Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.

BACKGROUND: This study aimed to determine the prevalence of genetic and environmental vascular risk factors in non diabetic patients with premature peripheral arterial disease, either peripheral arterial occlusive disease or thromboangiitis obliterans, the two main entities of peripheral arterial disease, and to established whether some of them are specifically associated with one or another of the premature peripheral arterial disease subgroups. METHODS AND RESULTS: This study included 113 non diabetic patients with premature peripheral arterial disease (diagnosis <45-year old) presenting either a peripheral arterial occlusive disease (N = 64) or a thromboangiitis obliterans (N = 49), and 241 controls matched for age and gender. Both patient groups demonstrated common traits including cigarette smoking, low physical activity, decreased levels of HDL-cholesterol, apolipoprotein A-I, pyridoxal 5'-phosphate (active form of B6 vitamin) and zinc. Premature peripheral arterial occlusive disease was characterized by the presence of a family history of peripheral arterial and carotid artery diseases (OR 2.3 and 5.8 respectively, 95% CI), high lipoprotein (a) levels above 300 mg/L (OR 2.3, 95% CI), the presence of the factor V Leiden (OR 5.1, 95% CI) and the glycoprotein Ia(807T,837T,873A) allele (OR 2.3, 95% CI). In thromboangiitis obliterans group, more patients were regular consumers of cannabis (OR 3.5, 95% CI) and higher levels in plasma copper has been shown (OR 6.5, 95% CI). CONCLUSIONS: According to our results from a non exhaustive list of study parameters, we might hypothesize for 1) a genetic basis for premature peripheral arterial occlusive disease development and 2) the prevalence of environmental factors in the development of thromboangiitis obliterans (tobacco and cannabis). Moreover, for the first time, we demonstrated that the 807T/837T/873A allele of platelet glycoprotein Ia may confer an additional risk for development of peripheral atherosclerosis in premature peripheral arterial occlusive disease.

Association of influenza vaccination with reduced risk of venous thromboembolism.

Influenza vaccination can reduce the risk of cardiovascular events in patients with coronary heart disease, but its impact on the risk of venous thromboembolism (VTE) has not been studied. It was the aim of this study to investigate whether influenza vaccination reduces the risk of VTE. We conducted a case-control study involving 1,454 adults enrolled in 11 French centers between 2003 and 2007, comprising 727 consecutive cases with a first documented episode of VTE and 727 age- and sex-matched controls. In the case and control groups 202 (28.2%) and 233 (32.1%) subjects, respectively, had been vaccinated against influenza during the previous 12 months. After multivariate regression analysis, the odds ratios (OR) for VTE associated with vaccination were 0.74 (95% confidence interval [CI], 0.57-0.97) and 0.52 (95% CI, 0.32-0.85), respectively, for the whole population and for subjects aged 52 years or less. The protective effect of vaccination was similar for deep venous thrombosis (OR 0.9, 95% CI, 0.60-1.35) and pulmonary embolism (OR 0.71, 95% CI, 0.53-0.94) and for both provoked (OR 0.71, 95% CI, 0.53-0.97) and unprovoked VTE (OR 0.85, 95% CI, 0.59-1.23). This case-control study suggests that influenza vaccination is associated with a reduced risk of VTE.

A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study.

Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63.98%) and 191 patients (66.8%) had a thrombophilia marker. Eighty nine (46.6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61.8% of patients with high risk of VTE. Among them, 37.7% were treated in the third trimester only and 24.1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0.35%) and two postpartum-related VTE (0.7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0.35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.

Dextran sulfate included in factor Xa assay reagent overestimates heparin activity in patients after heparin reversal by protamine.

A lack of correlation between activated partial thromboplastin time (aPTT), thrombin time (TT) and anti-factor Xa (AXa) activity was observed in patients after cardiac surgery with cardiopulmonary bypass (CBP). Indeed, AXa activity measured by the chromogenic assay, Coamatic Heparin, was higher than expected with regard to results obtained in coagulation assays. To account for this discrepancy, another AXa chromogenic assay was tested. First, AXa activity was measured with two chromogenic assays (Coamatic Heparin and Rotachrom Heparin) in plasma samples of 25 patients undergoing cardiac surgery at two time points after heparin reversal by protamine. AXa activity was significantly higher when measured with Coamatic Heparin than with Rotachrom Heparin in samples collected just after protamine infusion (p<0.01). Next, since Coamatic( Heparin contains dextran sulfate (DXS) to reduce the influence of heparin antagonists such as platelet factor 4 (PF4), whereas Rotachrom Heparin does not, we hypothesized that the dextran sulfate contained in the reagent might explain this discrepancy. We therefore performed in vitro studies consisting in neutralizing unfractionated heparin (UFH) with protamine and measuring AXa activity with the two chromogenic assays. An AXa activity was still measurable with Coamatic Heparin after neutralization, thus strongly suggesting that dextran sulfate dissociates protamine/heparin complexes. We conclude that Coamatic Heparin assays should be avoided when measuring AXa activity in plasma samples immediately after protamine infusion, as inaccurate results may lead to inadequate management of heparin reversal.