Late appearance of thrombotic thrombocytopenic purpura after autoimmune hemolytic anemia and in the course of chronic autoimmune thrombocytopenic purpura: two case reports

The association between thrombotic thrombocytopenic purpura (TTP) and autoimmune hematological conditions is reported in 2 patients. In a 35-year-old man, acute autoimmune hemolytic anemia (AIHA) was diagnosed in 1960; until 1965 he was free of disease, when he abruptly developed TTP and failed to respond to blood transfusions and corticosteroids. In a 14-year-old girl, autoimmune thrombocytopenic purpura (AITP) was diagnosed in 1981 and treated with corticosteroids and splenectomy. Four years later the patient was admitted with acute catastrophic signs and symptoms of TTP and failed to respond to plasmapheresis and plasma transfusions. The present case reports of associations between AIHA and AITP with TTP support the connection of the latter with abnormalities of the immune system.     

Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia

A new automated method to reliably quantify reticulated platelets, expressed as the immature platelet fraction (IPF), has been developed utilizing the XE-2100 blood cell counter with upgraded software (Sysmex, Kobe, Japan). The IPF is identified by flow cytometry techniques and the use of a nucleic acid specific dye in the reticulocyte/optical platelet channel. The clinical utility of this parameter was established in the laboratory diagnosis of thrombocytopenia due to increased peripheral platelet destruction, particularly autoimmune thrombocytopenic purpura (AITP) and thrombotic thrombocytopenic purpura (TTP). Reproducibility and stability results over 48 h were good. An IPF reference range in healthy individuals was established as 1.1-6.1%, with a mean of 3.4%. Patients in whom platelet destruction might be abnormal, were studied and two of these patients followed serially during the course of treatment. The IPF was raised in several disease states. The most significant increases in IPF values were found in patients with AITP (mean 22.3%, range 9.2-33.1%) and acute TTP (mean 17.2%, range 11.2-30.9%). Following patients during treatment demonstrated that as the platelet count recovered the IPF% fell. These results show that a rapid, inexpensive automated method for measuring the IPF% is feasible and should become a standard parameter in evaluating the thrombocytopenic patient.     

Autoimmune thrombocytopenia in a patient with small cell lung cancer developing after chemotherapy and resolving following autologous peripheral blood stem cell transplantation.

A 46-year-old white male with small cell lung cancer (SCLC) limited to the thorax developed autoimmune thrombocytopenic purpura (AITP), following a cyclophosphamide, paclitaxel and G-CSF-containing regimen for peripheral blood stem cell (PBSC) mobilization. AITP associated with small or non-small cell lung cancer has been reported. We considered that the AITP in this case may be a part of paraneoplastic syndrome, which is frequently seen in patients with SCLC. The patient received HDC and autologous PBSC transplantation (APBSCT) for SCLC and the AITP resolved following transplantation, thus supporting the concept of HDC + APBSCT for the treatment of autoimmune diseases.     

Thrombotic thrombocytopenic purpura complicating systemic lupus erythematosus. Case report and literature review from the plasmapheresis era.

Although thrombotic thrombocytopenic purpura (TTP) has been described in patients with systemic lupus erythematosus (SLE), the relationship between these 2 diseases is controversial. We recently treated a patient with longstanding SLE who developed TTP. The patient responded to therapy with aggressive plasmapheresis. Review of the literature revealed that TTP may occur in the setting of either active or inactive SLE. Survival in SLE associated TTP correlated with the use of plasma therapy (plasma infusion or plasmapheresis) rather than with the activity of the underlying autoimmune disease. We conclude that TTP and SLE represent distinct clinical entities that may occur together in an immunologically predisposed host. The use of plasma therapy appears to have had a significant impact on survival in these patients.     

High-dose methylprednisolone is an alternative treatment for adults with autoimmune thrombocytopenic purpura refractory to intravenous immunoglobulins and oral corticosteroids

Eight patients with severe chronic autoimmune thrombocytopenic purpura (AITP) refractory to high-dose intravenous immunoglobulin (IVIgG) and/or oral prednisone were treated with one to three infusions of high-dose methylprednisolone (HDMP) (15 mg/kg/day). The mean platelet count before treatment was 12 ± 10 × 10⁹/L. HDMP therapy led to a safe platelet count (>50 × 10⁹/L) after 2-5 days in five patients, and a minimal platelet increase (34 × 10⁹/L) able to stop bleeding in a sixth patient. The effect of HDMP was, however, translent in four of the five responders. No side effects were observed, even in the four patients older than 70 years. HDMP thus appears to be a good alternative in emergency situations or prior to surgery for patients with AITP refractory to conventional therapy.     

Rituximab was effective on refractory thrombotic thrombocytopenic purpura but induced a flare of hemophagocytic syndrome in a patient with systemic lupus erythematosus

We report the case of a patient with systemic lupus erythematosus (SLE) who first revealed hemophagocytic syndrome (HPS), which was treated successfully with glucocorticoid and intravenous cyclophosphamide. The patient then demonstrated refractory thrombotic thrombocytopenic purpura (TTP) with normal a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-13 activity that responded well to rituximab. After rituximab treatment, the patient showed a flare of HPS that was controlled by additional intravenous cyclophosphamide treatment. This case showed that TTP with normal ADAMTS-13 activity is B-cell dependent and indicated that B-cell depletion might exacerbate some autoimmune conditions in SLE.     

Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: disease activity and the use of cytotoxic drugs

Thrombotic thrombocytopenic purpura (TTP) is a rare and occasionally fatal haematologic disorder that can coexist with systemic lupus erythematosus (SLE) and other autoimmune diseases. We identified all cases of TTP seen in our institution over a 3 year period using a computerized database. We found that SLE activity (measured by the SLE Disease Activity Index) and TTP activity ran a parallel course in three patients with coexistent SLE and TTP. TTP in these three patients, although refractory to plasmapheresis, responded to cytotoxic therapy. These observations further support an autoimmune contribution to the pathogenesis of some cases of TTP. A literature review revealed that mortality in SLE patients with more severe, refractory TTP treated with plasmapheresis and cytotoxics, may not be higher than in patients responding to plasmapheresis alone (who are likely to have milder disease). These data suggest that cytotoxics may have a role in treatment of patients with active SLE and TTP refractory to plasmapheresis.     

Anti-phospholipid antibodies and thrombotic thrombocytopenic purpura

Anti-phospholipid antibodies were measured in 9 patients with active thrombotic thrombocytopenic purpura (TTP). 8 patients had primary TTP and one had TTP secondary to systemic lupus erythematosus (SLE). No patient showed circulating 'lupus' anticoagulants or false positive tests for syphilis. A solid phase immuno-assay for anti-cardiolipin antibodies (ACA) gave negative results in the patient with secondary TTP as well as in all but one case with primary TTP. ACA of IgG class were not found in any TTP patient while they were present in 10 out of 18 patients suffering from thrombocytopenia with active SLE. These data indicate that anti-phospholipid antibodies do not have a role in the development of thrombosis and thrombocytopenia with TTP.     

Anti-interleukin-2 receptor antibody (daclizumab) treatment of corticosteroid-refractory autoimmune thrombocytopenic purpura

We administered daclizumab, a humanized monoclonal anti-interleukin-2 receptor (IL-2R) antibody, to 11 patients with corticosteroid-refractory autoimmune thrombocytopenic purpura (AITP) every 2 weeks for five treatments. Of nine evaluable patients, one individual experienced a partial response. Lymphocyte phenotyping by flow cytometry indicated post-treatment binding of IL-2Ra by daclizumab in all patients. Mid-study serum soluble IL-2R levels in all patients increased 4-15 -fold over baseline values (p=0.004). Despite these measurable immunologic effects, blockade of the IL-2/IL-2R axis did not effectively abrogate the autoimmune response in this group of patients with corticosteroid-refractory AITP.     

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.     

Pulsed high-dose dexamethasone in chronic autoimmune haemolytic anaemia of warm type

The management of patients with autoimmune haemolytic anaemia of warm type (AIHA) is often problematic. Recently, pulsed high-dose dexamethasone (HDD) has been shown to be effective in the treatment of autoimmune thrombocytopenic purpura (AITP).
In this study we treated seven patients with AIHA with HDD. The regimen recommended for treatment of refractory AITP (40 mg dexamethasone for 4 d at the beginning of each 28 d cycle) was employed in almost all cases. Prior to dexamethasone administration, haemolysis was decompensated in all seven patients. HDD was well tolerated and led to an improvement of haemolysis in all cases.     

Thrombotic thrombocytopenic purpura and systemic lupus erythematosus.

Thrombotic thrombocytopenic purpura (TTP) is a rarely seen complicating systemic lupus erythematosus (SLE). The diagnosis of TTP in a setting of SLE is challenging since both share common features including thrombotic microangiopathy. We report two cases of SLE with TTP one with a good response when cyclophosphamide was given early with plasmapheresis and steroids; the other with a poor outcome in a patient given cyclophosphamide late in the course of the disease.     

Immune-mediated thrombocytopenias: basic and immunological aspects

Acute idiopathic or autoimmune thrombocytopenic purpura (AITP) is a disorder found mainly in children, usually preceded by a viral infection, with a higher incidence in the autumn and winter. The platelet-specific autoantibodies in acute childhood AITP are more often of the IgM class. Chronic AITP occurs mostly in adults. The platelet immunofluorescence test (PIFT) detects platelet-specific autoantibodies with a sensitivity of 65-75%. The autoantibodies in chronic AITP are classified as IgG in 95%, IgM in 26% and IgA in 4% of cases. The antibodies are usually bound to platelets and are detectable as free circulating antibodies in about 40%. AITP in pregnancy may cause neonatal AITP by autoantibodies of the IgG class which pass the placenta barrier. The rare neonatal alloimmune thrombocytopenic purpura (NAITP) are caused by IgG alloantibodies against HPA-1a in 75-90%, HPA1b in 3-5%, HPA 3a in 4-5%, HPA5b in 6-19% and against private platelet antigens in 3%. To confirm the diagnosis of NAITP requires extensive serological testing of the child, and the parents have to be typed for the important platelet-specific antigens by PIFT, monoclonal antibody immobilisation of platelet antigens (MAIPA) and/or enzyme-linked immunosorbent assay (ELISA) techniques. Three mechanisms of drug-induced thrombocytopenias are described. Platelets of both the donor and the patient are destroyed in post-transfusion thrombocytopenic purpura (PTP) but PTP does not occur again if incompatible platelets are re-administered.     

Recurrent thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus

We encountered a 39-year-old female patient with systemic lupus erythematosus (SLE) in whom thrombotic thrombocytopenic purpura (TTP) recurred. The patient was successfully treated with corticosteroid in combination with immunosuppressive agents. Because TTP complicating SLE is more resistant to treatment than idiopathic TTP, prompt diagnosis and efficacious initial treatment are critical.     

Warm-antibody autoimmune hemolytic anemia developing after thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) and warm-antibody autoimmune hemolytic anemia (AIHA) are uncommon diseases. Although TTP has been increasingly described in association with autoimmune antibodies, there are very few reports of the association with autoimmune hematological conditions, including idiopathic thrombocytopenic purpura and AIHA. Here we describe a patient with classic manifestations of TTP, who was successfully treated with plasma exchange. A few weeks later, she developed warm-antibody AIHA, which responded promptly to prednisone.     

A case report of the efficacy of apheresis for refractory autoimmune thrombocytopenia in a patient with systemic lupus erythematosus associated hemolytic anemia

Autoantibodies against platelets are found in patients with autoimmune thrombocytopenic purpura (AITP) as well as in thrombocytopenia associated with systemic lupus erythematosus (SLE). The high titer of platelet associated immunoglobulin G (PA IgG) suggests the presence of antibodies against platelets. Platelet associated antibodies are thought to play a major role in the pathogenesis of autoimmune thrombocytopenia. There is a possibility that double filtration plasmapheresis (DFPP) is effective in removing the antibodies against platelets from the peripheral blood. It is suggested that DFPP may reinforce the efforts of the conventional treatment, especially high-dose intravenous immunoglobulin therapy (IVIg). DFPP was performed for severe thrombocytopenia on a SLE patient with high PA IgG value, refractory to the conventional therapy including corticosteroid therapy and IVIg. The patient underwent three sessions of DFPP combined with IVIg and the corticosteroid therapy immediately before the initiation of IVIg. The severe thrombocytopenia improved drastically after the combination treatment, accompanied with the decrease of the PA IgG titer. It was suggested that DFPP combined with corticosteroid and IVIg was effective for severe autoimmune thrombocytopenia on SLE patients refractory to the conventional therapies.     

Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review

We describe a patient with systemic lupus erythematosus (SLE) who developed severe and acute thrombotic thrombocytopenic purpura (TTP). Detection of the fragmentation of peripheral red blood cells (RBC) helped the early diagnosis of TTP and the patient was rescued by extensive plasma exchange started promptly after the diagnosis. Because manifestations of TTP are similar to those in SLE, it is sometimes difficult to make an accurate diagnosis of TTP in SLE patients. We emphasise here the significance of the early diagnosis of TTP by the observation of fragmented RBC and the intensive therapy, including plasma exchange, for this very severe condition.     

Recurrent thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus

Abstract

We encountered a 39-year-old female patient with systemic lupus erythematosus (SLE) in whom thrombotic thrombocytopenic purpura (TTP) recurred. The patient was successfully treated with corticosteroid in combination with immunosuppressive agents. Because TTP complicating SLE is more resistant to treatment than idiopathic TTP, prompt diagnosis and efficacious initial treatment are critical.     

Lupus eritematoso sistémico y púrpura trombótica trombocitopénica: un caso refractario sin actividad lúpica asociada

The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab.     

Thrombotic thrombocytopenic purpura as an etiology of thrombocytopenia in systemic lupus erythematosus: case report

Thrombotic thrombocytopenic purpura (TTP) is an unusual complication of systemic lupus erythematosus (SLE). Although the reported association between SLE and TTP is increasing, a few cases do improve without plasmatherapy. We report a case of TTP which was successfully treated without plasmatherapy, which might be underestimated as an etiology of thrombocytopenia in SLE. TTP should always be considered as a concomitant disease when Coombs' negative hemolytic anemia or thrombocytopenia is seen in SLE patients.