RESUMO
BackgroundHeparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death. MethodsWe randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat. ResultsAt 28 days, the primary composite outcome occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69; 95% confidence interval [CI], 0.43 to 1.10; p=0.12). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22; 95%-CI, 0.07 to 0.65). The composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59; 95%-CI, 0.34 to 1.02). Major bleeding occurred in 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52; 95%-CI, 0.09 to 2.85). ConclusionsIn moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days. Trial registration numbers: NCT04362085; NCT04444700
RESUMO
BackgroundUnderstanding the association between Coronavirus Disease 2019 (COVID-19) and coagulopathy may assist clinical prognostication, and influence treatment and outcomes. We aimed to systematically describe the relationship between hemostatic laboratory parameters and important clinical outcomes among adults with COVID-19. MethodsA systematic review of randomized clinical trials, observational studies and case series published in PubMed (Medline), EMBASE, and CENTRAL from December 1, 2019 to March 25, 2020. Studies of adult patients with COVID-19 that reported at least one hemostatic laboratory parameter were included. ResultsData were extracted from 57 studies (N=12,050 patients) that met inclusion criteria. The average age of patients was 52 years and 45% were women. Of the included studies, 92.7% (N=38/41 studies) reported an average platelet count [≥] 150 x 109/L, 68.2% (N=15/22 studies) reported an average prothrombin time (PT) between 11-14 s, 55% (N=11/20 studies) reported an average activated partial thromboplastin time (aPTT) between 25-35 s, and 34.4% (N=11/32 studies) reported a D-dimer concentration above the upper limit of normal (ULN). Eight studies (7 cohorts and 1 case series) reported hemostatic lab values for survivors versus non-survivors. Among non-survivors, D-dimer concentrations were reported in 4 studies and all reported an average above the ULN. InterpretationMost patients had a normal platelet count, elevated D-dimer, PT and aPTT values in the upper reference interval; D-dimer elevation appeared to correlate with poor outcomes. Further studies are needed to better correlate these hemostatic parameters with the risk of adverse outcomes such as thrombosis and bleeding.
