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.     

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.     

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: a clinical and laboratory study of 100 cases

Summary The clinical and laboratory features of 100 patients with lupus anticoagulant (LA) are reviewed. Subjects were divided into three groups according to their age (1–5, 15–35, 45–89 years). Female prevalence was observed in each group and overall F/M ratio was 3/1. An underlying autoimmune disease (principally lupus erythematosus) was found in 47 cases (10% of the children, 80% of the 15–35-year-old patients and 37% of the elderly patients). Biological criteria for the LA diagnosis were prolonged activated partial thromboplastin time and diluted thromboplastin time (1.3 × control), not corrected after addition of control to patient's plasma. Thromboplastin time was normal in 77 patients. Other types of coagulation inhibitors were eliminated by specific factor assays (with a 10-fold increase of cephalin concentration when necessary). Twenty-three thrombotic episodes were observed. No significant difference was found in the incidence of thrombosis between the autoimmune and non-autoimmune disease group, but the age when first thrombosis occurred was clearly lower in the former. Fourteen obstetrical accidents were noted in eight women but 13 pregnancies terminated without accident. Four patients experienced haemorrhagic complications; they all presented with a severe thrombocytopenia associated with the LA. In our experience, LA is a frequent coagulation abnormality, associated in about half of the cases with a clearly defined autoimmune disease. Clinical presentation appears as notably different according to the patient's age; it is particularly noteworthy that in nine out of 10 children, LA disappeared spontaneously within 6 months.     

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.     

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.     

Anticardiolipin antibodies and lupus anticoagulant in patients treated with different methods of renal replacement therapy in comparison to patients with systemic lupus erythematosus

Summary Antiphospholipid antibodies were found to be associated with certain clinical manifestations such as recurrent venous thrombosis or arterial occlusions in a wide spectrum of immune disorders [6]. We analyzed the plasma concentration of two isotypes (IgG, IgM) of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) activity in 84 patients with end-stage renal disease. They were receiving different types of renal replacement therapy and had a high frequency of thrombotic vascular complications. The prevalence of positive tests and the mean ACA concentration obtained in the plasma of renal patients were compared with those in patients with systemic lupus erythematosus (SLE) and in healthy controls. When analyzed as a whole group, renal patients maintained on dialysis (n=45: hemodialysis,n=20; peritoneal dialysis) or with a functioning kidney transplant (n=19) did not differ in mean ACA concentration and LAC activity (n=84, ACA: IgG 10±7 U/ml, IgM 2±1 U/ml, LAC ratio: 1.0±0.2) from healthy subjects (n=50, ACA: IgG 10±3, IgM 2±1 U/ml, LAC ratio: 1.0±0.1) but they had a higher incidence of raised IgG-ACA titers (renal replacement 14% vs. normal controls 4%,p<0.05). No significant correlation was found between thrombotic events and raised ACA or LAC activity in dialysis patients. In contrast, the proportion of SLE patients (n=51) with a raised concentration of ACA was significantly higher (IgG: 69%, IgM: 29%) than that among patients with renal replacement therapy (IgG: 14%, IgM: 4%) or normal controls (IgG: 4%, IgM: 2%,p<0.002). Moreover, recurrent manifestations of thrombosis in SLE were associated with very high IgG-ACA (n=11, IgG 117±91 U/ml) and LAC activity (LAC ratio: 2.4±0.7) in comparison to SLE patients without thrombotic events (n=40, ACA: IgG 23±13). The results of our investigations demonstrate that the pathogenetic role of these phospholipid antibodies in end-stage renal disease is far from established.     

晚发性系统性红斑狼疮41例临床分析

目的了解晚发性系统性红斑狼疮(LOSLE)以及老年人SLE的临床与有关实验室检查特点。方法将41例50岁以后和60岁以后发病的LOSLE与按1∶1配比选择的同期50岁以前发病的一般SLE患者的有关临床与实验室检查资料进行比较分析。结果LOSLE患者男∶女为1∶31,有皮疹、脱发、关节肿痛、肌肉疼痛与压痛、雷诺征、浆膜炎、肺间质病变、肾脏病变和口眼干燥征等表现者依次为390%、171%、951%、537%、49%、341%、390%、488%和366%,血清抗核抗体检出率为585%、类风湿因子的检出率为317%,有并存症者占268%,误诊率为341%,上述情况与一般SLE相比差异有显著性(P<005或P<001)。此外,LOSLE患者应用糖皮质激素疗效较好,需加用细胞毒免疫抑制剂者较少(P<005)。老年人SLE的临床和主要实验室检查特点与LOSLE基本相同。结论LOSLE和老年人SLE有轻型化与非典型化倾向,临床诊断和治疗与一般SLE有所不同。     

Acquired activated protein C resistance is associated with the co-existence of anti-prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus

Venous thromboembolism (VTE) is one of the common manifestations in the anti-phospholipid (aPL) syndrome. We examined the levels of IgG antibodies (Abs) to beta2-glycoprotein I (beta2-GP I) and prothrombin, lupus anticoagulant (LA) activity, activated protein C resistance (APC-R), and factor V Leiden in 96 patients with systemic lupus erythematosus (SLE); 19 with VTE and 77 without VTE. Acquired APC-R, which was not found in any patient with the factor V Leiden mutation, was present in 33 (34.4%) out of the 96 patients with SLE. The presence of acquired APC-R was a strong risk factor for VTE. The SLE patients were divided into four groups according to the results of enzyme-linked immunosorbent assay (ELISA) and LA activity for each aPL Abs: ELISA+, LA+; ELISA+, LA-; ELISA-, LA+; and ELISA-, LA-. A significant association was observed between APC-R and the co-existence of anti-beta2-GP I Abs and LA activity or of anti-prothrombin Abs and LA activity. There was no association between APC-R and the presence of anti-beta2-GP I Abs, anti-prothrombin Abs, or LA activity alone. However, when multivariate logistical regression analysis was performed, it was clear that only the co-existence of anti-prothrombin and LA activity was a significant risk factor for APC-R. These findings indicate that the co-existence of anti-prothrombin Abs and LA activity may be an important factor in the pathogenesis of acquired APC-R in patients with SLE.     

系统性红斑狼疮合并肺动脉高压38例临床分析

目的 分析系统性红斑狼疮(SLE)合并肺动脉高压(PHT)的发病机制、临床特点、治疗及预后.方法 对38例诊断明确、资料完整的SLE合并PHT患者进行回顾性分析.结果 38例患者中出现肺动脉高压距SLE确诊的平均间隔期为2.3年;其中3例为严重PHT;伴明显的心力衰竭;雷诺现象27例;38例患者抗核抗体(ANA)均为阳性,抗dsDNA抗体阳性21例,抗Sm抗体阳性16例,抗SSA、SSB抗体阳性8例,抗磷脂抗体升高4例,类风湿因子(RF)升高13例,抗U1RNP抗体阳性15例;合并肺纤维化者7例.所有患者经激素及免疫抑制剂等治疗后,3例死亡,余35例病情稳定.结论 PHT是SLE的一个严重并发症,预后不良,雷诺现象是其早期的临床表现.早期诊断、早期联合治疗PHT是控制病情的关键.     

系统性红斑狼疮合并肠假性梗阻12例临床分析

目的 分析系统性红斑狼疮(SLE)合并肠假性梗阻病人的临床表现及实验室检查，提高对SLE合并肠梗阻的认识。方法对12例SLE合并肠梗阻的病人进行回顾性分析，收集整理其临床资料及有关实验室检查，分析其发病情况、临床累及脏器、实验室检查、病程、治疗及预后等特点。结果发病年龄2l～56岁，平均36岁，平均病程31个月。死亡5例。以肠梗阻为首发症状者2例。有肾脏累及者9例，血液系统累及者6例，中枢神经系统累及者2例，循环系统累及者8例。其他：胃肠出血4例，腹水4例。2例以肠梗阻为首发症状者入院前分别误诊为溃疡性结肠炎和肠炎。2例曾行剖腹探查并部分小肠切除术，病理报告均提示肠道血管炎。结论SLE合并肠梗阻患者病情较重，常伴有其他脏器累及，病死率较高。以肠梗阻为首发症状的SLE患者易被误诊。有肠梗阻症状并有其他脏器累及者应排除有无SLE可能。肠道血管炎是引起肠梗阻的主要原因。     

Clinical significance of anti-annexin V antibodies in patients with systemic lupus erythematosus

Annexin V has a calcium-dependent binding affinity for anionic phospholipids and activated platelets, and prevents prothrombinase activity. We investigated the clinical significance of IgG anti-annexin V antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG anti-annexin V antibodies by ELISA. IgG anti-annexin V antibodies were detected in 27 of 140 patients (19%). Significantly higher incidences of arterial or venous thrombosis, intrauterine fetal loss, and prolonged activated partial thromboplastin time were found in patients with anti-annexin V antibodies than in those without anti-annexin V antibodies. Three patients with thrombosis were found not to have anticardiolipin antibodies, but to show sustained serological reactions for anti-annexin V antibodies, irrespective of prednisolone administration. These results indicated the clinical characteristics of SLE patients with anti-annexin V antibodies, and that these antibodies may be associated with the pathogenesis of thrombotic events. Am. J. Hematol. 54:209–213, 1997 © Wiley-Liss, Inc.     

Steady improvement of prothrombin levels after cyclophosphamide therapy in pediatric lupus anticoagulant hypoprothrombinemia syndrome (LAHPS)

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare acquired disorder associated with several different conditions but mostly with systemic lupus erythematosus (SLE). LAHPS probably results from the presence of anti-Factor II antibodies, which usually counterbalance the prothrombotic effect of the lupus anticoagulant (LAC). In fact, Factor II deficiency in SLE is invariably associated with the presence of LAC. No consensus exists for the treatment of LAHPS. Corticosteroids, with or without the addition of vitamin K or blood products, have been a successful first-line treatment. Immunoglobulin (IVIG) treatment has been shown to be effective in the setting of acute bleeding. However, in some patients, conservative treatment is not enough to control bleeding, and the addition of immunosuppressive therapy, usually azathioprine, is needed. In our patients, Factor II deficiency reappeared after tapering steroids. Both children achieved normal Factor II levels with cyclophosphamide. This effect was long-lasting, a phenomenon that has not been documented in children prior to this report.     

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     

系统性红斑狼疮合并中枢神经系统感染30例临床分析

目的 探讨系统性红斑狼疮(SEE)合并中枢神经系统感染病例的临床表现、治疗及预后特点. 方法 回顾性分析30例诊断明确,资料完整的SLE合并中枢神经系统感染患者.结果 1986年1月至2007年3月共收治SLE患者3039例,其中合并中枢神经系统感染者30例占1%,平均年龄(34±11)岁,其中女性27例,男性3例.30例患者中结核性感染11例占37%,非结核的细菌感染11例占37%,真菌感染8例占26%.中枢神经系统感染的患者以发热、头痛、意识障碍为常见临床表现.预后方面3组间差异无统计学意义. 结论 SLE患者合并中枢神经系统感染表现不典型,最常见的是结核性脑膜炎,及早行腰椎穿刺检查有助于早诊断.低自蛋白血症、低C3及低颅压提示预后不佳.     

Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism

Venous thromboembolism (VTE) is a well-recognized complication of autoimmune haemolytic anaemia (AIHA), and is a major cause of morbidity and mortality in this disorder. However, the incidence, pathogenesis and risk-factors for VTE in AIHA remain poorly defined. Lupus anticoagulants (LA) and anticardiolipin (ACA) antibodies are autoantibodies directed against epitopes on prothrombin or beta2 glycoprotein I (beta2-GPI). Both LA and ACA (together called antiphospholipid antibodies, APLA) are associated with VTE. We have prospectively studied the occurrence of VTE and APLA in 30 patients with AIHA. VTE was objectively documented in eight (27%) patients. APLA were detected in 19 (63%) patients with AIHA, of whom nine (30%) had a LA and 17 (57%) ACA. Seven patients had both LA and ACA. Among the eight patients with VTE, LA was detected in five (63%) and ACA in four (50%). There was a statistically significant association between presence of LA and occurrence of VTE (RR: 7.50, 95% CI: 1.25-45.2, P = 0.03). VTE is a frequent and life-threatening complication of AIHA. Detection of the lupus anticoagulant in patients with AIHA identifies individuals at significantly increased risk for VTE. Future studies should address the role of prophylactic anticoagulation in patients with AIHA.     

系统性红斑狼疮患者血浆D-二聚体水平测定及其临床意义

目的 了解系统性红斑狼疮（ＳＬＥ）患者Ｄ－二聚体的水平测定及其临床价值。方法 用单克隆抗体乳胶凝集试验法测定５９例ＳＬＥ患者血浆Ｄ－二聚体水平。结果 （１）ＳＬＥ患者血浆Ｄ－二聚体水平较正常组显著增高（Ｐ〈０．００１）;（２）ＳＬＥ患者血浆Ｄ－二聚体水平与ＳＬＡＭ得分呈显著正相关（ｒ＝０．５５４,Ｐ〈０．００１）;（３）Ｄ－二聚体阳性组ＳＬＡＭ得分、发生血管炎、狼疮性肾炎均明显高于阴性组（Ｐ〈０．