warfarin and Brain-Neoplasms

Venous thromboembolism (VTE) disease, as defined by the occurrence of deep venous thrombosis or pulmonary embolism, occurs among 4 to 20% of patients with cancer and is a leading cause of death among these patients. Use of classical anticoagulation to treat VTE in a cancer patient is associated with a higher risk of major bleeding and of VTE recurrence as compared to noncancer patients. Updated comprehensive and systematic review of current data from the medical literature allows to reconsider the classical approach used for anticoagulant treatment in cancer patients and to implement adapted recommendations. In 2008, the use of daily subcutaneous low-molecular-weight heparin (LMWH) for at least three to six months is recommended as first line therapy to treat VTE disease in cancer patients. If LMWH are contra-indicated (renal insufficiency), other therapeutic approaches are warranted, such as use of unfractionated heparin (UFH) with early introduction of anti-vitamin K for at least three months or venous cava filter in case of absolute contra-indications to anticoagulation. VTE prophylaxis in cancer patients relies on the same therapeutic approaches as currently used for noncancer patients at high risk of VTE. The definition of more specific prophylactic approaches for patients with cancer considered at higher risks of VTE, will be the subject of many clinical trials in the forthcoming years.

Topics: Anticoagulants; Brain Neoplasms; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Risk Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin

Thromboembolic disease is common in patients with malignant brain tumors and represents a major cause of morbidity and mortality in these patients. The presenting signs and symptoms of deep venous thrombosis and pulmonary emboli can be subtle; thus, a high index of suspicion is required to ensure a timely diagnosis. The accuracy of non-invasive studies of the lower extremities and lungs have significant limitations. Venography and pulmonary angiography remain the best diagnostic techniques when difficult decisions arise regarding the need for anticoagulants in these patients. Patients with malignant brain tumors can be safely anticoagulated with heparin and warfarin, if these agents are monitored carefully. Continuous intravenous infusions of heparin are associated with lower risks of bleeding than intermittent boluses. Clinicians may wish to modify the recommended initial bolus dose of heparin in patients without life-threatening thromboembolic disease. Warfarin reduces the incidence of recurrent thromboembolic events. The incidence of warfarin-related bleeding can be lowered without compromising efficacy by maintaining the PT ratio at 1.3. Potential warfarin drug interactions must be considered, aspirin containing medications and NSAIDS should be avoided, and the platelet count should be kept above 50,000 using transfusions if required to prevent potentially life-threatening bleeding in anticoagulated patients. Thrombolytics are contraindicated in this patient population. Vena caval filters and thrombectomy are rarely required. Additional research is needed to determine the best techniques to prevent deep venous thrombosis and pulmonary embolism in patients with brain tumors.

Topics: Brain Neoplasms; Heparin; Humans; Incidence; Thromboembolism; Warfarin

The recognition that the vast majority of patients with small cell lung cancer have distant metastatic disease at the time of diagnosis led to the use of systemic chemotherapy and consequent major improvements in survival in the early to mid-1970's. In the past five years, however, the pace of therapeutic advances has slowed. Recently evaluated treatment strategies, including more intensive induction chemotherapy, "late intensive" therapy of responding patients, alternation of chemotherapeutic regimens, integration of chest irradiation with drug therapy, large field irradiation, and reappraisal of the value of surgical resection, are discussed in this review. Advances in understanding of the cell biology of small cell lung cancer which may eventually lead to new forms of treatment are summarized.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Small Cell; Combined Modality Therapy; Humans; Immunotherapy; Lung Neoplasms; Neoplasm Staging; Prognosis; Retrospective Studies; Time Factors; Warfarin

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

Topics: Anticoagulants; Brain Neoplasms; Humans; Warfarin

Patients with brain cancer are at a high risk of developing venous thromboembolism (VTE) and are underrepresented in clinical trials. This study compared the risk of recurrent VTE (rVTE), major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among VTE cancer patients initiating apixaban, low molecular weight heparin (LMWH), or warfarin stratified by patients with brain vs other cancer types.. Active cancer patients initiating apixaban, LMWH, or warfarin within 30 days after VTE diagnosis were identified from 4 US commercial and the Medicare databases. Inverse probability of treatment weights (IPTW) was used to balance patient characteristics. Cox proportional hazards models were used to evaluate the interaction between brain cancer status and treatment on outcomes (rVTE, MB, and CRNMB), with a p-value <0.1 indicating a significant interaction.. Of 30,586 patients with active cancer (5 % had brain cancer), apixaban (vs. LMWH and warfarin) was associated with lower risk of rVTE, MB, and CRNMB. Generally, no significant interactions (P > 0.1) were found between brain cancer status and anticoagulant treatment across outcomes. The exception was MB for apixaban [vs LMWH (p-value for interaction = 0.091)] with a higher reduction among those with brain cancer (HR = 0.32) than those with (HR = 0.72) other cancer.. Among VTE patients with all types of cancer, apixaban (vs LMWH and warfarin) was associated with a lower risk of rVTE, MB, and CRNMB. In general, anticoagulant treatment effects were not significantly different between VTE patients with brain cancer and those with other cancer.

Topics: Aged; Anticoagulants; Brain Neoplasms; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Medicare; Neoplasms; United States; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Brain Neoplasms; Craniotomy; Enoxaparin; Humans; Postoperative Complications; Precision Medicine; Risk; Venous Thromboembolism; Warfarin

A 74-year-old female current 75 pack-year smoker presented with shortness of breath and mild hemoptysis. Chest computed tomography showed a large right upper lobe mass compressing the superior vena cava, invading the right pulmonary veins, and occupying the majority of the left atrium. Brain magnetic resonance imaging revealed a 13 mm right parietal lesion with surrounding edema consistent with metastasis. A 3D TEE showed a large mobile mass in the left atrium. Bronchoscopy confirmed that the tumor mass was consistent with a moderately to poorly differentiated squamous cell carcinoma. She underwent chemotherapy, radiation, and immune therapy. She was also started on warfarin for anticoagulation after the initial chemotherapy with resolution of the left atrial mass. We feel that the patient most likely had carcinogenic thrombus in the pulmonary veins and left atrium.

Topics: Aged; Anticoagulants; Brain; Brain Neoplasms; Bronchoscopy; Carcinoma, Squamous Cell; Echocardiography, Three-Dimensional; Echocardiography, Transesophageal; Female; Heart Atria; Heart Neoplasms; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Warfarin

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Child; Cyclophosphamide; Dactinomycin; Female; Heparin; Humans; Jugular Veins; Rhabdomyosarcoma; Thrombosis; Tomography, X-Ray Computed; Vincristine; Warfarin

The risk of intracerebral hemorrhage (ICH) in patients receiving antithrombotic therapy is well known. However, there is sparse literature regarding the risk of intracerebral hemorrhage in patients receiving warfarin, who have an intracranial meningioma.. We report a case of a 66-year-old man who developed multifocal ICHs in the context of supratherapeutic anticoagulation. There was sparing of the intracranial meningioma despite the development and growth of multiple intraparenchymal hemorrhages that resulted in death. We also review the literature evaluating the risk of ICH in anticoagulated patients with an intracranial meningioma.. The findings of this case lend further support to the gradually developing notion of relative safety of anticoagulation in patients with meningioma. They also underscore the importance of close monitoring of the INR.

Topics: Aged; Anticoagulants; Brain Neoplasms; Diagnosis, Differential; Fatal Outcome; Humans; Intracranial Hemorrhages; Male; Meningioma; Tomography, X-Ray Computed; Warfarin

The authors report two cases of spontaneous intracranial haemorrhage after elective craniotomy for resection of cerebral tumour. Both patients had mechanical aortic valve prostheses and were on regular warfarin therapy. In both cases, warfarin therapy was discontinued 5 days prior to surgery and unfractionated heparin administered intravenously until 12 h before surgery. Both patients were re-anticoagulated with subcutaneous low molecular weight heparin within the first week postcraniotomy-both developed life-threatening intracranial haemorrhage requiring urgent evacuation. The authors emphasize the risk of re-anticoagulation without postoperative imaging and the disadvantages of therapeutic dose, low molecular weight heparin in the postoperative period.

Topics: Anticoagulants; Aortic Valve; Brain Neoplasms; Craniotomy; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Intracranial Hemorrhages; Male; Middle Aged; Postoperative Hemorrhage; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

When radiation is used to treat nervous system cancer, exposure of adjacent normal nervous system tissue is unavoidable, and radiation-induced injury may occur. Acute injury is usually mild and transient, but late forms of radiation-induced nervous system injury are usually progressive and debilitating. Treatment with corticosteroids, surgery, and antioxidants is often ineffective. We treated 11 patients with late radiation-induced nervous system injuries (eight with cerebral radionecrosis, one with a myelopathy, and two with plexopathies, all unresponsive to dexamethasone and prednisone) with full anticoagulation. Some recovery of function occurred in five of the eight patients with cerebral radionecrosis, and all the patients with myelopathy or plexopathy. Anticoagulation was continued for 3 to 6 months. In one patient with cerebral radionecrosis, symptoms recurred after discontinuation of anticoagulation and disappeared again after reinstitution of treatment. We hypothesize that anticoagulation may arrest and reverse small-vessel endothelial injury--the fundamental lesion of radiation necrosis--and produce clinical improvement in some patients.

Topics: Adult; Aged; Brain; Brain Neoplasms; Female; Glioblastoma; Heparin; Humans; Male; Middle Aged; Necrosis; Radiation Injuries; Spinal Cord Diseases; 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

Topics: Brain Neoplasms; Bromodeoxyuridine; Drug Synergism; Humans; Male; Middle Aged; Prothrombin Time; Warfarin

Mitotane (o,p'-DDD) is closely related to the organochlorine insecticides and shares their effects on drug metabolism. We have reported the first documented interaction of mitotane and warfarin in a human being. Because the potential for significant toxicity is great when mitotane and warfarin are used concomitantly, caution is recommended when titrating warfarin therapy in patients receiving mitotane. Other drugs susceptible to the influence of enzyme inducers should also be given with caution to patients receiving mitotane.

Topics: Adrenal Gland Neoplasms; Brain Neoplasms; Drug Interactions; Female; Humans; Hypoprothrombinemias; Middle Aged; Mitotane; Neoplasm Staging; Time Factors; 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

Analysis of 182 patients with chronic disseminated intravascular coagulopathy and malignancy shows common features. Migratory thrombophlebitis occurred in 96 patients while at least a single episode of thrombophlebitis was noted in 113. Seventy-five of the patients bled and 45 had arterial emboli in various organs. Twelve patients had the triad of thrombophlebitis, hemorrhage, and arterial emboli, often sequentially. Hematologic data showed derangements associated with intravascular coagulation, the most prominent of which were hypofibrinogenemia and thrombocytopenia. Other abnormalities included prolonged prothrombin time, increased fibrinogen-fibrin degradation products, decreased levels of factors V and VIII, cryofibrinogenemia, and microangiopathic hemolytic anemia. Forty-one patients had lesions of non-bacterial thrombotic endocarditis at autopsy; 31 of these had arterial emboli during life. None of the lesions were infected. Mitral and aortic valves were most frequently involved. No single mechanism that causes the disseminated intravascular coagulopathy has been identified. However, cell products--secretions and enzymes--and the cells themselves have been proposed as the procoagulant(s) responsible for the syndrome. In addition to treatment of the underlying neoplasm, symptomatic disseminated intravascular coagulopathy should be controlled. Heparin is the drug of choice for treatment of this problem, very little benefit having been observed with warfarin therapy. Long-term use of anticoagulants is potentially feasible for control of chronic disseminated intravascular coagulopathy, but without effective control of the underlying tumor ultimately will be unsuccessful.

Topics: Adult; Aged; Blood Cell Count; Blood Coagulation Factors; Blood Platelets; Brain Neoplasms; Breast Neoplasms; Chronic Disease; Disseminated Intravascular Coagulation; Female; Heparin; Humans; Kidney Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Prothrombin Time; Pulmonary Embolism; Solitary Pulmonary Nodule; Thrombophlebitis; 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

Topics: Animals; Brain Neoplasms; Cats; Dogs; Fluorouracil; Glioblastoma; Humans; Hypothermia, Induced; Laminectomy; Neurosurgery; Spinal Cord Injuries; Thymidine; Warfarin

Topics: Brain; Brain Neoplasms; Drug Synergism; Fluorouracil; Glioblastoma; Glycolysis; Humans; Intracranial Embolism and Thrombosis; Mitochondria; Warfarin

Topics: Aged; Blood Pressure Determination; Brain Abscess; Brain Neoplasms; Cerebral Hemorrhage; Dicumarol; Female; Follow-Up Studies; Hematoma, Subdural; Humans; Intracranial Embolism and Thrombosis; Male; Prothrombin Time; Warfarin