Heparin-Induced Thrombocytopenia in Severe COVID-19
Authors: Florence Daviet, Christophe Guervilly, Olivier Baldesi, Fanny Bernard-Guervilly, Estelle Pilarczyk, Adrien Genin, Laurent Lefebvre, Jean Marie Forel, Laurent Papazian, Laurence Camoin-Jau
Journal: Circulation (2020)

As the coronavirus disease 2019 (COVID-19) pandemic has spread throughout the world, important efforts have been made to describe its physiopathology and complications.In critically ill patients with COVID-19, a systemic inflammatory response associated with endothelial activation is observed. 1A high rate of thrombotic complications has been described, including deep vein thrombosis. 2 Although the mechanisms of thrombosis are unclear, anticoagulation with high doses of heparin has been proposed for these patients.Heparin-induced thrombocytopenia (HIT) is a severe, life-threatening drug reaction associated with a decrease in platelet count and a high risk of thrombosis caused by platelet-activating antibodies against PF4/heparin complexes. 3he atypical clinical and therapeutic context of the COVID-19 pandemic, with a broader indication of curative anticoagulation, could lead to a higher prevalence of HIT.In this context, we retrospectively reviewed all cases of HIT among patients presenting with COVID-19 acute respiratory distress syndrome (ARDS) in 2 intensive care units in southern France.We described 7 consecutive cases of HIT associated with COVID-19 ARDS between March 30 and April 18, 2020 (Table ).Patients or their relatives received information and signed a nonopposition form, according to French law, to be enrolled in COAG-COVID (Coagulopathy of COVID-19: A Pragmatic Randomized Controlled Trial of Therapeutic Anticoagulation Versus Standard Care).The study was approved by an ethics committee.All patients presented antibodies to PF4/heparin, as detected by a quantitative chemiluminescent immunoassay (HemosIL AcuStar HIT immunoglobulin G, PF4-H, normal value <1 U/ml).Diagnosis was confirmed for the 7 patients using the heparin-induced platelet aggregation test.Six patients were male, with a median age of 57 years (interquartile range, 46-63 years).The median body mass index was 26 (interquartile range, 25-30).Most patients had severe ARDS, with a median Pao 2 /Fio 2 ratio of 80 (interquartile range, 75-113).All but one were intubated and mechanically ventilated.Three were supported by venovenous extracorporeal membrane oxygenation for refractory hypoxemia.All patients were exposed to unfractionated heparin, including 5 after the administration of low-molecular-weight heparin for a median of 14 days (interquartile range, 11-16 days).All patients had curative anticoagulation objectives.The duration of heparin exposure before HIT diagnosis was >10 days for 6 patients.All patients presented a severe drop in platelet count.Five patients experienced at least 1 severe clinical thromboembolic event.Alternative anticoagulation was pursued with either danaparoid or argatroban.All platelet counts returned to normal values after the anticoagulation therapy was switched.At the observation period end point, 5 patients were discharged from the intensive care unit, including 3 from the hospital, and the remaining 2 were still in the intensive care unit.