Major hemorrhage and mortality in COVID-19 patients on therapeutic anticoagulation for venous thromboembolism

J Thromb Thrombolysis. 2022 Oct;54(3):431-437. doi: 10.1007/s11239-022-02666-w. Epub 2022 Jun 10.

Abstract

We observed multiple fatal intracranial hemorrhages shortly after initiating therapeutic anticoagulation for treatment of venous thromboembolism (VTE) in COVID-19 patients suggesting increased anticoagulation risk associated with COVID-19. The objective of this study is to quantify risk of major hemorrhage in hospitalized COVID-19 patients on therapeutic anticoagulation for deep venous thrombosis (DVT) or pulmonary embolism (PE). Hospitalized patients with COVID-19 receiving therapeutic anticoagulation for DVT, PE or both at four New York City hospitals were evaluated for hemorrhagic complications. These were categorized as major (including fatal) or clinically relevant non-major according to the criteria of the International Society of Thrombosis and Haemostasis. Hemorrhagic complications were correlated with clinical and laboratory data, ICD-10 code diagnoses and type of anticoagulation treatment. Minor hemorrhages were excluded. Major/clinically relevant hemorrhages occurred in 36 of 170 (21%) hospitalized COVID-19 patients being treated with therapeutic anticoagulation for VTE including 4 (2.4%) fatal hemorrhages. Hemorrhage was 3.4 times more likely with unfractionated heparin 27/76 (36%) compared to 8/81 (10%) with low molecular weight heparin (p = 0.002). Multivariate analysis showed that major hemorrhage was associated with intubation (p = 0.04) and elevated serum LDH (p < 0.001) and low fibrinogen (p = 0.05). Increased risk of hemorrhagic complications in treating VTE in hospitalized COVID-19 patients should be considered especially when using unfractionated heparin, in intubated patients, with low fibrinogen and/or elevated LDH. Checking serum fibrinogen and LDH before initiating therapeutic anticoagulation and monitoring coagulation parameters frequently may reduce bleeding complications.

Keywords: COVID-19; Complication; Deep venous thrombosis; Pulmonary embolism; Therapeutic anticoagulation.

MeSH terms

  • Anticoagulants / adverse effects
  • COVID-19 Drug Treatment*
  • COVID-19* / complications
  • Fibrinogen / therapeutic use
  • Hemorrhage / chemically induced
  • Hemorrhage / drug therapy
  • Heparin / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Pulmonary Embolism* / drug therapy
  • Venous Thromboembolism* / diagnosis

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Fibrinogen
  • Heparin