A case of primary antiphospholipid antibody syndrome presenting with dysfunctional uterine bleeding and cerebral infarction

Abstract

We report a 34-year-old woman who developed primary antiphospholipid antibody syndrome (APS) presenting with dysfunctional uterine bleeding and cerebral infarction. Antiphospholipid antibody syndrome presenting with bleeding manifestations is rare. We should recognize that APS may be associated with not only thrombosis but also bleeding.     

Primary myelofibrosis with fatal mesenteric arterial thromboembolism caused by antiphospholipid syndrome]

A 60-year-old woman was admitted to our hospital in February 1993 due to dizziness, dyspnea, abdominal pain, and high susceptibility to bleeding. Physical examination revealed livedo reticularis of the foot, but did not detect hepatosplenomegaly. Examination of the peripheral blood detected pancytopenia, leukoerythroblastosis, and tear-drop erythrocytes. Primary myelofibrosis (PMF) was diagnosed on the basis of bone marrow biopsy findings. Antiphospholipid syndrome (APS) was confirmed by positive response to anti-cardiolipin antibody and recurrent splenic infarction. Because of factor XIII deficiency, the patient experienced severe gingival bleeding after tooth extraction. Her condition was complicated by mesenteric arterial thromboembolism and she died of sepsis 5 years after onset. Although the incidence of immunopathy in PMF patients is high, few studies to date have focused on APS patients presenting with a variety of severe embolic symptoms. Our patient required careful monitoring due to bleeding tendency and thromboemboli.     

Rituximab treatment for resistant antiphospholipid syndrome

Antiphospholipid syndrome (APS) and catastrophic antiphospholipid syndrome (CAPS) can be challenging to treat. As they are rare, clinicians are not often exposed to these complex diseases. For the patient resistant to standard treatments new therapeutic directions can be perplexing, especially in the context of ongoing thromboses and bleeding episodes. We describe 3 patients, 2 with APS and one with CAPS, resistant to conventional medications, who responded to treatment with rituximab, an anti-CD20 monoclonal antibody. Since rituximab infusion, all the patients have had stable platelet counts and no further episodes of bleeding or thromboses.     

Potential risk of perioperative thromboembolism in patients with antiphospholipid syndrome who undergo transcatheter aortic valve implantation: A case series

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by a positive serum antiphospholipid antibody status. Patients with APS usually have an underlying hypercoagulable state, which can increase the risk of perioperative thromboembolism. We describe three patients with APS who underwent transcatheter aortic valve implantation for symptomatic severe aortic stenosis. Of them, two had complicated cerebrovascular events, and the other had no complications. Careful antithrombotic management is essential to minimize the risk of thromboembolism and bleeding in patients with APS.     

Communicating hydrocephalus in systemic lupus erythematosus with antiphospholipid antibody syndrome.

We report a case of communicating hydrocephalus in a 24-year-old woman with previously undiagnosed systemic lupus erythematosus (SLE) presenting with malignant hypertension, nephritis, serositis, and a seizure disorder of 16 months' duration. The patient demonstrated features of the antiphospholipid antibody syndrome (APS). In proposing cerebral venous thrombosis as a possible, yet unproven, pathophysiologic mechanism for the hydrocephalus in this case we have reviewed and summarized literature relating to SLE, APS, hydrocephalus and pseudotumor cerebri. In cases of unexplained pseudotumor cerebri or hydrocephalus, a search for SLE and APS should be considered.     

Longterm anticoagulation is preferable for patients with antiphospholipid antibody syndrome. result of a decision analysis

OBJECTIVE: Patients with antiphospholipid antibody syndrome (APS) have a high risk for rethrombosis. Anticoagulation with warfarin and aspirin reduces the frequency of recurrences. No universally accepted approach regarding the duration and intensity of antithrombotic therapy exists. We investigated the best antithrombotic regimen for patients with APS after the first deep venous thrombosis (DVT). METHODS: We identified 6 anticoagulation regimens used in such patients, the rates of morbidity and mortality associated with bleeding, and the rates of recurrent thrombosis associated with APS by literature search. A decision tree was developed and the expected risks and benefits of each anticoagulation regimen were assessed at 2 different time points: at one year and again 4 years after the initial thrombosis. RESULTS: Based on the decision analysis, longterm warfarin alone at an international normalization ratio (INR) between 3.0 and 4.0 had the highest expected utility of the 6 antithrombotic regimens, both one year and 4 years after the initial venous thrombotic event. Short term anticoagulation for only 6 months is less beneficial. Combination therapy of warfarin and aspirin (ASA) does not offer an improvement in the expected utility over warfarin alone. CONCLUSION: Although the applicability of this analysis to clinical decision-making is not entirely clear, patients with APS presenting with DVT appear to benefit from longterm warfarin (INR 3.0-4.0) that may be superior to warfarin (INR 2.0-3.0). Short term warfarin therapy seems to be less beneficial and the use of ASA does not offer a clear additional benefit. Randomized controlled trials are needed to provide a better basis for recommendations for the treatment APS.     

Pauci-immune glomerulonephritis associated with primary antiphospholipid syndrome

The antiphospholipid syndrome (APS) is characterized by thrombotic events associated with the presence of antiphospholipid antibodies. Renal involvement is a frequent feature in patients with APS. APS presenting with proteinuria showed that the renal involvement in this syndrome could also be a different form of glomerulonephritis. We describe a rare case report of pauci-immune vasculitis associated with primary APS in the absence of other underlying autoimmune disorders.     

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.     

Susac's syndrome or catastrophic antiphospholipid syndrome?

Susac's syndrome is a microangiopathic disorder of unknown pathogenesis presenting with encephalopathy, hearing loss and branch retinal artery occlusions. The term 'catastrophic' antiphospholipid syndrome (APS) is used to define a subset of the APS characterized by thrombotic microangiopathy with clinical evidence of three or more organ involvement developed in a short period of time. We describe a patient with typical features of Susac's syndrome, that appeared in less than a week, in whom aPL were detected, thus fulfilling criteria for 'probable' catastrophic APS.     

Cardiovascular abnormalities of the antiphospholipid antibody syndrome

The antiphospholipid antibody syndrome (APS) may present with serious cardiovascular complications which should be recognised by the cardiologist. The authors report a series of 6 cases of APS diagnosed after thrombotic events and the finding of antiphospholipid antibodies. The APS was primary in 5 cases and associated with tuberculous lymphadenitis in 1 case. There was cardiac involvement in 5 patients with pericardial effusion in 3 cases, complicated by tamponade as the presenting sign of primary APS in the other 2, valvular disease in one case (moderate mitral stenosis with aortic valve disease) and pulmonary embolism in one case. Five patients developed recurrent deep vein thrombosis of the legs. One patient had a transient ischaemic cerebral attack.     

Abdominal crisis in a young man with systemic lupus erythematosus

Medium-sized artery aneurysms are rare in patients with systemic lupus erythematosus (SLE). We report on a 21-year-old Chinese man with SLE and secondary antiphospholipid syndrome (APS) who presented with acute abdominal pain due to a ruptured right hepatic artery aneurysm. He was also found to have aneurysms of the left hepatic artery and splenic artery on autopsy. There have been only eight cases of hepatic artery aneurysm and one case of splenic artery aneurysm associated with SLE in the English literature. Abdominal aneurysm must be suspected in SLE patients presenting with acute abdominal pain, haemoperitoneum or occult bleeding.     

Long-term efficacy of immunoadsorbent plasmapheresis in a patient with Budd-Chiari syndrome due to antiphospholipid syndrome: case report with nine-year follow-up

We describe the safety and efficacy of long-term immunoadsorbent plasmapheresis (IAPP) with dextran sulfate-cellulose bead columns in antiphospholipid syndrome (APS). IAPP was administered to a 38-year old male Japanese patient with APS with Budd-Chiari syndrome (BCS), who had presented with refractory lower leg skin ulcers and arterial and venous thromboses including BCS. After hepatic vein transluminal angioplasty was performed, the combination of corticosteroid, aspirin and IAPP was administered because of an underlying bleeding tendency related to liver dysfunction. From February 1994 to February 2003, a total of 228 procedures were performed. No further thrombosis-related symptoms or bleeding have occurred for more than nine years, suggesting that IAPP with dextran sulfate cellulose columns is safe and effective for APS in preventing additional thrombotic events. This IAPP supplements anticoagulation, antiplatelet, corticosteroid and immunosuppressant therapies.     

Antiphospholipid syndrome presenting as unilateral renal artery occlusion: case report and literature review

The objective of this study is to report a case of primary antiphospholipid syndrome (APS) presenting as complete renal artery occlusion, and to review the literature on the subject. We describe the clinical presentation, course and outcome of one patient who presented with resistant hypertension later found to be due to thrombosis and complete occlusion of the left renal artery. We review the medical literature registered in the Medline PubMed database from 1966 to 2004 using keywords: antiphospholipid, Hughes syndrome, kidney, renal, renal artery thrombosis. We describe one patient and analyzed ten well-documented cases of renal artery thrombosis due to APS. Most of the patients were women, at a mean age of 32 years. All but one case had primary APS. The presenting symptom was hypertension in ten cases. Most patients had both lupus anticoagulant and anticardiolipin antibodies. Arterial occlusion was left sided in 55%, right sided in 27% and bilateral in 18%. Renal artery thrombosis is an uncommon presentation of APS. This entity should be considered in the differential diagnosis of severe hypertension.     

APS and the brain

Antiphospholipid antibody syndrome (APS) may present with neurological syndromes. Cerebrovascular disease, chorea/ballismus, epileptic seizures, headache, cognitive impairment, transverse myelopathy, Devic's syndrome and multiple sclerosis-like presentations feature among others. Cerebrovascular disease is one of the most common presenting symptoms of APS, second only to deep vein thrombosis, and accounts for half of neurological manifestations in patients with APS; accelerated atherogenesis and cardioembolism are the most likely mechanisms implicated. Though infrequent, chorea is consistently associated with APS; the pathogenetic role of antiphospholipid antibodies (APLab) in this case might be routed through cerebrovascular disease in some cases and through purely immunological pathways in others. Both ischemic and immunological mechanisms have been demonstrated in the pathogenesis of epileptic seizures, which may account for 7% of neurological manifestations in APS. Although frequent in APS, a causative link between APLab and most common types of headache (migraine and tension-type headache) is more than dubious. Cognitive impairment may derive from a well-defined clinical tableau of multi-infarct dementia. Nevertheless, (highly frequent) less severe cognitive impairment has also been associated with the presence of APLab in the absence of magnetic resonance findings. A relationship between APS and transverse myelopathy seems likely but small numbers in the studies published to date preclude definite statements; routinely testing for APLab patients with neurological manifestations suggestive of multiple sclerosis seems to be unrecommended at the present time.     

Autoantibodies to heparin from patients with antiphospholipid antibody syndrome inhibit formation of antithrombin III-thrombin complexes [see comments]

The antiphospholipid antibody syndrome (APS) is characteristically associated with thrombosis. Heparan sulfate (HS) is a physiologic endothelial cell surface modulator of normal anticoagulation, containing a specific oligosaccharide sequence that binds antithrombin III with high affinity and also is present in heparin, a related glycosaminoglycan. We hypothesized that a subset of antiphospholipid antibodies with high affinity for heparan sulfate/heparin epitopes may inhibit the function of HS, promoting a procoagulant state. Purified IgG from all seven patients with APS studied were reactive with heparin by enzyme-linked immunosorbent assay, whereas none of five controls had antiheparin reactivity. IgG antiheparin antibodies were purified from two APS patients by affinity chromatography on heparin-Sepharose. Specificity studies showed that low-affinity electrostatic interactions clearly did not account for the observed reactivity with heparin, and that APS IgG antiheparin antibodies were specifically reactive with a disaccharide present in the heparin pentasaccharide that binds antithrombin III. Furthermore, APS IgG antiheparin antibodies inhibited heparin-accelerated formation of antithrombin III-thrombin complexes. We conclude that antiheparan sulfate/heparin antibodies may be a cause of autoimmune vascular thrombosis in the antiphospholipid antibody syndrome.     

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.     

Validation of the Sapporo criteria for antiphospholipid syndrome

OBJECTIVE: To test the Sapporo criteria for the classification of the antiphospholipid syndrome (APS). METHODS: We classified 243 consecutive patients who had clinical diagnoses of primary APS (n = 49), secondary APS (n = 26), systemic lupus erythematosus (SLE) without clinical APS (n = 131), and lupus-like disease without clinical APS (n = 37). RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value were 0.71, 0.98, 0.95, and 0.88, respectively. False-negative findings were the result of patients being classified on the basis of minor criteria that were not included in the Sapporo criteria, such as livedo reticularis, thrombocytopenia, low-titer IgG or IgM anticardiolipin antibody, IgA anticardiolipin antibody, and anti-beta2-glycoprotein I antibody. Some patients with false-negative results were true seronegative cases. CONCLUSION: The Sapporo criteria for APS compare favorably with the American College of Rheumatology criteria for SLE and are usable for clinical studies.     

Reversible adult respiratory distress in primary antiphospholipid syndrome

Antiphospholipid antibody syndrome (APS) is a disorder caused by circulating antibodies reacting with biological membranes and characterized by recurrent thrombosis, chronic thrombocytopenia and miscarriages. It has been reported to occur either as a primary syndrome or secondary to systemic autoimmune disorders. We describe a case of primary APS in a young patient, in whom the clinical course was particularly severe and complicated by a respiratory distress syndrome. The patient was resistant to a number of treatments, and eventually responded to intravenous high dose corticosteroids.     

Primary antiphospholipid syndrome with multiorgan arterial and venous thromboses.

A 57-year-old man with no evidence of infection, vasculitis or connective tissue disease died with multiple organ thromboses after an acute illness. He was found to have lupus anticoagulant, IgG anticardiolipin antibody, false positive rapid plasma reagin, prolonged partial thromboplastin time, and thrombocytopenia. Venous and arterial thrombi leading to necrosis were found in his scrotum, testicles, upper and lower extremities, adrenals, kidneys, lungs, and brain. No other explanation could be found for his fatal illness, thus suggesting the primary antiphospholipid syndrome (APS). This is a documented case of primary APS associated with multiorgan arterial and venous thromboses of large and small vessels, presenting as a fulminant and fatal acute illness.     

Paediatric case report: primary antiphospholipid syndrome presented with non‐thrombotic neurological picture psychosis; treat by antidepressants alone?

The classical clinical picture of antiphospholipid antibody syndrome (APS) is characterized by venous and arterial thrombosis, fetal losses and thrombocytopenia in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disorder or secondary to a connective tissue disease, most frequently systemic lupus erythematosus. Central nervous system involvement is one of the most prominent clinical manifestations of APS, and includes thrombotic events, psychiatric features and a variety of other non‐thrombotic neurological syndromes. We present a 9‐year‐old Saudi girl who developed psychotic illness without thrombotic manifestations. Autoantibodies against cardiolipin were persistent and strongly positive while antinuclear antibodies and antibodies against double‐stranded DNA was absent. Her brain computed tomography, magnetic resonance imaging, magnetic resonance arteriography and magnetic resonance venography all were normal. There was no evidence of infection, drug intake or connective tissue disorders, So a diagnosis of primary APS was likely. Starting on antipsychotics only was unsatisfactory and marked improvement occurred after combined treatment with antidepressants (imipramin 10 mg and risperidal 0.2 mg, both once daily), small‐dose aspirin (100 mg) and hydroycloroquine (100 mg) both once dialy. Unfortunately aspirin was stopped by the family and 5 months later she developed right axillary vein thrombosis. This case presented psychotic illness. Investigations revealed the presence of anticardiolipin antibodies without a thromboembolic picture, mimicking Hughes syndrome but not fulfilling the criteria needed for the diagnosis. Thus, psychosis should be appreciated as a presenting symptom for primary APS and combined treatment with antipsychotics, aspirin and antimalarials is recommended.