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Catastrophic Antiphospholipid Syndrome

2001; Wolters Kluwer; Volume: 80; Issue: 6 Linguagem: Inglês

10.1097/00005792-200111000-00002

1536-5964

Ronald A. Asherson, Ricard Cervera, Jean‐Charles Piette, Yehuda Shoenfeld, Gerard Espinosa, Michelle Petri, Eugene Lim, T Lau, Anagha Gurjal, Anna Jędryka-Góral, H Chwalińska-Sadowska, Robin Dibner, Jorge Rojas-Rodríguez, Mario Garcı́a-Carrasco, John T. Grandone, Ann L. Parke, Paulo José Bastos Barbosa, Carlos Vasconcelos, Manuel Ramos‐Casals, Josep Font, M Ingelmo,

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Introduction Abbreviations used in this article: aCL, anticardiolipin antibodies, ANA, antinuclear antibodies, anti-dsDNA, anti-dsDNA antibodies, aPL, antiphospholipid antibodies, APS, antiphospholipid syndrome, ARDS, acute respiratory distress syndrome, CSF, cerebrospinal fluid, CT, computed tomography, DIC, disseminated intravascular coagulation, ECG, electrocardiogram, ENA, extractable nuclear antigen antibodies, ESR, erythrocyte sedimentation rate, HPF, high power field, INR, international normalized ratio, LA, lupus anticoagulant, PT, prothrombin time, PTT, partial thromboplastin time, SLE, systemic lupus erythematosus, TTP, thrombotic thrombocytopenic purpura, WBC, white blood count The antiphospholipid syndrome (APS), originally defined as the combination of venous or arterial thrombotic events, recurrent fetal loss, and, frequently, a moderate thrombocytopenia in association with antiphospholipid antibodies (aPL), was subsequently greatly expanded to include diverse conditions, for example, heart valve lesions, adrenal insufficiency, and pulmonary syndromes such as acute respiratory distress syndrome (ARDS), "capillaritis," and pulmonary alveolar hemorrhage, among others (16,17). It was then realized that several "microangiopathic syndromes" also existed, as opposed to large vessel occlusive disease. Single organs, such as the kidneys, heart, skin, and brain, have been affected by this "thrombotic microangiopathy" in the context of the "classic" or "simple" APS. The temporal occurrence of thrombotic events in patients with this classic APS usually extends over months or years. In 1992, the existence of a new "subset" was described in which multiple vascular occlusive events, usually affecting small vessels supplying organs and presenting over a short period of time, were the outstanding features. This subset was termed the "catastrophic" APS. Although large vessel occlusions were also present, their prevalence did not in any way approach that in patients with the classic APS. The occlusions occurred over days to several weeks, and more than 50% of patients usually succumbed despite seemingly adequate therapy, including anticoagulation, steroids, etc. (6). In 1998, a comprehensive review article with the clinical and laboratory description of 50 such patients was published (8). In the present paper we describe the clinical and serologic features of the largest series of patients with catastrophic APS hitherto reported, including 30 new cases from interested physicians in many different countries, as well as a comprehensive literature review of 50 additional recently published case reports with this syndrome. This new series, comprising a total of 80 patients, enables us to analyze further and clarify not only the clinical importance of this syndrome, but also its pathogenesis. Methods We undertook a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of catastrophic APS published in English, Spanish, and French from 1996 (when the previous comprehensive review series of catastrophic APS was completed [8]) through 2000 (keywords:lupus anticoagulant, coagulation inhibitor, lupus inhibitor, anticardiolipin, cardiolipin, anticardiolipin antibody, antiphospholipid, phospholipid, antiphospholipid antibody, antiphospholipid syndrome, catastrophic antiphospholipid syndrome). We also retrospectively analyzed several original cases categorized as having catastrophic APS that were not included in the previous series. Additionally, the bibliographies of all articles were systematically scanned for references not identified in the initial search. Patients were considered as having catastrophic APS if they presented an acutely devastating APS with multiple organ involvement, as previously defined (6). Data from these patients were summarized using a standardized data form, including sex, age, diagnosis of the underlying condition, precipitating factors, main thrombotic clinical manifestations, immunologic features, treatment, and evolution. Thirty new and previously unpublished cases (14 patients from the European Union, 8 from the United States, and 8 from other countries) were added to the literature review. The bilateral Fisher exact test was used for statistics. Case Reports The most relevant data of the 80 case reports are described in Tables 1 (general clinical manifestations), 2 (thrombotic manifestations and outcome), and 3 (laboratory findings). Twelve illustrative case reports are described in detail.TABLE 1: General clinical manifestations of 80 patients with catastrophic APSTABLE 1: —ContinuedTABLE 2: Thrombotic clinical manifestations of patients at the time of catastrophic APSTABLE 2: —ContinuedTABLE 2: —ContinuedTABLE 3: Laboratory findings of patients with catastrophic APSTABLE 3: —ContinuedCase 1 The patient was a 42-year-old Chinese female secretary with psoriasis of 2 years' duration, and systemic lupus erythematosus (SLE) diagnosed in 1992 when she presented with malar rash, arthritis, fever, cutaneous vasculitis, and Raynaud phenomenon. Positive serologies included antinuclear antibodies (ANA) (1/640, speckled); anti-dsDNA, anti-Ro/SS-A, and anti-RNP antibodies. Anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) were not assayed. Her disease ran a mild course with cutaneous flares, Raynaud phenomenon, and an episode of nephrotic syndrome in 1996, which responded to prednisolone alone. No renal biopsy was done. She remained well on just 1 mg of prednisolone a day. In January 1999, she complained of recent-onset effort dyspnea and postprandial abdominal bloating. Examination revealed borderline hypertension, small bilateral pleural effusions, mild pitting ankle edema, Raynaud phenomenon, cyanosed toes, weak lower limb pulses, and a vasculitic lesion on 1 toe. The urine examination was bland without proteinuria, the full blood counts and creatinine were normal, and the anti-dsDNA antibodies were negative. Prednisolone (20 mg bd) was prescribed as for a lupus "flare." On 2 February 1999 she was admitted with sudden-onset epigastric pain and painful toes. She was afebrile. The heart rate was regular (100/min) and blood pressure was elevated at 210/110 mmHg. A malar rash was evident. There was bilateral mild pitting pedal edema. All the toes were dusky, and the feet pulses were weak but still palpable. The abdomen was distended but not tender. Bowel sounds were sluggish. Cardiovascular, respiratory, and neurologic system examination was unremarkable. Full blood counts, creatinine, prothrombin time (PT), partial thromboplastin time (PTT), anti-thrombin-III, protein C, and protein S levels were all normal. D-dimers were elevated, but soluble monomers were absent. IgM aCL were positive at 11 MPL/mL (normal, 9), but IgG aCL and LA were negative. Chest X-ray showed a globular heart and clear lung fields. Small voltages were evident on the electrocardiogram (ECG), and 2-dimensional echocardiography confirmed a moderate-sized pericardial effusion with right atrial collapse. The pulmonary systolic pressure was elevated at 42 mmHg. Computed tomography (CT) of the abdomen revealed mild ascites, diffuse thickening of small intestinal loops, a wedge-shaped splenic infarct, and the presence of distal jejunal intramural gas, but no free gas. A severe lupus "flare" involving serositis and vasculitic gut with thrombotic complications was diagnosed. Intravenous pulse methylprednisolone was given for 3 days followed by intravenous pulse cyclophosphamide. Intravenous prostacyclin infusion was also initiated together with full anticoagulant dosage of subcutaneous low molecular weight heparin. Antibiotics (ceftriaxone, metronidazole) were also given for possible gut microperforations. By the next day, all the toes had become gangrenous. Magnetic resonance angiography of the lower limbs showed arterial cutoffs below the left knee and right midthigh. Embolectomy was done, removing bilateral clots. Aspirin (100 mg/day) was added, and low molecular weight heparin was switched to heparin infusion. On 4 February 1999 the right foot remained cold, with the toes demarcating. A repeat magnetic resonance angiography of the lower limbs showed that the right superior femoral artery was thrombosed at the midthigh. In addition, cardiac tamponade was evident by repeat 2-dimensional echocardiography. A repeat embolectomy was performed on the right leg, together with the opening of a pericardial window, which drained 700 mL. The patient no longer had ischemic leg pain the following day, and both feet were warm. However, she complained of renewed epigastric pain. Repeat CT of the abdomen revealed thrombosis of a branch of the superior mesenteric artery with jejunal wall thickening. The rest of the small intestinal wall thickening seen on the earlier CT had resolved. Over the next few days, the patient was pain-free, with PTT maintained at about 60 sec. On 10 February 1999, she became febrile, both legs felt cold and numb below the knees, the anterior and posterior compartments of both calves were exquisitely tender on palpation, and the feet were edematous and blistered with forefeet gangrene. Secondary infection and compartmental syndrome possibly from reperfusion injury necessitated bilateral below-knee amputations. Her condition continued to deteriorate over the subsequent days: she remained febrile and toxic and developed ascites with worsening abdominal distension. The pericardial fluid was noted to be cloudy with lung infiltrates seen on chest X-ray. Total white count had dropped to 3.2 ×10 9 /L with left shift, and disseminated intravascular coagulation (DIC) ensued. Despite switching antibiotics empirically to vancomycin and imipenem, as well as intensive hemodynamic support, she succumbed to overwhelming septic shock on 13 February 1999. The pericardial fluid culture subsequently grew vancomycin-sensitive Enterococcus. Comment: Catastrophic APS in a patient with a previous history of SLE may be misdiagnosed as a lupus "flare," but the vast majority of manifestations in this syndrome are due to microvascular thrombosis and not to vasculitis. Case 2 This 58-year-old woman with no significant past medical history presented on 12 June 1999 with fever, weakness, evanescent rash, and decreased appetite. She had been started on antibiotics 1 week earlier for an upper respiratory infection. Physical examination did not reveal any significant findings. She was, however, found to be in acute renal failure and was immediately started on hemodialysis. Her white blood count (WBC) was 7.2 g/L, hemoglobin was 10.5, platelet count was 127 × 10 9 /L, creatinine was 5.3, alkaline phosphatase was 257 U/L, SGPT was 178 U/L, and SGOT was 440 U/L. There was worsening of her neurologic status and a progressive decrease in the platelet counts. Magnetic resonance imaging (MRI) of the brain showed small acute cerebellar infarct on the left and generalized cerebral atrophy (Figure 1). Renal biopsy revealed thrombotic microangiopathy. She was treated with 100 mg methylprednisolone tid, intravenous gammaglobulins, and intravenous cyclophosphamide with no apparent response. She later became hypotensive, progressively unresponsive, comatose, and had to be intubated. She was then given plasmapheresis and dialysis. She was started on a 1 volume plasma exchange with either 100% fresh frozen plasma or with 50% plasma and 50% albumin solution (5%) and improved after 4–6 sessions of plasmapheresis, with regaining of consciousness as well as response to verbal stimuli (total number of phereses received = 20). She had regained strength in her upper extremities and was off the ventilator. Her clinical course was complicated by lower gastrointestinal and peritracheal bleeding, but she had received only 24 hours of intravenous heparin. She did not receive any further steroids. Laboratory findings in peripheral smear showed no schistocytes. The LA was positive and aCL screen showed an elevated IgG of 19.4 GPL (normal < 5) and an elevated IgM of 73.4 MPL (normal < 5). The ANA were weakly positive. DIC panel: D dimers 80 (normal <10).Fig. 1: Magnetic resonance imaging of the brain showing small acute cerebellar infarct on the left and generalized cerebral atrophy.Comment: An upper respiratory tract infection may precipitate catastrophic APS in a patient with no significant past medical history. Case 3 A 27-year-old man was admitted in June 1995 because of polyarthralgia, myalgia, and general weakness for 1 month. Two years earlier he had been diagnosed as having undifferentiated connective tissue disease (UCTD) with arthralgia, mitral as well as tricuspid valve insufficiency. The erythrocyte sedimentation rate (ESR) was 150 mm/h. There was anemia (hemoglobin 7.9 g/dL) but platelet counts were normal. Direct and indirect Coombs tests were negative. ANA were positive (1:320, homogeneous pattern), anti-dsDNA antibodies negative, IgG aCL positive. He was given 40 mg/day of prednisolone with benefit. He was maintained on 10 mg/day of prednisolone. After 3 months this therapy was discontinued and he remained relatively well until the time of the exacerbation. On admission, there was a systolic murmur audible in the mitral and tricuspid valve area. Investigations showed the following: ESR 18 mm/h, hemoglobin 6.4 g/dL, WBC 13.6 × 10 9 /L, platelet count 77 × 10 9 /L. Urinalysis demonstrated proteinuria (55 mg/dL) and hematuria (20–25 red blood cells/high power field) as well as red cell-granular casts. Urine culture was positive for Escherichia coli. Antibiotic therapy was given with benefit. BUN was elevated at 99 mg/dL (normal < 40 mg/dL) as was serum creatinine level at 1.76 mg/dL (normal < 1.3 mg/dL). Other biochemical tests were in the normal range. ANA titer was 1:80 (homogeneous pattern), anti-dsDNA antibodies were negative; IgG aCL and IgM aCL antibodies were negative, kaolin time was 49 sec (normal, 22–35 sec). ECG showed left ventricle hypertrophy. A diagnosis of SLE was made and the patient received 60 mg of prednisolone per day. Two weeks later he suddenly developed left chest pain, and cough with hemoptyses. Chest X-ray showed bilateral multiple pulmonary thromboembolism with coexisting pulmonary edema and pulmonary hypertension. The heart was enlarged with a mitral configuration. Serum fibrin degradation products level was 12.8 μg/mL (normal < 4 μg/mL). A diagnosis of APS complicating the course of SLE was made and the patient was given intravenous infusions of heparin, methylprednisolone (120 mg/day) and nitroglycerine. Despite intensive treatment the clinical picture worsened. The renal insufficiency parameters increased (BUN 342 mg/dL, creatinine 4.0 mg/dL, serum potassium 5.38 mEq/L [normal, 3.6–5.2 mEq/L]), oliguria developed with diuresis of only 150 mL/day (oliguric renal failure). Liver enzymes were also elevated (AST 1295 U/L, ALT 1636 U/L). Abdominal ultrasound examination showed an enlarged and hyperechogenic liver. The patient was transferred to the dialysis unit where he died after a few days because of cardiopulmonary and renal failure. Comment: A urinary infection may be another precipitating factor for the development of catastrophic APS. Case 4 A 28-year-old woman was admitted in October 1996 with dyspnea and hemoptysis. These symptoms had developed 1 week before her admission. Two days earlier she had had a fever of 39 °C. The night before she had developed seizures. A diagnosis of SLE had been made in September 1994 and she had been treated with prednisolone. In February 1995 she had developed right pleurisy. Two months later, due to increasing proteinuria, a renal biopsy was performed and mesangial proliferative glomerulonephritis was diagnosed. At that time, renal function was normal. Following the biopsy she developed a deep vein thrombosis in her left leg with thrombocytopenia (106 × 10 9 /L). ANA titer was 1:2,560 (speckled pattern) and anti-dsDNA, anti-RNP, and anti-Sm antibodies were present. The dosage of prednisolone was increased to 60 mg/day and heparin treatment was started. Subsequently oral anticoagulation was introduced. Three months later she was admitted to the internal medicine department because of abdominal pain, bilateral pedal edema, difficulties in concentration, and memory disturbances. Severe proteinuria (15 g/24 h) and thrombocytopenia (101 × 10 9 /L) were present. Inferior vena caval thrombosis was diagnosed by Doppler technique and streptokinase therapy was started. Brain CT scan revealed focal vascular lesions in the left hemisphere. Because of the presence of elevated IgG aCL (OD = 0.111; normal < 0.109) a diagnosis of APS secondary to SLE was made. She was maintained on prednisolone 50 mg/day and anticoagulants. Cyclophosphamide (1 g/mo intravenously) was added. In June 1996, she developed Salmonella enteritidis sepsis and the cyclophosphamide was withdrawn. With antibiotic therapy she recovered. Prednisolone (30 mg/day) and anticoagulation were continued and she was doing relatively well until the time of the present exacerbation and admission. She had generalized soft tissue edema in her lower and upper limbs as well as in the low back area. Hemorrhagic cough was present. There was a tachypnea (40/min) and she was pyrexial with a temperature of 38 °C. Her blood pressure was 90/60 mmHg and pulse rate was 130/min. Chest examination revealed moist fine rales and crepitations. Laboratory investigations showed an ESR of 60 mm/h with a hemoglobin of 7 g/dL, WBC of 17.8 × 10 9 /L, and platelet count of 338 × 10 9 /L. Urinalysis showed proteinuria of 3.92 g/24 h plus red cell and granular casts. Direct and indirect Coombs tests were negative, BUN and creatinine level were elevated (90 mg/dL and 2.12 mg/dL) with albumin level 1.97 g/dL. ANA titer was 1:320 (homogeneous pattern), anti-dsDNA antibodies and aCL were negative. No LA was present. Chest X-ray examination showed general cardiac enlargement and signs of pulmonary edema. In the left subclavicular region, a focal area of increased density suggesting pulmonary thrombosis was present. Echocardiographic examination disclosed general hypokinesis of the left ventricular muscle with segmental akinesis in the distal part of the septum, anterior and lateral wall, and apex. The possibility of a flat periwall thrombus was suggested. The heart valves were normal morphologically and functionally. A pericardial effusion of 10 mm was present. A diagnosis of ARDS due to pulmonary embolism during the course of SLE with APS was made and intensive treatment commenced. The patient was given methylprednisolone (165 mg/day), heparin infusion, intravenous gammaglobulin, digoxin, and diuretics. Due to severe anemia she received 600 mL of packed red cells, oxygen therapy, and fresh frozen plasma and 20% albumin. In a few days she gradually improved. Signs of cardiopulmonary insufficiency diminished, and the hemorrhagic cough and peripheral edema disappeared. Chest X-ray examination showed remarkable improvement in the pulmonary circulation with a decreased cardiac diameter. The dose of methylprednisolone was gradually tapered, heparin was replaced by oral anticoagulants, and other drugs were given orally. She suddenly developed diffuse abdominal pain in the subumbilical area. X-ray examination of the abdomen showed the presence of single fluid levels suggesting an ileus. Doppler examination showed residual thrombus with partial revascularization in the inferior vena cava and its branches below the level of the renal veins. Her symptoms diminished with symptomatic treatment. After 2 weeks she was discharged on prednisolone (55 mg/day) and oral anticoagulation. A day later, she suddenly developed pulmonary edema and died. Comment: Although involvement of small vessels is the hallmark of catastrophic APS, large vessels (that is, inferior vena cava) may occasionally be thrombosed. Case 5 A 26-year-old woman was admitted in November 1997 with epistaxis and hemorrhagic cough. For 5 days previously she had reported the presence of hematuria as well as right chest pain. A day before the admission she had melena. In 1985 a diagnosis of SLE had been made. She had been treated with prednisolone. Over the following years, she had been hospitalized many times due to exacerbations of SLE. In 1995 proteinuria of 1.1 g/24 h, hematuria and red cell/granular casts appeared, CH50 activity was undetectable, and anti-dsDNA antibodies were positive. She was treated with methylprednisolone (60 mg/day) and cyclophosphamide (1 g/mo). At the time of these exacerbations, she presented with petechiae, purpuric mucosal lesions, ecchymosis, and bruising. In January 1997 the diagnosis of APS in the course of SLE was made because of repeated venous thrombosis in her lower limbs, thrombocytopenia, the presence of LA and elevated IgG aCL antibodies (OD = 0.166; normal < 0.109). She was treated with low-dose heparin during the acute episodes and maintained on aspirin (75 mg/day). The dosage of prednisolone had varied from 30 mg to 80 mg per day. On admission, she was pale and dyspneic with purpuric mucosal lesions in her mouth. Skin ecchymosis and lower limb edema were present. Her blood pressure was 190/100 mmHg with tachycardia. Laboratory investigations showed an ESR of 42 mm/h, hemoglobin 9.2 g/dL, WBC 4.9 × 10 9 /L, and platelets of 61 × 10 9 /L. Urinalysis revealed proteinuria (5.3 g/24 h) and hematuria. BUN and creatinine levels were increased (74 mg/dL and 1.29 mg/dL, respectively). Serum potassium level was 5.75 mEq/L (normal, 3.6–5.2 mEq/L). ANA titer was 1:5,120 (homogeneous pattern) and anti-dsDNA antibodies were positive. CH50 activity was undetectable. Direct and indirect Coombs tests were negative, IgG aCL were positive (OD = 0.153). IgM aCL were negative, fibrinogen degradation products were elevated at 160 μg/mL (normal < 7.7 μg/mL). The chest X-ray examination showed multiple diffuse interstitial lesions in both lungs. A diagnosis of pulmonary thromboembolism was made, but pulmonary infection could not be ruled out. She received 80 mg of methylprednisolone daily and heparin infusion, cefuroxime, and oxygen therapy. Despite this treatment she deteriorated. Anemia increased (hemoglobin 7.7 g/dL), and leukopenia appeared, 3.5 × 10 9 /L. The bilirubin level gradually increased from 1.79 to 2.31 mg/dL, and renal insufficiency developed (BUN 210 mg/dL, creatinine 1.8 mg/dL). She received intravenous methylprednisolone in pulses, and transfusions of packed red cells. Her clinical status worsened and the patient was transferred to the intensive care unit. Cardiopulmonary insufficiency increased. Bronchoscopy was performed and the presence of Pneumocystis carinii infection was revealed. Despite antibiotic therapy the patient died due to respiratory insufficiency and pneumothorax. Comment: Laboratory features of DIC may appear in the course of catastrophic APS. Case 6 A 67-year-old woman was admitted in March 1998 because of weakness in her left upper limb and urinary incontinence. For the past 20 years, she had been treated for hypertension. In October 1997, she was hospitalized because of acute dyspnea. Exacerbation of chronic cardiac insufficiency was evident with calcified aortic valve stenosis and mitral valve insufficiency, ischemic heart disease, hypertension, chronic pyelonephritis, left hand paresis, left lower limb ulceration, cholelithiasis, and cataract. CT brain scan showed bilateral organized focal lesions in the occipital areas with generalized cortical atrophy. The laboratory investigations showed ESR of 123 mm/h and proteinuria of 1.9 g/24 h. The ANA titer was 1:20,480 (pattern not evaluated). Creatinine and BUN levels were elevated (24 mg/dL and 118 mg/dL, respectively). During her admission, her general state was relatively good. The blood pressure was 120/80 mmHg. Murmurs of aortic stenosis and mitral incompetence were present. Chest X-ray showed cardiomegaly and pulmonary hypertension. The pressure in the pulmonary trunk was 30 mmHg. Laboratory investigations showed an ESR of 66 mm/h. Urinalysis disclosed proteinuria (168 mg/dL), with red cells and granular casts. Urine culture was positive for E. coli 10. BUN and creatinine levels were elevated (133 mg/dL and 3.7 mg/dL, respectively). ANA titer was 1:80 (homogeneous pattern), anti-dsDNA antibodies were negative, CH50 activity was 22 U (normal > 25 U), IgG aCL antibodies were high positive (0.407). IgM aCL were negative. Kaolin cephalin time was elevated at 84.5 sec (normal, 22–35 sec). The presence of LA was confirmed. A diagnosis of primary APS was made and low-dose aspirin (75 mg/day) was added. Because of urinary tract infection, ceftazidime (500 mg twice daily) was started. She suddenly developed dyspnea and cough. Chest examination revealed bilateral basal crepitations at the lung bases which diminished after intravenous diuretic administration, but the next day symptoms reappeared. Chest X-ray confirmed the diagnosis of ARDS. She was given 40 mg of prednisolone and transferred to the intensive care unit. Despite intensive treatment with heparin, nitroglycerin, and oxygen therapy, she worsened. Two days later, she developed mental confusion and Biot breathing, and died of cardiorespiratory insufficiency. Comment: ARDS is a common manifestation in the course of catastrophic APS and is a frequent cause of death. Case 7 The patient was a 64-year-old man with a past medical history of hypertension, coronary artery disease (myocardial infarction and coronary bypass surgery), rheumatoid arthritis, APS with resulting thrombophlebitis, renal insufficiency, anemia, nausea, vomiting, anorexia, and fatigue. He was due to start peritoneal dialysis 1 week before his presentation, but catheter placement was deferred due to elevated PT. On admission, the jugular venous pressure was elevated, he had pitting edema of the lower extremities, and rheumatoid deformities of the hands. Laboratory tests showed a BUN of 90 mg/L, creatinine of 6.6 mg/dL, platelet count of 53 × 10 9 /L, hemoglobin of 9.9 g/L, and hematocrit of 31.1. Chest X-ray demonstrated cardiomegaly and a left pleural effusion. The patient was admitted for treatment of renal failure complicated by congestive heart failure. Hemodialysis was started on hospital day 1. Treatment with steroids and anticoagulation was continued. He had developed ulceration of both lower legs and calf pain. A venous Doppler ultrasound was negative for venous thrombosis. The patient was also noted to have intermittent weakness and loss of coordination of both hands, upper abdominal pain, occasional chest pain, an elevated amylase of 97 U/L, and elevated lipase of 975 U/L. The patient's platelets dropped to 10 × 10 9 /L and Coumadin was withheld. He was then found to have elevated anti-DNA antibodies in addition to aCL, and a skin biopsy showed basement membrane IgM deposition in blood vessels. Intravenous immunoglobulin treatment and plasmapheresis were started for treatment of thrombocytopenia. On day 6, he began to exhibit Cheyne-Stokes respirations. His left ventricular ejection fraction at that time was 18%. Coumadin could not be resumed due to extreme thrombocytopenia. A repeat Doppler of the leg veins now showed nonocclusive thromboses bilaterally. Steroids, intravenous gammaglobulin, and plasmapheresis were continued. On day 14, the patient developed painful tongue ulceration and was treated with acyclovir for herpes simplex. On day 40, the patient's platelets had recovered to 46 × 10 9 /L and Coumadin was resumed. He continued to have dyspnea and occasional Cheyne-Stokes respirations. On day 43, he was intubated for severe shortness of breath and transferred to the intensive care unit. An ECG at that time showed atrial fibrillation and a new right bundle branch block. Fever was present. Lactic acid was elevated at 5.7, and the fever was again treated with antibiotics. His condition improved with resolution of the ECG changes. He was extubated. Theophylline was started to help improve respiration. On day 51, he again developed fever and had an elevated WBC of 21.9 × 10 9 /L. He was again treated for sepsis and with antibiotics. Pulmonary infiltrations were noted on a chest X-ray. His platelets fell to 27 × 10 9 /L on day 52. Intravenous gammaglobulin and plasmapheresis treatments were resumed. He was found to have Guaiac-positive stool at the time. On day 53, he became increasingly disorientated, had a generalized tonic-clonic seizure, and was unresponsive. A CT scan of the head was negative for a bleed. He had a severe drop in blood pressure to 60/40 mmHg. An ECG showed no new changes. His mental status slowly improved. The platelet count recovered and Coumadin was restarted on day 55. He continued to show Cheyne-Stokes breathing. The theophylline treatments were continued after dose adjustment. On day 67, he developed transient left hemiparesis which recurred several days later. The left facial and upper extremity weakness appeared to be transient. He received dialysis for the following 2 weeks. No recurrence of the seizures were observed. He continued to exhibit Cheyne-Stokes breathing, but less than previously. On day 72, the patient had an acute change in mental status and became lethargic. At that time he had a temperature spike to 102.6 °F and watery diarrhea. He was treated with antibiotics, but continued to spike fevers up to 103.6 °F and developed hypotension with a blood pressure of 90/60 mmHg. An abdominal X-ray was consistent with a small bowel obstruction. It was decided to continue supportive care including dialysis, but no new invasive therapy would be done. The patient died 80 days after admission. At autopsy, multiple small and medium-sized vessel thrombi in different stages of organization were found within multiple organs without vasculitis. Com