warfarin and Paraneoplastic-Syndromes

We describe a 58-year old female patient with rapid development of arterial and venous thromboembolisms, including deep vein thrombosis (DVT) in the lower limbs, recurrent cerebral infarctions and bilateral pulmonary emboli. Her laboratory data on admission showed positive anticardiolipin antibody of IgG isotype (IgG aCL) and positive anti-beta2 glycoprotein-I antibody of IgG isotype (IgG abeta2-GPI), and decreased protein C activity and protein S antigen. Systemic examinations revealed the presence of an ovarian cancer. Surgical resection was attempted, but her cancer infiltrated the pelvic wall and could not be resected. Despite treatment with unfractionated heparin followed by warfarin, she died due to recurrent episodes of cerebral infarction. This case was considered as probable catastrophic antiphospholipid syndrome (CAPS), which might be associated with ovarian cancer. Known as Trousseau's syndrome, arterial and, more commonly, venous thrombosis is a frequent complication of cancer and sometimes a harbinger of occult cancer. Our case indicates that there is an overlap between antiphospholipid syndrome (APS) and Trousseau's syndrome. It is important to bear in mind that a thrombotic event associated with cancer can be the first manifestation of CAPS.

Topics: Adenocarcinoma, Clear Cell; Adolescent; Adult; Aged; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Antiphospholipid Syndrome; Carboplatin; Cerebral Hemorrhage; Cerebral Infarction; Docetaxel; Fatal Outcome; Female; Humans; Male; Middle Aged; Neoplasms; Neoplasms, Unknown Primary; Ovarian Neoplasms; Palliative Care; Paraneoplastic Syndromes; Protein C Deficiency; Protein S Deficiency; Pulmonary Embolism; Taxoids; Thrombophilia; Thrombophlebitis; Warfarin

Venous thromboembolism (VTE) and particularly idiopathic VTE may be paraneoplastic phenomena. The merits of screening patients with idiopathic VTE for occult cancer are still under debate, and randomized studies are required to establish its potential cost-effectiveness. Cancer and its related surgery greatly increase the risk of VTE. Thromboprophylaxis using agents such as low-molecular-weight heparin (LMWH) has proved to be safe and effective in reducing the incidence of postoperative VTE. The ENOXACAN II study has shown that prolonging the standard 1-week regimen of the LMWH enoxaparin to 4 weeks may further reduce the incidence of postoperative VTE. Enoxaparin has also shown potential benefits in the secondary prevention of VTE and the reduction of bleeding complications. Emerging data indicate that LMWH may improve survival rates in cancer patients with VTE, making this a very important area for future research.

Topics: Antineoplastic Agents; Double-Blind Method; Enoxaparin; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Meta-Analysis as Topic; Multicenter Studies as Topic; Neoplasms; Paraneoplastic Syndromes; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Thromboembolism; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin

Patients with cancer have an increased risk of venous thromboembolism (VTE) compared with a healthy population. The risk increases as cancer progresses and this is reflected in the number of hospice inpatients with VTE. These patients also have an increased risk of bleeding due to tumour site, complications of treatment, progressive liver involvement and concurrent medication such as nonsteroidal anti-inflammatory agents. Therefore anticoagulation of cancer patients with VTE is fraught with difficulty. This audit of hospice inpatients taking warfarin showed a high incidence of bleeding which was possibly improved with very stringent international normalized ratio (INR) monitoring: 15 episodes in 17 patients improved to 11 episodes in 18 patients. Patient numbers were small and the two groups heterogeneous, thus formal statistical analysis could not be applied. One patient in each group continued to thrombose despite over anticoagulation with warfarin. Monitoring of INR increased from an average of once every six days to once every 2.4 days. Such frequent monitoring is likely to be highly impractical in many hospice and general practice settings. Control of warfarin as measured by average percentage of INRs in, above or below the therapeutic range if anything appeared to be worse in the second group. Any bleeding in these patients was distressing. As a result of this audit, practice in Huntershill Marie Curie Centre has changed. Low molecular weight heparins are proven to be efficacious in the treatment of VTE, are renally excreted and therefore do not interact with many commonly used concurrent medications. They can be administered once daily and do not need monitoring of anticoagulant effect. Thus they will be used in patients for whom anticoagulation is indicated during a six-month period, after which practice will be again reviewed.

Topics: Anticoagulants; Female; Hospice Care; Hospices; Humans; International Normalized Ratio; Male; Medical Audit; Palliative Care; Paraneoplastic Syndromes; Practice Guidelines as Topic; Prospective Studies; Retrospective Studies; Scotland; Thromboembolism; Warfarin