Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring
Authors: Susen Sophie , Tacquard Charles Ambroise , Godon Alexandre , Mansour Alexandre , Garrigue Delphine , Nguyen Philippe , Godier Anne , Testa Sophie , Levy Jerrold H. , Albaladejo Pierre , Gruel Yves ,   on behalf of GIHP and GFHT, Albaladejo P. , Blais N. , Bonhomme F. , Borel-Derlon A. , Cohen A. , Collet J.-P. , de Maistre E. , Fontana P. , Huet D. Garrigue , Godier A. , Gruel Y. , Godon A. , Ickx B. , Laporte S. , Lasne D. , Llau J. , Le Gal G. , Lecompte T. , Lessire S. , Levy J. H. , Longrois D. , Madi-Jebara S. , Mansour A. , Mazighi M. , Mismetti P. , Morange P. E. , Motte S. , Mullier F. , Nathan N. , Nguyen P. , Pernod G. , Rosencher N. , Roullet S. , Roy P. M. , Schlumberger S. , Sié P. , Steib A. , Susen S. , Tacquard C. A. , Testa S. , Vincentelli A. , Zufferey P. , Borel-Derlon A. , Boissier E. , Dumont B. , de Maistre E. , Gruel Y. , James C. , Lasne D. , Lecompte T. , Morange P. E. , Nguyen P. , Siguret V. , Susen S. 
Published: June 2020

COVID-19 is an infection induced by the SARS-CoV-2 coronavirus, and severe forms can lead to acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) management. Severe forms are associated with coagulation changes, mainly characterized by an increase in D-dimer and fibrinogen levels, with a higher risk of thrombosis, particularly pulmonary embolism. The impact of obesity in severe COVID-19 has also been highlighted.

In this context, standard doses of low molecular weight heparin (LMWH) may be inadequate in ICU patients, with obesity, major inflammation, and hypercoagulability. We therefore urgently developed proposals on the prevention of thromboembolism and monitoring of hemostasis in hospitalized patients with COVID-19.

Four levels of thromboembolic risk were defined according to the severity of COVID-19 reflected by oxygen requirement and treatment, the body mass index, and other risk factors. Monitoring of hemostasis (including fibrinogen and D-dimer levels) every 48 h is proposed. Standard doses of LMWH (e.g., enoxaparin 4000 IU/24 h SC) are proposed in case of intermediate thrombotic risk (BMI < 30 kg/m2, no other risk factors and no ARDS). In all obese patients (high thrombotic risk), adjusted prophylaxis with intermediate doses of LMWH (e.g., enoxaparin 4000 IU/12 h SC or 6000 IU/12 h SC if weight > 120 kg), or unfractionated heparin (UFH) if renal insufficiency (200 IU/kg/24 h, IV), is proposed. The thrombotic risk was defined as very high in obese patients with ARDS and added risk factors for thromboembolism, and also in case of extracorporeal membrane oxygenation (ECMO), unexplained catheter thrombosis, dialysis filter thrombosis, or marked inflammatory syndrome and/or hypercoagulability (e.g., fibrinogen > 8 g/l and/or D-dimers > 3 μg/ml). In ICU patients, it is sometimes difficult to confirm a diagnosis of thrombosis, and curative anticoagulant treatment may also be discussed on a probabilistic basis. In all these situations, therapeutic doses of LMWH, or UFH in case of renal insufficiency with monitoring of anti-Xa activity, are proposed.

In conclusion, intensification of heparin treatment should be considered in the context of COVID-19 on the basis of clinical and biological criteria of severity, especially in severely ill ventilated patients, for whom the diagnosis of pulmonary embolism cannot be easily confirmed.