Cognitive dysfunctions and cerebral microbleeds in adult patients with haemophilia A: a clinical and MRI pilot-study.

BACKGROUND: Studies providing information about the cognitive profile of adult haemophiliacs are lacking. AIMS: To assess the neuropsychological profile in a group of Haemophiliac patients; to detect asymptomatic cerebral microbleeds (CMBs) and any correlation between CMBs and cognitive dysfunctions; to verify how several contributing factors may determine cognitive dysfunctions and/or Magnetic Resonance Imaging (MRI) findings. METHODS: Adult haemophiliacs without history of brain bleeding were prospectively enrolled on Padua Haemophilia Centre. Patients underwent: i) "Short Neuropsychological Test" assessing cognitive functions (Short Neuropsychological Examination) to obtain an overall cognitive performance (OCP) profile standardised on a cohort matched for age, sex, cultural profile; ii) MRI of the brain to evaluate areas of brain atrophy or haemorrhagic lesions. We collected information on anti-haemorrhagic treatment, cardiovascular risk profile, viral infections, birth trauma. RESULTS: 49 adults with haemophilia (31 severe-moderate, 18 mild) were enrolled. 73% of patients presented a reduction in OCP. According to OCP, no significant difference between severe and mild haemophilia was observed though scores tended to be worse in severe haemophilia (mean Z score 0.20 ± 0.10 vs s0.15 ± 0.11). Considering risk factors, OCP correlated significantly with coronary artery disease (p=0.02). MRI findings in 44 patients, indicated CMBs were inversely related to OCP (R=-0.32 p<0.05). CMBs were associated with cardiovascular risk factors (p=0.018). CONCLUSIONS: Adult haemophiliacs seem to present high prevalence of mild cognitive dysfunctions that doesn't correlate with the severity of haemophilia probably for the few number of patients evaluated. OCP impairment seems to be related to the presence of CMBs and of risk factors for cardiovascular disease.

Outcome of long-term prophylaxis after cerebral hemorrhage in a patient with severe hemophilia B.

Reports of intracerebral hemorrhage (ICH) in patients with hemophilia B are relatively rare. We describe the first clinical results of the use of a monoclonal antibody purified factor IX (FIX) concentrate (Mononine) after an ICH and the long-term outcome of prophylaxis with this product to prevent recurrences. A 44-year-old male with severe hemophilia B was referred to our department because of nausea, vomiting, left lower limb hemiplegia, and left arm paresis. Computed tomography (CT) revealed a right frontal intraparenchymal bleed. The patient was treated with replacement therapy with FIX for 40 days. Computed tomography scans performed on day 40 after the event showed complete disappearance of the cerebral hematoma from the parenchymal tissue. Subsequently, the patient received 25.6 IU/kg(-1) of FIX twice a week. At the 48-month follow-up visit, no more major or minor bleeding events had occurred. Long-term prophylaxis after ICH is recommended.

The risk of cancer progression in women with gynecological malignancies and thrombophilic polymorphisms: a pilot case-control study.

Cancer produces a hypercoagulable state, which might lead to thrombosis, and on contrary, unprovoked venous thromboembolism might be the manifestation of an occult cancer. In this pilot case-control study, we assessed the risk of gynecological malignant diseases related to the presence of the factor V Leiden and prothrombin G20210A polymorphisms. Fifty-two women underwent an operation for gynecological malignancy and were enrolled in the study. Women who underwent an operation for gynecological nonmalignant disease in the same days of cases were considered as controls. The presence of factor V Leiden and prothrombin G20210A was assessed in case and control groups. In all, 7 out of 52 cases were carriers of the 2 polymorphisms compared with 20 out of 198 controls (odds ratio = 1.3; 95% confidence interval, 0.6-3.0). The results were also similar when the risk was considered separately for the site of cancer. As for advanced and metastatic malignancies, the odds ratios were 2.3 (95% confidence interval, 0.9-6.0) and 3.3 (95% confidence interval, 1.0-11), respectively, compared to noncancer patients. When these 2 groups were compared to nonadvanced cancer group, the odds ratios for carriers of polymorphisms were 2.7 (95%confidence interval, 0.7-11.0) and 3.9 (95%confidence interval, 0.8-18.6) for advanced cancer and metastatic malignancies, respectively. Women with factor V Leiden or prothrombin G20210A polymorphisms who developed gynecological malignancy might present with a higher stage of cancer at the time of surgery. Larger case-control studies in similar cohort of patients are needed to confirm these findings.

Idraparinux: review of its clinical efficacy and safety for prevention and treatment of thromboembolic disorders.

BACKGROUND: Idraparinux is a synthetic pentasaccharide that binds to antithrombin with high affinity. In view of its long half-life, it is suitable for once-a-week administration. OBJECTIVE: To review the evidence favoring the use of idraparinux for the acute and long-term treatment of patients with venous thromboembolism (VTE) and for the prevention of thromboembolic events in patients with atrial fibrillation (AF). METHODS: All preclinical and clinical studies carried out with the use of idraparinux were sought through electronic searches of MEDLINE from January 1, 1999 up to December 31, 2007. RESULTS: The administration of idraparinux in subcutaneous fixed doses of 2.5 mg once weekly was found to be as effective and safe as conventional antithrombotic therapy in the initial treatment of patients with deep vein thrombosis, but less effective than standard therapy in the initial treatment of patients with primary pulmonary embolism. During a 6-month extension of thromboprophylaxis, idraparinux was effective in preventing recurrent VTE but was associated with an increased risk of bleeding versus placebo. Finally, in patients with AF the long-term treatment with idraparinux was as effective as vitamin K antagonists, but caused more bleeding. CONCLUSIONS: In its current formulation, idraparinux can be recommended only for the initial treatment of patients with deep vein thrombosis. The bioequipotency of a biotinylated version of idraparinux (idrabiotaparinux), whose effects can be reversed by a neutralizing agent (avidin), is under investigation in the treatment of VTE at present, as is the use of lower doses in patients with AF.