Features Of Primary Antiphospholipid Syndrome Research Articles

Hospital based prospective longitudinal clinical and immunologic study of 179 patients of primary anti-phospholipid syndrome

To study the clinical and immunological features of primary antiphospholipid syndrome (APS), and to analyze the differences between primary APS and APS associated with autoimmune rheumatic disease (ARD/APS). This prospective, longitudinal study, carried out from December 2004 to July 2011 included 179 patients with primary APS and 52 patients of ARD/APS diagnosed as per modified 2006 Sapporo's Criteria. Out of 179 patients of primary APS, 12 were male and 167 were female. The mean age at the time of study entry was 27 ± 4.33 years. Venous thrombosis was noted in 33 (18.43%) patients. Seventeen patients had deep vein thrombosis and 11 (7.19%) had cortical vein and/or cortical sinus thrombosis. Arterial thrombosis was noted in 19 (10.61%) patients, out of which nine had intracranial arterial thrombosis. Thirty-two (17.85%) had recurrent early fetal losses (< 10 weeks) and 97 (54.18%) had late fetal loss (> 10 weeks). Immunoglobulin G (IgG) and IgM aCLA were present in 141 (78.77%) and 32 (17.87%) patients respectively, whereas lupus anticoagulant was present in 99 (55.3%) patients. In patients with bad obstetric outcome, lupus anticoagulant positivity was significantly more prevalent (P < 0.05) than aCLA positivity. Both venous and arterial thrombosis were significantly more common (P < 0.05) in ARD/APS. However, late fetal loss was significantly more prevalent (P < 0.001) in primary APS. Primary APS may lead to a variety of clinical manifestations due to venous and/or arterial thrombosis, which at times may be lethal. It is also an important cause of early and late pregnancy loss(es) and other pregnancy morbidities.

Acute adrenal failure as the presenting feature of primary antiphospholipid syndrome in a child

IntroductionAntiphospholipid syndrome (APS) is characterized by recurrent arterial and venous thrombosis and detection of antiphospholipid antibodies (aPLs). This syndrome may be associated with connective tissue disorders, or with malignancies, but it may also appear in isolated form (primary APS). We report on a pediatric patient presenting with acute adrenal failure as the first manifestation of primary APS.Case reportA previously healthy 11-year-old boy developed fever, abdominal pain, and vomiting. An abdominal computed tomography scan showed nodular lesions in the adrenal glands. He was referred to our Department and a diagnosis of APS and acute adrenal failure was considered, based on positive aPLs (IgG and IgM), elevated ACTH levels and low cortisol levels. Other features were anemia, thrombocytopenia, elevated inflammatory parameters, hypergammaglobulinemia, prolonged partial thromboplastin time, positive antinuclear, anticardiolipin, anti-platelet antibodies, with negative double-stranded DNA antibodies. Lupus anticoagulant and Coomb’s tests were positive. MRI revealed a bilateral adrenal hemorrhage. A treatment with intravenous metylprednisolone, followed by oral prednisone and anticoagulant, was started, resulting in a progressive improvement. After 2 months he also showed hyponatremia and elevated renine levels, indicating a mineralcocorticoid deficiency, requiring fludrocortisones therapy.ConclusionThe development of acute adrenal failure from bilateral adrenal haemorrhage in the context of APS is a rare but life-threatening event that should be promptly recognized and treated. Moreover, this case emphasizes the importance of the assessment of aPLs in patients with acute adrenal failure in the context of an autoreaction.

Immunological features of primary anti-phospholipid syndrome in connection with endothelial dysfunction

To describe how certain peripheral immune parameters reflect the inflammatory alterations in patients with primary APS. Twenty-eight patients with newly diagnosed primary APS were studied. The control group included 26 patients with stable coronary disease and 38 healthy individuals. Peripheral blood lymphocyte subgroups were quantified, intracellular cytokines were measured by flow cytometry, soluble cytokines and auto-antibodies were assessed using ELISA. Endothelial dysfunction was evaluated by measuring endothelium-dependent (flow-mediated; FMD) vasodilation. Carotid duplex ultrasound was performed to quantify the carotid artery intima-media thickness (IMT). Stiffness parameters, augmentation index (AIx) and pulse wave velocity (PWV) were assessed by TensioClinic technology. Serum IL-4 and IL-6 levels were significantly higher in APS. CD4+IL10+ and CD8+IL10+ cell percentages in APS were significantly increased compared with controls. Th 0 and T cytotoxic 0 cell percentages were significantly decreased in patients compared with controls. FMD in APS was significantly lower, while IMT was higher than that of controls. FMD showed strong association with stiffness parameters, AIx and PWV. A significant negative linear correlation was detected between PWV and CD8+IL10+ cell percentages and significant positive linear correlation was found between PWV and CD8+IL10- cell percentage. In APS, the orchestrated pro-inflammatory cascade can eventually result in endothelial dysfunction, leading to the characteristic vascular abnormalities of the disease.

Outcome of primary antiphospholipid syndrome in childhood.

The objective of this paper is to investigate the long-term outcome of primary antiphospholipid syndrome (APS) in the paediatric age. The features of unselected patients with primary APS who had disease onset before the age of 16 years were retrospectively analysed in three Italian referralcentres. Clinical and laboratory manifestations were assessed to establish whether, at the end of follow-up, the final diagnosis was still primary APS or whether they had developed definite SLE or lupus-like syndrome. Fourteen patients, nine boys and five girls, who had the presenting clinical manifestation of APS between three and 13 years of age (median nine years) and were followed for two to 16 years (median six years). Six patients presented with deep vein thrombosis, five with cerebral stroke, two with peripheral artery occlusion and onewith myocardial infarction. During follow-up, four patients had one or more recurrences of vascular thrombosis. At last observation, 10 patients could still be classified as having primary APS, two had developed SLE, one lupus-like syndrome and one Hodgkin's lymphoma. In conclusion; our analysis suggests that some children who present with the features of primary APS may progress to develop SLE or lupus-like syndrome.

Morphology of vascular, renal, and heart lesions in the antiphospholipid syndrome: Relationship to pathogenesis

A growing body of evidence suggests that aPL are not only serological markers of the antiphospholipid syndrome (APS), but may also directly contribute to the development of thrombosis and other manifestations, including the APS vasculopathy. The latter has been documented in leptmeninges, lung, skin, myocardium, peripheral arteries, and kidney. Renal lesions, a common feature of primary antiphospholipid syndrome (PAPS), include occlusion of principal renal arteries or their main branches, TMA, cortical ischemia, and renal vein thrombosis. Within the cardiac manifestations associated with aPL, valvular involvement is the most common. Histologic findings in valve specimens are consistent with a noninflammatory lesion characterized by intravalvular capillary thrombosis, laminar or verrucous superficial thrombosis, vascular proliferation, fibrosis, and calcification. Even though there is general consensus that endothelial damage triggers the chain of events that results in valve thickening, fusion, rigidity, and ultimately functional abnormalities, we believe that more experimental work remains to be done on the initial valve insult in APS.

Diastolic dysfunction is a feature of the antiphospholipid syndrome

Recurrent thrombi, thrombocytopenia, pregnancy loss, and stroke in association with medium to high concentrations of anticardiolipin antibodies are well-recognized features of antiphospholipid syndrome. Cardiac manifestations of primary antiphospholipid syndrome (PAPS) also have been documented but involve structural and valvular heart disease. Diastolic dysfunction in PAPS has not been well described. Therefore, 10 patients with PAPS (nine women and one man) of mean age 30 ± 7 years (range 20 to 46 years) and 10 healthy age-, sex-, weight-, and height-matched control subjects were studied by echocardiography. Anticardiolipin antibody concentrations of patients with PAPS were >80 immunoglobulin G phospholipid units as determined by enzyme-linked immunosorbent assay. Doppler-derived parameters of left ventricular filling showed a significant association between PAPS and diastolic dysfunction compared with control, as evidenced by a decrease in peak early filling velocity (52 ± 10 cm/sec vs 67 ± 12 cm/sec; p <0.01), a decrease in the ratio of peak early to peak atrial filling velocities (1.03 ± 0.40 vs 1.52 ± 0.28; p < 0.005), a decrease in the mean deceleration rate of early filling (338 ± 75 cm/sect vs 590 ± 227 cm/sec 2; p < 0.005), and an increase in the percentage of atrial contribution to filling and deceleration time. Left ventricular mass, diastolic filling time, and heart rate did not differ between groups. Left ventricular systolic function was normal and ejection fraction did not differ between patients with PAPS and control subjects (63% ± 2% vs 65% ± 7%; p not significant). These data demonstrate that left ventricular diastolic dysfunction in the absence of systolic impairment is a feature of PAPS. Additional studies are needed to determine the potential causative role of anticardiolipin antibodies in diastolic dysfunction of PAPS.