Cardiac manifestations in the antiphospholipid syndrome

Experimental evidence reveals that aPL are not only markers of APS, but also may play a causative role in the development of vascular thrombosis and pregnancy morbidity. The pathogenic mechanisms of aPL seem to be heterogeneous, including endothelial cell activation, the direct inhibition of the activated protein C pathway, abnormalities in platelet function, and in complement activation. aPLs induce proadhesive, proinflammatory, and procoagulant molecules that provide a persuasive explanation for induction of thrombosis in APS. Cardiac manifestations in APS include valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. aPL may be associated with accelerated atherosclerosis in APS patients. Valve disease is the most important and most common cardiac manifestation of APS. The precise mechanism by which valves become deformed is not yet fully known.     

Cardiac manifestations of the antiphospholipid syndrome.

The antiphospholipid syndrome has been associated with multiple cardiac abnormalities. The earliest reports were of valvular disease, including verrucous endocarditis, as well as valvular thickening and insufficiency. Subsequently, antiphospholipid antibodies were implicated in coronary artery disease manifested by premature myocardial infarction and coronary artery bypass graft occlusion. In addition, there have been rare reports of intracardiac thrombi and diffuse cardiomyopathy in association with antiphospholipid antibodies. In this review, we discuss the nature and prevalence of the cardiac manifestations of the antiphospholipid antibody syndrome as well as some of the proposed pathophysiologic mechanisms. We also provide examples from our own experience. The expanding spectrum of cardiac disease associated with antiphospholipid antibodies suggests an important role for these antibodies in certain types of cardiac pathology.     

Osteoarticular manifestations of antiphospholipid syndrome

In conclusion, arthralgias represent a rather common osteoarticular manifestation of primary and secondary APS, while arthritis is mainly described in SLE-related APS. Osteonecrosis is frequently described in association with aPL in patients with and without autoimmune disorders. The presence of osteonecrosis in primary APS patients in the absence of corticosteroid use suggests an association between osteonecrosis and APS. Clinicians should be aware of this possible clinical manifestation of APS, because early diagnosis may lead to early management. A systematic screening for aPL in all cases with diagnosed osteonecrosis in the absence of precipitating factors should be considered.     

抗磷脂综合征的心血管系统表现

抗磷脂综合征（APS）是一种累及多器官的系统性自身免疫性疾病,临床以反复发作的动静脉血栓形成、自发性流产、血小板减少以及持续的血清抗磷脂抗体阳性为主要特征。心脏是APS的重要靶器官之一。本文从APS的心血管系统表现如心瓣膜病变、心肌梗死、心腔内血栓形成、冠状动脉微血管血栓形成及治疗策略方面作一综述。     

Neurologic manifestations of the antiphospholipid syndrome

Neurologic disorders are among the most prominent clinical manifestations associated with the antiphospholipid syndrome. Such neurologic disorders are predominantly related to focal central nervous system thrombo-occlusive events. This review summarizes the latest data regarding the clinical aspects of stroke and other neurologic manifestations associated with antiphospholipid antibodies.     

Endocrinologic manifestations of the antiphospholipid syndrome

Our objective was to study the endocrinologic manifestations of the antiphospholipid syndrome (APS). We reviewed the medical literature from 1968 until 2005 using MEDLINE and the key words: APS, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid antibodies, adrenal, thyroid, parathyroid, pituitary, diabetes, ovaries and testes. Adrenal insufficiency is the most common endocrinologic manifestation and can be the presenting symptom of APS. In patients with autoimmune thyroid disease circulating aPL have been detected. However, no clinical manifestations of APS have been described. A few cases of hypopituitarism have been reported, including a case of Sheehan's syndrome. aPL has been detected in the sera of diabetic patients, probably associated with some macroangiopathic complications. Finally only very few cases of ovarian and testicular involvement have been reported. The adrenals are the most commonly involved glands in the APS. Clinicians should keep a high index of suspicion for adrenal insufficiency in patients with APS.     

Neurologic manifestations of the antiphospholipid syndrome

Antiphospholipid syndrome is an important cause of neurologic morbidity. The clinical criteria for antiphospholipid syndrome include only cerebrovascular arterial and venous thrombosis, but many other neurologic manifestations have been associated with antiphospholipid antibodies (aPL). This review discusses the role of aPL in cerebrovascular manifestations and in some of the other neurologic manifestations commonly associated with these antibodies, as well as data pertaining to the pathophysiology of aPL-associated neurologic manifestations and treatment issues.     

Dermatologic manifestations of the antiphospholipid syndrome

A wide variety of dermatologic manifestations has been described in the antiphospholipid syndrome (APS). The most frequent skin lesion is livedo reticularis, present not only on the limbs but also on the trunk, with a fine irregular pattern. It belongs to the arterial subset of APS. Circumscribed ulcerations, resembling livedoid vasculitis, may be the first manifestation of APS. Ulcerations may also occur as a late complication of recurrent venous thrombosis. Extensive skin necrosis is a classic manifestation of catastrophic APS. Pseudo-vasculitis lesions are misdiagnosed if a skin biopsy is not performed, especially in the context of systemic lupus erythematosus. In systemic lupus erythematosus, primary anetoderma is always associated with antiphospholipid antibodies.     

Renal manifestations of the antiphospholipid syndrome

The antiphospholipid syndrome is characterized by recurrent arterial and venous thromboses and pregnancy morbidity in association with antiphospholipid antibodies. Recurrent thrombotic events are associated with significant morbidity and mortality. Renal involvement encompasses the whole renal vasculature and may lead to proteinuria, renal impairment, hypertension, and end-stage renal failure. Renal involvement is especially difficult to distinguish from glomerulonephritis when the antiphospholipid syndrome develops in patients with systemic lupus erythematosus. This article reviews the diagnosis and treatment of the major features of this syndrome, with particular reference to the kidney.     

抗磷脂综合征的心脏病变

目的分析抗磷脂综合征合并心脏受累的临床特点、治疗和预后,提高对本病的认识。方法对72例抗磷脂综合征患者临床资料进行回顾性分析。结果72例抗磷脂综合征患者中,心脏受累患者48例,二尖瓣受累发病率最高。心脏受累与血栓事件显著相关,与部分激活的凝血活酶时间延长相关。瓣膜病变与脑梗死和器官血栓事件相关。20例有血栓事件并心脏受累的抗磷脂综合征患者接受了抗凝治疗,未再发生血栓事件。结论抗磷脂综合征累及心脏表现为瓣膜异常、冠状动脉血栓、心肌受累和肺动脉高压等,心脏受累可能与高凝状态相关。     

The abdominal manifestations of the antiphospholipid syndrome

OBJECTIVES: To study the abdominal manifestations of the antiphospholipid syndrome (APS). METHODS: We reviewed the medical literature from 1968 to 2006 using MEDLINE and the key words: APS, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid (aPL) antibodies, catastrophic antiphospholipid syndrome, liver, hepatic biliary, pancreas, spleen, gastrointestinal and abdominal. RESULTS: Liver involvement is the most frequent abdominal manifestation associated with APS. Various hepatic manifestations have been reported including Budd-Chiari syndrome, hepatic-veno-occlusive disease and occlusion of small hepatic veins, nodular regenerative hyperplasia, hepatic infarction, cirrhosis, portal hypertension, autoimmune hepatitis and biliary cirrhosis. Acute intestinal infarction, intestinal angina, and intestinal bleeding have also been reported in association with aPL in addition to few sporadic cases of splenic infarction and acute pancreatitis. CONCLUSION: A high index of suspicion for any signs of abdominal involvement should be considered in patients with APS. In addition screening for aPL should be carried out in patients who present with hepatic vein occlusion and unexplained signs of intestinal angina.     

The hematologic manifestations of the antiphospholipid syndrome

Various hematological pathologies have been described in association with antiphospholipid syndrome (APS). Thrombocytopenia is frequently found in APS patients, its incidence has ranged from 22-42% in different series, it is usually moderate (>50x10(9)/L) without clinical manifestation and requires no intervention. A high percentage of patients with isolated idiopathic thrombocytopenic purpura have antiphospholipid antibodies, however the pathogenetic role and the clinical importance of these antibodies in this condition is still not clear. Other hematological manifestations reported in association with APS include: bone marrow necrosis, and various thrombotic microangiopathic syndromes such as: thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, and catastrophic APS. A high index of suspicion is needed for the early recognition and treatment of these conditions.     

Clinical manifestations of the antiphospholipid syndrome.

We studied a large cohort of patients with systemic lupus erythematosus (SLE) to determine which manifestations associate with the antiphospholipids (aPL) and to ascertain when 2 or more such manifestations coexist, the association with aPL is stronger and the titers tend to be higher. We have confirmed that when aPL occur within SLE, they may account for some disease manifestations. We also described a similar syndrome occurring in the absence of a primary condition which we termed primary antiphospholipid syndrome (APS). Thus, we were able to construct preliminary criteria for the classification of APS as it occurs in SLE. With appropriate additions and exclusions to rule out SLE, these criteria could be applied to the classification of primary APS.     

Life-threatening cardiac manifestations of primary antiphospholipid syndrome

We report a rare case of primary antiphospholipid syndrome (APS) in a 43-year-old man presenting as recurrent acute coronary stent thrombosis and complicated by three myocardial infarctions. As illustrated in this report, in APS patients recurrent life-threatening arterial thrombotic events may occur in spite of recommended anticoagulant therapy. We conclude that the APS should be considered as a potential cause of acute coronary syndrome, particularly in young individuals with a history of recurrent thrombotic events and/or with abnormal coagulation test results. Further studies are needed to determine the best therapeutic strategy for APS patients with acute coronary syndrome.