both at prophylactic (hazard ratio [HR] = 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p < 0.001) and therapeutic doses (HR = 0.15; 95% CI: 0.07 to 0.32; p < 0.001) compared with no AC. Bleeding rates were similar among tAC and remaining patients (19 vs. 18%; p = 0.877). In deceased COVID-19 patients, AC was associated with a delay in death in a dose-dependent manner. Randomized trials are required to prospectively investigate the benefit and safety of higher doses of AC in this population.
Highlights
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) is a novel coronavirus identified as the cause of several cases of severe pneumonia in December 2019 in Wuhan, China, later designated as novel coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO).[1,2] It has since spread exponentially to become a global pandemic.[3,4] An increasing body of evidence suggests hypercoagulability as an important component in the pathogenesis of severe COVID-19
Treatment with Anticoagulation Sixty-seven (53%) patients received therapeutic anticoagulation (tAC) with intravenous unfractionated heparin (UFH) employed in 87%; for 3% treatment was with subcutaneous enoxaparin, whereas 10% of patients were continued on home oral anticoagulants (7% direct oral anticoagulants and 3% warfarin)
The number of days on tAC did not significantly differ between patients who were treated in the intensive care unit (ICU) and those who were not
Summary
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) is a novel coronavirus identified as the cause of several cases of severe pneumonia in December 2019 in Wuhan, China, later designated as novel coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO).[1,2] It has since spread exponentially to become a global pandemic.[3,4] An increasing body of evidence suggests hypercoagulability as an important component in the pathogenesis of severe COVID-19. Catheters have been supplemented by laboratory data consistent with activation of the coagulation cascade as quantified by elevated D-dimer and fibrinogen in conjunction with low antithrombin levels.[5] The prevalence of disseminated intravascular coagulation (DIC) per International Society for Thrombosis and Haemostasis (ISTH) criteria was markedly higher in deceased patients compared with survivors (71 vs 0.6%).[6] Two studies employing thromboelastography have shown a coagulation profile consistent with hypercoagulability in the context of severe systemic inflammation.[7,8] That hypercoagulability is of particular clinical importance is supported by multiple autopsy case series reporting pulmonary and other visceral microthromboses.[9,10,11]
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