Catastrophic antiphospholipid syndrome presented with severe hypertension,adult respiratory distress syndrome and unilateral adrenal haemorrhagic infarction

We are reporting a case of catastrophic antiphospholipid syndrome (CAPS) in an adult female manifested with severe hypertension followed by adrenal haemorrhagic infarction and adult respiratory distress syndrome. Adrenal involvement appears to be exceedingly high in CAPS and adult respiratory distress syndrome (ARDS) is the prevailing pulmonary manifestation in this condition, compared with these impediments in patients with simple antiphospholipid syndrome (APS). Even though the above manifestations are well recognized, their combination as an initial presentation of CAPS is uncommon.     

The acute respiratory distress syndrome in catastrophic antiphospholipid syndrome: analysis of a series of 47 patients

BACKGROUND: The acute respiratory distress syndrome (ARDS) is a non-cardiogenic form of pulmonary oedema characterised by severe hypoxaemia refractory to oxygen therapy, with diffuse pulmonary infiltrates on chest radiographs. It can be precipitated by various serious medical and surgical conditions, including systemic autoimmune diseases. The "catastrophic" variant of the antiphospholipid syndrome (APS) is an accelerated form of this systemic autoimmune condition which results in multiorgan failure because of multiple small vessel occlusions. OBJECTIVE: To analyse the clinical and laboratory characteristics of patients with catastrophic APS who develop ARDS. METHODS: Cases with ARDS were selected from the web site based international registry of patients with catastrophic APS (CAPS registry) (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) and their characteristics examined. RESULTS: Pulmonary involvement was reported in 150 of 220 patients with catastrophic APS (68%) and 47 patients (21%) were diagnosed as having ARDS. Nineteen (40%) of these patients died. Pathological studies were undertaken in 10 patients and thrombotic microangiopathy was present in seven. There were no differences in age, sex, precipitating factors, clinical manifestations, or mortality between catastrophic APS patients with and without ARDS. CONCLUSIONS: ARDS is the dominant pulmonary manifestation of catastrophic APS. Thus the existence of ARDS in the context of an APS makes it necessary to rule out the presence of the catastrophic variant of this syndrome.     

Catastrophic antiphospholipid antibody syndrome in systemic lupus erythematosus: an autopsy case report of a young woman

Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome (APS) characterized by disseminated microangiopathy that results in multiorgan failure. CAPS mainly occurs in association with systemic lupus erythematosus (SLE). Clinically, CAPS mimics disseminated SLE vasculitis, intravascular coagulation (DIC), and particularly thrombotic thrombocytopenic purpura (TTP). We describe an autopsy case of young woman with CAPS in SLE, which is difficult to differentiate from TTP secondary to SLE.     

Acute respiratory failure associated with catastrophic antiphospholipid syndrome

We present a case of multiple organ dysfunction syndrome with acute respiratory failure due to alveolar haemorrhage associated with antiphospholipid antibodies in a 42-year-old woman with a medical history of antinuclear antibody-negative systemic lupus erythematosus and antiphospholipid syndrome. Severe respiratory failure, circulatory shock and acute renal failure necessitated artificial ventilation, inotropic and vasopressor therapy, and continuous venovenous haemofiltration. A tentative diagnosis of haemorrhagic lupus pneumonitis or pulmonary manifestation of antiphospholipid syndrome was made. Lupus anticoagulant, IgG anticardiolipin and anti-beta2-glycoprotein I antibodies were positive. High-dose glucocorticoid, anticoagulation with heparin, plasmapheresis and cyclophosphamide improved her clinical condition. Despite this, the patient died several days later of spontaneous intracranial haemorrhage. This case illustrates the uncommon manifestation of acute respiratory failure associated with antiphospholipid syndrome.     

Cœur et médecine interne : lupus systémique et syndrome des antiphospholipides

Cardiac involvement in systemic lupus (SL) and antiphospholipid syndrome (APS) can be due to variables and involve different presentations. Pericarditis is the most common lupus manifestation and occurs in 16% to 25% of patients. While corticosteroids are usually very effective, colchicine may avoid steroids and prevent relapse. Myocarditis during SL is rare and often inaugural. They may manifest as chest pain, acute heart failure, arrhythmias or conduction disturbances, and may progress to dilated cardiomyopathy and/or permanent heart failure. Their prognosis is however generally good, even in the absence of treatment with cyclophosphamide for the less serious forms. Finally, coronary involvement in SL is most often due to atherosclerotic, thrombotic origin (generally in the context of associated APS), and exceptionally explained by coronary vasculitis. During APS, valve disease is frequent and usually asymptomatic. Thrombotic damage can be (1) coronary, typically manifesting as a myocardial infarction in a young subject with healthy coronary arteries, (2) much more rarely intracardiac, or (3) microcirculatory, generally as part of a catastrophic antiphospholipid syndrome (CAPS) leading to a multiorgan failure. Finally, iatrogenic cardiac manifestations can exceptionally be seen during treatment with cyclophosphamide or antimalarials characterized by conduction disorders and/or heart failure.     

Acute respiratory distress syndrome due to cyanotic spell in an infant with tetralogy of Fallot

Acute respiratory distress syndrome (ARDS) is characterized by fulminant respiratory failure due to noncardiac pulmonary edema. This can be triggered by a heterogeneous group of diseases. We report an unusual case of an infant who developed severe ARDS in association with a severe cyanotic attack due to tetralogy of Fallot.     

Bilateral adrenal hemorrhage: A rare presentation of catastrophic anti-phospholipid syndrome

Catastrophic anti-phospholipid syndrome (CAPS) is characterized by microvascular thrombosis in multiple sites leading to multi-organ damage. It is a rare and fatal complication of antiphospholipid syndrome (APS). We present a rare case of CAPS that presented with bilateral (b/l) adrenal hemorrhage making the diagnosis challenging in this otherwise rare disease. A 51-year-old female was initially admitted with abdominal pain and found to have bilateral adrenal hemorrhage. Patient had a fulminant disease course in which she had thrombotic manifestations involving multiple organ systems. This case was especially challenging as the patient's bilateral adrenal hemorrhage was the first manifestation of CAPS; the diagnosis of APS had to be made while treatment for presumed CAPS was emergently commenced for this life-threatening disease. Key to managing this condition is having a high index of suspicion for the diagnosis in patients presenting with multi-organ failure and multiple thromboses and hemorrhage.     

Le syndrome catastrophique des antiphospholipides

The catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition resulting from rapidly progressive widespread thromboses mainly affecting the microvasculature in the presence of antiphospholipid antibodies. Within a few days, the patients develop multiorgan failure with pulmonary distress, renal failure with severe hypertension, cerebral, cardiac, digestive or cutaneous involvement. CAPS develops in less than 1% of patients with antiphospholipid syndrome, either primary or associated with systemic lupus erythematosus. CAPS reveals the antiphospholipid syndrome in about 50% of cases. CAPS may be precipitated by infectious diseases, surgical procedures or discontinuation of anticoagulation. CAPS overall mortality rate has decreased in the past decade and is now around 30%. Within our hospital, it has been reduced to 10%. The main differential diagnoses are other thrombotic microangiopathies, and heparin-induced thrombocytopenia. The treatment of CAPS consists of the empirical association of anticoagulation and corticosteroids, plus plasma exchange or intravenous immunoglobulins. Cyclophosphamide is added in patients with systemic lupus erythematosus. The prevention of CAPS is based upon the adequate management of the perioperative period when surgery cannot be avoided, the prompt treatment of infections and the education of patients with antiphospholipid syndrome.     

Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation

We report on a 32-year old female patient with primary antiphospholipid syndrome (PAPS) and several thromboembolic events despite stable doses of oral anticoagulation, good patient compliance and maintained INR values of >3. Over the preceding 3 years the patient had presented a wide spectrum of manifestations of APS, including recurrent venous and arterial thromboses, cardiac, gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a mild thrombocytopenia and the most feared manifestation of the catastrophic antiphospholipid syndrome (CAPS). Life-threatening bilateral subdural bleeding occurred while she was anticoagulated. The clinical features appeared to be refractory to oral anticoagulation with phenprocoumon. They were life threatening on each occasion and she developed repetitive episodes of organ damage with cardiac insufficiency (NYHA III), pulmonary hypertension and other residual defects. Even during heparinization recurrent thromboembolism supervened as well as livedo reticularis of the extremities. Lupus anticoagulants (LAC), anticardiolipin (aCL) antibodies and anti-₂-glycoprotein-1 (₂GPI) titers were all markedly elevated. This case report shows that recurrent episodes of thrombosis can occur despite seemingly adequate anticoagulation in patients with CAPS.Abbreviations aCL Anticardiolipin - aPL Antiphospholipid - APS Antiphospholipid syndrome - ARDS Adult respiratory distress syndrome - ₂GP1 ₂-glycoprotein-1 - CAPS Catastrophic APS - HELLP syndrome Hemolysis, elevated lever enzymes, low platelet count - ICA Index of circulating antibodies - INR International normalized ratio - LAC Lupus anticoagulants - NYHA New York Heart Association - SLE Systemic lupus erythematosus     

Thrombotic microangiopathy with liver, gut, and bone infarction (catastrophic antiphospholipid syndrome) associated with HELLP syndrome

Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is a thrombotic microangiopathy complicating pregnancy and shares many clinical and biological features with thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Thrombotic microangiopathy is also a pathological feature of catastrophic antiphospholipid syndrome (CAPS). An association between refractory HELLP syndrome and antiphospholipid syndrome (APS) has been reported in a few cases. We describe a 19-year-old woman with APS and multiorgan failure conforming to a diagnosis of CAPS who developed refractory HELLP syndrome.     

Recurrent episodes of hemorrhagic alveolitis in relapsing catastrophic antiphospholipid syndrome: the same side of the dark moon

Catastrophic antiphospholipid syndrome (CAPS) is a rare variant of antiphospholipid syndrome characterized by widespread thrombotic microangiopathy and multiorgan failure. Clinically, CAPS signs and symptoms can mimic vasculitis of systemic lupus erythematosus, disseminated intravascular coagulation, and thrombotic thrombocytopenic purpura. CAPS is burdened by high mortality, nearly 50 % in most series. However, patients surviving the acute phase rarely suffer of CAPS relapses. Moreover, concomitant pulmonary hemorrhagic alveolitis is a very rare complication warranting an ominous prognosis. Only few reports of relapsing CAPS are described in literature, and pathogenetic mechanisms are poorly understood and the optimal treatment is yet unknown. We report a case of a young man suffering from multiple relapses of CAPS and recurrent hemorrhagic pulmonary alveolitis refractory to aggressive combination treatment.     

Relapsing catastrophic antiphospholipid syndrome: report of three cases

BACKGROUND: The catastrophic variant of the antiphospholipid syndrome (CAPS), also now known as Asherson's syndrome, is defined as a potential life-threatening variant of the antiphospholipid syndrome, which is characterized by multiple small-vessel thrombosis that can lead to multiorgan failure. Relapses in patients with the CAPS are very uncommon. OBJECTIVE: To describe the clinical and laboratory features of patients with relapsing episodes of CAPS. METHODS: Three patients with relapsing CAPS are presented with their clinical and laboratory features. RESULTS: Seven episodes of CAPS that occurred in the 3 patients reported were analyzed. The median time between the episodes of CAPS was 12.5 months (range, 2.5-48). Precipitating factors were identified in 2 episodes only (Legionella respiratory tract infection and periodontal infection). The most significant manifestations of the episodes were renal involvement (5 episodes), central nervous system and cardiac involvement (4 episodes), and pulmonary and hepatic involvement (3 episodes each). Interestingly, laboratory features of definite microangiopathic hemolytic anemia (MHA) were present in 5 of 7 episodes of relapsing CAPS. The remaining episodes presented with thrombocytopenia, schistocytes, and anemia but data concerning hemolysis and Coombs tests were not reported. Rituximab was used in 2 episodes. CONCLUSIONS: Relapses occur very infrequently in patients with the CAPS. The presence of MHA is common in these patients, suggesting that an association between MHA and relapses of CAPS could be present and that a "continuum" between various MHAs might exist, as recently suggested.     

A case of antiphospholipid syndrome presenting with pulmonary truncus and main pulmonary artery thrombosis

In patients with antiphospholipid syndrome (APS), thromboembolism and pulmonary hypertension are the most common pulmonary manifestations. Thrombotic obstruction at the level of the main and/or proximal pulmonary arteries is rare. We report a 40-year-old woman without any history of previous arterial and/or venous thrombosis who presented with severe dyspnea and was found to have pulmonary hypertension and positivity for anticardiolipin antibodies. Computed tomography revealed pulmonary truncus thrombosis extending to both right and left pulmonary arteries. The patient and her family refused surgical treatment. She had a prolonged hospital course, was unresponsive to thrombolytic, anticoagulant, antiplatelet, and immunosuppressive treatments, and died of right ventricle and respiratory failure 5 weeks later. This is the first reported case with thrombosis of pulmonary truncus and main pulmonary arteries concurrent with APS.     

Pathophysiology of the catastrophic antiphospholipid syndrome (CAPS)

Antiphospholipid antibodies (APA) are a common cause of acquired thrombophilia. APA recognize plasma phospholipid-binding proteins (e. g., beta(2)-glycoprotein I, prothrombin, annexin V, etc.). Catastrophic antiphospholipid syndrome (CAPS) is an uncommon variant of the antiphospholipid syndrome. CAPS patients often present with multiorgan failure. Precipitating factors include surgical procedures, drugs, and discontinuation of anticoagulant therapy. Increasingly, infections are recognized as a major precipitating condition. The majority of patients present with renal involvement as well as evidence of acute respiratory distress syndrome (ARDS). This review discusses the clinical and pathophysiologic aspects of CAPS as well as the differenital diagnosis.     

Multiorgan failure due to rapid occlusive vascular disease in antiphospholipid syndrome: the ‘catastrophic’ antiphospholipid syndrome

The term ‘catastrophic’ antiphospholipid syndrome (CAPS) is defined as an accelerated form of antiphospholipid syndrome (APS) usually resulting in multiorgan failure. These patients have in common: (i) clinical evidence of multiple organ involvement developing in a very short time period; (ii) histopathological evidence of multiple small vessel occlusions (a minority also have large vessel thrombosis); and (iii) laboratory confirmation of the presence of antiphospholipid antibodies (aPL), usually in high titres. Although less than 1% of patients with the APS develop this complication, its potentially lethal outcome emphasizes its importance in clinical medicine.     

Catastrophic antiphospholipid syndrome associated with malignancies (case report and review of the literature)

We describe a 58-year old female patient with rapid development of arterial and venous thromboembolisms, including deep vein thrombosis (DVT) in the lower limbs, recurrent cerebral infarctions and bilateral pulmonary emboli. Her laboratory data on admission showed positive anticardiolipin antibody of IgG isotype (IgG aCL) and positive anti-beta2 glycoprotein-I antibody of IgG isotype (IgG abeta2-GPI), and decreased protein C activity and protein S antigen. Systemic examinations revealed the presence of an ovarian cancer. Surgical resection was attempted, but her cancer infiltrated the pelvic wall and could not be resected. Despite treatment with unfractionated heparin followed by warfarin, she died due to recurrent episodes of cerebral infarction. This case was considered as probable catastrophic antiphospholipid syndrome (CAPS), which might be associated with ovarian cancer. Known as Trousseau's syndrome, arterial and, more commonly, venous thrombosis is a frequent complication of cancer and sometimes a harbinger of occult cancer. Our case indicates that there is an overlap between antiphospholipid syndrome (APS) and Trousseau's syndrome. It is important to bear in mind that a thrombotic event associated with cancer can be the first manifestation of CAPS.     

Progression of antiphospholipid antibody syndrome to catastrophic antiphospholipid antibody syndrome acutely with cessation of antithrombotic therapy

Catastrophic antiphospholipid antibody syndrome (CAPS) is a serious condition that is often unrecognised with a high mortality. Cessation of anticoagulation in antiphospholipid antibody syndrome (APS) can have devastating consequences with progression to CAPS. Making a diagnosis of APS can however be challenging because of the evolving diagnostic criteria and difficulty in confirming thromboses. Management of these patients can also be complex, especially in those with coexistent thrombocytopenia. New potential treatments are emerging targeted on the immunomodulation of APS rather than just prevention of thrombosis. This article aims to highlight these diagnostic and management difficulties by reporting and discussing three cases of APS with progression to CAPS following cessation of anticoagulation, one with fatal consequences, with confirmation of CAPS on autopsy, and two with successful treatment and outcomes.     

Transient myopia with severe chemosis as an initial manifestation of systemic lupus erythematosus

A 24-year-old woman suffered from blurred vision and periorbital edema with remittent fever. She was diagnosed as having systemic lupus erythematosus (SLE), complicated with myopia and retinopathy and severe chemosis. Antiphospholipid syndrome (APS), hemophagocytic syndrome, and liver involvement were also proven. We considered that APS might cause chemosis as a result of thrombosis-induced perfusion failure in the conjunctiva. In such cases, APS should be considered and anticoagulation therapy associated with steroid therapy should be initiated. In systemic lupus erythematosus (SLE), chemosis, severe hepatitis, and hemophagocytic syndrome (HPS) are rare complications. It is well known that many cases of SLE are complicated with antiphospholipid syndrome (APS), which causes arteriovenous thrombosis. We report a case of SLE with transient myopia and severe chemosis complicated with severe hepatitis and HPS. As this patient had antiphospholipid antibodies, these ocular complications were considered to be related to APS. Received: August 23, 2000 / Accepted: November 24, 2000     

恶性抗磷脂综合征7例临床分析并文献复习

目的：探讨恶性抗磷脂综合征（CAPS）的临床特点及预后，以期提高临床医生对该病的认识及诊治水平。方法：回顾性分析我院风湿科收治的7例恶性抗磷脂综合征患者临床表现、实验室检查及预后等资料并复习相关文献。结果：7例CAPS患者中，1例为原发APS，6例为SLE继发APS。静脉血栓发生5例次，主要是下肢深静脉血栓、眼中央静脉栓塞；动脉血栓13例次，以脑梗死为主（6例次）。6例抗心磷脂抗体阳性，3例抗β2-GPⅠ抗体阳性，3例狼疮抗凝物阳性。5例患者在1周内相继出现心、肺、肾等多器官功能衰竭而导致死亡。结论：CAPS患者短时间内发生大量微血栓形成，可导致多器官功能衰竭。本病的预后差，及早诊断、及时治疗是改善患者预后的关键。     

Efficacy of Eculizumab in a Patient With Immunoadsorption-Dependent Catastrophic Antiphospholipid Syndrome: A Case Report

Catastrophic antiphospholipid syndrome (CAPS) is a rare but devastating complication in patients with antiphospholipid syndrome (APS) with a high morbidity and mortality.We describe a case of a 30-year old female patient with immunoglobulin A (IgA) deficiency who underwent splenectomy because of idiopathic thrombocytopenic thrombocytopenia. Subsequently, an APS and finally systemic lupus erythematosus was diagnosed. After an uncomplicated pregnancy that was terminated by cesarean section, the patient developed severe CAPS with cerebral, myocardial, renal, and pulmonary involvement.Because of IgA deficiency, standard therapy consisting of plasmapheresis and intravenous immunoglobulins in addition to steroids was not tolerated. After 8 sessions of immunoadsorption (IAS), massive pulmonary hemorrhage was controlled but relapsed twice whenever IAS was terminated. As other immunosuppressive agents were considered dangerous because of the risk of infections in the face of severe hypogammaglobulinemia, we administered eculizumab, an inhibitor of the terminal complement pathway, which led to a persistent control of her disease. Interestingly, eculizumab therapy was associated with a further decline of complement C3 and C4 serum levels. The patient developed a subsequent flare of her systemic lupus erythematosus, potentially indicating that complement inhibition by eculizumab is not effective in preventing lupus flares.Taken together, we describe a unique case of life-threatening and difficult-to-treat CAPS with a good clinical response after terminal complement complex inhibition with eculizumab. Further controlled trials are necessary to investigate the value of eculizumab in patients with CAPS.