Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin

Blood. 2017 Jun 22;129(25):3379-3385. doi: 10.1182/blood-2017-02-767285. Epub 2017 May 3.


Venous thromboembolism occurs in up to one-third of patients with primary brain tumors. Spontaneous intracranial hemorrhage (ICH) is also a frequent occurrence in these patients, but there is limited data on the safety of therapeutic anticoagulation. To determine the rate of ICH in patients treated with enoxaparin, we performed a matched, retrospective cohort study with blinded radiology review for 133 patients with high-grade glioma. After diagnosis of glioma, the cohort that received enoxaparin was 3 times more likely to develop a major ICH than those not treated with anticoagulation (14.7% vs 2.5%; P = .036; hazard ratio [HR], 3.37; 95% confidence interval [CI], 1.02-11.14). When enoxaparin was analyzed as a time-varying covariate, anticoagulation was associated with a >13-fold increased risk of hemorrhage (HR, 13.26; 95% CI, 3.33-52.85; P < .0001). Overall survival was significantly shorter for patients who suffered a major ICH on enoxaparin compared with patients not receiving anticoagulation (3.3 vs 10.2 months; log-rank P = .012). We applied a validated ICH prediction risk score PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke), and observed that all major ICHs on enoxaparin occurred in the setting of a PANWARDS score ≥25, corresponding with a sensitivity of 100% (95% CI, 63% to 100%) and a specificity of 40% (95% CI, 25% to 56%). We conclude that caution is warranted when considering therapeutic anticoagulation in patients with high-grade gliomas given the increased risk of ICH and poor prognosis after a major hemorrhage on anticoagulation. The PANWARDS score may assist clinicians in identifying the patients at greatest risk of suffering a major intracranial hemorrhage with anticoagulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Brain Neoplasms / complications*
  • Cohort Studies
  • Enoxaparin / adverse effects
  • Enoxaparin / therapeutic use*
  • Female
  • Glioma / complications*
  • Humans
  • Intracranial Hemorrhages / chemically induced*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Venous Thromboembolism / prevention & control*
  • Young Adult


  • Anticoagulants
  • Enoxaparin