Incidence of cancer after a first episode of idiopathic venous thromboembolism treated with 3 months or 1 year of oral anticoagulation.

BACKGROUND: A prolonged treatment with oral anticoagulants has been claimed to reduce the incidence of newly diagnosed cancer in the long-term follow-up of patients with venous thromboembolism. OBJECTIVES: In a multicenter prospective study we assessed the incidence of newly diagnosed clinically overt cancer in patients with a first episode of idiopathic venous thromboembolism (VTE) treated with oral anticoagulants for 3 months or 1 year. PATIENTS AND METHODS: Consecutive patients with an idiopathic venous thromboembolism who had completed 3 months of oral anticoagulant therapy without having a recurrence, bleeding or newly diagnosed cancer were randomized to discontinue oral anticoagulant therapy or to continue it for nine additional months. Idiopathic venous thromboembolism was defined as thrombosis occurring in the absence of known cancer, known thrombophilia, or temporary risk factors for venous thromboembolism. All patients were followed up for at least 1 year after randomization. RESULTS: A total of 429 patients, 265 patients with DVT and 164 with PE, were followed up for an average of 43.7 months after randomization. A newly diagnosed cancer occurred in 32 patients (7.5%), 13 (6.2%) of the 210 patients treated for 3 months and 19 (8.7%) of the 219 patients treated for 1 year (RR = 0.71, 95% confidence interval 0.36-1.41). CONCLUSIONS: The incidence of newly diagnosed clinically overt cancer is not reduced in patients with idiopathic venous thromboembolism treated with 1-year anticoagulant treatment compared with patients treated for 3 months.

Sensitivity and specificity of denaturing high-pressure liquid chromatography for unknown protein C gene mutations.

Screening methods for unknown DNA sequence variations are laborious, expensive, and relatively insensitive. To evaluate the sensitivity and specificity of denaturing high-pressure liquid chromatography (DHPLC) screening for unknown protein C gene (PROC) mutations, we studied 31 PROC-deficient patients. Eleven amplimers containing 4 kb of the PROC gene and spanning all exons, splice junctions, and the putative promoter and 3'-untranslated regions were amplified by PCR for each patient. Each amplimer (n = 341) was sequenced with a fluorescence-based method, and screened by DHPLC. Sequencing identified 10 unique mutations and three polymorphisms. Combining all mutations and polymorphisms, 227 amplimers were homozygous wildtype, and 63 and 51 were heterozygous and homozygous mutant, respectively. DHPLC screening correctly identified all amplimers (100% sensitivity and specificity). DHPLC is a rapid, automated, sensitive and specific screening method for unknown mutations within the PROC gene, and may be a useful screening method for unknown mutations within other genes.

Building effective prophylaxis of deep vein thrombosis in the outpatient setting.

Perioperative prophylaxis of venous thromboembolism (VTE) usually coincides with the duration of hospital stay, typically lasting between 5 and 14 days. However, mounting evidence indicates that the risk of postoperative VTE persists for at least five weeks after orthopaedic surgery and six weeks following general surgery, suggesting that prolonged prophylaxis may reduce the burden of thromboembolic complications. As interest in extending prophylaxis grows, however, economic pressures and patient preferences are contributing to ever shorter hospital stays, giving rise to an exploration of administering prolonged prophylaxis to ambulatory patients at home. Effective outpatient prophylaxis for VTE must be safe, simple to use and convenient for patients to maximize compliance. Low-molecular-weight heparins (LMWHs) are at least as safe and effective as standard low-dose unfractionated heparin (UFH) in preventing thromboembolic events, and can be administered subcutaneously at a fixed daily dose without monitoring. Clinical studies in patients with total hip replacement have demonstrated that LMWHs, administered at home once daily for up to four weeks following hospital discharge, are safe and well-tolerated and significantly reduce the incidence of post-discharge deep vein thrombosis. Due to the high costs of treating thromboembolic complications and post-thrombotic syndrome, appropriately targeted prolonged thromboprophylaxis may be cost-effective.

Dermatan sulphate in patients with heparin-induced thrombocytopenia.

Patients with thromboembolic diseases who develop heparin-induced thrombocytopenia (HIT) type II require an alternative anticoagulation strategy. Dermatan sulphate (DS) was administered to five patients with thromboembolic diseases who developed HIT type II and showed an in vitro cross-reactivity with low molecular weight heparins. The platelet count and the extension of thrombosis were monitored during DS administration. In four of the five patients the platelet count rapidly increased after heparin was discontinued and DS started. A low platelet count persisted in the single patient with cross-reactivity to DS, up to 4 d after its discontinuation. None of the patients experienced thrombus extension, haemorrhagic side-effects or other adverse events.

[Pulmonary embolism and cerebral stroke from paradoxical embolism in a young woman]. / Embolia polmonare ed ictus cerebrale da embolia paradossa in una giovane donna.

We describe a case of pulmonary embolism and ischemic stroke due to paradoxical embolism in a healthy young woman taking oral contraceptives to treat an ovarian cyst. It was not possible to identify the site of the thromboembolus. Ultrasound techniques played an important role in identifying the peripheral arterial obstructions and in diagnosing acute pulmonary hypertension. Transesophageal echocardiography provided detailed information on both the morphology and the evolution of the atrial thrombus straddling the foramen ovale within the aneurysmal interatrial septum. The patient was given anticoagulant treatment, initially with heparin and subsequently with warfarin over a period of six months. Repeated ultrasound controls showed no thrombus, regression of the signs of pulmonary hypertension and, lastly unchanged systemic arterial obstruction.