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

Abstract

• Therapeutic enoxaparin was associated with a greater than threefold increased risk of major ICH in patients with glioma.• The PANWARDS risk score was a sensitive predictor of major ICH in glioma.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 5 .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 5 .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. (Blood. 2017;129(25):3379-3385)

Intracranial hemorrhage with direct oral anticoagulants in patients with brain tumors

“…Our group and others noted a significantly increased risk of ICH in patients with primary brain tumors treated with LMWH compared with no anticoagulation [3,4]. Reassuringly, we did not observe any ICH among the 20 patients with primary brain tumors treated with DOACs, compared with an ICH rate of 18% at 1 year with LMWH.…”

Risk of Arterial Thromboembolism in Patients With Cancer

“…Besides standard acute recanalization therapies when indicated, these patients sometimes receive empiric long-term anticoagulation because of concerns for cancer-mediated hypercoagulability, and low-molecular-weight heparins are generally preferred over vitamin K antagonists because of extrapolation from randomized trials of venous thromboembolism treatment in patients with cancer (37). However, low-molecular-weight heparins are daily injections, which can be onerous, and are associated with increased bleeding risk, including intracranial hemorrhage (38), which is a major concern for patients with ischemic stroke. Direct oral anticoagulants are another option for cancer-associated thrombosis, although oncological guidelines recommend against their routine use outside of clinical trials (39).…”

Therapeutic Anticoagulation in Patients with Primary Brain Tumors or Secondary Brain Metastasis

“…Therefore, balancing the risks of thrombosis and hemorrhage is essential, and anticoagulation is generally avoided in patients with a history of previous intracranial hemorrhage, bleeding diathesis, thrombocytopenia (<50,000/μL), coagulopathy, or ongoing life‐threatening extracranial bleeding . A recent matched cohort analysis found that the platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, and stroke score for intracranial hemorrhage, initially developed for risk stratification in patients without cancer, accurately predicted intracranial bleeding in patients with malignant glioma . However, this model must be validated by independent datasets before it can be adopted widely.…”