An Immunoenzyme Histochemical Technique for the Detection of Platelet Antibodies from the Serum of Patients with Idiopathic (Autoimmune) Thrombocytopenic Purpura (ITP)

The resent report describes a simple, reproducible, semi-quantitative immunohistochemical assay for the detection of antiplatelet antibody. Evaluation of the technique in 10 children with active idiopathic (autoimmune) thrombocytopenic purpura (ITP), seven children with thrombocytopenia due to other causes, and 12 normal individuals revealed that the assay consistently and reliably distinguished children with ITP from the other groups. Individuals who had had multiple platelet transfusions and individuals with systemic lupus erythematosus (SLE) also had antiplatelet antibodies detectable using this technique although the levels were less than those of individuals with ITP. The method can be used effectively to monitor the course of ITP and the effects of therapy.     

Anticardiolipin antibodies in autoimmune thrombocytopenic purpura

Using a recently devised solid phase radioimmunoassay to detect anticardiolipin antibodies, we report the presence of these antibodies in 30 of 96 patients with chronic autoimmune thrombocytopenic purpura (AITP). IgG anticardiolipin antibody levels were elevated in 14 patients and IgM anticardiolipin antibody levels were elevated in 27 patients. We suggest that these antibodies may mediate peripheral platelet destruction by binding to phospholipids in the platelet membrane. It is also conceivable that the presence of anticardiolipin antibodies may select a subpopulation of patients with chronic AITP who may go on to develop other autoimmune disorders, such as systemic lupus erythematosus.     

Plasma exchanges as treatment of severe acute immune thrombocytopenic purpura

INTRODUCTION: High dose steroids and intravenous immunoglobulins are the gold treatment of acute immune thrombocytopenic purpura, before splenectomy for severe and refractory forms of the disease. Authors report two cases of severe acute refractory immune thombocytopenia with a dramatic response to plasma exchanges. EXEGESIS: The first case was an idiopathic form, complicated by hemorragic peritoneal effusion. After failure of steroids, intravenous immunoglobulins and splenectomy and 2 courses of rituximab, plasmapheresis normalized in 3 days platelet count. In the second observation, ITP was associated to systemic lupus with antiphospholipids antibodies and multivisceral failure, despite steroids and intravenous immunoglobulins. After 3 plasma exchanges, platelet count was normalized, and the patient is under remission after 24 months follow-up. CONCLUSION: Plasmapheresis must be evaluated as an emergency treatment in refractory forms of acute immune thrombocytopenic purpura.     

Pancreatitis leading to thrombotic thrombocytopenic purpura in systemic lupus erythematosus: a case report and review of literature

Pancreatitis is a well-established but unusual complication of thrombotic thrombocytopenic purpura (TTP). It is also an unusual complication of systemic lupus erythematosus (SLE). However, TTP occurring as a consequence of acute pancreatitis in a patient with SLE has never been reported. We report a 24-year-old African American woman with active systemic lupus (SLE) who developed thrombotic thrombocytopenic purpura (TTP) following an episode of acute pancreatitis. The TTP was manifested by low-grade fever, microangiopathic hemolytic anemia, renal insufficiency, altered mental status, seizures and thrombocytopenia. The patient was initially treated with pulse corticosteroids with inadequate response and subsequently with daily plasmaphresis, leading to full remission. This case represents first report of pancreatitis leading to TTP in a patient with systemic lupus erythematosus.     

Splenectomy does not cure the thrombocytopenia of systemic lupus erythematosus

Fourteen patients with systemic lupus erythematosus had splenectomies done between 1960 and 1982 for treatment of severe thrombocytopenia. Thrombocytopenia persisted or recurred within 1 month postoperatively in five patients and within 6 months in three others. Three patients had late recurrence (18, 30, and 54 months after splenectomy); in two it was probably related to withdrawal of immunosuppressive agents or corticosteroids. Median lowest platelet count before splenectomy and median platelet count at relapse or failure of splenectomy were both 8000/microL. Only two patients maintained normal platelet counts without need for corticosteroids or other treatment. These results differ from those in patients with idiopathic thrombocytopenic purpura. Other treatments should be tried before splenectomy is done for thrombocytopenia in patients with systemic lupus erythematosus.     

Circulating lupus coagulation inhibitor in two sisters, one with disseminated lupus erythematosus and the other with immunologic thrombocytopenic purpura]

Familial cases of lupus anticoagulant were rarely described. We report the observation of two sisters with lupus anticoagulant, one with thrombocytopenic purpura and the other with systemic lupus erythematosus.     

Thrombotic thrombocytopenic purpura preceding systemic lupus erythematosus.

The case of a patient admitted with thrombotic thrombocytopenic purpura nine years after developing systemic lupus erythematosus (SLE) is reported. Thrombotic thrombocytopenic purpura associated with SLE has been described on other occasions, but in most patients the diagnosis of SLE precedes that of thrombotic thrombocytopenic purpura. The unusual sequence and the chronological separation of the two diseases is emphasised.     

rhTPO在系统性红斑狼疮合并难治性血小板减少性紫癜治疗中的应用

目的评价国产重组人血小板生成素（rhTPO）用于系统性红斑狼疮（SLE）合并难治性血小板减少性紫癜的可行性及安全性。方法对12例SLE并难治性血小板减少性紫癜患者行国产rhTPO皮下注射,15000U／d,疗程14d。检测用药前、用药后7、10、14d及停药3个月后的血小板数,判定疗效及不良反应情况。结果用药前血小板计数为（14．3±5．2）×10^9／L,用药后7、10、14d分别为（37．8±9．3）×10^9／L、（64．2±15．6）×10^9／L、（84．3±25．7）×10^9／L,与用药前相比,P均〈0．01。停药后3个月血小板计数为（53．2±15．6）×10^9／L,与治疗前比较,P〈0．01。总有效率为83．33％,仅2例出现轻微不良反应。结论rhTPO治疗SLE合并难治性血小板减少性紫癜疗效确切,且较为安全。     

Thrombotic thrombocytopenic purpura associated with myasthenia gravis

A case of thrombotic thrombocytopenic purpura (TTP) associated with myasthenia gravis (MG) is reported. A 56-year-old woman was admitted to our hospital on April 27, 1988, because of easy fatigue and double vision. She was diagnosed as having myasthenia gravis from her neurological and laboratory findings. On the 14th hospital day, she developed fever, jaundice, hematuria, purpura and consciousness disturbance. Hematological examination revealed marked anemia, thrombocytopenia, fragmented red blood cells, elevated bilirubin and LDH level. Coagulation studies were almost normal. She was diagnosed as having TTP and treated with corticosteroid, antiplatelet agents and plasma exchange. Clinical condition and laboratory findings improved by the 23rd hospital day. It has been reported that TTP is associated with various autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, Sj?gren's syndrome or idiopathic thrombocytopenic purpura. However TTP associated with MG appears the first report. This case may suggest that one of pathogenesis of TTP is autoimmune mechanism.     

Development and characterization of monoclonal antiplatelet autoantibodies from autoimmune thrombocytopenic purpura-prone (NZW x BXSB)F1 mice

Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, progressive thrombocytopenia, lupus nephritis, and degenerative coronary vascular disease with myocardial infarction. Platelet-associated IgG (PAIgG) on the platelet surface mediates platelet destruction by the reticuloendothelial system in the autoimmune thrombocytopenic purpura (ATP) of W/BF1 mice. Because the epitopes targeted in ATP by PAIgG have not been identifiable using serum from thrombocytopenic W/BF1 mice, we developed seven hybridomas secreting antiplatelet monoclonal antibodies (MoAbs) using splenocytes of thrombocytopenic W/BF1 mice. Epitopes recognized by three MoAbs were similar to those recognized by PAIgG, because eluted IgG from platelets of thrombocytopenic W/BF1 mice inhibited platelet binding by MoAbs in competitive micro-enzyme-linked immunosorbent assay. Hybridoma cells or purified Ig from the ascites of two clones (2A12 and 6A6), when injected into nude mice produced acute thrombocytopenia, elevated the levels of PAIgG, purpura, and megakaryocytosis. MoAbs of two clones also reacted with single-stranded DNA or double-stranded DNA, and one of these clones (4-13) bound to cardiolipin (CL) but was nonpathogenic in nude mice, suggesting that anti-CL and antiplatelet autoantibodies can be distinct. On immunoblotting analysis, antiplatelet MoAbs frequently bound a 100-Kd platelet protein. These MoAbs contribute to an understanding of the etiopathogenesis of ATP and the several antigens and autoantibodies involved.     

Bilateral nephrectomy for the treatment of refractory lupus nephritis with features overlapping with thrombotic microangiopathy resembling thrombotic thrombocytopenia purpura

We report a patient with a diagnosis of systemic lupus erythematosus who concurrently developed a syndrome of thrombotic microangiopathy that resembled thrombotic thrombocytopenic purpura. The patient underwent plasma exchange and immunosuppressive therapy for months before clinical improvement was finally achieved through bilateral nephrectomy. Ultimately, our patient died of disseminated aspergillosis from prolonged immunosuppression. We believe that recognition of bilateral nephrectomy as a potential treatment earlier in her course would have spared her this unfortunate demise. We hope that this review of current literature will help the reader to consider bilateral nephrectomy in patients with refractory systemic lupus erythematosus with clinical overlap of thrombotic microangiopathy resembling thrombotic thrombocytopenic purpura.     

Ticlopidine-induced lupus: a report of 4 cases

Drug-induced lupus has been associated with various medications. Ticlopidine hydrochloride is a platelet aggregation inhibitor that has been associated with thrombotic thrombocytopenic purpura, which is believed to be immune mediated. We describe 4 patients with drug-induced lupus following the institution of ticlopidine therapy. The 4 patients, who had systemic lupus erythematosus following ticlopidine use, were examined between 1997 and 1999. The clinical features of these patients, namely, older age of onset, presence of pleurisy and arthritis, and paucity of central nervous system, renal, or skin involvement, are consistent with drug-induced lupus. All had detectable antihistone antibodies. All 4 patients had clinical and serological improvement following ticlopidine withdrawal, allowing cessation or reduction of corticosteroid therapy. We suspect that ticlopidine can cause drug-induced lupus, and that this exposure should be considered particularly in the examination of elderly patients with systemic lupus erythematosus.     

Refractory thrombotic thrombocytopenic purpura in a lupus nephritis patient

Thrombotic thrombocytopenic purpura is an uncommon disease and is rare in systemic lupus erythematosus. Rarely, patients do not respond to plasma exchange therapy, and treatment options are limited and often disappointing, thus it is a therapeutic challenge to clinicians. We report a patient with lupus nephritis who developed refractory thrombotic thrombocytopenic purpura and was subsequently treated with cyclosporin A. An immediate and sustained response was demonstrated, and she remained well; eventually she was able to be cyclosporin free after the acute episode. Cyclosporin A can be a safe and effective therapeutic option in patients with refractory thrombotic thrombocytopenic purpura.     

Thrombotic thrombocytopenic purpura and systemic lupus erythematosus.

We report two patients with systemic lupus erythematosus who subsequently developed thrombotic thrombocytopenic purpura. In each case the coexistence of these two conditions was confirmed by pathological findings. Both patients responded to treatment, but one eventually died. A review of the literature suggests a possible relationship between the two disorders.     

Cyclic immune thrombocytopenia responsive to thrombopoietic growth factor therapy.

We report a patient with cyclic thrombocytopenia and antiplatelet antibodies, a variant of chronic immune thrombocytopenic purpura (ITP), with a several year history of periodic fluctuation of the platelet count, megakaryocytic hyperplasia and high-titer anti-GPIb-specific antiplatelet antibodies. The patient was resistant to multiple forms of therapy but has responded to the thrombopoietic growth factor, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). This case suggests that some patients with classic ITP may respond to thrombopoietic growth factors.     

Specific antiplatelet autoantibodies in patients with antiphospholipid antibodies and thrombocytopenia

By means of immunoblotting and monoclonal antibody immobilization of platelet antigens (MAIPA) we have studied the specificity of antiplatelet antibodies in patients with antiphospholipid antibodies and thrombocytopenia defined as presence of anticardiolipin IgG and a platelet count below 100 × 10⁹/l. The study group consisted of 10 patients with systemic lupus erythematosus (SLE), 8 patients with primary anti-phospholipid syndrome (PAPS) and 16 patients with idiopathic thrombocytopenic purpura (ITP). The comparison group was formed by 17 patients with classical chronic ITP without anticardiolipin IgG. We identified the 80–100, 130–150 and 150–170 KD surface proteins that comigrate with GPIIIa, GPIIb and GPIb and a 50–70 KD cytoplasm band by immunoblot. In patients with classical chronic ITP, the prevalence of the antiplatelet antibodies against GPIIIa was 53% on immunoblot assay and 47% on MAIPA. In ITP patients who had also anti-phospholipid antibodies in serum, the percentage of reactivity to GPIIIa declined to 37% on immunoblot and 21 % on MAIPA but it was not statistically different from the percentage observed in patients with classical ITP. Autoantibodies to platelet surface glycoproteins were almost absent in SLE and PAPS patients, who showed a significant prevalence (78%) of IgG reactivity to the 50–70 KD internal platelet protein which was frequently encountered also in patients with ITP and aPL (56%). Our study provides additional evidence that platelet antigens in patients with phospholipid-associated secondary immune thrombocytopenia are different from those of primary ITP, and that surface glycoproteins were not involved.     

Platelet antibody binding in systemic lupus erythematosus

Using a combination of enzyme-linked immunosorbent assay and SDS-PAGE with protein blot (Western blotting), increased levels of serum platelet bindable immunoglobulin (SPBIg) were demonstrated in 10 of 10 thrombocytopenic patients with systemic lupus erythematosus (SLE) (7.0-60 fg Ig/platelet) with consistent binding to SDS-PAGE platelet fractions of approximate molecular weight (120 and 80 kDa). This pattern of Ig binding was characteristic of SLE and was not seen in 20 normal volunteers and infrequently seen in 20 patients with idiopathic thrombocytopenic purpura.     

Antibodies against platelet glycoproteins and antiphospholipid antibodies in autoimmune thrombocytopenia

Abstract: Autoantibodies against platelet glycoproteins (anti-GP) are found in the majority of patients with autoimmune thrombocytopenia (AITP) as well as in thrombocytopenia associated with systemic lupus erythematosus (SLE). Some of these patients may have anti-phospholipid antibodies (anti-PL). To evaluate the pathogenetic significance of anti-PL and anti-GP antibodies in AITP and SLE patients, we investigated anti-cardiolipin (anti-CL), anti-phosphatidylserine (anti-PS) and anti-GP antibodies (anti-GPIIb-IIIa and anti-GPIb-IX) in 71 patients with AITP and 3 thrombocytopenic patients with SLE. Anti-GP antibodies were detected in 52 (70%) patients. Fifty-six (73%) patients showed anti-PL antibodies. Seven patients (6 AITP, 1 SLE) with both anti-GPIIb-IIIa and IgG anti-PL antibodies were followed during treatment with corticosteroids. Antibodies were measured before treatment and at the time of platelet-peak. Anti-GPIIb-IIIa antibodies decreased in all or became undetectable in five. In contrast, IgG anti-PS and IgG anti-CL antibodies decreased only moderately or remained positive. Adsorption experiments, using gelfiltered platelets, erythrocyte (Ec)-inside-out-vesicles and purified GPIIb-IIIa, showed that anti-GP and anti-PL antibodies have distinct specificities and do not crossreact. We conclude that anti-PL and anti-GP antibodies may be present simultaneously in some patients with immune mediated thrombocytopenia. Although anti-PS as well as anti-CL antibodies may be responsible for thrombocytopenia, we speculate that anti-GPIIb-IIIa antibodies are more related to the severity of thrombocytopenia.     

Systemic lupus erythematosus presenting as thrombotic thrombocytopenic purpura

We describe a 10-year-old girl, who presented with thrombotic thrombocytopenic purpura (TTP) and shortly thereafter developed systemic lupus erythematosus (SLE). The association between TTP and SLE is known, but this is the first report of SLE presenting as TTP.     

Haemolytic-uraemic syndrome during severe lupus nephritis: efficacy of plasma exchange

Systemic lupus erythematosus (SLE) has been described as a cause of thrombotic microangiopathy, especially thrombotic thrombocytopenic purpura (TTP). Haemolytic-uraemic syndrome (HUS) is less frequent in SLE. We report a case of such an association during an episode of severe lupus nephritis in a young woman, who was successfully treated with steroids, cyclophosphamide and especially plasma exchange with plasma replacement. This report highlights the importance of recognising atypical HUS in SLE patients by looking for schistocytes in case of haemolytic anemia with a negative antiglobulin test, in order to begin plasma exchange.