The IgM isotype of anti-annexin A5 antibodies and multiple positivity of conventional antiphospholipid antibodies: increasing the number of clinical manifestations of primary antiphospholipid syndrome.

We evaluated the importance of anti-annexin A5 antibodies (aanxA5 Abs) for clinical (thrombosis and/or recurrent pregnancy loss) and serologic (presence of antiphospholipid antibodies: lupus anticoagulant (LA), anticardiolipin (aCL), and anti-ß2 glycoprotein I (aß2GPI) antibodies) features of patients with primary antiphospholipid syndrome (PAPS). Our study included 70 patients with PAPS according to the international consensus criteria for APS. The mean age of the analyzed patients was 45.97 ± 12.72. The disease duration above 5 years was present in 31/70 of patients. Concentrations of analyzed antibodies were measured by ELISA. Cutoff values were set in accordance to the manufacturers' recommendations. History of recurrent pregnancy loss was associated with double positivity for aanxA5 IgM and LA (χ (2) = 4.000, P = 0.046) and triple positivity for aanxA5 IgM + LA + aß2GPI IgM (χ (2) = 4.168, P = 0.041). Venous thromboses were associated with triple positivity for aanxA5 IgM + aCLIgG + aß2GPI IgM (χ (2) = 3.965, P = 0.046). The IgG isotype of aanxA5 Abs was in positive correlation with aCL Abs of the IgG (r = 0.310, P = 0.009) and IgM (r = 0.254, P = 0.034) isotype. The presence of the clinical manifestations of PAPS is increasing with the number of positive conventional aPL and the IgM aanxA5 Abs tests. This new combination of Abs is beneficial even when the number of patients with positivity for aanxA5 Abs is low. This is important in further detection of patients prone to recurrence of thrombotic episodes.

[Cardiac Manifestations in Antiphospholipid Syndrome--A Brief Review of the Literature].

Antiphospholipid syndrome (APS) or Hughes syndrome represents a systemic autoimmune disorder characterized by arterial and/or venous thrombosis, multiple and recurrent fetal losses, accompanied by persistently elevated levels of antiphospholipid antibodies (aPL). This syndrome is considered primary if unassociated with any other connective tissue disease, or secondary if it appears in association with other autoimmune disorders, mainly systemic lupus erythematosus. Cardiac manifestations in APS are integral part of the syndrome. aPL are involved in the pathogenesis of pseudoinfective endocarditis (Libman Sacks) and other valvular manifestations presented as their thickening and dysfunction. Intracardiac thrombi and myxomas, pulmonary hypertension and left ventricular dysfunction are also distinguishing features of APS. On the other hand, accelerated atherosclerosis, proven in APS and also aPL mediated, is accountable for the development of coronary and peripheral artery disease. This leads to higher cardiovascular mortality rate in the population of patients with low incidence of the traditional atherosclerosis risk factors. Furthermore, recent studies implied that presence of certain aPL could be a risk factor for a specific cardiac manifestation. Bearing all this in mind, early diagnosis of cardiac manifestations, control and abolition of traditional risk factors, as well as close cardiac follow-up of APS patients, are crucial in reducing their cardiovascular mortality.

Cardiac autonomic dysfunction in patients with systemic lupus, rheumatoid arthritis and sudden death risk.

INTRODUCTION: The manifestations of autonomic nervous system (ANS) dysfunction in autoimmune diseases have been the subject of many studies. However, the published results pertaining to such research are controversial. Sudden cardiac death due to fatal arrhythmias is frequent in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). OBJECTIVE: To analyse risk predictors of sudden cardiac death related to the degree of autonomic dysfunction. METHODS: We performed cardiovascular ANS assessment in 90 patients in this case-controlled study, including 52 (6 male, 46 female) patients with SLE, 38 (6 male, 32 female) with RA and 41 (23 male, 17 female) healthy subjects. The methodology included a comprehensive ECG analysis (with Schiller software AT-10) of QTc interval, late potentials, short-term heart rate variability (HRV) and nonlinear HRV (Poincare plot) analysis; 24-hour Holter ECG monitoring with ECG QTc interval analysis, HRV analysis; 24-hour blood pressure monitoring with systolic and diastolic blood pressure variability; cardiovascular autonomic reflex tests (according to Ewing). Vagal dysfunction was established by performing 3 tests: Valsalva maneuver, deep breathing test and heart rate response to standing test. Dysfunction of the sympathetic nervous system was examined by applying 2 tests: blood pressure response to standing and handgrip test. RESULTS: In all cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the healthy subjects. Severe autonomic dysfunction was more common in RA. QTc interval was more prolonged in patients with SLE. Both diseases were associated with depressed heart rate variability compared to controls, the reduction being greater in RA patients. In the patients with SLE, autonomic dysfunction is predominantly with higher sympathetic activity while in RA vagal predominance is evident. CONCLUSION: SLE and RA are associated with severe autonomic dysfunction and the presence of significant risk predictors related to the onset of sudden cardiac death.

Amputation of digits or limbs in patients with antiphospholipid syndrome.

OBJECTIVE: To describe the characteristics of patients with peripheral vascular disease leading to amputation of digits or limbs encountered in patients with the antiphospholipid syndrome (APS). METHODS: Twenty-one cases derived from several geographical centers (Brazil, Serbia, Italy, Israel, United Kingdom, and South Africa) are presented. The major clinical, serological, and histopathological data (where available) of this cohort are described, documented, and analyzed. RESULTS: Patients were suffering mainly from systemic lupus erythematosus (9 patients) or primary APS (8 patients). Peripheral vascular occlusions occurred during the course of the catastrophic APS in 5 patients. The vascular occlusions occurred both early and very late in the course of the disease (time after APS diagnosis, 0-38 years). Vasculitis was present in 7 patients and 5 demonstrated the typical antiphospholipid antibody (aPL)--vasculopathy with complicating bland thrombosis. Myocardial infarctions had occurred in 4 patients but it was not possible to determine whether they suffered from premature atherosclerotic disease or whether the infarctions were aPL-related. The appearance of livedo reticularis preceding the arterial thrombosis was noted in 9 patients. Cryoglobulinemia was detected in only 1 patient. CONCLUSIONS: Peripheral vascular disease leading to amputation of digits or limbs is a severe complication encountered in patients with APS. In the absence of histopathology, it may be difficult to distinguish whether concomitant atherosclerotic occlusions, vasculitis, or aPL-related thrombosis of peripheral vessels is the main cause of the vascular ischemia. Treatment should, therefore, include full anticoagulation as well as corticosteroids and immunosuppression in these patients.