The antiphospholipid syndrome: an update

Antiphospholipid syndrome is an autoimmune disorder defined by the association between antiphospholipid antibodies (i.e., lupus anticoagulant and anticardiolipin antibodies) and venous or arterial thrombosis or obstetric complications. In spite of the recent advances, many aspects of this disease remain unclear. Although the antigenic targets of this heterogeneous group of autoantibodies have been determined, being negatively charged phospholipids-binding proteins, their precise pathogenic mechanism is still being determined. The most important advances in the pathophysiology, diagnosis and treatment of this condition are discussed in this review.     

Catastrophic antiphospholipid syndrome

Catastrophic antiphospholipid syndrome is a rapidly progressive life-threatening disease that causes multiple organ thromboses and dysfunction in the presence of antiphospholipid antibodies. A high index of clinical suspicion and careful investigation are required to make an early diagnosis so that treatment with anticoagulation and corticosteroids can be initiated; plasma exchange and/or intravenous immunoglobulins can be added if the life-threatening condition persists. Despite aggressive treatment and intensive care unit management, patients with catastrophic antiphospholipid syndrome have a 48% mortality rate, primarily attributable to cardiopulmonary failure. This article reviews the current information on the etiopathogenesis, clinical manifestations, diagnosis, management, and prognosis of catastrophic antiphospholipid syndrome.     

Antibodies to various phospholipids in SLE patients with primary antiphospholipid syndrome]

Antiphospholipid antibodies (aPL) represent a heterogeneous population reacting with negatively charged, less frequently neutral phospholipids and/or phospholipid-binding serum proteins. The study was made of antibodies to a wide spectrum of phospholipids: to negatively charged phospholipids such as phosphatide acid (aPA), cardiolipin (aCL), phosphatidylcholine (aPS), phosphatidylinositol (aPI), phosphatidylglycerol (aPG) and to neutrally charged phospholipid--phosphatidylcholine (aPC)--in 54 patients with systemic lupus erythematosus (SLE) and 29 patients with primary antiphospholipid syndrome (PAPS). The test for lupus anticoagulant (LAC) was also made. aPL in SLE patients free of antiphospholipid syndrome were detected in 61, 36 and 9% (aPC, aPS and aPA, aCL, respectively). aPI and aPG did not exceed normal values. 81% of SLE patients with antiphospholipid syndrome were LAC positive and 88% aPL positive. 60, 53, 44, 40, 13 and 17 were positive to aPC, aPA, aPS, aCL, aPG and aPI, respectively. Among patients with PAPS, the highest positivity was by LAC, occurrence of the other aPL was the same as in SLE patients with antiphospholipid syndrome. aCL, aPA, aPC, aPS, aPG and aPI were found in 55, 52, 41, 38, 31 and 21% of cases, respectively. In clinical manifestations of antiphospholipid syndrome and negative tests for LAC and aCL it is advisable to make tests for aPS and aPC. aPC occur in SLE patients more frequently than the other aPL: in 63% of SLE patients free of antiphospholipid syndrome and in 60% of SLE patients with this syndrome. Antibodies to other phospholipids, but not to cardiolipin, were present in SLE + APS in half of the cases but in SLE + PAPS in one third of the patients. Occurrence of aCL in the serum of SLE + PAPS patients is associated with the presence of antibodies to any other phospholipid irrespective of the charge. The severity of vascular changes did not correlate with the number of aPL variant found in the serum.     

Pseudoinfectious endocarditis in antiphospholipid syndrome

The antiphospholipid syndrome (APhS) is autoimmune non-inflammatory trombotic vasculopathy, associated with damage of vessels of any caliber and localization that determines the diversity of clinical manifestations of this syndrome. One of possible localizations of thrombosis in AphS is pseudoinfective endocarditis (PsIE). We have performed analysis of clinical and laboratory features of APhS, associated with PsIE. 28 APhS patients with PsIE, average age--44+/-13 years, were included in the study. Among them 21 patients had primary form of APhS, 7 cases had secondary form of APhS. For statistical treatment of the results the logistic regression (SPSS for Windows. Release 11.5.0.) was used, the confidence level of differences between groups was determined with the use of Student's test. Heart valve abnormalities occurred in 100% of patients and included valvular thickening, induration and sclerosis, the presence of valve vegetations, focip of calcinosis and different grade of valve dysfunction. Mitral and aortal valve vegetations occurred with the same incidence (64%), both valves were been involved in 29% of cases. Positive associations with presence/development of PsIE in APhS from multivariant model data included mitral valve lesion (OR: 0.029), focal cardiofibrosis (OR: 0.084), prior valve lesion (OR: 0.087), negative associations--hemicrania (OR: 8.627) and secondary form of APhS (OR: 6.425). Moderately high titer of lupous anticoagulant (multivariant model) (OR: 3.753) seemed to be prognostic marker of PsIE. In half of patients with APhS and PsIE systemic embolisms appeared, embolic cerebrovascular complications were the most frequent (32%). The possibility of development of hemodynamically significant valve dysfunction that needs valve replacement and nececcity of making of differential diagnosis with infective endocarditis are related to other aspects, important for clinical practice.     

Pathophysiology of the antiphospholipid syndrome

Antiphospholipid syndrome is a distinct disorder with the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Its serological marker is the presence of antiphospholipid antibodies in the blood of these patients. The relation between the presence of antibodies against anionic phospholipids and thromboembolic complications is well established over the last 25 years but the pathophysiology of the syndrome is largely unclear. Even after all these years, there is a persisting debate about the specificity and sensitivity of the assays for the detection of antiphospholipid antibodies. We now accept that antibodies to beta2-glycoprotein I rather than to anionic phospholipids are the major pathological antibodies, although there is no clear consensus on how the presence of these antibodies correlates with the different clinical manifestations of the syndrome. In this review, we discuss the current methods of detection of the antibodies and our insight into the pathobiology of the syndrome. We propose a mechanism for describing how the presence of anti-beta2-glycoprotein I antibodies relates to the different clinical manifestations observed.     

Soluble adhesion molecules in antiphospholipid syndrome associated with systemic lupus erythematosus and in primary antiphospholipid syndrome

AIM: To evaluate clinical implications of measurements of the level of soluble cell molecules of adhesion (sCMA) in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) and primary APS (PAPS). MATERIAL AND METHODS: Serum levels of sP-selectine, sE-selectine, sVCAM-1 were determined with enzyme immunoassay (R&D, USA) in 23 SLE with APS, 15 SLE patients free of APS and 19 patients with PAPS. RESULTS: Mean levels of sE-selectine and sVCAM-1 in SLE patients with APS, PAPS and SLE was higher than in donors. Elevated mean levels of sP-selectine were observed only in SLE patients free of APS. These patients also showed a correlation between sVCAM-1 level and the disease activity (p < 0.01). CONCLUSION: The development of immunopathological process in APS is associated with increased concentration of sCMA.     

Polyarteritis nodosa complicated by antiphospholipid syndrome

Polyarteritis nodosa is a necrotizing vasculitis of small and medium-sized arteries that spares the smallest blood vessels (arterioles, venules, and capillaries). Antiphospholipid syndrome is an autoimmune disorder characterized by venous or arterial thrombosis and/or by fetal losses, associated with antiphospholipid antibodies. The association of both diseases is infrequent. This case report discusses a male patient with a diagnosis of polyarteritis nodosa who, after 7 years of being diagnosed with vasculitis, showed ischemic lesions in his legs associated with high titers of anticardiolipin antibodies, along with angiographic and histologic evidence of thrombosis. Despite immunosuppressive and anticoagulant therapy, his lesions progressed, and both legs had to be amputated.     

A review of antiphospholipid antibody syndrome

PURPOSE: To review the pathophysiology, clinical presentation, and management options for antiphospholipid antibody syndrome (APS), a potentially life-threatening coagulation disorder. DATA SOURCES: Selected scientific literature, consensus guidelines, and expert opinion. CONCLUSIONS: Clinical features that should alert the clinician to consider APS include recurrent fetal loss, arterial or venous thrombosis, thrombocytopenia and livedo reticularis. One should be suspicious of this diagnosis in a younger patient, one with an autoimmune disease, or family history of autoimmune disease. To confirm the diagnosis one needs both clinical and laboratory abnormalities. IMPLICATIONS FOR PRACTICE: The signs and symptoms of APS are varied and could be confused with many disorders. The primary care provider needs to be aware of this syndrome in order to include it in the differential diagnosis and appropriately recognize and refer the patient in a timely manner.     

Kidney damage in primary antiphospholipid syndrome

AIM: To characterize clinical manifestations, course and laboratory signs of nephropathy in primary antiphospholipid syndrome (PAS). MATERIAL AND METHODS: 6 patients with PAS and renal affection were observed for 10 years since 1991. They were examined for anticardiolipin antibodies and/or lupus anticoagulant. Renal tissue was studied morphologically in one patient. RESULTS: In all the patients renal damage manifested with arterial hypertension associated with isolated proteinuria. The majority of the patients had renal dysfunction. All of them had elevated level of antibodies to cardiolipin primarily in combination with lupus anticoagulant. Histological changes of renal tissue presented with thrombotic microangiopathy of glomerular and extraglomerular vessels, intimal proliferation and vascular wall thickening with occlusion of their lumen which combined with morphological indicators of focal segmental glomerulosclerosis. CONCLUSION: The thrombotic process in the intrarenal vessels in PAS dictates the necessity to develop novel approaches to treatment of such patients. In addition to immunodepressants the treatment should include indirect anticoagulants and antiaggregants.