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.
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).
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.
To determine if anti-endothelial cell antibodies (AECA) and plasma markers of endothelial cell function are related to disease severity in systemic lupus erythematosus (SLE).
We measured AECA by ...human umbilical vein endothelial cell binding, endothelial markers von Willebrand factor, soluble thrombomodulin, and soluble E-selectin by ELISA, and disease severity by SLEDAI and SLICC/ACR in 35 patients with SLE.
Despite high levels of IgG AECA (p = 0.001) and von Willebrand factor (p = 0.0007) compared to 21 healthy controls, we found a positive correlation only between IgG AECA and the SLEDAI index (r = 0.393, p = 0.021).
IgG AECA seem to be related to disease activity in SLE, possibly in a pathogenic role. Conversely, plasma markers of endothelial cell damage seem to be an epiphenomenon and may simply be related to excess inflammation.
To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline ...compliance.
This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).
We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with “timely long-term prophylaxis” as compared with “delayed long-term prophylaxis”: hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with “long-term prophylaxis guideline compliance” vs “long-term prophylaxis anticipation.”
This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.
Abstract Many risk factors of aseptic osteonecrosis (AO) are well-known, even if 40% of events are idiopathic. Intravascular thrombosis is one of the physiopathological mechanisms of AO. The aim of ...this study is to determine the influence of coagulopathies on AO set-up. We performed a prospective case–control study, with 39 cases and 39 controls matched on age and sex. Cases are defined according to radiological criteria, and controls as non-affected by renal or hepatic insuffiency, and without inflammatory syndrome. Well-known AO risk factors were studied. Assessment of thrombosis was based on anti-phospholipid, anti ß2 Glycoprotein I, antiprothrombin, anti-cardiolipin, antithrombin, protein S and C, factor V Leiden, prothrombin gene and MTHFR mutations. 71% of cases presented a classical AO risk factor, vs. 38% of the controls. A significant association was also found between smoking and risk of AO. No significant difference in coagulopathy frequency was shown between cases and controls (56.4% vs. 48.7% respectively, p > 0.05). Only abusive consumption of alcohol and tobacco is associated with risk of AO. Our study did not demonstrate any implication of coagulopathies in AO susceptibility. Further studies are needed to investigate more precisely these features.
Summary
Factor VIII inhibitor bypass activity (FEIBA) is a recommended first‐line bypassing agent for bleeding episodes in patients with acquired haemophilia A (AHA). Due to the low incidence of AHA, ...available clinical data on FEIBA treatment are limited. The study aim was to delineate practice patterns in FEIBA treatment of AHA patients, the haemostatic efficacy of FEIBA, including criteria for its assessment, and safety. A prospective registry was established of AHA patients receiving FEIBA for bleeding episodes or prophylaxis at the time of invasive procedures. Data were collected at 16 participating centres in France. Patients were followed up for 3 months. Haemostatic efficacy, FEIBA regimen and FEIBA‐related adverse events were documented. Thirty‐four patients averaging 81.8 years old with standard deviation (SD) 8.1 years were included in the study: 33 for acute bleeding and one for haematoma evacuation. The mean initial dose of FEIBA for acute bleeding was 75.4 U kg−1 (SD, 7.7 U kg−1), most often administered twice daily, and the median duration of FEIBA treatment was 4.0 days (interquartile range, 2.2–8.0 days). FEIBA was effective in managing 88.0% of bleeding episodes (95% confidence interval, 75.8–94.5%). No baseline variables influencing treatment response could be identified. The sensitivity and specificity of an objective haemostatic efficacy scale in predicting sequential investigator assessments of haemostatic efficacy were 45.3% and 84.1% respectively. Four patients experienced a total of six serious adverse events possibly related to FEIBA. In the first prospective study specifically focused on FEIBA treatment of patients with AHA, 88.0% of bleeding episodes were effectively managed.
Intracranial haemorrhage (ICH) is known to be a severe although uncommon complication of haemophilia. A national survey has been conducted in France in order to collect information about ICHs which ...occurred in haemophiliacs between 1991 and 2001 and to propose recommendations for the diagnostic and treatment of ICH. Within this period, 123 episodes of ICH were recorded from 106 patients. Two‐thirds of ICH concerned patients with severe haemophilia. Half of the cases occurred in patients under 15 years of age, 67.2% of which were post‐traumatic. Ten cases occurred in neonates with three fatal outcomes. Overall mortality was high (21.9%) suggesting that availability of clotting factor concentrates has not improved the prognosis of this event. Morbidity was also high with 60% of long‐term sequelae. The following parameters have been identified as prognostic factors for death: thrombocytopenia, HCV infection, intraventricular or intraparenchymatous haemorrhage. A delay in diagnosis was mentioned in 43.3% of cases, often related to the lack of recognition of the initial symptoms, which may be very common (apathy, tearfulness in young children and headache in elder patients). Delayed replacement therapy was recorded in 37.2% of cases. Emergency units initially dealt with half of these patients. Information concerning recognition and management of these episodes, not only in severe haemophilia, but also in moderate and mild forms, should be regularly supplied to paediatricians in maternity and physicians from emergency units, as well as to patients and their relatives.
Introduction: The “French paradox”, a low cardiovascular mortality compared to the prevalent risk factors, has been attributed to the regular use of red wine, and to the polyphenols it contains. ...These have among other effects an antioxidant and antithrombotic effect. The French paradox is maximal in southwest France, a region which is the region of production of armagnac, an oak cask aged spirit also rich in polyphenols.
Method: We tested the effects of a freeze-dried extract of 12-year-old armagnac (EA88) on in vitro human platelet adhesion, and on aggregation induced by collagen or ADP, in the presence or absence of hypoxanthine–xanthine oxidase (HX/XO), at concentrations ranging from 5×10
−9 to 5×10
−3 g/l, after 15–60 min incubation. We also tested the effects of 2-week oral treatment with 1, 5 and 25 mg/kg EA88 in a rat arteriovenous shunt thrombosis model.
Results: EA88 inhibited ADP-induced but not collagen-induced human platelet aggregation in vitro in a concentration- and incubation time-dependent manner, which was greater in the presence of HX/XO. In vivo, giving rats a daily oral dose of EA88 for 2 weeks inhibited thrombus formation in a dose-dependent manner, for doses consistent with the habitual human use of armagnac.
Conclusion: Armagnac extract EA88 had an antiplatelet and antithrombotic effect that if confirmed in man could contribute to explain the intensity of the French paradox in southwest France.
Hyperhomocysteinaemia is a risk factor for premature atherosclerosis and venous thromboembolic disease. Supplementation with folic acid and vitamin B6 has been shown to decrease plasma homocysteine ...but data fail to assess an effect on the progression of vascular disease. We measured plasma homocysteine and two markers of endothelial injury (plasma soluble thrombomodulin and von Willebrand factor) at baseline and after 3 months of treatment with folic acid and vitamin B6. After this treatment there was a significant decrease in fasting soluble thrombomodulin (−15 ng/ml, 95%CI 5–22.2). Von Willebrand factor was significantly raised after methionine load at baseline but did not significantly rise after supplementation.
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