Spontaneous and severe haematomas in patients with COVID-19 on low-molecular-weight heparin for paroxysmal atrial fibrillation

To the editor. From the early beginning of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, clinicians have faced not only the respiratory complications of coronavirus diseases 2019 (COVID19) but also a series of vascular phenomena, which worsen the patient prognosis. Coronavirus-associated coagulopathy and thromboembolism represent one of the leading causes of death in these patients, through endothelial dysfunction and a hypercoagulable state. Notwithstanding data on vascular diseases during COVID-19 are scarce, alterations of parameters implicated in the coagulative process, such as fibrinogen, prothrombin time (PT), factor VIII and Ddimer, have been described. Major societies recommend routine use of thromboembolism prophylaxis with low molecular weight heparin (LMWH) or fondaparinux (if thrombocytopenia is present). Chinese data suggest that prescribing anticoagulant treatment according to high D-dimer levels and sepsis-induced coagulopathy (SIC) score equal to or higher than 4 is associated with a favourable outcome. Also, some data showed that heparin exerts anti-inflammatory effects, which can help reduce tissue damages caused by cytokine storm. However, to date, no randomised clinical trials are available to indicate type, dosage and duration of anticoagulation treatment, specifically. Moreover, risk of bleeding and prevalence of haemorrhages (possibly due to preventative strategies for thromboembolic events) were not yet precisely determined in COVID19, even if HAS-BLED score is useful to estimate the risk of bleeding in other conditions. We herein report three cases of major bleeding, occurred in three patients with COVID-19 who were prescribed anticoagulant treatment for paroxysmal atrial fibrillation. For all our patients, indication for anticoagulant was present according to Padua, and CHA2DS2-VASC score scores. Case #1. 74-year-old male suffering from Parkinson disease, lung fibrosis, and hypertension was admitted to the emergency department for acute respiratory failure on April 17, 2020, and tested positive for SARS-CoV-2. He was diagnosed with paroxysmal atrial fibrillation (CHA2DS2-VASC score=3) and was prescribed LMWH (4000 UI, subcutaneously twice daily). Padua score was 5. HASBLED score was 2. He was transferred of care to our unit on April 18, 2020, where oxygen support was prescribed with high flow nasal cannula (HFNC) 40% FiO2 40 liters/minute. The patient reported an accidental fall, without apparent consequences on April 18, with CT scan results not showing anything significant, but for lung disease. Coagulation parameters at the admission were: D-dimer 0.30 mg/l (normal values 0-0.55 mg/l), fibrinogen 216 mg/dl (normal values 200-400 mg/dL), PT 64% (normal values 70-120%), PTT 33 seconds (normal values 2236.6 seconds), and INR 1.40. SIC score was 4. After one week he rapidly developed hypotension (blood pressure 85/45 mmHg) and severe anaemia (haemoglobin levels decreased from 13.1 to 6.9 g/dl) over three days. Coagulation parameters were: D-dimer 0.39 mg/l (normal values 0-0.55 mg/l), fibrinogen 135 mg/dl (normal values 200-400 mg/dL), PT 49% (normal values 70-120%), PTT 43 seconds (normal values 22-36.6 seconds), and INR 1.62. SIC score remained 4. He underwent a CT scan, which showed massive serum-blood collection (10 cm diameter) displacing the left kidney and hematoma with ongoing bleeding in the ipsilateral psoas muscle (see Figure 1, panel A). He received several blood and plasma transfusions and supportive care immediately, but unfortunately, he died after two days (April 28).