Laros-Van Gorkom, B.A.P.

Factor VIII deficiency does not protect against atherosclerosis (Article)

2012-01-01T00:00:00Z

Summary. Background: Hemophilia A patients have a lower cardiovascular mortality rate than the general population. Whether this protection is caused by hypocoagulability or decreased atherogenesis is unclear. Objectives: To evaluate atherosclerosis and endothelial function in hemophilia A patients with and without obesity as well as in matched, unaffected controls. Methods: Fifty-one obese (body mass index [BMI]≥30kgm-2) and 47 non-obese (BMI≤25kgm-2) hemophilia A patients, and 42 obese and 50 matched non-obese male controls were included. Carotid and femoral intima-media thickness [IMT] and brachial flow-mediated dilatation (FMD) were measured as markers of atherogenesis and endothelial function. Results: The overall population age was 50±13 years. Carotid IMT was increased in obese subjects (0.77±0.22mm) as compared with non-obese subjects (0.69±0.16mm) [mean difference 0.07mm (95% confidence interval [CI] 0.02-0.13, P=0.008)]. No differences in mean carotid and femoral IMT between obese hemophilic patients and obese controls were found (mean difference of 0.02mm [95% CI -0.07-0.11, P=0.67], and mean difference of 0.06mm [95% CI -0.13-0.25, P=0.55], respectively). Thirty-five per cent of the obese hemophilic patients and 29% of the obese controls had an atherosclerotic plaque (P=0.49), irrespective of the severity of hemophilia. Brachial FMD was comparable between obese hemophilic patients and obese controls (4.84%±3.24% and 5.32%±2.37%, P=0.45). Conclusion: Hemophilia A patients with obesity develop atherosclerosis to a similar extent as the general male population. Detection and treatment of cardiovascular risk factors in hemophilic patients is equally necessary.

Effect of fibrinolysis on bleeding phenotype in moderate and severe von Willebrand disease (Article)

2011-10-06T00:00:00Z

Patients with von Willebrand disease (VWD), the most common inherited bleeding disorder, display large variation in bleeding tendency, which is not completely related to VWF levels. The cause of variability in clinical expression is largely unknown. The effect of plasma fibrinolytic capacity on bleeding tendency in VWD patients has not been investigated. We hypothesized that enhanced fibrinolysis may result in a more severe bleeding phenotype. Therefore, we measured the fibrinolytic potential in patients with moderate or severe VWD to investigate the contribution of fibrinolysis to the bleeding tendency. Fibrinolytic potential was measured as plasma clot lysis time (CLT) with and without addition of potato carboxypeptidase inhibitor (PCI) in 638 patients with moderate or severe VWD who participated in a nationwide multicentre cross-sectional study. Bleeding severity was measured using the Bleeding Score (BS).The CLTs were significantly longer, indicative of hypofibrinolysis, in men compared to women with VWD [106.2 (IQR 95.7-118.1) vs. 101.9 (IQR 92.8-114.0) min]. The CLTs prolonged with increasing age. No association was found between VWF or FVIII levels and CLT, or between VWF or FVIII levels and CLT+PCI. No association was observed for BS in a model with 10log-transformed CLT, adjusted for age, gender, VWF:Act and FVIII [b=6.5 (95%CI -0.3 to 13.4)]. Our study showed that the plasma fibrinolytic potential does not influence bleeding tendency in VWD patients and therefore does not explain the variability in bleeding phenotype in VWD.

Health-related quality of life among adult patients with moderate and severe von Willebrand disease (Article)

2010-07-01T00:00:00Z

Background: von Willebrand Disease (VWD) is the most frequent inherited bleeding disorder. It is unknown how this disorder affects quality of life. Objectives: This nationwide multicenter cross-sectional study determined health-related quality of life (HR-QoL) in adult patients with moderate or severe VWD, and assessed whether bleeding severity and type of VWD are associated with HR-QoL. Methods: HR-QoL was assessed using the Short Form (SF)-36, and bleeding severity was measured using the Bleeding Score (BS). Results: Five hundred and nine patients participated; 192 males and 317 females, median age and range 45 (16-87) and 47 (16-84) years, respectively. Compared with the general population, HR-QoL in VWD patients was lower in the vitality domain (61 vs. 66 P < 0.001 for females, 67 vs. 72 P < 0.001 for males). Patients with the most severe bleeding phenotype (highest quartile BS, BS > 17) had a lower HR-QoL in eight domains than patients with a less severe bleeding type (lowest quartile BS, BS < 7) in the univariate analysis. After adjustment for age, gender, co-morbidity and employment/educational status, a more severe bleeding phenotype was associated with lower scores on the domains of physical functioning, role limitations due to physical functioning, bodily pain, general health, social functioning and physical component summary. Conclusions: HR-QoL is lower in VWD patients compared with the general population. HR-QoL is strongly associated with bleeding phenotype.