Antiphospholipid Syndrome Risk Evaluation

The antiphospholipid syndrome is an acquired autoimmune disorder produced by high titers of antiphospholipid antibodies that cause both arterial and veins thrombosis as well as pregnancy-related complications and morbidity, as clinical manifestations. This autoimmune hypercoagulable state, often associated with coronary artery disease and recurrent Acute Myocardium Infraction, has severe consequences for the patients, being one of the main causes of thrombotic disorders and death. Therefore, it is extremely important to be preventive; being aware of how probable is to have that kind of syndrome. Despite the updated of the APS classification published as Sydney criteria, diagnosis of this syndrome remains challenging. Further research on clinically relevant antibodies and standardization of their quantification are required to improve clinical risk assessment in APS. This work will focus on the development of a diagnosis support system to antiphospholipid syndrome, built under a formal framework based on Logic Programming, in terms of its knowledge representation and reasoning procedures, complemented with an approach to computing grounded on Artificial Neural Networks. The proposed model allowed to improve the diagnosis, classifying properly the patients that really presented this pathology (sensitivity about 92%) as well as classifying the absence of APS (specificity ranging from 89% to 94%)

Resistant arterial hypertension in a patient with adrenal incidentaloma multiple steno-obstructive vascular lesions and antiphospholipid syndrome

Resistant hypertension is defined as above of blood pressure (≤ 140/90 mmHg) despite therapy with three or more antihypertensive drugs of different classes at maximum tolerable doses with one bling a diuretic. An important consideration in defining a patient with resistant hypertension is the mislabeling of secondary hypertension as resistant hypertension. Here, we report a patients with resistant hypertension caused by multiple stenoocclusive arteries due to antiphospholipid syndrome and coexisting with subclinical Cushing’s syndrome

Diagnosis of antiphospholipid syndrome in routine clinical practice.

The updated international consensus criteria for definite antiphospholipid syndrome (APS) are useful for scientific clinical studies. However, there remains a need for diagnostic criteria for routine clinical use. We audited the results of routine antiphospholipid antibodies (aPLs) in a cohort of 193 consecutive patients with aPL positivity-based testing for lupus anticoagulant (LA), IgG and IgM anticardiolipin (aCL) and anti-ß(2)glycoprotein-1 antibodies (aß(2)GPI). Medium/high-titre aCL/aβ(2)GPI was defined as >99th percentile. Low-titre aCL/aβ(2)GPI positivity (>95(th )< 99(th) percentile) was considered positive for obstetric but not for thrombotic APS. One hundred of the 145 patients fulfilled both clinical and laboratory criteria for definite APS. Twenty-six women with purely obstetric APS had persistent low-titre aCL and/or aβ(2)GPI. With the inclusion of these patients, 126 of the 145 patients were considered to have APS. Sixty-seven out of 126 patients were LA-negative, of whom 12 had aCL only, 37 had aβ(2)GPI only and 18 positive were for both. The omission of aCL or aβ(2)GPI testing from investigation of APS would have led to a failure to diagnose APS in 9.5% and 29.4% of patients, respectively. Our data suggest that LA, aCL and aβ(2)GPI testing are all required for the accurate diagnosis of APS and that low-titre antibodies should be included in the diagnosis of obstetric APS

Patients with Essential thrombocythaemia have an increased prevalence of antiphospholipid antibodies which may be associated with thrombosis

A significant proportion of patients with Essential Thrombocythaemia (ET) have thrombotic complications which have an important impact upon the quality, and duration of their life. We performed a retrospective cross sectional study of the prevalence of antiphospholipid antibodies (APA) in 68 ET patients. Compared to 200 elderly controls (> 50 years) there was a significant increase in anticardiolipin IgM (p < 0.0001) and anti β2 glycoprotein I (anti-β2GPI) IgM (p < 0.0001) antibodies in ET. Thrombosis occurred in 10/20 with APA and 12/48 without, p = 0.04, relative risk 2.0 (95% confidence intervals 1.03-3.86); these patients did not differ in terms of other clinical features. The prevalence of thrombosis in patients with dual APA (6/7) was significant when compared to those with single APA (p = 0.02) and the remaining patients (p < 0.0002). Also anti-β2GPI IgM antibodies either alone, or in combination with another APA, were associated with thrombosis (p = 0.02). These results suggest that the prevalence of APA in ET and their influence upon thrombotic risk merit investigation in a larger study

Clinical and laboratory practice for lupus anticoagulant testing : an International Society of Thrombosis and Haemostasis Scientific and Standardization Committee survey

Background Current guidelines have contributed to more uniformity in the performance and interpretation of lupus anticoagulant (LA) testing. However, points to reconsider include testing for LA in patients on anticoagulation, cut-off values, and interpretation of results. Objectives The aim of this International Society of Thrombosis and Haemostasis Scientific and Standardization committee (ISTH SSC) questionnaire was to capture the spectrum of clinical and laboratory practice in LA detection, focusing on variability in practice, so that the responses could inform further ISTH SSC recommendations. Methods Members of the ISTH SSC on Lupus Anticoagulant/Antiphospholipid Antibodies and participants of the Lupus Anticoagulant/Antiphospholipid Antibodies Programme of the External quality Control of diagnostic Assays and Tests Foundation were invited to complete a questionnaire on LA testing that was placed on the ISTH website using RedCap, with data tallied using simple descriptive statistics. Results There was good agreement on several key recommendations in the ISTH and other guidelines on LA testing, such as sample processing, principles of testing, choice of tests, repeat testing to confirm persistent positivity and the use of interpretative reporting. However, the results highlight that there is less agreement on some other aspects, including the timing of testing in relation to thrombosis or pregnancy, testing in patients on anticoagulation, cut-off values, and calculation and interpretation of results. Conclusions Although some of the variability in practice in LA testing reflects the lack of substantive data to underpin evidence-based recommendations, a more uniform approach, based on further guidance, should reduce the inter-center variability of LA testing

Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography

Lupus anticoagulants (LAC) consist of anti phospholipid antibodies, detected via their anti coagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the anti-phospholipid syndrome. We have analyzed whether detection of this syndrome would benefit from thrombin generation measurements. Therefore, calibrated automated thrombography was done in normal plasma (n=30) and LAC patient plasma (n=48 non-anticoagulated, n=12 on oral anti coagulants), diluted 1: 1 with a normal plasma pool. The anti-beta(2)-glycoprotein I monoclonal antibody 23H9, with known LAC properties, delayed the lag time and reduced the peak height during thrombin generation induction in normal plasma dose-dependently (0-150 mu g/ml). At variance, LAC patient 1: 1 plasma mixtures manifested variable lag time prolongations and/or peak height reductions. Coupling these two most informative thrombin generation parameters in a peak height/lag time ratio,and upon normalization versus the normal plasma pool, this ratio distributed normally and was reduced in the plasma mixtures, for 59/60 known LAC plasmas. The normalized peak height/lag time ratio correlated well with the normalized dilute prothrombin time,diluted Russell's viper venom time and silica clotting time, measured in 1: 1 plasma mixtures (correlation coefficients 0.59-0.72). The anticoagulant effects of activated protein C (0-7.5 nM) or 23H9 (0-150 mu g/ml), spiked in the 1: 1 LAC plasma mixtures were reduced for the majority of patients, compatible with functional competition between patient LAC and activated protein C and LAC and 23H9, respectively. Hence,the normalized thrombin gene ration-derived peak height/lag time ratio identifies LAC in plasma with high sensitivity in a single assay, irrespective of the patient's treatment with oral anticoagulants

Influence of anticardiolipin and anti-β2 glycoprotein I antibody cutoff values on antiphospholipid syndrome classification

Background: Anticardiolipin (aCL) and anti-beta 2 glycoprotein I (a beta 2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach.Methods: The study included samples from 114 patients with thrombotic APS, 138 patients with non-APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and a beta 2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay-specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods.Results: Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated.Conclusions: We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.Background: Anticardiolipin (aCL) and anti-beta 2 glycoprotein I (a beta 2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach.Methods: The study included samples from 114 patients with thrombotic APS, 138 patients with non-APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and a beta 2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay-specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods.Results: Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated.Conclusions: We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.A

Audio-vestibular symptoms in systemic autoimmune diseases

Immune-mediated inner ear disease can be primary, when the autoimmune response is against the inner ear, or secondary. The latter is characterized by the involvement of the ear in the presence of systemic autoimmune conditions. Sensorineural hearing loss is the most common audiovestibular symptom associated with systemic autoimmune diseases, although conductive hearing impairment may also be present. Hearing loss may present in a sudden, slowly, rapidly progressive or fluctuating form, and is mostly bilateral and asymmetric. Hearing loss shows a good response to corticosteroid therapy that may lead to near-complete hearing restoration. Vestibular symptoms, tinnitus, and aural fullness can be found in patients with systemic autoimmune diseases; they often mimic primary inner ear disorders such as Menière’s disease and mainly affect both ears simultaneously. Awareness of inner ear involvement in systemic autoimmune diseases is essential for the good response shown to appropriate treatment. However, it is often misdiagnosed due to variable clinical presentation, limited knowledge, sparse evidence, and lack of specific diagnostic tests. The aim of this review is to analyse available evidence, often only reported in the form of case reports due to the rarity of some of these conditions, of the different clinical presentations of audiological and vestibular symptoms in systemic autoimmune diseases

Determination and Correlation of Anticardiolipin Antibody with High Sensitivity C- reactive Proteins and its Role in Predicting Short Term Outcome in Patients with Acute Coronary Syndrome

Anticardiolipin antibody (aCL) is considered to be an independent risk factor while high sensitivity C reactive protein (hsCRP) is an established marker for coronary artery disease. This study was conducted to determine levels of aCL antibodies and hsCRP, their correlation and role in predicting recurrence of events in patients presenting with Acute Coronary Syndrome (ACS). Sixty patients admitted with Acute Coronary Syndrome were followed up for 7 days or until discharge. Patients were classified into two groups as those having experienced an ischemic event needing intervention within 7 days (Group I) and other having an event free recovery (Group II). aCL antibody and hsCRP levels were estimated and compared in these two groups. Twenty age and sex matched disease free persons served as controls. The levels of aCL were significantly higher in patients with ACS as compared to the controls (p=0.020). However the levels of aCL in Group I (13.39±9.46 GPL-U/ml) and Group II (13.51±9.93 GPL-U/ml) were not significantly different (p =0.838). The mean hsCRP levels were higher in cases with an event (23.30±10.68 mg/dl) than in cases without an event (20.60±11.45mg/dl) though it was not significant statistically (p=0.389). aCL and CRP were not found to be significantly correlated in causing the recurrence of events(p=0.178). Therefore anticardiolipin antibody is an independent risk factor which could be implicated in the pathogenesis of ACS. However it is not significantly associated with recurrence of short-term events in patients with ACS. Also, aCL antibody does not have significant correlation with hSCRP in causing recurrence of events in the patients of acute coronary syndrome