warfarin and Lupus-Erythematosus--Systemic

This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome (APS).. We performed a literature search using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. We also performed a meta-analysis of randomized controlled trials (RCTs) investigating the effectiveness and safety of DOACs versus warfarin in patients with APS.. Five RCTs involving 648 patients with APS (330 in DOAC-treated and 318 in control groups) were included in the meta-analysis. Among the patients included in the analysis, 29 (8.8%) patients experienced recurrent thrombosis in the DOAC treatment group, and 10 patients (3.1%) had thrombosis recurrence in the warfarin treatment group, resulting in a higher incidence in DOAC-treated than in the warfarin-treated groups [odds ratio (OR) = 2.163, 95% CI = 0.985-4.748,. DOACs were associated with higher rates of arterial thrombosis than warfarin in patients with APS, especially in the triple-positive group. However, a higher risk of recurrent venous thrombosis was not found in APS patients treated with DOACs compared to those treated with warfarin.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Humans; Lupus Erythematosus, Systemic; Randomized Controlled Trials as Topic; Thrombosis; Warfarin

Peripheral vascular disease is the rarest vascular complication in systemic lupus erythematosus. Some theories propose that immune complexes may promote inflammation in the vessel, and disrupt it in a manner that may cause ischemia.. A 14-year-old Asian girl presented with intermittent claudication as the chief complaint followed by discoloration of her left big toe for 2 weeks prior to admission. Her medical history showed that 1 month prior to admission she had photosensitivity, rash, and arthralgia, with positive antinuclear antibody test, positive anti-double-stranded DNA test, positive anti-ribosomal protein P, and complement C4 (7.4 mg/dL); she was diagnosed as having systemic lupus erythematosus and started therapy. A local examination of her left toe showed black discoloration, low pulsation, localized tenderness, and decreased sensation. Laboratory results showed C-reactive protein of 1.16 mg/dL and D-dimer of 2.28 uG/mL. A computed tomography angiogram showed near total occlusion of her popliteal artery; critical limb ischemia was confirmed. Peripheral arteriography was performed with invasive strategy. After the procedure, the flow was improved to distal, but there was inflammation in the vessel, so we decided to stop the procedure because of the risk of dissection. Our patient was given atorvastatin and warfarin, and we maximized her systemic lupus erythematosus therapy with prednisone. There were two follow-ups. The first follow-up was 1 week after the procedure. Our patient attended her first follow-up at our out-patient department with no symptoms and improvement in her toe's discoloration; warfarin was stopped, and clopidogrel and cilostazol were added for thrombus prevention therapy, she was then scheduled for debridement. The second follow-up was done 2 months after the first follow-up and discoloration was improved. The third follow-up, 5 months after the second follow-up, showed improvement.. Critical limb ischemia is a rare complication of systemic lupus erythematosus that requires immediate treatment. Due to our limited resources, we improvised a strategy to achieve the best possible outcome in our patient by using a combination of invasive treatment and medication.

Topics: Adolescent; Anticoagulants; Endovascular Procedures; Female; Hallux Valgus; Humans; Immunosuppressive Agents; Intermittent Claudication; Ischemia; Lower Extremity; Lupus Erythematosus, Systemic; Treatment Outcome; Warfarin

Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.

Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Female; Humans; Infarction; Kidney; Kidney Diseases; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Pregnancy; Renal Veins; Thrombosis; Warfarin

Osteonecrosis is a relatively common comorbidity in systemic lupus erythematosus (SLE), but avascular necrosis in multiple sites is unusual. Multifocal osteonecrosis is defined as osteonecrotic lesions affecting three or more separate anatomic sites. We report a case of a 24-year-old woman diagnosed with SLE when she presented with mucocutaneous, haematological and mild renal manifestations. Initially, she was treated with prednisone and hydroxychloroquine and her condition remained stable. Two years later, she developed severe bilateral pretibial ulcers intractable to immunosuppressive therapy and broad-spectrum antibiotics. MRI of both legs disclosed osteonecrosis of the distal tibia, proximal tibia, distal fibula and talus bilaterally. She had elevated anticardiolipin antibodies for which she was treated with chronic anticoagulation resulting in complete healing of the leg ulcers and no further episodes of osteonecrosis. In addition to this case, we review the demographic, clinical and pharmacological features of 14 cases reported in the literature.

Topics: Adult; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Female; Fibula; Humans; Leg Ulcer; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Osteonecrosis; Talus; Tibia; Warfarin; Young Adult

The antiphospholipid antibody syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Anti-thrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients. which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associated thrombocytopenia is multifactorial and its relation to thrombotic risk poorly characterized. However, the presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents. Clinical trials have demonstrated that patients with antiphospholipid antibodies and venous thromboembolism should be treated with vitamin K antagonists (warfarin); that ischemic stroke may be treated with aspirin or warfarin; and that women with recurrent pregnancy loss should receive prophylactic-dose heparin and aspirin. However, application of these trial results to patients with APS-associated thrombocytopenia can be challenging since there are limited data on the optimal use of antithrombotic agents in this setting. Issues such as determining the platelet threshold at which antithrombotic agents can be safely used and managing patients with both bleeding and thromboembolic complications remain unresolved. Ultimately the risks and benefits of antithrombotic therapy, balanced against the severity of the thrombocytopenia and its potential bleeding risks, need to be assessed using an individualized patient approach.

Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Aspirin; Blood Transfusion; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Lupus Erythematosus, Systemic; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Thrombocytopenia; Thrombophilia; Venous Thromboembolism; Warfarin

We present a case of systemic lupus erythematosus with symptomatic sensorineural hearing loss which was successfully treated with azathioprine, as assessed both clinically and radiologically. We also present a review of the relevant literature.. A woman with systemic lupus erythematosus presented with sensorineural hearing loss, initially on the right and subsequently developing on the left over several months. An audiogram revealed profound neurosensory hearing loss bilaterally. The patient was treated with prednisone 60 mg daily and azathioprine 200 mg daily. An improvement on the left was noted on follow-up audiography as well as on magnetic resonance imaging of the internal auditory canals and surrounding structures.. Sensorineural hearing loss has been described in autoimmune disorders but is rare. Aural symptoms have been described, with varying incidences (0-57.5 per cent), in systemic lupus erythematosus. However, symptomatic sensorineural hearing loss is rare in systemic lupus erythematosus. Prednisone appears essential when an immunological or vasculitic cause is found. The use of azathioprine should be considered, as well as follow-up with magnetic resonance imaging to detect improvement.

Topics: Adult; Anticoagulants; Antimetabolites; Audiometry, Pure-Tone; Azathioprine; Drug Therapy, Combination; Female; Hearing Loss, Sensorineural; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Nystagmus, Pathologic; Prednisone; Treatment Outcome; Warfarin

Topics: Adult; Age Factors; Antibodies, Antiphospholipid; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Family Practice; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Thromboembolism; Treatment Outcome; Warfarin

Warfarin and azathioprine may be prescribed concurrently in patients requiring both anticoagulation and immunosuppression. However, a potential interaction between the 2 drugs, resulting in an increased warfarin requirement, may be overlooked in clinical practice.. A 67-year-old woman was treated with warfarin (initial mean dose, 24 mg/wk [3.5 mg/d]) for >3 years for recurrent deep vein thrombosis associated with systemic lupus erythematosus. Soon after commencing warfarin, azathioprine 150 mg/d was introduced for its steroid-sparing effect. Warfarin was titrated to a mean dose of 60 to 75 mg/wk (8.5-10.5 mg/d) over the next 18 months. Her dose of azathioprine was then increased to 200 mg/d. Subtherapeutic international normalized ratio (INR) levels required an increase in the warfarin dose to a mean of 130 mg/wk (18.5 mg/d). Subsequent discontinuation of azathioprine resulted in a dramatic increase in her INR levels (from 1.8 to 14.0 four weeks after discontinuation).. A temporal relationship, demonstrating the interaction between warfarin and azathioprine, was evident at various times during therapy for our patient. This case, together with 7 additional published cases, is comprehensively reviewed here using previously described criteria for establishing a definite interaction between warfarin and other drugs.. The evidence supports a clinically important inhibitory action of azathioprine on warfarin and calls for closer monitoring of INR levels when azathioprine doses are altered during concurrent administration with warfarin.

Topics: Aged; Anticoagulants; Azathioprine; Drug Antagonism; Female; Humans; Immunosuppressive Agents; International Normalized Ratio; Lupus Erythematosus, Systemic; Venous Thrombosis; Warfarin

The patient is a 34-year-old female with systemic lupus erythematosus and secondary antiphospholipid antibody syndrome, who evolved with convulsive crises, partially controlled with an anticonvulsant, and auscultation of a cardiac murmur, whose investigation showed the presence of a mitral valve vegetation. Once the diagnosis of Libman-Sacks endocarditis was established, therapy with warfarin sodium was initiated, and, after 6 months of oral anticoagulation, the patient had total control of the convulsive crises and the valvular vegetation disappeared on echocardiography. This study discusses the occurrence of Libman-Sacks endocarditis in systemic lupus erythematosus, its association with antiphospholipid antibody syndrome, and the anticoagulant therapy. A literature review is also provided.

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Echocardiography, Transesophageal; Endocarditis; Female; Humans; Lupus Erythematosus, Systemic; Mitral Valve; Warfarin

Since 1987 the antiphospholipid syndrome has been recognized as a major cause of acquired thrombophilia, whether it is associated with systemic lupus erythematosus or occurs as a free-standing syndrome (primary form). This autoimmune condition associates in young patients recurrent thrombosis (both venous and/or arterial) and/or a variety of obstetric complications with the persistent presence of antiphospholipid antibodies (aPL). These traditionally comprise anticardiolipin antibodies and lupus anticoagulants, respectively detected by immunological and clotting tests. Despite their name aPL do not bind to phospholipids per se, but are directed at phospholipid-binding plasma proteins, especially beta 2-glycoprotein I and prothrombin. Because the risk of recurrence is high, the standard of care is prolonged and high-intensity warfarin (INR near 3) after a venous thromboembolic event, together with the management of associated vascular risk factors. Prevention of adverse obstetric outcomes is frequently achieved by a combination of low-dose aspirin and heparin.

Topics: Adult; Aged; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Female; Fibrinolytic Agents; Heparin; Humans; Lupus Erythematosus, Systemic; Middle Aged; Platelet Aggregation Inhibitors; Pregnancy; Recurrence; Risk Factors; Thrombophlebitis; Warfarin

Antiphospholipid antibody positive patients are at risk for venous and arterial thrombosis. The risk of recurrent thromboembolism is high. Although the standard of care is high-intensity warfarin after a thromboembolic event, some studies indicate that this degree of anticoagulation is not needed. There is an urgent need of clinical trials to address management of thrombosis in antiphospholipid syndrome.

Topics: Anticoagulants; Antiphospholipid Syndrome; Aspirin; Hemorrhage; Heparin; Humans; Lupus Erythematosus, Systemic; Risk Factors; Thrombosis; Warfarin

Topics: Antithrombin III Deficiency; Blood Coagulation Factors; Female; Fetal Diseases; Heparin; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombocytopenia; Thromboembolism; Warfarin

Topics: Aging; Animals; Child; Chloral Hydrate; Dogs; Drug Antagonism; Drug Resistance, Microbial; Endoplasmic Reticulum; Enzyme Induction; Female; Genetics, Microbial; Griseofulvin; Humans; Hypnotics and Sedatives; Infant, Newborn; Insecticides; Lupus Erythematosus, Systemic; Male; Mice; Microscopy, Electron; Microsomes; Molecular Biology; Penicillinase; Phenobarbital; Porphyrias; Rabbits; Rats; Steroids; Warfarin

Rivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.. This randomised, controlled, open-label, phase 2/3, non-inferiority trial, done in two UK hospitals, included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism, with a target international normalised ratio of 2·5. Patients were randomly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily. Randomisation was done centrally, stratified by centre and patient type (with vs without systemic lupus erythematosus). The primary outcome was percentage change in endogenous thrombin potential (ETP) from randomisation to day 42, with non-inferiority set at less than 20% difference from warfarin in mean percentage change. Analysis was by modified intention to treat. Other thrombin generation parameters, thrombosis, and bleeding were also assessed. Treatment effect was measured as the ratio of rivaroxaban to warfarin for thrombin generation. This trial is registered with the ISRCTN registry, number ISRCTN68222801.. Of 116 patients randomised between June 5, 2013, and Nov 11, 2014, 54 who received rivaroxaban and 56 who received warfarin were assessed. At day 42, ETP was higher in the rivaroxaban than in the warfarin group (geometric mean 1086 nmol/L per min, 95% CI 957-1233 vs 548, 484-621, treatment effect 2·0, 95% CI 1·7-2·4, p<0·0001). Peak thrombin generation was lower in the rivaroxaban group (56 nmol/L, 95% CI 47-66 vs 86 nmol/L, 72-102, treatment effect 0·6, 95% CI 0·5-0·8, p=0·0006). No thrombosis or major bleeding were seen. Serious adverse events occurred in four patients in each group.. ETP for rivaroxaban did not reach the non-inferiority threshold, but as there was no increase in thrombotic risk compared with standard-intensity warfarin, this drug could be an effective and safe alternative in patients with antiphospholipid syndrome and previous venous thromboembolism.. Arthritis Research UK, Comprehensive Clinical Trials Unit at UCL, LUPUS UK, Bayer, National Institute for Health Research Biomedical Research Centre.

Topics: Anticoagulants; Antiphospholipid Syndrome; Equivalence Trials as Topic; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prevalence; Rivaroxaban; Survival Rate; Thrombosis; Treatment Outcome; United Kingdom; Warfarin

The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS.. The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin.. Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed.. If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5.

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Prospective Studies; Quality of Life; Recurrence; Rivaroxaban; Thrombin; Venous Thromboembolism; Warfarin

The objectives of this study are to examine the efficacy and safety of low-dose aspirin (LDA) vs LDA plus low-intensity warfarin (LDA + W) in the primary thrombosis prevention of aPL-positive patients with SLE and/or obstetric morbidity and the role of clinical and serological markers in the development of thrombosis.. In this 5-year prospective, randomized, open, controlled trial, 166 patients with aPL were randomly assigned using a minimization protocol to receive treatment with LDA (n = 82) or LDA + W [international normalized ratio (INR) = 1.5] (n = 84). Sixty-six patients who declined randomization were followed up in an observational arm. Clinical and laboratory characteristics and medication side effects were recorded.. There were no differences in the number of thromboses between patients treated with LDA (4/82) or LDA + W (4/84) [hazard ratio (HR) 1.07, 95% CI 0.27, 4.3]. The incidence of thrombosis in the randomized patients was 8/166 (1.8 events/100 person-years) (HR 1.07, 95% CI 0.27, 4.3) and in the observational arm was 7/66 (4.9 events/100 person-years) (HR 2.43, 95% CI 0.87, 6.79). Sixty-five of 66 patients included in the observational arm received LDA. None of the examined clinical or serological factors appeared to predict thrombosis. Medication side effects included mild gastrointestinal symptoms in the LDA group (n = 2) and bleeding in the LDA + W group (n = 11; 1 nasal and 10 menorrhagia). The risk difference for bleeding was 13% (CI 6, 20).. No differences in the number of thromboses were observed between patients treated with LDA vs those treated with LDA + W. More episodes of bleeding were detected in the LDA + W group. The LDA + W regime was significantly less safe and not as acceptable as LDA alone.. ISRCTN81818945; http://isrctn.org/.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Autoimmune Diseases; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Lupus Erythematosus, Systemic; Male; Middle Aged; Outcome Assessment, Health Care; Pregnancy; Pregnancy Complications; Prospective Studies; Thrombosis; Treatment Outcome; Warfarin

Although osteonecrosis of femoral head (ONF) is one of the serious complications in systemic lupus erythematosus (SLE) associated with corticosteroid therapy, there has been few trials of prevention of ONF described. We aimed to prevent ONF in steroid-treated SLE patients using anticoagulant, warfarin, conducting a multicenter prospective study. Sixty newly diagnosed SLE patients requiring 40 mg/day or more prednisolone were alternately assigned to either of two groups; a warfarin group and a control one. Warfarin (1 to approximately 5 mg/day) was started together with the beginning of steroid therapy and continued at least for three months. Patients were observed for the development of silent ONF by magnetic resonance imaging (MRI) and symptomatic ONF by plain radiography for over five years. The warfarin group consisted of 31 patients (62 hips) and the control one 29 patients (58 hips). Silent ONF developed in 13 hips (21%) and 19 hips (33%) in the warfarin group and the control group, respectively (P = 0.13). On the other hand, warfarin tended to prevent symptomatic ONF; only three hips of 62 (4.8 %) in the warfarin group and eight hips of 58 (14%) in the control group (P = 0.08) developed silent ONF. It was also found that silent ONF developed, if it did, very early; within three months in 16 of 18 patients (89%). Among risk factors for silent ONF, steroid pulse therapy was most outstanding and it seemed to overcome the effect of warfarin. Taken together, for the time being, anti-coagulant therapy, if not significantly sufficient, may be of use for the prevention of steroid-induced ONF in SLE. We consider that this study added to important evidence for the pathogenesis and prevention of ONF.

Topics: Adolescent; Adult; Anticoagulants; Female; Femur Head Necrosis; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Magnetic Resonance Imaging; Male; Middle Aged; Prednisolone; Prospective Studies; Pulse Therapy, Drug; Risk Factors; Time Factors; Warfarin

Fifty-seven pregnancies in women with antiphospholipid syndrome (APS) are presented. These were treated with s.c. enoxaparin and low dose aspirin. In fourteen pregnancies warfarin was prescribed between weeks 15-34 (warfarin group). The decision to switch to warfarin depended on a morbidity score, and the patient's consent. Neither teratogenicity nor significant maternal, fetal or neonatal hemorrhage was observed. Despite the higher pretreatment morbidity score of the warfarin group, the live birth rate was high in both groups: 86% in the warfarin group and 87% in the non-warfarin group. There was no significant difference in week of delivery, birth weight, or incidence of thrombosis between the groups. The study demonstrates the efficacy and safety of anticoagulants during pregnancy. The use of LMWH in pregnant women with APS not being moot, warfarin might be justified in selected patients.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Autoimmune Diseases; Enoxaparin; Female; Hemorrhage; Humans; Infant, Newborn; Lupus Erythematosus, Systemic; Nervous System Diseases; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, Multiple; Safety; Thrombosis; Warfarin

The optimal intensity of oral anticoagulant therapy for the prevention of thromboembolism in patients with antiphospholipid antibodies (APLA) and systemic lupus erythematosus is controversial. Retrospective studies have suggested that patients with APLA are resistant to oral anticoagulant therapy, with a targeted International Normalization Ratio (INR) of 2.0 to 3.0, and that a higher intensity of anticoagulation (INR: 2.6 to 4.5) is required to prevent recurrent thromboembolism. To investigate if patients with APLA are resistant to the anticoagulant effect of low intensities of warfarin therapy, we performed a randomized trial in which 21 patients with APLA and systemic lupus erythematosus were allocated to receive one of three intensities of warfarin (INR: 1.1 to 1.4, 1.5 to 1.9 or 2.0 to 2.5) or placebo for four months. The main outcome was the effect of each intensity of warfarin therapy on prothrombin fragment 1+2 level (F1+2), that was used as a marker of coagulation activation. When F1+2 levels in patients allocated to the three warfarin intensities were compared to F1+2 levels in the placebo group, there was a statistically significant decrease (p<0.05) in the patient group receiving warfarin with a targeted INR of 2.0 to 2.5 at two, three and four months, and in the patient group with a targeted of INR 1.5 to 1.9 at three months. We conclude that in patients with APLA and systemic lupus erythematosus, warfarin therapy, with a targeted INR of 2.0 to 2.5, is effective in suppressing coagulation activation, and therefore, might be effective in preventing thromboembolism.

Topics: Adolescent; Adult; Antibodies, Antiphospholipid; Blood Coagulation; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Thromboembolism; Warfarin

To assess retrospectively three antithrombotic treatments in the secondary prevention of thrombosis in the antiphospholipid syndrome (APS), 23 patients (six systemic lupus erythematosus, seven lupus-like disease and 10 primary antiphospholipid syndrome) were included in this study. Treatments assessed were: (1) aspirin 75 mg daily, (2) warfarin (international normalised ratios (INRs) 2.0-2.9) +/- aspirin 75 mg daily, and (3) warfarin (INRs > 2.9) +/- aspirin 75 mg daily. Where patients had received two or three of these treatments successively, the periods of time on each treatment were added and the number of patients with recurrence(s) on each treatment were compared by Fisher's exact probability test. 'High' anticoagulation (INRs > 2.9) +/- aspirin 75 mg daily was more effective than aspirin 75 mg daily, there was a trend in favour of 'high' anticoagulation (P = 0.066). No statistically significant difference could be demonstrated when comparing 'low' anticoagulation +/- aspirin 75 mg daily with aspirin 75 mg daily (P = 0.092). These results suggest that aggressive anticoagulation with or without low-dose aspirin is effective in preventing further thromboembolic events in APS.

Topics: Adolescent; Adult; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prospective Studies; Thrombosis; Warfarin

Cerebrovascular accidents (CVAs) or strokes are part of the common thrombotic manifestations of Systemic Lupus Erythematosus (SLEs) and Antiphospholipid syndrome (APS). Such neurological thrombotic events tend to occur in patients with SLE at a higher frequency when Antiphospholipid antibodies (aPLs) are present, and tend to involve the large cerebral vessels. The mechanism of stroke in SLE can be driven by complement deposition and neuroinflammation involving the blood-brain barrier although the traditional cardiovascular risk factors remain major contributing factors. Primary prevention with antiplatelet therapy and disease activity controlling agent is the basis of the management. Anticoagulation via warfarin had been a tool for secondary prevention, especially in stroke recurrence, although the debate continues regarding the target international normalized ratio (INR). The presence of either of the three criteria antiphospholipid antibodies (aPLs) and certain non-criteria aPL can be an independent risk factor for stroke. The exact mechanism for the involvement of the large cerebral arteries, especially in lupus anticoagulant (LAC) positive cases, is still to be deciphered. The data on the role of non-criteria aPL remain very limited and heterogenous, but IgA antibodies against β2GPI and the D4/5 subunit as well as aPS/PT IgG might have a contribution. Anticoagulation with warfarin has been recommended although the optimal dosing or the utility of combination with antiplatelet agents is still unknown. Minimal data is available for direct oral anticoagulants (DOACs).

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Stroke; Thrombosis; Warfarin

Limited evidence exists to guide the management of recurrent thrombosis occurring despite therapeutic anticoagulation in patients with thrombotic antiphospholipid syndrome (APS). In this case series, fondaparinux, with or without an antiplatelet agent, provided an effective and safe option in three patients with thrombotic APS, all two triple and one single positive for antiphospholipid antibodies, who had recurrent venous and/or arterial thromboembolism. Rituximab was also used in all patients. Recurrent events occurred despite therapeutic anticoagulation, including at high-intensity, with warfarin and subsequent low-molecular-weight heparin. There were no major bleeding events. Adjunctive therapies used for thrombosis included catheter-directed thrombolysis and rituximab.

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Lupus Erythematosus, Systemic; Platelet Aggregation Inhibitors; Rituximab; Thrombosis; Warfarin

We report on the natural history of a cohort of patients presenting with transient ischemic attack or stroke and nonbacterial thrombotic endocarditis treated with warfarin.Patients with valvular vegetations on echocardiography, stroke, or transient ischemic attack presenting to a single neurologist were included. All patients were treated with warfarin until the vegetation resolved or for two years, then were switched to aspirin and had at least one clinical and echocardiographic follow-up.Twenty-nine patients were included and followed for a median of 27 months. Average age was 42 years and 72% were female. Two patients had vegetations on two valves. Five patients (17%) had recurrent strokes, three had systemic lupus erythematosus and antiphospholipid antibodies, one had antiphospholipid antibodies alone and one had neither condition. Three of the five patients did not have resolution of the vegetation at the time of the event. The valvular vegetations resolved in 23 of the 31 affected valves (74%) after a median of 11 months (range 4.5-157.5). Eleven patients had at least one follow-up echocardiogram after resolution of the vegetation and none had recurrent vegetations after warfarin was stopped.This study should serve to provide general recommendations regarding treatment of patients with TIA/stroke with nonbacterial thrombotic endocarditis. Valvular vegetations resolve in most patients and the risk of recurrent stroke is low. Warfarin can safely be switched to aspirin in most patients when the vegetation resolves or after two years if it does not resolve. Prolonged warfarin may be warranted in patients with systemic lupus erythematosus, positive antiphospholipid antibodies, and a persistent vegetation.

Topics: Adult; Echocardiography; Endocarditis; Female; Humans; Lupus Erythematosus, Systemic; Stroke; Warfarin

Low levels of total C4b-binding protein (C4BPt), a circulating inhibitor of the classical/lectin complement pathways, were observed in patients with antiphospholipid antibodies (aPLs) and during warfarin treatment.. To investigate the associations between aPL and C4BPt in patients with persistently positive (++) aPL, with/without clinical manifestations and systemic lupus erythematosus (SLE), and in controls. Furthermore, we explored the impact of anticoagulation on C4BPt and in relation to complement activation.. In a cross-sectional design we investigated defined subgroups: primary (p) antiphospholipid syndrome (APS,. Overall, C4BPt is 20% decreased in aPL++ patients, regardless of SLE, APS, clinical manifestations, and aPL profile. C4BPt levels associate positively with complement proteins C1q, C2, C3, and C4, and negatively with complement activation product C3dg. In the SLE group, warfarin treatment contributes to approximately half of the C4BPt reduction (9%) CONCLUSION:  Both aPLs and warfarin are associated with C4BPt reduction. Complement activation in aPL++ patients may partly be explained by impaired inhibition through depressed C4BPt levels. Further studies are needed to understand the clinical implications.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Biomarkers; Blood Coagulation; Case-Control Studies; Complement Activation; Complement C4b-Binding Protein; Cross-Sectional Studies; Down-Regulation; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Warfarin

A 34-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted to our hospital for exacerbation of renal dysfunction, hemolytic anemia and thrombocytopenia. Twenty-two years before admission, she was diagnosed with SLE. Eight years before, lupus anticoagulant (LAC) positivity was detected without any thrombotic findings. Fourteen months before, renal function started to worsen. Three months before, unprovoked left leg swelling appeared. She was diagnosed with deep vein thrombosis (DVT) by ultrasonography. Blood examination revealed mild anemia, thrombocytopenia, and renal dysfunction. Rivaroxaban was started after which the left leg swelling subsided. When she was referred to our hospital, LAC was positive, but hypocomplementemia nor elevation of serum anti-double-stranded DNA antibodies was detected. Renal biopsy showed acute and chronic thrombotic microangiopathy (TMA) without concurrent lupus nephritis. Brain magnetic resonance imaging showed new small multiple cerebral infarcts. Antiphospholipid antibody syndrome (APS), causing renal TMA, new cerebral infarction, and DVT was diagnosed. Rivaroxaban was changed to warfarin. Two months after admission, renal impairment improved, and the complete disappearance of DVT and brain infarcts was confirmed. This case suggests that warfarin may be more effective than direct oral anticoagulants in the treatment of APS-associated renal TMA.

Topics: Adult; Antiphospholipid Syndrome; Female; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Rivaroxaban; Thrombotic Microangiopathies; Treatment Outcome; Warfarin

Antiphospholipid syndrome (APS) is a clinical disorder that creates an increased risk of arterial or venous thrombotic events or pregnancy-associated complications and includes the presence of autoantibodies against negatively charged phospholipids. This syndrome is often associated with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE). Libman-Sacks endocarditis is a form of non-bacterial thrombotic endocarditis and is infrequently seen in APS. There are few data documenting the echocardiographic response of APS valve disease to medical treatment. This is an unusual case of a young female patient with SLE and APS who had chorea and non-bacterial thrombotic aortic valve endocarditis. Echocardiography revealed that the vegetation had receded after a combination of warfarin and immunosuppressive therapy.

Topics: Adult; Echocardiography, Transesophageal; Endocarditis; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Warfarin; Young Adult

Topics: Anticoagulants; Antiphospholipid Syndrome; Antirheumatic Agents; Drug Therapy, Combination; Endocarditis; Follow-Up Studies; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Male; Treatment Outcome; Vitamin K; Warfarin; Young Adult

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Humans; Lupus Erythematosus, Systemic; Rituximab; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Echocardiography; Endocarditis; Female; Heart Valve Diseases; Humans; Ischemic Attack, Transient; Lupus Erythematosus, Systemic; Tricuspid Valve; Warfarin

Topics: Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Lupus Erythematosus, Systemic; Rivaroxaban; Thrombosis; Warfarin

Topics: Adult; Aneurysm, False; Aneurysm, Ruptured; Drug Overdose; Dyspnea; Echocardiography, Doppler, Color; Humans; Leg Ulcer; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Treatment Outcome; Venous Thrombosis; Ventricular Dysfunction, Left; Warfarin

Topics: Antiphospholipid Syndrome; Humans; Lupus Erythematosus, Systemic; Rivaroxaban; Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Pregnancy; Pregnancy Complications; Rivaroxaban; Secondary Prevention; Venous Thromboembolism; Warfarin; Young Adult

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Drug Substitution; Female; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Mesenteric Veins; Middle Aged; Morpholines; Portal Vein; Recurrence; Retrospective Studies; Rivaroxaban; Splenic Vein; Stroke; Thiophenes; Thromboembolism; Thrombophilia; Treatment Failure; Venous Thrombosis; Warfarin

Early graft thrombosis and bleeding complications remain important causes of early graft loss following kidney transplantation in patients with antiphospholipid syndrome. Anti-β2-glycoprotein I IgG is a disease-specific antibody in patients with antiphospholipid syndrome. Although plasmapheresis is partially effective for antibody removal, the optimal treatment allowing successful transplantation in patients with antiphospholipid syndrome has not been established. This is the first report of a patient with antiphospholipid syndrome who successfully underwent living-donor kidney transplantation following prophylactic plasmapheresis for removal of anti-β2-glycoprotein I IgG.. A 37-year-old Japanese female was scheduled to undergo a living-donor kidney transplant from her mother. At age 25 years, she experienced renal vein thrombosis, was diagnosed with antiphospholipid syndrome secondary to systemic lupus erythematosus, and was subsequently treated with prednisolone and warfarin. At age 37 years, she was diagnosed with end stage kidney disease, requiring maintenance hemodialysis because of recurrent renal vein thrombosis despite taking anticoagulation therapy. The pretreatment protocol consisted of prophylactic plasmapheresis plus full anticoagulation therapy to counteract the risks of early graft thrombosis. Anticardiolipin and anti-β2-glycoprotein I IgGs were successfully removed by both double filtration plasmapheresis and plasma exchange. The allograft kidney began to function soon after transplantation. No obvious thrombotic complications were observed after transplantation, although anti-β2-glycoprotein I IgG increased to the level observed before plasmapheresis. One year after transplantation, the patient's kidney function remains stable while receiving anticoagulation therapy as well as a maintenance immunosuppressive regimen.. Prophylactic plasmapheresis plus full anticoagulation therapy may be an effective strategy in patients with antiphospholipid syndrome undergoing living-donor kidney transplantation.

Topics: Adrenal Cortex Hormones; Adult; Anticoagulants; Antiphospholipid Syndrome; Autoantigens; beta 2-Glycoprotein I; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Lupus Erythematosus, Systemic; Plasma Exchange; Plasmapheresis; Preoperative Care; Renal Dialysis; Thrombophilia; Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Constriction, Pathologic; Female; Hepatic Artery; Humans; Liver Diseases; Lupus Erythematosus, Systemic; Radiography; Warfarin

Topics: Adolescent; Antiphospholipid Syndrome; Comorbidity; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Infarction; Intestines; Kidney; Lupus Erythematosus, Systemic; Prednisolone; Tomography, X-Ray Computed; Treatment Outcome; Vasculitis; Warfarin

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Stroke; Thalamus; Warfarin

Topics: Abdominal Pain; Anticoagulants; Antiphospholipid Syndrome; Fatal Outcome; Female; Fever; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mesenteric Arteries; Mesenteric Veins; Postprandial Period; Vasculitis; Warfarin; Young Adult

Bilateral optic neuritis is an extremely uncommon complication of pediatric systemic lupus erythematosus and sporadic cases are reported in the literature. The authors describe an 11-yr-old girl who presented with fever and progressively increasing pallor for 4 months, headache for 7 days, severe anemia and hepatosplenomegaly. Soon after admission, she developed rapid deterioration of vision, worsening to no perception of light with afferent pupillary defect. Fundoscopy showed bilateral optic neuritis. Investigations revealed autoimmune hemolytic anemia and thrombocytopenia. Anti-dsDNA and anti-phospholipid antibodies were positive. Magnetic resonance venography showed multiple thrombi in the cerebral venous sinuses, for which anticoagulant therapy was initiated. She was managed with intravenous methylprednisolone followed by cyclophosphamide pulse therapy for 6 months along with oral prednisolone. Though she went into remission, visual outcome has been dismal, with development of bilateral optic atrophy, and absence of perception of light.

Topics: Anemia, Hemolytic, Autoimmune; Anti-Inflammatory Agents; Anticoagulants; Antiphospholipid Syndrome; Cerebral Veins; Child; Cyclophosphamide; Female; Heparin; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Methylprednisolone; Optic Neuritis; Prednisolone; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Warfarin

Exercise training has emerged as a potential therapeutic strategy to counteract the decline in physical function and aerobic capacity in pediatric rheumatic disease.. We report for the first time on the effects of exercise training in juvenile systemic lupus erythematosus (JSLE) and antiphospholipid syndrome (APS).. A 15-yr-old boy with JSLE and APS treated with warfarin, azathioprine, and prednisone underwent a 12-wk aerobic exercise training program to improve his physical capacity and functioning. Before and after the 12-wk exercise program, the patient was submitted to incremental cardiopulmonary tests to determine VO(2peak), peak and submaximal exercise intensity, and time to exhaustion. In addition, a 6-min square-wave test was performed for assessing metabolic parameters. Functioning was assessed by using the visual analog scale. Laboratory parameters of inflammation were also assessed at baseline and 48 h after the last training session.. All the cardiopulmonary parameters (e.g., VO(2max) = +36.0%, time to exhaustion = +67.8%, peak exercise intensity = +16.7%) and the metabolic cost of movement (e.g., energy expenditure = -28.3% to -33.3%, VO(2) = -29.3% to -33.4%) were improved. Both disease activity and cumulative damage scores did not change after the intervention, and no evidence of exercise-induced exacerbation of inflammation was observed. Visual analog scale scores were also improved according to the patients' evaluation (before intervention = 8 vs after intervention = 10), parents' evaluation (before intervention = 8 vs after intervention = 10), and physicians' evaluation (before intervention = 6 vs after intervention = 9).. This is the first evidence that a 12-wk supervised aerobic training program can be safe and effective in improving aerobic conditioning and physical function in a patient with JSLE and APS. In light of these findings, the therapeutic effects of exercise training in pediatric rheumatic diseases merit further investigations.

Topics: Adolescent; Anaerobic Threshold; Antiphospholipid Syndrome; Azathioprine; Drug Therapy, Combination; Energy Metabolism; Exercise Test; Exercise Therapy; Exercise Tolerance; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Oxygen Consumption; Pain Management; Pain Measurement; Prednisone; Treatment Outcome; Warfarin

Antiphospholipid syndrome is an autoimmune disease that presents with recurrent arteriovenous thrombosis, repeated pregnancy loss and elevated titres of antiphospholipid antibodies in the blood. It is a common cause of acquired thrombosis and can manifest within any part of the vascular tree. Inferior Venacava thrombosis at outset, however, is not a common manifestation of systemic lupus erythematosus associated-antiphospholipid syndrome particularly in children. Here, we present a 14-year old girl who developed antiphospholipid syndrome as a presenting manifestation of systemic lupus erythematosus.

Topics: Adolescent; Antihypertensive Agents; Antiphospholipid Syndrome; Female; Glucocorticoids; Heparin; Humans; Hydrochlorothiazide; Lupus Erythematosus, Systemic; Prednisone; Vena Cava, Inferior; Venous Thrombosis; Warfarin

A 34-year old woman with dizziness, headache and both upper and lower extremities weakness was admitted to hospital. She had a history of photosensitivity but no asthma or allergy. On physical examination, malar rash and livedo reticularis were noted. White blood cell count was 18500/microL with 7585 eosinophils (41%). She also had positive antinuclear antibody (ANA), anti-double stranded DNA antibody (anti-ds-DNA antibody) and anticardiolipin antibody (aCL antibody). Echocardiography revealed left and right ventricular obliteration with fibromatous biventricular endothelial thickening. Brain MRI showed changes in favour of white matter ischaemia and lacunar infarction. Hypereosinophilic syndrome (HES) and systemic lupus erythematosus may be considered to have occurred concurrently in this patient.

Topics: Adrenal Cortex Hormones; Adult; Anticoagulants; Antirheumatic Agents; Azathioprine; Diagnosis, Differential; Drug Therapy, Combination; Echocardiography; Eosinophilia; Female; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Methylprednisolone; Syndrome; Warfarin

Between 20% and 40% of patients with systemic lupus erythematosus (SLE) have positive blood tests for antiphospholipid antibodies (aPLs). This article explains what tests are used to detect these antibodies and outlines the complexities of interpreting and acting upon a positive result. If aPLs are persistently positive, the patient may develop antiphospholipid syndrome (APS) characterised by vascular thrombosis, pregnancy morbidity or both. In patients with SLE who are aPL-positive but have not developed APS, there is some evidence that low-dose aspirin should be used prophylactically, but it is not conclusive. APS in patients with SLE is clinically similar to primary APS and should be treated in the same way, with anticoagulation to prevent recurrent thrombosis or with aspirin and sometimes heparin to prevent pregnancy loss. Current best practice in use of these treatments is discussed. However, these treatments are not ideal as they can have major side effects such as haemorrhage. Research which may lead to better, more targeted therapy for APS is discussed at the end of the article.

Topics: Algorithms; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Female; Humans; Lupus Erythematosus, Systemic; Male; Pregnancy; Pregnancy Complications; Warfarin

A 13-year-old boy with Mycoplasma pneumoniae pulmonary infection developed deep vein thrombosis and pulmonary embolism. He was found to have protein S deficiency and transient antiphospholipid antibodies. Though uncommon, it is important to consider venous thromboembolic disease in children whose clinical course is atypically severe.

Topics: Adolescent; Anticoagulants; Antiphospholipid Syndrome; Heparin; Humans; Lupus Erythematosus, Systemic; Male; Pneumonia, Mycoplasma; Protein S Deficiency; Pulmonary Embolism; Venous Thrombosis; Warfarin

Interstitial granulomatous dermatitis (IGD) is a recently described, rare dermatological entity. The clinical features are diverse and the precise aetiology is unknown. We present a rare and atypical case of IGD in a patient with systemic lupus erythematosus (SLE). A 26-year-old woman had been diagnosed with SLE when she was 15 years old. The diagnosis was based on cutaneous, articular, pulmonary, haematological and immunological features. The patient presented with a cutaneous diffuse macular eruption on the limbs, appearing in a cockade (rosette) pattern with a violaceous centre and erythematous surround. The face and trunk were spared. The cutaneous histological features led us to consider a diagnosis of IGD. The lesions disappeared after 15 days of systemic steroid therapy. This case is a new clinical form of IGD with an atypical location and clinical presentation. IGD has usually been associated with drug-related adverse reactions and autoimmune diseases. Reports in the literature of IGD in patients with SLE are rare.

Topics: Adult; Azathioprine; Dermatitis; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Lupus Erythematosus, Systemic; Prednisolone; Skin; Warfarin

Antiphospholipid syndrome is a well-defined entity that is characterized by spontaneous abortion, thrombocytopenia, and recurrent arterial and venous thromboses. A partially calcified right atrial thrombus mimicking myxoma with recurrent pulmonary embolism has not been previously reported in a patient who also had systemic lupus erythematosus and secondary antiphospholipid syndrome. Herein, we describe the case of a 37-year-old woman with systemic lupus erythematosus and secondary antiphospholipid syndrome who was admitted to the hospital with progressive exertional dyspnea. Ventilation-perfusion scanning showed multiple parenchymal defects in the lungs that portended pulmonary embolism. In addition, the scanning revealed normal regional ventilation. Transthoracic and transesophageal echocardiography showed a right atrial mass that was highly suggestive of myxoma, and the patient subsequently underwent surgery. A histologic examination showed an organized, partially calcified thrombus. Intracardiac thrombus has been rarely reported as a complication of antiphospholipid syndrome. In our patient, the preoperative investigations could not differentiate the partially calcified right atrial thrombus from a myxoma, and the diagnosis was made postoperatively.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Anticoagulants; Antineoplastic Agents; Antiphospholipid Syndrome; Coronary Thrombosis; Diagnosis, Differential; Female; Heart Atria; Humans; Immunologic Factors; Lupus Erythematosus, Systemic; Myxoma; Perfusion; Pulmonary Embolism; Risk Factors; Rituximab; Ultrasonography; Warfarin

Argatroban is a direct thrombin inhibitor approved for the treatment of heparin-induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on renal replacement therapy (Reddy and Grossman, Ann Pharm 2005;39:1601-1605). The elimination half-life of argatroban is approximately 50 min. Lupus anticoagulants can cause baseline elevation of the PTT and hence it is difficult to monitor the effects of anticoagulants such as heparin, lepirudin, or argatroban in patients with antiphospholipid antibody syndrome. Heparin levels may be used as an alternative for heparin monitoring but plasma levels of argatroban are not commercially available. A chromogenic antifactor IIa assay could be useful for monitoring argatroban in the presence of a lupus anticoagulant, but it is not widely available at present. We report a patient with end-stage renal disease, maintained on peritoneal dialysis with HIT, who demonstrated a markedly prolonged half-life when treated with argatroban despite the discontinuation of therapy. This case also demonstrates the lack of guidelines for the monitoring of argatroban therapy in the presence of an underlying lupus anticoagulant.

Topics: Anticoagulants; Antiphospholipid Syndrome; Arginine; Cholangiopancreatography, Endoscopic Retrograde; Female; Half-Life; Heparin; Humans; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Middle Aged; Peritoneal Dialysis; Pipecolic Acids; Sulfonamides; Thrombocytopenia; Treatment Outcome; Warfarin

In antiphospholipid syndrome (APS), there is a high prevalence of valvular heart disease which leads to increased risk of thrombo-embolic events, in particular, cerebrovascular events. We present a patient with cerebral infarction, previous deep-vein thrombosis, and miscarriages with positive lupus anticoagulant and anticardiolipin antibodies. Echocardiographic examination revealed mitral valve leaflet thickening and verrucous vegetations consistent with Libman-Sacks endocarditis, which is commonly associated with APS. In patients with combined Libman-Sacks endocarditis and antiphospholipid antibodies, anticoagulation therapy with warfarin is indicated due to high risk of valvular thrombus formation and subsequent embolization.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Cerebral Infarction; Endocarditis; Female; Humans; Intracranial Embolism; Lupus Erythematosus, Systemic; Venous Thrombosis; Warfarin

The antiphospholipid antibody syndrome (APLS) is characterised by the presence of antiphospholipid antibodies in association with thrombotic disorders of the arterial and/or venous system, spontaneous abortion and thrombocytopenia. Several studies have shown that end-stage renal disease patients with APLS are at extremely high risk for graft thrombosis and graft loss after kidney transplantation.. We report on the treatment and clinical courses of 6 APLS renal transplant patients.. Of 3 patients treated with low-dose subcutaneous heparin two had early graft loss due to venous graft thrombosis; of those patients treated by systemic heparin (PTT goal 45-55 s) and followed by coumadin (INR 2.5-3.0) only one had early graft loss whereas 2 grafts are doing well 2 years post-transplant.. Our experience as well as recently published data suggest that kidney transplantation can be performed successfully in APLS patients if anticoagulation therapy is performed consistently. A general APL antibody screening prior to kidney transplantation does not seem to be justified at present. A prospective, randomised multicenter study is warranted to evaluate the management of these patients with respect to intensity, type and duration of anticoagulation therapy.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Graft Survival; Heparin; Humans; Injections, Intravenous; Injections, Subcutaneous; Intraoperative Care; Kidney Transplantation; Lupus Erythematosus, Systemic; Partial Thromboplastin Time; Postoperative Complications; Risk Factors; Thrombosis; Warfarin

Movement disorders have only rarely been reported in association with antiphospholipid syndrome (APS). In such cases, chorea is the most common disorder observed, with occasional reports of hemidystonia, Parkinsonism, and hemiballism. We report here on 3 cases of APS (3 women ages 16, 46, and 56 years) who presented with movement disorders, including tics, tremor, myoclonus, and a corticobasal syndrome, never or rarely reported in association with this disease. Mild executive dysfunction was observed in all 3 patients. We also report the successful treatment of two of these patients with mild oral anticoagulation (INR 2-3). Movement disorders in APS seem more clinically heterogeneous than previously thought. Oral anticoagulation should be considered in the treatment of movement disorders associated with APS.

Topics: Adolescent; Antiphospholipid Syndrome; Brain; Cerebral Infarction; Diagnosis, Differential; Dyskinesias; Electroencephalography; Electromyography; Female; Follow-Up Studies; Frontal Lobe; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Middle Aged; Movement Disorders; Myoclonus; Neurologic Examination; Neuropsychological Tests; Occipital Lobe; Phenindione; Phenprocoumon; Sneddon Syndrome; Spinocerebellar Degenerations; Tics; Tourette Syndrome; Tremor; Warfarin

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Topics: Adult; Antibody Specificity; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cross Reactions; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Heparin; Hirudins; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Platelet Factor 4; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombophilia; Warfarin

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Clinical Trials as Topic; Female; Hemorrhage; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Pregnancy; Recurrence; Retrospective Studies; Risk; Vitamin K; Warfarin

The coexistence of human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE) is being increasingly reported and, because of the immunological disturbances demonstrated in HIV-infected patients, diagnostic and therapeutic difficulties may arise when the 2 conditions coexist. Antiphospholipid antibodies are demonstrable in patients with both conditions, but clinical manifestations of the antiphospholipid syndrome (APS) in HIV-infected patients, although reported, are uncommon.. We describe a patient with HIV infection and SLE who manifested 4 episodes of deep vein thrombosis (DVT) complicated by pulmonary embolism. Enzyme-linked immunosorbant assay was used to test for the presence of antiphospholipid antibodies, including anticardiolipin antibodies, anti- beta 2-glycoprotein 1 antibodies, and antiprothrombin antibodies (anti-PT). Additionally, we performed a computer-assisted search of the literature (via the Medline database) to identify all reported cases of HIV infection plus SLE.. We document the case of 35-year-old African woman with HIV infection and SLE who developed recurrent episodes of DVT and pulmonary embolism in the presence of anti-PT and discuss in depth the pathogenic role of these antibodies and the clinical challenges posed to clinicians by the coexistence of HIV and SLE in the same patient.. Immunological reconstitution in HIV-infected patients contributes to the appearance of multiple autoimmune conditions, including SLE and APS. The recognition of the coexistence of these autoimmune disorders in HIV-infected patients has important implications in the treatment of and prognosis for these individuals.

Topics: Adrenal Cortex Hormones; Adult; Anti-HIV Agents; Antibodies; Anticoagulants; Female; HIV Infections; Humans; Lupus Erythematosus, Systemic; Prothrombin; Pulmonary Embolism; Venous Thrombosis; Warfarin

The antiphospholipid syndrome is an antibody-mediated hypercoagulable state characterized by recurrent venous and arterial thromboembolic events. Several studies have determined that the frequency of antiphospholipid syndrome in patients presenting with a venous thromboembolic event is between 4% and 14%. Because of the high risk for recurrent thromboembolism in these patients, current recommendations suggest a longer, potentially lifelong, course of antithrombotic therapy following an initial event. Although most authorities agree on an extended course of therapy, considerable controversy surrounds the optimal target therapeutic INR for patients with antiphospholipid syndrome. For an initial venous thromboembolic event, a target INR of 2.0 to 3.0 is supported by two prospective, randomized clinical trials. In contrast, relatively limited data exist for an initial arterial thromboembolic event in patients who have the antiphospholipid syndrome, and therapeutic recommendations range from aspirin to warfarin with a high target INR. Recurrent thromboembolic events can be extremely difficult to treat, and some patients may benefit from the addition of immunosuppressive therapies. Importantly, as many as 50% of the initial thromboembolic events sustained by patients with antiphospholipid antibodies occur in the setting of additional, coincident prothrombotic risk factors, indicating the importance of addressing any additional risk factors, such as hypercholesterolemia, in these patients. Prospective studies are needed to address the role of thromboprophylactic strategies in asymptomatic individuals with antiphospholipid antibodies in the absence of additional risk factors.

Topics: Animals; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cardiolipins; Disease Models, Animal; Humans; Incidence; International Normalized Ratio; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Renal Dialysis; Venous Thromboembolism; Warfarin

Topics: Acute Kidney Injury; Adult; Anticoagulants; Biopsy; Female; Glomerulosclerosis, Focal Segmental; Hematuria; Humans; Hypertension, Pulmonary; International Normalized Ratio; Lupus Erythematosus, Systemic; Lupus Nephritis; Pneumonia; Pulmonary Embolism; Warfarin

Spontaneous appearance of acquired anticoagulants is a rare phenomenon. We present two cases, where such antibodies against factor VIII were masked by warfarin therapy. The two patients were anticoagulated with warfarin due to mechanical heart valve and recurrent thromboembolic events, respectively. Different therapies against the inhibitor of factor VIII were used in the two cases. One patient received corticosteroids and high-dose gammaglobulin with temporary effect and was then effectively treated with cyclophosphamide. The other patient was successfully treated with cyclosporine. The special problems of keeping the balance between thrombosis and bleeding in this group of patients with need of anticoagulation due to mechanical heart valves or other thrombogenic factors are discussed.

Topics: Autoantibodies; Blood Coagulation Disorders; Factor VIII; Female; Heart Valve Prosthesis; Hemophilia A; Hemorrhage; Humans; Lupus Erythematosus, Systemic; Middle Aged; Thromboembolism; Warfarin

A 34-year-old woman with systemic lupus erythematosus and high titres of antiphospholipid antibodies was admitted to hospital suffering a viral illness but developed haemorrhagic and necrotic areas on the neck and anterior chest 7 days following cessation of warfarin. Anticoagulation had been initiated following a retinal vein thrombosis, but was ceased on day 4 of admission when she was found to be excessively anticoagulated (international normalized ratio (INR) > 10). However, at the time of developing the cutaneous lesions, the INR was sub-therapeutic. Histology of a skin biopsy from the neck revealed thrombosis of upper dermal blood vessels without vasculitis, consistent with antiphospholipid antibody-related skin necrosis. This case illustrates one of the cutaneous features that can occur in patients with elevated titres of antiphospholipid antibodies and the importance of closely monitoring anticoagulation in such patients.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Biopsy, Needle; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Humans; Immunohistochemistry; Lupus Erythematosus, Systemic; Neck; Necrosis; Risk Assessment; Severity of Illness Index; Skin Diseases; Treatment Outcome; Warfarin

Topics: Adult; Anticoagulants; Azathioprine; Drug Antagonism; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Warfarin

Pulmonary hypertension (PH) sometimes occurs in patients with systemic lupus erythematosus (SLE). We report a case of 51-year-old-woman with PH associated with SLE. She had been diagnosed as SLE on the basis of pericardial effusion, hematological disorder, positive antinuclear antibody, and hypocomplementemia. Despite minimal lupus activity, she had marked elevation of pulmonary arterial pressure (101/53 mmHg) and decreased cardiac index (1.5 l/min/m2). Symptoms related to PH were progressive under treatment with oral corticosteroids, oxygen, calcium antagonists, and warfarin. After 17 months of epoprostenol treatment, she died of pulmonary infarction. SLE-associated PH is often severe and progressive even in association with minimal activity.

Topics: Anticoagulants; Autoimmune Diseases; Calcium Channel Blockers; Disease Progression; Epoprostenol; Fatal Outcome; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lupus Erythematosus, Systemic; Middle Aged; Oxygen; Prednisolone; Pulmonary Embolism; Warfarin

A rare manifestation of systemic lupus erythematosus (SLE) is cerebral venous sinus thrombosis (CVST), in which early diagnosis and aggressive therapy are of prime importance for favorable outcome. The pathogenesis of CVST is largely unknown, but it is thought to be caused by cerebral vasculitis, antiphospholipid antibodies or other conditions associated with enhanced coagulability. We describe two cases of SLE with CVST which were not associated with antiphospholipid antibodies. Both cases were treated with immunosuppressants (intravenous methylprednisolone and cyclophosphamide pulse therapy) and anticoagulant drugs (heparin and subsequent maintenance therapy with warfarin). There was a marked improvement of neurologic symptoms with the disappearance of thrombus in a follow-up MRI. The possibility of CVST should be considered in any patients with SLE who show neuropsychiatric manifestations.

Topics: Adult; Anti-Inflammatory Agents; Anticoagulants; Brain; Cyclophosphamide; Female; Glucocorticoids; Heparin; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Methylprednisolone; Middle Aged; Radiography; Sinus Thrombosis, Intracranial; Treatment Outcome; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Enoxaparin; Female; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Pulmonary Embolism; Sagittal Sinus Thrombosis; Thrombophlebitis; Warfarin

It is possible that platelet activation may play a pathogenic role in the increased risk of thrombosis associated with antiphospholipid antibodies (APA). In this study, levels of in vivo platelet activation were measured in 20 patients with primary antiphospholipid syndrome (PAPS) and 30 systemic lupus erythematosus (SLE) patients (14 of whom had secondary APS) using sensitive flow cytometry. Soluble P-selectin levels were also assayed. Platelet CD63 expression was significantly higher in PAPS than normal controls (P = 0.007), as well as SLE patients with and without secondary APS (P = 0.03 and P = 0.002 respectively). PAC-1 binding was significantly higher in PAPS than the control group (P = 0.007) and SLE patients without APS (P = 0.015). Platelet-leucocyte complexes were significantly higher in SLE patients than both PAPS and the control group, and platelet-monocyte complexes were significantly increased in PAPS compared with the control group. (Platelet-leucocyte complexes were also significantly higher than controls in 10 rheumatoid arthritis (RA) patients without APA). Soluble P-selectin levels were significantly higher in PAPS and SLE patients than the control group. Platelet CD62p expression, annexin V binding and platelet microparticle numbers were not increased in PAPS or SLE patients. We conclude that there is evidence of increased platelet activation in PAPS and SLE, and this is important to note as it may have potential therapeutic implications with respect to use of antiplatelet agents in these patients.

Topics: Adult; Aged; Annexin A5; Antiphospholipid Syndrome; Arthritis, Rheumatoid; Aspirin; Blood Platelets; Cell Aggregation; Cell Degranulation; Dual Specificity Phosphatase 2; Female; Humans; Leukocytes; Lupus Erythematosus, Systemic; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Count; Protein Phosphatase 2; Protein Tyrosine Phosphatases; Thrombosis; Warfarin

Systemic lupus erythematosus is a non-organ specific, autoimmune disease characterised by antinuclear antibodies and vasculitis. This may manifest itself with areas of cutaneous necrosis which may require extensive excision and reconstruction. Major areas of skin and soft tissue loss may require coverage with either local or microvascular free tissue transfer. This presents potential difficulties in patients with generalised vasculitis. We present the case of a professional cellist with extensive soft tissue loss in her dominant hand, successfully reconstructed with a free latissimus dorsi muscle flap, treated with peri- and postoperative anticoagulation and corticosteroids.

Topics: Adult; Anticoagulants; Contraindications; Female; Heparin; Humans; Lupus Erythematosus, Systemic; Plastic Surgery Procedures; Surgical Flaps; Tourniquets; Warfarin

A 15 year-old girl was admitted to the hospital because of fever, polyarthlargia, dry cough, dyspnea, butterfly rash and multiple oral aphthas. The diagnosis of systemic lupus erythematosus (SLE) was made based on renal disorders, pancytopenia, positive antinuclear antibody and positive for antibodies to double-stranded DNA. On admission, she developed progressive dyspnea with highly active SLE. The patient was complicated with both pulmonary hypertension (PH) and interstitial pneumonitis (IP), judging from increased pulmonary sound by an auscultation, interstitial shadows especially at bilateral lower lung and enlarged shadow of right atrium in a chest rentgenogram, ground glass pattern of bilateral middle to lower lung in a chest computed tomographic scan, increased pulmonary artery pressure, 53 mmHg, by an ultrasound cardiograph (UCG). Combination of methylprednisolone pulse therapy, cyclosporin A and plasma exchanges was effectively administered, which resulted in improvement of disease activity of SLE, IP and PH. However, two months later, although disease activity of SLE was completely reduced, recurrence of PH by UCG and multiple pulmonary embolism (PE) which was observed by a chest rentgenogram and a pulmonary blood flow scintigraphy was further complicated. Administration of cyclophosphamide pulse therapy and warfarin therapy improved both PE and PH. The patient had PH at the different clinical course of SLE; 1) PH maybe induced by severe IP at the active phase of SLE and 2) PH brought about from multiple PE at the inactive phase of SLE. Thus, the case is thought to be suggestive of elucidating the pathogenesis of PH of several systemic autoimmune diseases including SLE.

Topics: Adolescent; Cyclophosphamide; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Lupus Erythematosus, Systemic; Plasma Exchange; Pulmonary Embolism; Pulse Therapy, Drug; Recurrence; Treatment Outcome; Warfarin

Clotting-based activated protein C (APC) assays have limitations when testing patients on oral anticoagulant (OA) therapy or with a lupus anticoagulant (LA). Predilution in factor V (FV)-deficient plasma and testing with phospholipid-rich Russell Viper venom (RVV)-based methods have been shown to be the most suitable methods when testing these patient groups, respectively. We evaluated a modified RVV based clotting test (Gradileiden V test; Gradipore, Sydney, Australia) in a large patient cohort and determined its sensitivity to the FV Leiden mutation. We also examined whether normal plasma can be used to dilute plasma from warfarinized patients without compromising sensitivity to the FV Leiden mutation. A total of 1,956 plasmas were studied including congenital protein C (five plasmas), and protein S deficiency (five plasmas), LA (29 plasmas), FV Leiden heterozygote (102 plasmas), and homozygote (five plasmas), warfarin (54 plasmas), standard heparin therapy (37 plasmas) and normal healthy controls (21 plasmas). Molecular analysis was performed on all samples. The effect of FV Leiden concentration on the APC ratio was examined by determining the APC resistance of a homozygous plasma serially diluted in six sources of normal plasma (NP). The relationship was non-linear and dependent on the initial APC ratio of the chosen source of NP. APC resistance was demonstrated in the varying sources of NP in dilutions of 1/4 (25% FV Leiden) to 1/32 (3% FV Leiden). A 1/2 dilution in pooled NP is recommended for patients on OA therapy because the test remains sensitive at levels of 25% FV Leiden and this is the dilution routinely used for other applications in a coagulation laboratory. The effect of a LA on the APC ratio was similarly studied by determining the APC resistance of a homozygous plasma serially diluted in two sources of LA-positive plasma. This relationship was also non-linear and dependent on the initial APC ratio of the LA-positive plasma. APC resistance was demonstrated in dilutions of 1/16 (6% FV Leiden) to 1/64 (1.5% FV Leiden) demonstrating the sensitivity of the test to APC resistance in the presence of a LA. Our results show the modified RVV-based test clearly predicts the presence of factor V Leiden in a large cohort of patients. The method offers advantages when testing patients with a LA and patients receiving warfarin providing a 1/2 predilution step in pooled NP is performed. Pooled NP does not affect the sensitivity of the test to the mutati

Topics: Activated Protein C Resistance; Anticoagulants; Factor V; Heparin; Heterozygote; Homozygote; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Mutation; Protein C; Protein S Deficiency; Warfarin

The dilute Russell viper venom time and kaolin clotting time (KCT) are very sensitive screening tests for lupus anticoagulant activity. However, due to the high turbidity of the kaolin reagent it is difficult to accommodate the KCT on the optical end point automation of today. We evaluated five recently reported screening tests (the silica clotting time, the Textarin/Ecarin ratio, the Taipan venom time, the factor V ratio, and a kaolin clotting time using low-turbidity kaolin) as potential alternatives to the KCT. The sensitivity and specificity of the silica clotting time compared well to KCT, detecting 10/12 KCT positive samples and showing equal sensitivity to dilution of lupus positive plasma. In addition, the silica clotting time allows for a confirmatory phospholipid correction procedure. False-positive results were seen in 2 of 15 warfarinised samples. A second assay utilising the ratio of extrinsic/intrinsic factor V assays was not affected by either warfarin or heparin. This assay also gave positive results with 3 of 23 samples previously screened as lupus negative but exhibiting anticardiolipin positivity. It was therefore concluded that a combination of the silica clotting time and dilute Russell viper venom time met the requirements of lupus sensitivity with demonstration of phospholipid dependence and optical end point compatibility. The factor V ratio is a useful second-line screen for both anticoagulated patients and anticardiolipin antibody-positive samples.

Topics: Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Automation; Blood Coagulation Tests; Elapid Venoms; Endopeptidases; Evaluation Studies as Topic; Factor V; False Positive Reactions; Heparin; Humans; Kaolin; Liver Diseases; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Nephelometry and Turbidimetry; Partial Thromboplastin Time; Peptide Hydrolases; Postoperative Period; Prothrombin; Prothrombin Time; Silicon Dioxide; Warfarin

Severe pulmonary hypertension (PHT) occurring in patients with systemic lupus erythematosus (SLE) is uncommon. Different modalities have been tried in the treatment for this condition but have not been effective because of progressive increase of pulmonary resistance over time. Our patient with SLE and PHT with antiphospholipid syndrome (APS), a condition which has previously never been described, responded rapidly to combination treatment with immunosuppression, anticoagulation and vasodilator therapy.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Cyclophosphamide; Diltiazem; Female; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Prednisone; Vasodilator Agents; Warfarin

The authors report an unusual case of acute renal failure occurring in a patient with systemic lupus erythematosus and antiphospholipid antibodies. Kidney biopsy revealed glomerular thrombosis, in the absence of glomerulonephritis. The authors stress the clinical and biological signs that suggest the thrombotic nature of kidney failure in lupus patients.

Topics: Acute Kidney Injury; Adult; Antibodies, Antiphospholipid; Anticoagulants; Biopsy; Capillaries; Female; Heparin; Humans; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Thrombosis; Warfarin

Topics: Adult; Antiphospholipid Syndrome; Azathioprine; Cyclophosphamide; Female; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Prednisone; Thrombophlebitis; Warfarin

Catastrophic antiphospholipid antibody syndrome, reported in a minority of patients with circulating antiphospholipid antibodies, is characterized by widespread vascular occlusions. The term "catastrophic" has been used to describe the severity of symptomatology, sometimes leading to death. We describe a girl aged 11 years, fulfilling diagnostic criteria for systemic lupus erythematosus, with recurrent episodes of thromboembolic phenomena involving lung and skin, complicated with disseminated intravascular coagulation. Treatment with warfarin ultimately resulted in effective control of the disease.

Topics: Anticoagulants; Antiphospholipid Syndrome; Child; Disseminated Intravascular Coagulation; Female; Fingers; Humans; Ischemia; Lupus Erythematosus, Systemic; Warfarin

To describe the presentation, course, and management of serious hemorrhagic complications of anticoagulant therapy for patients with antiphospholipid syndrome (APS).. Charts of patients identified with serious bleeding complications from anticoagulation for APS were reviewed.. Patients included 6 women and one man with systemic lupus erythematosus (SLE) and one woman with primary APS. One patient had 3 separate hemorrhagic events. There were 6 episodes of subdural hematoma in 5 patients, one episode of pericarditis with tamponade, one episode of hemoptysis, and one episode of ovarian hemorrhage. In 2 patients, symptoms related to hemorrhage were initially attributed to active SLE. Duration of anticoagulation was between one month and 10 years at the time of bleed. International normalized ratio (INR) and prothrombin time were above the intended range in 6/9 episodes. There were no deaths and no permanent sequelae due to bleeding. Anticoagulant therapy was resumed in 6/7 patients.. The management of APS must include vigilance, patient education, and anticoagulation to maintain the INR between 3 and 3.5. To prevent hemorrhagic complications, low molecular weight heparin is an option that deserves further study.

Topics: Adolescent; Adult; Anticoagulants; Antiphospholipid Syndrome; Fatal Outcome; Female; Hemorrhage; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Warfarin

Nineteen children who presented with thromboses over a 7-year period were found to have a lupus anticoagulant (LA). The initial thrombosis was proximal deep vein thrombosis (DVT) in six children, central nervous system (CNS) in five, primary pulmonary in four, distal DVT in two, central venous in one, and proximal arterial in one. Five children were diagnosed with systemic lupus erythematosus (SLE), including two children for whom thrombosis was the presenting sign of SLE. The remaining 14 children were diagnosed with the antiphospholipid antibody (APA) syndrome. The APA syndrome was manifest by venous or arterial thrombosis in association with a positive LA; positive anticardiolipin antibodies and a fine, speckled antinuclear antibody (ANA) pattern were additionally found in the majority of children. Approximately one-half of the children with SLE or the APA syndrome had a pulmonary embolus, and one-half developed recurrent thrombosis. Oral anticoagulation with coumadin to achieve an INR of > 2.0 prevented thrombosis recurrence. The recognition of a LA in children with thrombosis necessitates evaluation for SLE, APA, and other autoantibodies.

Topics: Adolescent; Antiphospholipid Syndrome; Child; Child, Preschool; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Thrombosis; Warfarin

The antiphospholipid-antibody syndrome is a thrombophilic disorder in which venous or arterial thrombosis, or both, may occur in patients with antiphospholipid antibodies. The optimal treatment of these patients is unclear. We assessed the efficacy of warfarin, low-dose aspirin, or both in the secondary prevention of thrombosis in patients with the syndrome.. One hundred forty-seven patients (124 [84 percent] of whom were female) with the antiphospholipid-antibody syndrome and a history of thrombosis were studied retrospectively. The syndrome was primary in 62 patients and was associated with systemic lupus erythematosus in 66 patients and lupus-like disease in 19. Each patient's history was reviewed.. One hundred one patients (69 percent) had a total of 186 recurrences of thrombosis. The median time between the initial thrombosis and the first recurrence was 12 months (range, 0.5 to 144 months). Treatment with high-intensity warfarin (producing an international normalized ratio of > or = 3) with or without low-dose aspirin (75 mg per day) was significantly more effective (P < 0.001 by the log-rank test) than treatment with low-intensity warfarin (producing an international normalized ratio of < 3) with or without low-dose aspirin or treatment with aspirin alone in preventing further thrombotic events (recurrence rates per patient-year, 0.013, 0.23, and 0.18, respectively). The rate of recurrence of thrombosis was highest (1.30 per patient-year) during the first six months after the cessation of warfarin therapy. Complications involving bleeding occurred in 29 patients during warfarin therapy and were severe in 7 (0.071 and 0.017 occurrence per patient-year, respectively).. The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high. Long-term anticoagulation therapy in which the international normalized ratio is maintained at or above 3 is advisable in these patients.

Topics: Adolescent; Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Recurrence; Retrospective Studies; Thrombosis; Warfarin

A 41-year-old woman with systemic lupus erythematosus and lupus anticoagulant developed aortic thrombosis. The patient was receiving low dose aspirin. Aortography showed a complete obliteration of the infrarenal aorta. Computed tomography and magnetic resonance imaging showed no evidence of aortitis. The patient improved with medical treatment. Six other published cases are reviewed.

Topics: Adult; Antiphospholipid Syndrome; Aorta, Abdominal; Aortic Diseases; Aortography; Calcium Channel Blockers; Drug Therapy, Combination; Female; Humans; Lupus Erythematosus, Systemic; Thrombosis; Tomography, X-Ray Computed; Warfarin

To develop a specific test for lupus anticoagulant activity with reduced sensitivity to coagulation factor deficiency that would be suitable for analysis of plasmas from patients receiving oral anticoagulants.. A coagulation test based on the Taipan snake venom time (TSVT) with a platelet neutralisation procedure (PNP) was developed and compared with dilute Russell's viper venom time (DRVVT). The TSVT was used to test plasmas from patients receiving oral anticoagulant or heparin with mild liver dysfunction and with documented lupus anticoagulant.. The optimised conditions for the TSVT were established and a reference range was determined in normal healthy subjects. Results were considered positive for lupus anticoagulant if the ratio was > or = 1.1 and was reduced by > or = 10% or to < 1.1 in the PNP. In 43 samples from patients receiving oral anticoagulants there was no correlation between level of anticoagulation and TSVT, and only seven samples had increased TSVTs. Of these, five corrected on mixing with normal plasma and two gave equivocal results. The patients with mild liver dysfunction all had normal TSVTs. The TSVT in plasmas from patients receiving heparin correlated with the heparin concentrations (as measured by the APTT, r2 = 0.81). Some anticoagulated plasmas showed correction in the PNP and were regarded as false positive. Fourteen of 17 patients known to have lupus anticoagulant (on the basis of DRVVT results) were also positive by the TSVT; two of the remaining three were borderline and one was negative.. The TSVT showed satisfactory intra-assay precision and reasonable sensitivity to lupus anticoagulant, compared with the DRVVT. The TSVT was influenced by the presence of heparin but was not sensitive to the effects of oral anticoagulant. Like other lupus anticoagulant tests, it does not seem to have a 100% detection rate, but this may be due to the presence of lupus anticoagulant subtypes with distinct activities or the requirement of cofactors other than prothrombin or beta 2 glycoprotein-I.

Topics: Adult; Elapid Venoms; Female; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Middle Aged; Prothrombin Time; Sensitivity and Specificity; Thrombosis; Warfarin

We describe a test for LA based on the specific APTT behaviour of LA plasmas when the incubation time with the APTT reagent is increased from 1 to 20 min. "1-10 APTT" test was defined as the difference (s) between results of the APTT performed with 1 and the one performed with 10 min incubation. A test value > 11 s (upper normal limit determined on 134 normal plasmas) was considered positive for a LA. The test distinguished all the LA patients studied (n = 40) from patients with factor VIIIc inhibitors, patients receiving heparin or warfarin therapy and also patients with congenital factor deficiencies, except those with prekallikrein and factor XII deficiencies. The test detected LA in warfarin (n = 3) and in heparin (n = 2) LA anticoagulated patients. Among 195 patients referred for LA screening, the test detected LA in 5 patients with normal standard APTT. This simple test, using a single reagent for screening and confirmatory procedures is sensitive and fairly specific for LA when combined with mixing studies. However, since the test was defined using one APTT reagent, the performances of other reagents have to be assessed.

Topics: Abortion, Habitual; Female; Heparin; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Migraine Disorders; Partial Thromboplastin Time; Pregnancy; Sensitivity and Specificity; Time Factors; Warfarin

The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.

Topics: Adult; Aged; Antibodies, Anticardiolipin; Cardiolipins; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Thrombin; Thromboembolism; Warfarin

To determine the clinical course and influence of antithrombotic therapy in patients with lupus anticoagulant or anticardiolipin antibodies, or both, after the first thromboembolic event.. Retrospective survey of consecutive patients treated according to their physician's best judgment.. Secondary and tertiary referral practice.. Seventy patients (48 women [69%]) with a mean age (+/- SD) of 45.5 +/- 17.3 years. The antiphospholipid syndrome was primary in 51 patients (73%) and secondary to systemic lupus erythematosus in 14 patients (20%) and to chronic idiopathic thrombocytopenic purpura in 5 patients (7%).. Site of initial and recurrent thrombotic events (venous or arterial), as well as kind (aspiring, heparin, or warfarin) and intensity of anticoagulation.. Total follow-up after the first thrombotic event was 361.0 patient-years (mean [+/- SD], 5.2 +/- 5.6 years per patient). Thirty-seven patients (53%) had 54 recurrent events, with 2 patients experiencing fatal events. Arterial events were followed by arterial events, and venous events by venous events, in 49 of 54 instances (91%). Recurrence rates during "no treatment;" aspirin therapy; or low-, intermediate-, or high-intensity warfarin therapy (international normalized ratios [INRs] less than or equal to 1.9, 2.0 to 2.9, and greater than or equal to 3.0, respectively, or rabbit brain thromboplastin prothrombin time ratios of approximately less than 1.3, 1.3 to 1.5, and greater than 1.5, respectively) were 0.19, 0.32, 0.57, 0.07 (P = 0.12), and 0.00 (P less than 0.001) per patient-year. The follow-up periods for the five types of therapy were 161.2, 37.8, 11.3, 40.9, and 110.2 patient-years, respectively. The highest INR coincident with thrombosis was 2.6. Five warfarin-treated patients had five significant bleeding events (0.031 per patient-year).. Recurrent thrombosis is a potentially serious problem for patients with lupus anticoagulant or anticardiolipin antibodies or both. The site of the first event (arterial or venous) tended to predict the site of subsequent events. Intermediate- to high-intensity warfarin therapy may confer better antithrombotic protection than low- to intermediate-intensity warfarin therapy or aspirin therapy. Further studies are needed to define more precisely the rethrombosis rate and optimal type, intensity, and duration of antithrombotic therapy.

Topics: Aged; Antiphospholipid Syndrome; Aspirin; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Recurrence; Retrospective Studies; Thrombosis; Warfarin

Eight patients, 3 with systemic lupus erythematosus (SLE) or "SLE-like" disease, 1 with sarcoidosis, and 4 with no connective tissue disease had transient ischemic attacks (TIA) or cerebral infarctions associated with high levels of anticardiolipin antibodies (ACA). Cerebral ischemic events included amaurosis fugax, recurrent hemispheric TIA, cerebral infarction, and multi-infarction dementia. Treatment with acetylsalicylic acid was ineffective in 3 patients. Warfarin, alone or in combination with dipyridamole or steroids, may reduce the risk of further cerebrovascular events.

Topics: Adult; Aged; Antiphospholipid Syndrome; Aspirin; Autoantibodies; Brain Ischemia; Cardiolipins; Cerebral Infarction; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Neurologic Examination; Prednisolone; Warfarin

Topics: Aged; Autoantibodies; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Female; Glycoproteins; Humans; Infarction; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Necrosis; Phospholipids; Protein C Deficiency; Protein S; Skin; Warfarin

Antibodies to cardiolipin, closely related to the 'lupus anticoagulant', are strongly implicated in the pathogenesis of thrombosis. We record six patients, all with high titres of these antibodies (greater than SD) in serum, who developed recurrent vascular occlusions six to 12 weeks after warfarin withdrawal. Five of the six had deep vein thrombosis, while the sixth suffered a myocardial infarction. To minimise the risk of 'recurrent' thrombosis it is strongly suggested that such patients remain on long-term anticoagulation, pending the reduction of high antibody levels.

Topics: Adolescent; Adult; Antibodies; Autoimmune Diseases; Cardiolipins; Female; Humans; Lupus Erythematosus, Systemic; Male; Myocardial Infarction; Recurrence; Thrombophlebitis; Warfarin

The clinical pharmacology of ibuprofen (Motrin, Upjohn) in relation to the pathophysiologic aspects of various diseases is explained. An understanding of prostaglandin's numerous effects can help the clinician to expand the use of ibuprofen (as in Barttern's syndrome) and to exercise caution as warranted, as when treating patients with renal disease. Knowledge of ibuprofen's clinical pharmacology may also enable practitioners to prescribe the drug rationally in situations not well represented in the literature, as in the elderly or in individuals with bleeding diatheses or severe liver disease. The use of ibuprofen in multiple-drug therapy with aspirin, warfarin, phenytoin, digoxin, or lithium is explored. Perusal of the literature enables the clinician to gain an awareness of patient subpopulations warranting careful use of medication, including the elderly or individuals with systemic lupus erythematosus, mixed connective tissue disease, or aspirin-induced asthma.

Topics: Arthritis, Rheumatoid; Aspirin; Bartter Syndrome; Cyclooxygenase Inhibitors; Digoxin; Drug Hypersensitivity; Drug Interactions; Ductus Arteriosus, Patent; Humans; Ibuprofen; Indomethacin; Kidney; Kinetics; Lithium; Liver; Lupus Erythematosus, Systemic; Mixed Connective Tissue Disease; Phenytoin; Platelet Aggregation; Prostaglandins E; Warfarin

Specific radioimmunoassays, sensitive to plasma levels of less than 1% of normal, were developed for protein C and Factor X. In 31 normal subjects, mean plasma antigen levels were as follows: protein C, 3.23 +/- 0.79 microgram/mL (2 SD); Factor X, 7.74 +/- 1.81 microgram/mL. In patient son chronic warfarin therapy, protein C and factor X were depressed equivalently: protein C, 42% +/- 20% (of a pooled plasma reference); Factor X, 44% +/- 24%. Protein C antigen fell much more rapidly than Factor X antigen when warfarin therapy was begun, creating an initial period of potential hypercoagulability. In patients with severe liver disease, mean protein C antigen (25% +/- 17%) was lower than Factor X antigen (51% +/- 29%). Protein C antigen levels did not appear to be a sensitive indicator of compensated intravascular coagulation or systemic fibrinolysis induced by infusion of streptokinase. Clinical implications of these findings are discussed.

Topics: Blood Coagulation Factors; Cross Reactions; Disseminated Intravascular Coagulation; Factor X; Female; Glycoproteins; Hematologic Diseases; Hemostasis; Humans; Kinetics; Liver Diseases; Lupus Erythematosus, Systemic; Pregnancy; Protein C; Radioimmunoassay; Streptokinase; Warfarin

A case of intramural hematoma of the gastric cardia occurring in a young woman with S.L.E. and on warfarin is presented and discussed. This unusual case illustrates the importance of careful evaluation of radiological mass lesions of the cardia.

Topics: Adult; Aged; Cardia; Child; Female; Hematoma; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Radiography; Stomach Diseases; Warfarin

Topics: Adenosine Triphosphate; Animals; Blood Platelets; Humans; Lactates; Liver Cirrhosis; Lupus Erythematosus, Systemic; Neuraminic Acids; Neuraminidase; Platelet Adhesiveness; Purpura, Thrombocytopenic; Rabbits; Time Factors; Uremia; von Willebrand Diseases; Warfarin

A 56-year-old male patient diagnosed as a case of procainamide-induced systemic lupus erythematosus (SLE) was found to have a lymphoproliferative disorder at postmortem examination.Contrary to other immune disorders, the association of SLE with neoplasia is a rare occurrence. The present case raises the question of whether a relationship exists between the lupus diathesis and lymphoreticular neoplasia. The study of the incidence of neoplasia in families of patients with SLE may prove helpful in establishing this relationship.

Topics: Aortic Diseases; Autopsy; Blindness; Bone Marrow; Digoxin; Drug Therapy, Combination; Heart Diseases; Heparin; Humans; Immunologic Deficiency Syndromes; Kidney; Lupus Erythematosus, Systemic; Lymph Nodes; Lymphoma; Male; Middle Aged; Procainamide; Quinidine; Retinal Artery; Spleen; Thromboembolism; Warfarin