Stroke and antiphospholipid syndrome-antiphospholipid antibodies are a risk factor for an ischemic cerebrovascular event.

Testing for antiphospholipid antibodies could be an important part in determining the cause of a cerebrovascular event (CVE). Currently, it is also unknown whether antiphospholipid antibodies represent a risk factor for the development of a CVE and whether the selected therapy options are efficacious. So, this study aimed at (1) determining the frequency of patients experiencing a CVE and fulfilling the laboratory criterion for an antiphospholipid syndrome (APS), (2) investigating whether the persistent presence of antiphospholipid antibodies represented a risk factor for a CVE, and (3) focusing on the efficacy of the selected treatment strategy in the first year after the CVE. Eighty-nine patients with an acute CVE were prospectively followed for 1 year. At least two sera from each were tested for lupus anticoagulants, anticardiolipin, anti-ß2-glycoprotein I, anti-phosphatidylserine/prothrombin and anti-annexin V antibodies. Twenty out of eighty-nine (22%) of CVE patients fulfilled the criteria for APS (17/20 for definitive and 3 for probable APS). There was a significant association between persistently present antiphospholipid antibodies and the CVE (OR, 4.62). No statistically significant difference was found in the CVE recurrence rate between APS-CVE and non-APS-CVE patients being treated mainly with acetyl salicylic acid. Antiphospholipid antibodies represent an independent risk factor for a CVE. In the first year after the CVE, antiplatelet therapy seemed to be sufficient in secondary CVE thromboprophylaxis in most APS patients.

Added value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome: lessons learned from year-long routine measurements.

The international classification criteria for definite antiphospholipid syndrome (APS) include three laboratory measurements: lupus anticoagulant (LA), IgG and IgM isotypes of anti-cardiolipin (aCL) and anti-ß2glycoprotein I antibodies (anti-ß2GPI). When persistently elevated, they are specific for APS; however, many patients that fulfil clinical criteria may exhibit negative serological results. These "seronegative" APS (SN-APS) are exposed to an increased thrombotic risk. The aims of our cross-sectional, retrospective study of consecutive autoimmune patients' samples were to evaluate the association of non-criteria antiphospholipid antibodies (aPL) with thrombosis and obstetric events, to calculate the risk score for adverse events and to assess the specific contribution of single aPL positivity in SN-APS. LA, aCL, anti-ß2GPI and anti-phosphatidylserine/prothrombin antibodies (aPS/PT) of IgG, IgM, and IgA isotypes were determined in sera of 323 patients with autoimmune disorders. Medical records of all patients were carefully analyzed. aCL, anti-ß2GPI and aPS/PT of IgG and IgA isotypes were significantly associated with thrombosis while none of the IgM aPL showed such association. aPS/PT of all isotypes, aCL and anti-ß2GPI of IgG and IgA isotype showed significant correlation to obstetric events. When considering results of aPS/PT ELISA, we could additionally identify 3% of thrombotic patients and 2% of obstetric patients. Thrombotic and obstetric risk scores were calculated showing significantly higher association to clinical events, as compared to evaluating individual risk factors. aPS/PT could represent an additional biomarker in SN-APS patients. IgA aPL are associated with thrombosis and obstetric complications. Risk scores accounting different aPL and conventional risk factors, better assesses risk for adverse event, as compared to evaluating individual factors alone.

Evidence of hypercoagulability and inflammation in young patients long after acute cerebral ischaemia.

INTRODUCTION: Young subjects with acute cerebral ischaemia - stroke or transient ischaemic attack - form an etiologically heterogeneous and often not clearly explained group of patients. The aim was to investigate possible disturbances in haemostasis and inflammation long after an acute cerebral ischaemic event. MATERIALS AND METHODS: Forty-four consecutive patients referred after having suffered from acute cerebral ischaemia before the age of 45 participated 1 to 9 years (median value 5 years) after the event. At the time of blood sampling 33 (75%) patients were receiving antithrombotic treatment. Forty-six apparently healthy subjects of the same age group served as controls. In all subjects global haemostasis parameters (overall haemostasis, coagulation and fibrinolytic potential), thrombophilia, several markers of haemostasis activation and inflammation were determined. RESULTS: Patients did not differ from controls in most of the conventional risk factors and the presence of most forms of thrombophilia, although in seven (17.5%) patients the weak presence of lupus anticoagulants was observed. Patients had significantly increased overall haemostasis and coagulation potential, increased soluble P-selectin and D-dimer, decreased overall fibrinolysis potential and increased fibrinogen and C-reactive protein compared to controls. The subgroups of patients receiving antiplatelet treatment, with thrombophilia and recurrent acute cerebral ischaemia, did not differ significantly from the other patients. CONCLUSIONS: In young patients long after acute cerebral ischaemia an imbalance in the haemostatic system and a minor, but significant degree of inflammation was detected. The mechanisms behind haemostatic imbalance seem to be enhanced thrombin generation, platelet activation and depressed fibrinolysis.

Antibodies against annexin A5: detection pitfalls and clinical associations.

Antiphospholipid syndrome (APS) has been defined as a clinical and laboratory entity. Laboratory criteria include the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA), collectively termed as antiphospholipid antibodies (aPL). However, there has been a rising interest in antibodies against so-called protein cofactors, particularly in beta(2)-glycoprotein I. In the early 90s, annexins were considered as target antigens for aPL, but at present the exact role of antibodies against annexins (aANX) remains puzzling. This review is concerned with annexin V or annexin A5 (ANXA5), a widespread member of the annexin family, and antibodies directed towards it. We have endeavoured to summarise essential information about the detection of anti-annexin V antibodies (aANXA5) and their clinical relevance. This review has also brought together some relevant published data concerning the structure, physiological role and therapeutic potential of ANXA5.

Successful treatment of brain ischemia with supplementation therapy in a patient with hyperhomocysteinemia.

The effectiveness of homocysteine-lowering therapy on stroke prevention is still unclear. Although randomized controlled epidemiological trials have yielded mixed findings, a multicenter trial did not show any beneficial effect. Genetic studies are still lacking. Therefore, we report on a female patient with transient ischemic attacks and the thermolabile variant of methylenetetrahydrofolate reductase (TT genotype), who benefited from supplemental therapy for homocysteine lowering.

Rational Laboratory Diagnostics of Antiphospholipid Antibodies: Anti-Cardiolipin, Anti-ß2-Glycoprotein I, Anti-Prothrombin and Anti-Annexin V Antibodies.

A possible co-appearance of anticardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2-GPI), anti-prothrombin (aPT) and anti-annexin V (aANXV) antibodies of IgG, IgM and IgA class were studied in 58 patients with SLE alone and 32 patients APS in the view of rational laboratory diagnostics. The presence of anti-phospholipid antibodies (aPL) were defined by our in-house ELISA methods. Out of 17 aCL negative SLE patients 6 had other antigenically defined aPL antibodies. In 13 patients only IgA but not IgG and IgM anti-ß2GPI were detected. Different combinations of aPL subsets were equally distributed in APS and SLE groups. The prevalence of aANXV were similar in APS and SLE patients which was not the case with other aPL. Our findings support the idea of measuring additional subsets of aPL (aPT and aANXV) in unclear cases. IgA (either aCL or anti-ß2-GPI) improved neither the diagnostic specificity nor diagnostic sensitivity, but only increased the frequency of the total anti-ß2-GPI.

Monitoring ankylosing spondylitis therapy by dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging.

OBJECTIVE: The effects of different therapies on enthesitis/osteitis in active ankylosing spondylitis (AS) were evaluated by magnetic resonance imaging (MRI). The aim was to assess the role of quantitative MRI in the evaluation of AS treatment efficacy. MATERIALS AND METHODS: Thirty patients with active spondylitis or bilateral sacroiliitis were selected and followed up for 1 year. Ten of the patients were treated only with non-steroidal anti-inflammatory drugs, 10 patients additionally received at baseline an intravenous pulse of glucocorticoids and 10 patients were treated with regular infusions of infliximab. Disease activity was measured according to clinical instruments and laboratory tests. For each patient, one selected inflamed lesion was followed from baseline through control visits quantitatively by diffusion-weighted imaging (DWI) measuring the apparent diffusion coefficient (ADC) and by dynamic contrast-enhanced imaging (DCEI) with evaluation of the enhancement factor (f(enh)) and enhancement gradient (g(enh)). RESULTS: Clinical and quantitative MRI parameters diminished significantly with regression of the inflammatory activity. The improvement in AS was most pronounced in patients treated with infliximab; after 12 months the ADC diminished from an average of 1.31 to 0.88 x 10(-3) mm(2)/s, f(enh) from 1.85 to 0.60, and g(enh) from 3.09 to 1.40 %/s. CONCLUSION: Diffusion-weighted imaging and DCEI were shown to be effective in quantifying changes in inflammation in skeletal lesions during the treatment of AS, and could therefore be convenient for assessing treatment efficacy. To the best of our knowledge this is the first time DWI was used to evaluate the activity of skeletal inflammation in rheumatic diseases such as AS.