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Background Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-beta 2glycoprotein I (beta 2GPI) proved to be pathogenic, but are not included in the current classification criteria. Objectives Investigate the clinical value of detecting anti-DI IgG in APS. Patients/Methods From eight European centers 1005 patients were enrolled. Anti-cardiolipin (CL) and anti-beta 2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash (R) beta 2GPI domain I assay. Results Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-beta 2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG was added to the criteria aPLs or used as a substitute for anti-beta 2GPI IgG/anti-CL IgG, ORs for clinical symptoms hardly improved. Upon removing anti-DI positive patients, lupus anticoagulant remained significantly correlated with clinical complications. Anti-DI IgG are mainly present in high-risk triple positive patients, showing higher levels. Combined anti-DI and triple positivity confers a higher risk for clinical symptoms compared to only triple positivity. Conclusions Detection of anti-DI IgG resulted in higher ORs for clinical manifestations than the current APS classification criteria. Regardless of the platform used to detect anti-beta 2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash (R) did not improve the clinical associations, possibly due to reduced exposure of the pathogenic epitope of DI. Our results demonstrate that anti-DI IgG potentially helps in identifying high-risk patients.

The vibro-acoustic environment generated during a rocket launch induces dynamic loads which may damage critical components of spacecraft and scientific instruments. The research is focused on the vibro-acoustic response of the Wide Field Imager (WFI) instrument subjected to an intense diffuse sound field. Noise-induced structural vibrations in low- to mid-frequency can be computed by means of coupled FEM-BEM numerical models. Nevertheless, this approach is unsuited to calculations of cavity-structure interactions of light-weight and thin structures. In this paper the application and assessment of the elasto-acoustic FEM-FEM coupling approach for the cavity - optical blocking thin foil filter interactions is investigated. The diffuse sound field excitation is reconstructed by matching values of the sound pressure level to these obtained from experimental measurements. The viscosity effects on the wave propagation in thin layers are included by using the visco-thermal fluid model. The accuracy and efficiency of this approach are investigated and results obtained are compared to measured data from a reverberant test chamber. The results show that a very good agreement is obtained in terms of the acoustic pressure in the vicinity of the optical blocking filter. The behaviour of mechanical vibrations is correctly reproduced, although some considerable discrepancies in the levels of the vibrations are observed. The case of strong coupling between the cavity acoustic field and the filter membrane is finally discussed.

Essentials Antibodies to domain 1 of β2 glycoprotein I (aD1) are a subset of antiphospholipid antibodies. We evaluated the added diagnostic value of an automated aD1 assay in antiphospholipid syndrome. AD1 IgG correctly classifies patients at risk for thrombosis. Agreement between aD1 and aβ2GPI IgG is high, limiting the added value of aD1 in our setting. Click to hear Professor de Groot's perspective on new mechanistic understanding in antiphospholipid syndrome SummaryBackground Laboratory diagnosis of antiphospholipid syndrome (APS) includes lupus anticoagulant (LAC), anticardiolipin (aCL) or anti-β2 glycoprotein I (aβ2GPI) antibodies. Antibodies targeting domain 1 of β2GPI (aD1) constitute a pathogenic subset of autoantibodies. Objectives In this cohort study, we determined the clinical performance characteristics, additional diagnostic value and the contribution to APS risk stratification of an automated aD1 assay. Patients/Methods LAC, aCL, aβ2GPI and aD1 IgG were measured in 101 APS patients, 123 patients with autoimmune disorders, 82 diseased controls and 120 healthy controls. aD1 antibodies were detected by QUANTA Flash® Beta2GPI-Domain 1 chemiluminescence immunoassay. Results With a cut-off value of 20.0 CU, the aD1 IgG assay identifies APS patients in a clinically affected patient cohort with a sensitivity of 53.5% and specificity of 98.8%. It implied a high odds ratio (OR) for clinical events (OR, 17.0; 95% confidence interval [CI], 7.1–40.5). aD1 IgG did not add diagnostic value to the formal aPL panel because aβ2GPI IgG was nearly as specific but more sensitive for APS (sensitivity 56.4%) with a higher OR for clinical events (36.2; 95% CI, 11.1–117.9). High aD1 titers identify triple-positive patients and patients with thrombosis in a β2GPI-dependent LAC-positive population. Agreement between aD1 IgG and aβ2GPI IgG was high (positive and negative agreement 91.7% and 98.4%, respectively). Conclusion Detection of aD1 IgG correctly classifies patients at risk of thrombosis. However, the contribution of aD1 IgG to APS diagnosis and risk stratification depends upon the solid phase assays used for aCL and aβ2GPI detection.

Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome) is a rare, systemic, small- to medium-sized vessel necrotizing vasculitis. The disease is characterized by common cardiac involvement, which remains the major determinant of mortality [(1)][1]. Glucocorticoids and

Venous thromboembolism (VTE) has been considered the dominant major life threatening vascular complication after non-cardiac surgery, but recent studies have shifted the emphasis toward myocardial injury after non-cardiac surgery (MINS) as a common adverse event in the peri-operative setting. The aim of the present study was to compare the incidence and influence on mortality of two dominant venous and arterial events in the peri-operative period by prospectively screening a consecutive cohort of patients undergoing vascular surgery.This was a sub-study of Vascular Events In Non-cardiac Surgery Patients Cohort Evaluation (VISION), the main objective of which was to evaluate major peri-operative complications after non-cardiac surgery. Patients undergoing vascular surgery had their blood collected to measure the Roche fifth generation high sensitivity troponin T (hsTnT) assay before and four times after surgery (6-12 h post-operatively, on the first, second, and third day following the procedure). MINS was defined as an elevated post-operative hsTnT ≥65 ng/L or an hsTnT ≥20 to65 ng/L with an absolute change of ≥5 ng/L that was judged to be due to ischaemia. All patients underwent ultrasound venous compression testing for deep vein thrombosis (DVT) before, 4, and 7 days after surgery and follow-up was performed by telephone 30 days and 1 year after surgery.In total, 164 consecutive patients were included in this sub-study. MINS was diagnosed in 39 patients (23.8%) and DVT in four patients (2.4%). The 1 year mortality was higher in MINS (9/39 [23.1%]) than non-MINS patients (9/125 [7.2%]; p = .006). None of the patients who developed DVT died in the first year after surgery.MINS is a common complication after vascular surgery. It occurs more frequently than DVT and is associated with high 1 year mortality.

Summary. Background: The classification criteria for antiphospholipid syndrome (APS) were updated in 2006. Objective: The aim of the study was to analyze associations between clinical complications and laboratory test abnormalities typical for APS in a group of patients with autoimmune diseases, based on the recently updated criteria. Patients/methods: Three hundred and thirty-six patients were enrolled into the study, with the majority (n = 235) suffering from systemic lupus erythematosus. Laboratory determinations included: lupus anticoagulant (LA), anticardiolipin (aCL) and anti-beta2-glycoprotein I (anti-β2GPI) antibodies (ABs) [of both immunoglobulin G (IgG) and IgM class]. Results: A significant association was found between laboratory and clinical features of APS; odds ratios (ORs) for thrombosis associated with the presence of LA, aCL, and anti-β2GPI Abs were 4.04 [95% CI: 2.44–6.68], 3.71 (95% CI 2.32–5.92) and 2.57 (95% CI 1.60–4.1), respectively. Detailed analysis showed marked differences between the risk of clinical complications associated with the presence of an antibody in the IgG class (OR 4.15, 95% CI 2.42–7.12, and OR 4.77, 95% CI 2.37–9.61 for aCL and anti-β2GPI, respectively) and in the IgM class (OR 2.2, 95% CI 1.31–3.70, and OR 1.9, 95% CI 1.15–3.14 for aCL and anti-β2GPI, respectively). The postulated inclusion of anti-β2GPI antibody positivity into the previous laboratory criteria changed only slightly the number of patients diagnosed with APS (from 112 to 117). Conclusions: The updated APS classification criteria clearly represent a step forward. However, our results argue against the use of overall positivity for aCL or anti-β2GPI, and favor a clear distinction between the IgG and IgM classes of antiphospholipid ABs. Patients with both LA and anti-β2GPI IgG or LA and aCL IgG positivity may represent the subgroups at the highest risk of thrombotic complications.

Antiphospholipid syndrome is an autoimmune disease which combines vascular thrombosis and/or pregnancy complications with the presence of antiphospholipid antibodies. It could be a devastating and sometimes life-threatening condition. As vascular thrombosis presents as typical venous or arterial thromboembolism diagnosis is based on laboratory data. Therefore proper performance and interpretation of laboratory tests is crucial. Broader knowledge about clinical and laboratory aspects of the syndrome and their associations are essential for proper evaluation and management of the patients.

OBJECTIVES To assess the effects of aspirin compared with simvastatin on thrombin generation in hypercholesterolemic men, and to establish whether the reduction of elevated blood cholesterol by simvastatin would affect the action of aspirin on thrombin formation. BACKGROUND Aspirin inhibits thrombin formation, but its performance is blunted in hypercholesterolemia. By virtue of altering lipid profile, statins could be expected to influence thrombin generation. METHODS Thirty-three men, aged 34 to 61 years, with minimal or no clinical symptoms, serum total cholesterol >6.5 mmol/liter and serum triglycerides

Recombinant human gamma interferon was used to treat 10 atopic dermatitis patients. Recombinant gamma interferon was administered weekly for three consecutive days at 50 microg/M2 SQ for four weeks. All patients' dermatitis improved with recombinant gamma interferon therapy and plasma tumor necrosis factor-alpha levels rose with treatment. Recombinant gamma interferon treatment positively correlated with reduced total plasma fibrinolysis as measured by the fibrin lysis plate, plasmin-alpha2antiplasmin complexes, and tissue type plasminogen activator levels. Accordingly, plasminogen activator inhibitor levels increased. Treatment also was associated with a transient increase in thrombin-antithrombin III complexes. Recombinant gamma interferon resulted in a significant increase in C1 inhibitor antigen but not activity. Plasma prekallikrein, high molecular weight kininogen, and factor XII levels were not decreased. However, 5 of the 10 atopic dermatitis patients before therapy had circulating cleaved plasma high molecular weight kininogen detected on immunoblot, indicating prior kallikrein formation. The cleaved, circulating plasma high molecular weight kininogen disappeared in four out of the five original patients who were reexamined at one year after treatment. These combined data indicated that recombinant gamma interferon treatment reduced total plasma fibrinolysis. In untreated atopic dermatitis, circulating cleaved high molecular weight kininogen also may be a presenting manifestation.

Aspirin (ASA) not only inhibits platelet function, but increase in the rate of factor Va inactivation [12]. In patients also exerts additional anticoagulant actions. These actions are coupled with prevention of platelet activation by thromboxane (TX) A2, because only activated platelets are the source of prothrombinase and tenase complexes on their surface. Thus, ASA decreases thrombin formation in vitro and in vivo, in blood emerging from small skin incisions [1,2]. Yet, some patients experience recurrent arterial thrombotic events despite long-term preventive ASA therapy. Various reasons may lead to such episodes, one of them being so-called ASA resistance [3]. This phenomenon is still poorly defined; it could include the clinical inability of ASA to protect patients from cardiovascular events, as well as the failure of ASA to inhibit platelet function in a laboratory test system (e.g. platelet aggregation) [4], or to suppress overall TXA2 production [5]. There are at least two possible explanations for the ASA resistance phenomenon. One is hypercholesterolemia, probably by its virtue to change the physico-chemical properties of the platelet cell membrane [6]. Thus, cholesterol and atherogenic lipoproteins may increase platelet aggregability and TXA2 production [7,8], and support assembly of the prothrombinase complex and thrombin generation [9]. In patients with markedly elevated and borderline high cholesterol levels, ASA in a commonly used doses (75–300 mg/day) has negligible effect on thrombin formation, as measured by microquantitative analytical technique, at the site of microvascular injury [10,11]. On the other hand, 3 months treatment of such patients with simvastatin significantly depresses blood clotting in vivo, mainly through a reduction in thrombin generation [10,11]. Here, statin treatment seems to interfere with several interconnected steps leading to thrombin formation. They include the reduction in the rates of prothrombin activation, factor Va generation, fibrinogen cleavage, factor XIII activation, and a parallel