Thomas Sailer

Anti- β 2-glycoprotein I antibodies are associated with pregnancy loss in women with the lupus anticoagulant

The presence of lupus anticoagulant (LA) predisposes to fetal loss and to venous and arterial thrombosis; however, a subgroup of women is unaffected by pregnancy loss. Currently, no predictive markers are available for the identification of women positive for LA at increased risk for pregnancy loss. It was the aim of our study to investigate whether increased anti-beta2-GPI-antibodies predict pregnancy loss in women positive for LA. We performed a cross-sectional study in a cohort of 39 women with persistent LA, who had in total 111 pregnancies. Fifteen women had exclusively normal pregnancies (30 pregnancies) and 24 women had pregnancy losses (81 pregnancies). Anti-beta2-GPI-antibodies were determined using a semiquantitative enzyme linked immunoassay (QUANTA Lite beta2 GPI IgG and IgM; Inova Diagnostics). Increased levels of anti-beta2-GPI antibodies were significantly associated with pregnancy loss [odds ratio (OR) 9.6, 95% confidence interval (CI) 1.6-56.4]. This risk was even higher in the subgroup of women (n = 16) with more than two miscarriages or fetal loss after the first trimester [OR 13.1, 95% CI 1.4-126.3]. There was no significant association between anticardiolipin antibodies and pregnancy loss [OR 3.5, 95% CI 0.7-17.6]. The co-existence of anti-beta2-GPI and anticardiolipin antibodies was also predictive for pregnancy loss [OR 6.1, 95% CI 1.3-29.7]. Interestingly, the prevalence of thrombosis was similar between women with normal pregnancy (87%) and those with pregnancy loss (75%). We conclude that increased levels of anti-beta2-GPI antibodies are predictive for pregnancy loss among women positive for LA, and that prophylactic treatment should be considered in these women even without a history of previous pregnancy loss.

Circulating procoagulant microparticles in patients with venous thromboembolism

Circulating microparticles (MPs) are small vesicles released from the membrane of almost all cells as a result of cell activation or apoptosis [1–4]. They have a size of less than 1 μmand theirmembrane consists mainly of phospholipids and proteins. MPs are generated under physiological conditions in healthy individuals and display an integral function in the process of coagulation, inflammation, cell remodelling and proliferation [4,5]. MPs play an important role in the initiation and propagation of coagulation [1]. Increasing evidence suggests that MPs are involved in the pathomechanism of thrombotic disease [1–4]. It has been demonstrated that MPs initiate thrombin generation [5]. One major hallmark is the exposure of phosphatidylserine (PS) on MPs that enables the assembly of clotting factors on their surface necessary for the formation of the prothrombinaseand tenase-complex [6–10]. In resting cells aminophospholipids such as PS aremainly sequestrated in the inner leaflet of the plasmamembrane, whereas sphingomyelin and phosphatidylcholine are exposed to the vascular compartment [11]. When cells are stimulated, the asymmetric distribution of phospholipids is disturbed resulting in the externalization of PS on the outer leaflet. Furthermore,MPs have been found to express tissue factor (TF), and thus to provide an environment favourable to initiation and support of coagulation [12,13].

The angiotensin-converting enzyme insertion/deletion polymorphism and serum levels of angiotensin-converting enzyme in venous thromboembolism : Data from a case control study

The angiotensin-converting enzyme (ACE) has been suggested to affect blood coagulation and fibrinolysis. Results from literature on the role of the frequent insertion/deletion (I/D) polymorphism in the ACE gene in venous thromboembolism (VTE) are controversial. Only limited data on ACE serum levels inVTE exist. We determined the ACE I/D polymorphism by genotyping and ACE serum levels by an enzymatic assay in 100 high-risk patients with objectively confirmed recurrentVTE and at least one event of an unprovoked deep venous thrombosis or pulmonary embolism. One hundred twenty-five age- and sex-matched healthy individuals served as controls. ACE genotype frequencies were not significantly different between patients (DD: 26.0%, ID: 52.0%, II: 22.0%) and controls (DD: 29.6%, ID: 44.8%, II: 25.6%; p = 0.56). Neither individuals with ACE DD genotype nor those with ACE ID genotype had a higher risk for VTE in comparison to those with ACE II genotype (odds ratio and [95% confidence interval]: 1.0 [0.5-2.1] and 1.4 [0.7-2.6], respectively). Serum ACE levels (U/l) did not differ between patients (median = 25.25, 25th -75th percentile: 20.20-33.70) and controls (24.20, 17.85-34.50, p = 0.49). In the total population involved in the study the ACE DD genotype (n = 63: 36.00 [26.40-43.00]) was associated with higher ACE levels than the ACE ID genotype (n = 108: 24.10 [19.80-31.48], p < 0.001) and the ACE II genotype (n = 54: 19.35 [15.00-22.95], p < 0.001). In conclusion, we found a significant association of the ACE I/D polymorphism with ACE serum levels. However, neither the serum levels nor the I/D genotype were associated with VTE.

The FcγRIIa polymorphism R/H131, autoantibodies against the platelet receptors GPIbα and FcγRIIa and a risk for thromboembolism in lupus anticoagulant patients

There is a clear propensity of individuals with lupus anticoagulant (LA) for thromboembolic disease (TE). Yet, it is not clear how individuals at risk for TE can be differentiated from those who are not.The FcγRIIa receptor is the only Fc receptor expressed by platelets.As platelets can be activated via this receptor, we have compared gene frequencies of the FcγRIIa polymorphism R/H131 in 46 and 27 patients with (LA/TE+) and without TE (LA/TE-), respectively, in an exploratory study. Furthermore, we investigated the presence of autoantibodies against FcγRIIa and/or GPIbα , which is in close proximity to the FcγRIIa and interacts with it functionally, and a possible linkage of antibody formation to HLA class II alleles.The FcγRIIa-R/R131 genotype was significantly less frequent in patients with LA compared to controls (p