key: cord-0989092-ajezk7kr
authors: Marietta, Marco; Coluccio, Valeria; Luppi, Mario
title: More on: ‘COVID‐19 coagulopathy in Caucasian patients’
date: 2020-05-22
journal: Br J Haematol
DOI: 10.1111/bjh.16772
sha: 26a4f66248df99823a95cbf05af7ad9cf3e36270
doc_id: 989092
cord_uid: ajezk7kr

We read with interest the report from Fogarty and colleagues about COVID-19 coagulopathy in Caucasian patients. [1] However, we think that some aspects of this report may deserve further attention. The major concern regards the doses of low-molecular weight heparin (LMWH) used for thromboprophylaxis in this study. Indeed, the Authors report on a weight-adjusted dose of enoxaparin higher than that registered in Europe for the prophylaxis of venous thromboembolism (VTE) in hospitalized acutely ill medical patients.

We read with interest the report from Fogarty et al. 1 about coronavirus disease 2019 (COVID-19) coagulopathy in Caucasian patients. However, we think that some aspects of this report may deserve further attention. The major concern regards the doses of low-molecular-weight heparin (LMWH) used for thromboprophylaxis in this study. Indeed, the authors report on a weight-adjusted dose of enoxaparin higher than that registered in Europe for the prophylaxis of venous thromboembolism (VTE) in hospitalised acutely ill medical patients. We are aware that a pro-thrombotic derangement of the haemostatic system has been found in most severe forms of COVID-19 infections, 2 and that this finding negatively affects the prognosis in patients with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pneumonia. 3 In these patients, LMWH at doses registered for prevention of VTE, i.e. enoxaparin 4000 iu subcutaneously daily, has been shown to be associated with a reduced risk of death 4 and is currently recommended by the World Health Organization, as well as by scientific societies. [5] [6] [7] LMWH has also been shown to protect glycocalyx from shedding, displaying anti-inflammatory and immunomodulatory properties. 8 Of note, in vitro and in vivo experimental studies have shown that human coronaviruses utilise heparin sulphate proteoglycans for attachment to target cells, 9 suggesting a role for heparin in the therapeutic armamentarium against COVID-19. It is therefore conceivable that higher doses of LMWH than those used for VTE prevention in acutely ill medical patients, might improve anti-inflammatory activity, mitigate cytokines storm and improve the disease prognosis.

However, evidence is not yet available as to whether higher doses of heparin can improve the prognosis of patients with more severe COVID-19 without affecting the safety related to bleeding.

Relevant to this, it would have been advisable that the authors reported the rate of major bleeding and kidney impairment requiring LMWH dose adjustment in their study population. Pending further evidence, we suggest more caution in suggesting the use LMWH doses higher than those used for VTE prophylaxis, outside of either an established diagnosis of VTE or of a clinical trial.

Moreover, we observe that the coagulopathy was assessed by the International Society for Thrombosis and Hemostasis (ISTH) Scientific and Standardization Committee (SSC) overt Disseminated Intravascular Coagulation (DIC) score. In our opinion, a proper and possibly, more tailored approach would have been to use the more focussed Sepsis Induced Coagulopathy score, 10 which has already been adopted in the specific setting of patients with COVID-19. 4 This approach would have been advisable in order to strengthen the message conveyed by the authors that the coagulopathy observed in patients with COVID-19 is a quite different pathophysiological entity compared with the classical picture of DIC. Relevant to this, the expression 'pulmonary intravascular coagulopathy (PIC)' proposed by the authors fits well with the peculiar clinical and pathological pictures of coagulopathy and severe acute respiratory distress syndrome often observed in SARS-Cov-2 pneumonia.

Future trials will hopefully address the compelling clinical issues related to efficacy and safety of either a more intense anti-coagulation with LMWH or the use of unfractionated heparin in patients with severe COVID-19. 

Coagulopathy in Caucasian patients

Hypercoagulability of COVID-19 patients in Intensive Care Unit. A report of thromboelastography findings and other parameters of hemostasis

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected. Interim guidance 28

ISTH interim guidance on recognition and management of coagulopathy in COVID-19

COVID-19 and haemostasis: a position paper from Italian Society on Thrombosis and Haemostasis (SISET)

The role of heparin in sepsis: much more than just an anticoagulant

Human coronavirus NL63 utilizes heparan sulfate proteoglycans for attachment to target cells

Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation