Empirical systemic anticoagulation is associated with decreased venous thromboembolism in critically ill influenza A H1N1 acute respiratory distress syndrome patients

J Vasc Surg Venous Lymphat Disord. 2019 May;7(3):317-324. doi: 10.1016/j.jvsv.2018.08.010. Epub 2018 Nov 23.


Background: An association between increased venous thromboembolism (VTE) events and influenza A H1N1 (H1N1) was noted in the first 10 patients with severe acute respiratory distress syndrome (ARDS). An empirical systemic anticoagulation protocol (heparin intravenous infusion) was initiated when autopsy of patients with severe hypoxemia confirmed multiple primary pulmonary thrombi and emboli. The purpose of this study was to examine the relationship between H1N1 and VTE events and to assess the efficacy of empirical systemic heparin anticoagulation in preventing VTE and death in H1N1 severe ARDS patients.

Methods: An observational cohort study of critically ill severe ARDS patients with possible H1N1 viral pneumonia was performed in a surgical intensive care unit in a single 990-bed academic tertiary care center. Early empirical systemic heparin anticoagulation for all severe ARDS patients with possible H1N1 viral pneumonia was initiated as a VTE preventive strategy.

Results: Univariate comparisons and multivariate logistic regression were used to identify risk factors for VTE. Independent risk factors for VTE included H1N1, culture-positive bacterial pneumonia, and vasopressor requirement. Independent risk factors for pulmonary embolism included H1N1, culture-positive bacterial pneumonia, and male sex. H1N1 ARDS patients had 23.3-fold higher risk for pulmonary embolism and 17.9-fold increased risk for VTE. Kaplan-Meier analysis and log-rank test confirmed that empirical systemic heparin anticoagulation provided significant protection from thrombotic events in the H1N1-positive but not in the H1N1-negative critically ill ARDs patients. In multivariate analysis, adjusting for H1N1 status, patients without empirical systemic anticoagulation were 33 times more likely to have any VTE compared with those treated with empirical systemic heparin anticoagulation (P = .01).

Conclusions: Critically ill patients with H1N1 ARDS have increased risk of venous thrombotic complications, particularly pulmonary thromboembolism. Empirical systemic heparin anticoagulation in this cohort of patients significantly reduced VTE incidence without increased hemorrhagic complications.

Keywords: Anticoagulants; Deep venous thrombosis; H1N1; Influenza A; Pulmonary embolism; Venous thromboembolism.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Blood Coagulation / drug effects*
  • Critical Illness
  • Female
  • Hemorrhage / chemically induced
  • Heparin / administration & dosage*
  • Heparin / adverse effects
  • Humans
  • Influenza A Virus, H1N1 Subtype / pathogenicity*
  • Influenza, Human / complications
  • Influenza, Human / diagnosis
  • Influenza, Human / drug therapy*
  • Influenza, Human / virology
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / diagnosis
  • Pulmonary Embolism / prevention & control*
  • Pulmonary Embolism / virology
  • Respiratory Distress Syndrome / complications
  • Respiratory Distress Syndrome / diagnosis
  • Respiratory Distress Syndrome / drug therapy*
  • Respiratory Distress Syndrome / virology
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / prevention & control*
  • Venous Thromboembolism / virology
  • Venous Thrombosis / blood
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / prevention & control*
  • Venous Thrombosis / virology


  • Anticoagulants
  • Heparin