Summary Intracranial hemorrhage (ICH) is common in patients with brain tumors. We compared rates of ICH with DOACs and low molecular weight heparin. DOACs were associated with a lower incidence of ICH in primary brain tumors. DOACs appear safe to administer to patients with brain tumors. Summary BackgroundDirect oral anticoagulants (DOACs) are efficacious in the treatment of cancer‐associated thrombosis but are associated with an increased risk of hemorrhage compared with low‐molecular‐weight heparin in certain malignancies. Whether the DOACs increase the incidence of intracranial hemorrhage (ICH) in patients with brain tumors is not established. ObjectivesTo determine the cumulative incidence of ICH in DOACs compared with Low‐molecular‐weight heparin (LMWH) in patients with brain tumors and venous thromboembolism. Patients and methodsA retrospective comparative cohort study was performed. Radiographic images for all ICH events were reviewed and the primary endpoint was cumulative incidence of ICH at 12 months following initiation of anticoagulation. Results and conclusionsA total of 172 patients with brain tumors were evaluated (42 DOAC and 131 LMWH). In the primary brain tumor cohort (n = 67), the cumulative incidence of any ICH was 0% in patients receiving DOACs vs. 36.8% (95% confidence interval [CI], 22.3–51.3%) in those treated with LMWH, with a major ICH incidence of 18.2% (95% CI, 8.4–31.0). In the brain metastases cohort (n = 105), DOACs did not increase the risk of any ICH relative to enoxaparin, with an incidence of 27.8% (95% CI, 5.5–56.7%) compared with 52.9% (95% CI, 37.4–66.2%). Similarly, DOAC did not increase the incidence of major ICH in brain metastases, with a cumulative incidence 11.1% (95% CI, 0.5–40.6%) vs. 17.8% (95% CI, 10.2–27.2%). We conclude that DOACs are not associated with an increased incidence of ICH relative to LMWH in patients with brain metastases or primary brain tumors.

Venous thromboembolism (VTE) with concurrent thrombocytopenia is frequently encountered in patients with cancer. Therapeutic anticoagulation in the setting of thrombocytopenia is associated with a high risk of hemorrhage. Retrospective analyses suggest the utility of modified-dose anticoagulation in this population. To assess the incidence of hemorrhage or thrombosis according to anticoagulation strategy, we performed a prospective, multi-center, observational study. Patients with active malignancy, acute VTE, and concurrent thrombocytopenia (platelet count < 100,000/µL) were enrolled. The cumulative incidences of hemorrhage or recurrent VTE were determined considering death as a competing risk. Primary outcomes were centrally adjudicated and comparisons made according to initial treatment with full-dose or modified-dose anticoagulation. A total of 121 patients were enrolled at six hospitals. Seventy-five patients were initially treated with full-dose anticoagulation (62%), 33 (27%) with modified-dose anticoagulation, while 13 (11%) received no anticoagulation. Most patients who received modified-dose anticoagulation had a hematologic malignancy (31 of 33, 94%) and an acute DVT (28 of 33, 85%). In patients who initially received full-dose anticoagulation, the cumulative incidence of major hemorrhage at 60 days was 12.8% (95% CI, 4.9-20.8%) and 6.6% (95% CI, 2.4-15.7%) in those who received modified-dose anticoagulation (Fine-Gray HR 2.18, 95% CI 1.21-3.93). The cumulative incidence of recurrent VTE at 60 days in patients who initially received full-dose anticoagulation was 5.6% (95% CI, 0.2-11%) and 0% in patients who received modified-dose anticoagulation. In conclusion, modified-dose anticoagulation appears to be a safe alternative to therapeutic anticoagulation in patients with cancer who develop DVT in the setting of thrombocytopenia.

Stem cells have a number of properties, which make them excellent candidates for the treatment of various neurologic disorders, the most important of which being their ability to migrate to and differentiate predictably at sites of pathology in the brain. The disease-directed migration and well-characterized differentiation patterns of stem cells may eventually provide a powerful tool for the treatment of both localized and diffuse disease processes within the human brain. A thorough understanding of the molecular mechanisms governing their migratory properties and their choice between different differentiation programs is essential if these cells are to be used therapeutically in humans. This review focuses on summarizing the migration and differentiation of therapeutic neural and mesenchymal stem cells in different disease models in the brain and also discusses the promise of these cells to eventually treat various forms of neurologic disease.

Direct oral anticoagulants (DOACs) are increasingly prescribed in treatment of cancer-associated thrombosis, but limited data exist regarding safety of DOACs in patients with brain metastases. We aimed to determine the incidence of intracranial hemorrhage (ICH) in patients with brain metastases receiving DOACs or low-molecular-weight heparin (LMWH) for venous thromboembolism or atrial fibrillation. An international 2-center retrospective cohort study was designed. Follow-up started on the first day of concomitant anticoagulation and brain tumor diagnosis. At least 2 brain imaging studies were mandated. The primary outcome was the cumulative incidence of any spontaneous ICH at 12-month follow-up with death as a competing risk. Major ICH was defined as spontaneous, ≥10 mL in volume, symptomatic, or requiring surgical intervention. Imaging studies were centrally reviewed by a neuroradiologist blinded for anticoagulant type. PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke) score for prediction of ICH was calculated. We included 96 patients with brain metastases (41 DOAC, 55 LMWH). The 12-month cumulative incidence of major ICH was 5.1% in DOAC-treated patients and 11.1% in those treated with LMWH (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.09-2.21). When anticoagulation was analyzed as a time-varying covariate, the risk of any ICH did not differ between DOAC- and LMWH-treated patients (HR, 0.98; 95% CI, 0.28-3.40). PANWARDS score was not associated with ICH risk. This international 2-center study suggests comparable safety of LMWH and DOACs in patients with brain metastases.