Intracranial haemorrhage associated with systemic anticoagulation in ventilated COVID-19 Intensive care patients

Abstract

Introduction COVID-19 induces a pro-inflammatory, hypercoagulable state with marked elevations of ferritin, C-reactive protein, interleukin, and D-dimers. Observed consequences include pro-thrombotic disseminated intravascular coagulation (DIC) with a high rate of venous thromboembolism (VTE) and elevated D-dimers with high fibrinogen and low anti-thrombin levels. Pulmonary congestion appears to be due to micro-vascular thrombosis and occlusion on pathological examination.1 The acquired pro-thrombotic state and associated poorer outcomes seen in critically ill COVID-19 patients 2,3 have led to such patients being treated empirically with systemic anticoagulants. Unfractionated heparin (UFH) or low molecular weight heparin (LMWH) have both been used.2,3 Methods Review of COVID-19 positive adult patients admitted to the critical care unit between 10th March and 13th May 2020 with severe respiratory failure requiring invasive ventilation. Results In that period we admitted 59 patients. 6 (10%) females, 56 (90%) males. 45 (76%) patients required therapeutic anticoagulation (27 UFH, 14 LMWH, 4 argatroban). 4 (8.9%) of the 45 anticoagulated patients suffered catastrophic intracranial haemorrhage and subsequently died. Discussion The risk for any significant haemorrhage in patients systemically anticoagulated for VTE with unfractionated heparin (UFH) is 2-3%, 4 and that of anticoagulant-related intracranial haemorrhage (AICH) in patients systemically anticoagulated with UFH is 1-2.7% (in patients treated for ischaemic stroke) and 4% with argatroban.5 We report a much higher incidence of nearly 9%. The cases we present fulfilled the advised criteria for systemic anticoagulation. Despite four-hourly monitoring of APPT and anti-Xa activity on the intensive care unit there were significant fluxes in these laboratory markers of anticoagulation. These may be associated with the uncharted nature of this disease process.It is impossible to disassociate the necessary therapeutic-intensity anticoagulation with the observed heightened frequency of life-ending intracranial haemorrhage in these patients.