Fondaparinux Use in Patients With COVID-19: A Preliminary Multicenter Real-World Experience

The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.

Background A relatively high mortality of severe coronavirus disease 2019 (COVID‐19) is worrying, and the application of heparin in COVID‐19 has been recommended by some expert consensus because of the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. Methods Coagulation results, medications, and outcomes of consecutive patients being classified as having severe COVID‐19 in Tongji hospital were retrospectively analyzed. The 28‐day mortality between heparin users and nonusers were compared, as was a different risk of coagulopathy, which was stratified by the sepsis‐induced coagulopathy (SIC) score or D‐dimer result. Results There were 449 patients with severe COVID‐19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin) for 7 days or longer. D‐dimer, prothrombin time, and age were positively, and platelet count was negatively, correlated with 28‐day mortality in multivariate analysis. No difference in 28‐day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P  = .910). But the 28‐day mortality of heparin users was lower than nonusers in patients with SIC score ≥4 (40.0% vs 64.2%, P  = .029), or D‐dimer >6‐fold of upper limit of normal (32.8% vs 52.4%, P  = .017). Conclusions Anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID‐19 patients meeting SIC criteria or with markedly elevated D‐dimer.

Abstract Background Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world. Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned. Objectives To determine the incidence of VTE in patients with severe NCP. Methods In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled. The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed. Results The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died. The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc. If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%. Conclusions The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis. The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.