Tromboprofilaxis en COVID-19: ¿seguimos en la neblina? Translated title: Thromboprophylaxis in COVID-19: still in the fog?

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.

Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.

Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19). We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n=5) and purpuric skin rash (n=3). The pattern of COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the inter-alveolar septa by neutrophils. No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic ARDS, were not prominent. These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the alternative and lectin-based complement pathways. The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin. In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the inter-alveolar septa and the cutaneous microvasculature of two cases examined. In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state. It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.