Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases

To define clinical and laboratory characteristics of the lupus anticoagulant (LA), we reviewed our experience (219 subjects). Subjects were divided into group A, those with the LA and the diagnosis of lupus erythematosus, group B, those with the LA but nonlupus diagnoses, and group C, those with drug-related lupus syndromes. The typical laboratory findings consisted of a prolonged and inhibited plasma clot time (an average of 1.9 times control time) which was proportionately more prolonged than the partial thromboplastin time or activated partial thromboplastin time (APTT) (average 1.3 times control). Ninety-eight percent had a prolonged plasma clot time and 94% had a prolonged partial thromboplastin time. The prothrombin and thrombin times were prolonged in 33 and 25% of subjects, respectively. Washed platelets shortened the APTT in the 22 subjects so tested. Monoclonal protein peaks were seen in 7% of patients. Seventeen episodes of bleeding were observed, but in all but one instance there was another hemostatic defect present. In the 18 patients who underwent major operations, there were no hemorrhagic complications. Fifty-eight episodes of thrombosis were observed with the same incidence in group A (25%) as in group B (26%). Bleeding is rare with the LA but thrombosis is common even without SLE and lupuslike syndromes. The plasma clot time in platelet-rich plasma is more prolonged, and in our experience, is more sensitive in detecting the lupus anticoagulant than is the partial thromboplastin time.     

Clinical analysis of 125 patients with the lupus anticoagulant

:A retrospective analysis of 125 consecutive lupus anticoagulant (LA) positive patients and 125 age, sex matched lupus anticoagulant negative controls is reported with the aims of defining further the clinical spectrum of disease, determining at-risk subgroups and management strategies. There was no significant difference in the incidence or pattern of complications in those with systemic lupus erythematosus (SLE) and related disorders, and those without SLE. Venous thromboembolism, immune thrombocytopenia, foetal loss, depression and hypertension were statistically more common in the LA group than in the control group. In contrast to previous reports, children aged ten years or less with the LA developed significantly more complications than controls. Patients with the LA secondary to drugs also developed complications, a finding which is also at variance with previous reports. There was a significant difference in the outcome of arterial disease (p < 0.04) and venous thromboembolism ( p < 0.001) when long term anticoagulation was part of the treatment regimen. (Aust NZ J Med 1993; 23: 151–156.)     

Clinical manifestations and laboratory findings in patients with lupus anticoagulants

Clinical and laboratory features were evaluated in 48 patients with lupus anticoagulants and the efficiency of three different assays in the detection of lupus anticoagulants was compared. The diagnosis of lupus anticoagulants was based on a prolonged activated partial thromboplastin test not corrected in a mixture of 1:1 with normal plasma and lack of specific inhibitors against coagulation factors. Platelet neutralization procedure was positive for lupus anticoagulants in 98% of the patients, tissue thromboplastin inhibition ratio in 79%, and kaolin clotting time index in 77%. At least one of the assays was positive in 100% of the cases. The largest minority of the patients (31%) suffered from systemic lupus erythematosus. The others had a variety of non-immunological disorders. In the 13 patients who had been operated on, only 1 with renal failure developed hemorrhagic complications after renal biopsy due to thrombocytopathy. The incidence of recurrent spontaneous miscarriage, immune thrombocytopenia and positive direct antiglobulin test, anti-nuclear and anti-DNA antibodies and VDRL was significantly higher in patients with lupus anticoagulants and systemic lupus erythematosus compared to patients with lupus anticoagulants but without systemic lupus erythematosus.     

Diagnosis of lupus anticoagulant in the lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature

We report a severe hemorrhagic disorder in two pediatric patients with lupus anticoagulant (LA) associated to acquired factor II (prothrombin) deficiency. In both patients, hemorrhagic symptoms resolved after corticosteroid therapy. Serial coagulation studies showed that Staclot LA assay was more sensitive than DVVconfirm and Staclot PNP tests to confirm the presence of LA when associated with severe factor II deficiency. Both patients had non-neutralizing anti-prothrombin antibodies and their titers inversely correlated with factor II activity (r = -1.0, P < 0.0001). Associated findings in these patients included positive immunologic tests for systemic lupus erythematosus, a positive anti-cardiolipin antibody, and anti-beta(2) GPI antibodies in one case. Our findings point out the difficulty in diagnosing LA associated with acquired factor II deficiency and suggest that, in confirmation of its phospholipid dependency, the inclusion of a source of normal human plasma in the test sequence to correct for any factor deficiency and a confirmatory step utilizing hexagonal (II) phase phospholipids may be crucial to the diagnosis of LA in some patients with LA-hypoprothrombinemia syndrome.     

High prevalence of thrombocytopenia in SLE patients with a high level of anticardiolipin antibodies combined with lupus anticoagulant

The relationship between thrombocytopenia and the level of anticardiolipin antibodies (aCL) and/or the existence of lupus anticoagulant (LA) ware studied in 146 patients with systemic lupus erythematosus (SLE). These patients were divided into six groups: A, those LA positive with a high level of aCL (>10 U/ml) (10 cases); B, those LA positive with a low level of aCL (3–10 U/ml) (15 cases); C, those LA positive but aCL negative (<3 U/ml) (12 cases); D, LA negatives with a high level of aCL (12 cases); E, LA negatives with a low level of aCL (16 cases); and F, aCL and LA double negatives (81 cases). The prevalence of thrombocytopenia (platelet count ≦ 100 × 10⁹/L) was by far the highest in group A (9/10 cases, 90.0%, P < 0.005, Fisher's exact probability test) as compared with group B (4/15 cases, 26.7%), group C (4/12 cases, 33.3%), group D (1/12 cases, 8.3%), group E (4/16 cases, 25.5%), and group F (9/81 cases, 11.1%). When the relationship between moderate thrombocytopenia and arterial or venous thrombosis was studied in these patients with SLE, thrombocytopenia was detected in 10 (83.3%, P < 0.005, Fisher's exact probability test) of 12 patients with arterial thrombosis; however, it was present in only 4 (23.5%) of 17 patients with venous thrombosis and in 14 (12.3%) of 114 patients without thrombosis. These findings suggest that a high aCL activity combined with LA positively reflects a high risk for both thrombocytopenia and arterial thrombosis. Am. J. Hematol 58:55–60, 1998. © 1998 Wiley-Liss, Inc.     

Platelet autoantibodies detected by immunoblotting in systemic lupus erythematosus: association with the lupus anticoagulant, and with history of thrombosis and thrombocytopenia

71 patients with systemic lupus erythematosus (SLE) were studied for the occurrence of platelet antibodies by immunoblotting. Binding of IgG antibodies to platelet protein antigens was observed in 39 of the 71 patients. The most frequently detected and exceptionally strongly reacting antibodies were directed against platelet protein antigens with an approximate molecular weight of 65 kDa under nonreducing conditions. These antibodies were autoreactive and, when followed, they usually persisted. Interestingly, in this group of well-defined SLE patients, platelet antibodies against the most common targets (65 kDa) were significantly associated with the lupus anticoagulant, a history of thrombocytopenia and thrombosis, particularly with arterial occlusions. The lupus anticoagulant, on the other hand, correlated significantly only with venous thrombosis. In addition to the lupus anticoagulant, platelet antibodies against this unknown platelet protein may thus be a marker of a higher risk of thrombosis in SLE patients.     

Lupus anticoagulant in children with thrombosis

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. © 1995 Wiley-Liss, Inc.     

Massive hepatic infarction in systemic lupus erythematosus

Summary Liver disease in systemic lupus erythematosus, as demonstrated by abnormal histopathology, is rare and usually mild; typically, this hepatic disease is of chronic nature and not related to a hypercoagulable state. A patient is described in whom life-threatening hypercoagulability in association with systemic lupus erythematosus resulted in extensive liver infarction. Follow-up radionuclide liver scintigraphy suggested that regenerative recovery in the infarcted areas of the liver may be delayed or absent, but there was no evident functional hepatic impairment.     

Resolution of Hypoprothrombinemia‐Lupus Anticoagulant Syndrome (HLAS) after multidrug therapy with rituximab: a case report and review of the literature

Hypoprothrombinemia associated with a lupus anticoagulant (LA) was first reported in the literature over 50 years ago. The hypoprothrombinemia‐lupus anticoagulant syndrome (HLAS) is a rare bleeding diathesis that has been associated with LAs in adult and paediatric patients with systemic lupus erythematosus (SLE) and with transient LAs due to other causes. There are no standard recommendations for treating haemorrhage associated with this syndrome. Herein, we report a patient with SLE and HLAS who achieved a durable remission following treatment with intravenous immune globulin (IVIG), prednisone and rituximab.     

Lupus anticoagulant,Factor V Leiden,and methylenetetrahydrofolate reductase gene mutation in a lupus patient with cerebral venous thrombosis

We describe the case of a young Lebanese woman with systemic lupus erythematosus (SLE) and a positive lupus anticoagulant (LAC) who developed right internal jugular vein and sigmoid sinus thrombosis. Coagulation studies showed that in addition to the LAC the patient was heterozygous for the factor V (FV) Leiden mutation, and C677T mutation of the methylenetetrahydrofolate reductase gene. The high prevalence of FV Leiden in the eastern Mediterranean region suggests that we should probably screen our SLE patients in this area, especially those with anticardiolipin antibodies and/or LAC who have no history of thrombosis, for this and other thrombophilia markers. The detection of such abnormalities may have major practical consequences for the long-term management of these patients to prevent further thrombotic episodes.Abbreviations APS Antiphospholipid syndrome - CVT Cerebral venous thrombosis - LAC Lupus anticoagulant - DVT Deep vein thrombosis - SLE Systemic lupus erythematosus - SVC Superior vena cava     

Lupus anticoagulant testing: improvements in performance in a UK NEQAS proficiency testing exercise after dissemination of national guidelines on laboratory methods

Laboratory screening for lupus anticoagulant (LA) has been shown to be suboptimal in several studies. Guidelines have recently been published by an expert group for the British Committee for Standards in Haematology, in an attempt to standardize and improve screening procedures. The value of using screening tests conforming with these guidelines was investigated in a United Kingdom National External Quality Assessment Scheme (UK NEQAS) proficiency testing exercise. The correct diagnosis was achieved by 97% of laboratories for a LA-negative sample. However, 18.3% of centres reported a false-negative result for a sample from a LA-positive subject. A significantly higher proportion of centres that used methods conforming with the published guidelines achieved the correct diagnosis for this sample (P < 0.002, chi-square test). A wide variety of screening tests were used by laboratories in this study. Within-method agreement could be improved by the use of a common normal pooled plasma to determine ratios. However, between-method agreement was not improved by this procedure. We conclude that adoption of methods compliant with national guidelines may improve the diagnosis of LA. There is a need, however, for reference and standardization materials to ensure further improvement in the accuracy of LA methods.     

系统性红斑狼疮男性患者临床及免疫学特征

目的 分析142例男性系统性红斑狼疮(SLE)患者起病时首发及发病过程中临床表现特征、自身抗体分布以及其他实验室指标改变特征,探讨SLE男性患者的临床及免疫学特征.方法 收集1994年4月至2010年4月于本院风湿免疫科住院的男性SLE患者142例,年龄12 ～ 68岁,平均年龄31.9岁;同期住院女性SLE患者320...     

系统性红斑狼疮合并淋巴瘤临床特征

目的探讨系统性红斑狼疮(SLE)合并恶性淋巴瘤(ML)的临床特点。方法回顾1998年1月至2012年2月北京协和医院收治的9例SLE合并ML患者的临床资料,分析其临床表现、实验室检查指标、淋巴瘤病理分型、治疗及预后。结果 SLE合并ML患者共9例,占同期SLE入院患者的0.18%;其中女性患者7例,男性患者2例;SLE平均发病年龄43.1岁(24～57岁),SLE平均确诊年龄为44.7岁(29～57岁),淋巴瘤平均确诊年龄为48.7岁(39～63岁),SLE发病到合并淋巴瘤病程均数为3.8年(1～15年)。淋巴瘤病理类型以非霍奇金淋巴瘤(NHL)为主,共7例,占77.8%(7/9),且淋巴瘤结外受累多见,共7例,占77.8%(7/9)。淋巴瘤在消化系统、呼吸系统、骨髓等部位均可发生,其中胃肠道受累3例,支气管和肺受累2例,骨髓受累2例。SLE合并ML患者中100%出现关节痛、淋巴结肿大及发热。实验室检查结果发现9例患者中6例补体减低,9例乳酸脱氢酶升高,5例红细胞沉降率(ESR)升高大于100mm/h。SLE合并ML的患者6例对化疗敏感,4例死亡,2例死因均为淋巴瘤消化道受累;2例诊断淋巴瘤放弃治疗后死亡。结论当SLE患者出现不明原因持续发热、淋巴结肿大、ESR持续大于100mm/h,乳酸脱氢酶持续偏高者需警惕SLE合并淋巴瘤的可能。当SLE合并淋巴瘤时结外受累多见,SLE合并ML多数对化疗敏感,但消化道受累时预后差。