warfarin and Glioma

Topics: Animals; BCG Vaccine; Brain Neoplasms; Carcinoma, Hepatocellular; Culture Techniques; DNA, Neoplasm; Fluorouracil; Glioma; Humans; Kinetics; Liver Neoplasms; Mice; Mitosis; Neoplasms, Experimental; Neuroblastoma; RNA, Neoplasm; Warfarin

Patients with central nervous system (CNS) malignancies have a substantial risk for developing both thrombotic and bleeding disorders. The risk of venous thromboembolism (VTE) is substantially higher in these patients, both in the perioperative period and throughout their disease course. Patients with CNS malignancy harbor a latent hypercoagulability, which predisposes to VTE, as do postoperative immobility, hemiparesis, and other factors. The management of VTE in these patients is complex, given the significant morbidity and mortality associated with intratumoral hemorrhage. In the past, the perceived risk of intracranial hemorrhage limited the use of anticoagulation for the management of VTE with many favoring nonpharmacologic methods for prophylaxis and treatment. Inferior vena cava (IVC) filters have since lost favor at many centers given significant complications, which appear to be more frequent in patients with CNS malignancy. Recent studies have demonstrated safe and efficacious use of anticoagulation in these patients with a low incidence of intracranial hemorrhage. Treatment of established VTE is now recommended in this population with many centers favoring low-molecular-weight heparin (LMWH) versus oral warfarin for short- or long-term treatment. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, we recommend LMWH in patients with newly diagnosed VTE and a CNS malignancy.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Bevacizumab; Central Nervous System Neoplasms; Fondaparinux; Glioblastoma; Glioma; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Vena Cava Filters; Venous Thromboembolism; Venous Thrombosis; Warfarin

Twenty-three patients with malignant glial neoplasms were treated with anticoagulant therapy for thromboembolic complications. Fifteen patients had deep vein thrombosis alone, and 8 patients had both deep vein thrombosis and pulmonary embolism. Serum prothrombin times were maintained at 1.25 times control for an average of 5.8 months per patient, for a total patient exposure to warfarin therapy of 132 patient-months (11 patient-years). Only 1 patient suffered a recurrent pulmonary embolism, and this occurred during an episode of gastrointestinal bleeding, when anticoagulant therapy had to be discontinued prematurely. All patients were followed with serial computed tomographic or magnetic resonance imaging scans, and no patient showed radiographic evidence of intratumoral hemorrhage either during or after warfarin therapy. One patient, who died from a large recurrent glioblastoma, was found at autopsy to have scattered foci of intratumoral hemorrhage. This series, together with a review of the available literature, suggests that oral anticoagulant therapy is both a safe and effective means of treating thromboembolic complications in patients with residual malignant glial tumors.

Topics: Adult; Aged; Anticoagulants; Brain Neoplasms; Female; Gastrointestinal Hemorrhage; Glioma; Heparin; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Pulmonary Embolism; Warfarin

The effects of racemic sodium warfarin (warfarin) and sodium heparin (heparin) on brain tumor cells were assessed in the rat C6 glioma cell line. After anticoagulant treatment lasting up to 5 days, cell growth was not inhibited by warfarin at low doses (10(-4) to 10(-5) M), but both cell growth and cellular adherence to culture plates were inhibited at high doses (10(-3) to 10(-2) M). Sodium heparin, even at high doses, did not affect cell growth or adherence. Warfarin (10(-3) M) significantly decreased and heparin (12.6 U/ml) had no effect on [3H]thymidine and [14C]leucine incorporation after 3- or 24-hour anticoagulant treatment. Colony formation studies examined the effects of 24-hour warfarin (10(-3) M) or heparin (12.6 U/ml) pretreatment plus a 2-hour incubation with one of seven anticancer agents. Supra-additive toxic effects were produced by warfarin plus chlorambucil, heparin plus chlorambucil, heparin plus carmustine, and heparin plus teniposide. At low doses of warfarin (10(-5) M) or heparin (0.126 U/ml), heparin plus carmustine and heparin plus teniposide remained synergistic.

Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Cell Division; Cell Line; Cell Survival; DNA Replication; Glioma; Heparin; Kinetics; Protein Biosynthesis; Rats; Warfarin

The authors report two cases of delayed radiation necrosis of the brain. In these cases a dramatic clinical and computerized tomographic improvement was noted after the institution of anticoagulant therapy. Based on a review of the literature, a possible causal mechanism is suggested. It was believed from both the clinical observation and the literature review that the anticoagulant agents had a direct effect upon the improvement in these patients. Laboratory data are needed to determine the role of anticoagulant therapy in the treatment of delayed radiation necrosis of the brain.

Topics: Adult; Brain Diseases; Brain Neoplasms; Carcinoma; Female; Glioma; Heparin; Humans; Male; Necrosis; Radiation Injuries; Thyroid Neoplasms; Tomography, X-Ray Computed; Warfarin

Topics: Adult; Aged; Brain; Brain Neoplasms; Cerebral Hemorrhage; Female; Glioma; Humans; Infarction; Intracranial Aneurysm; Intracranial Arteriovenous Malformations; Male; Middle Aged; Tomography, X-Ray Computed; Warfarin