Progressive appearance of overlap syndrome together with autoantibodies in a patient with fatal thrombotic microangiopathy

We describe an extraordinary patient with overlap syndrome (systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis) having positive autoantibodies against Sm, double stranded DNA, DNA topoisomerase I, and centromere, together with rheumatoid factor. The patient had multiple organ involvement resulting from thrombotic microangiopathy that mimicked so-called normotensive scleroderma renal crisis, and died mainly of massive pulmonary hemorrhage caused by thrombotic thrombocytopenic purpura. The clinical presentations of the case support the concept of strong associations between disease-specific autoantibodies and clinical features.     

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.     

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.     

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.     

Recurrent thrombotic microangiopathy in a renal allograft. Case report and review of the literature

Thrombotic microangiopathy in a renal allograft may either reflect a recurrence of the patient's original disease, i.e., thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, or more commonly may be a manifestation of allograft rejection. This report describes a patient in whom irreversible renal failure developed during thrombotic thrombocytopenic purpura. Two years later while her condition was in clinical remission, she received a 2 DR-matched cadaveric allograft. Nineteen days following transplantation, thrombotic microangiopathy developed in the graft with eventual loss of allograft function despite vigorous plasmapheresis therapy. Multiple factors in addition to possible recurrent disease that may have contributed to this event were identified. The literature on thrombotic microangiopathy and renal transplantation is reviewed.     

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.     

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.     

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.     

Cryosupernatant Plasma Exchange in the Treatment of Antiphospholipid Antibody Syndrome with Lupus Nephritis

Abstract: We report a case of a 22-year-old female with antiphospholipid antibody syndrome (APS) associated with systemic lupus erythematosus in whom cryosupernatant plasma exchange was effective and improved both the refractory venous thrombosis in her legs and relapsing thrombocytopenia. A renal biopsy specimen showed not only features of active lupus nephritis but also renal arteriolar thrombosis which is considered to be a type of thrombotic microangiopathy (TMA). Because a pathological role of unusually large von Willebrand factor (vWF) multimers has been reported in patients with TMA including thrombotic thrombocytopenic purpura, plasma exchange using replacement with cryosupernatant, which is free of unusually large vWF multimers, is likely to be an option of treatment modality for patients with refractory and chronic relapsing APS manifesting TMA.     

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.     

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.     

Fatal thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus

An immunologic mechanism, possibly immune complex mediated, has been suggested as the basis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP). The evidence supporting this concept has been the association of TTP with systemic lupus erythematosus and the successful therapy of TTP by plasmapheresis. However, most investigators have failed to demonstrate elevated circulating immune complexes during the course of TTP. This report describes a young woman with systemic lupus who developed TTP as a terminal event. Elevated levels of immune complexes were associated with periods of active lupus but were not detectable at the time she developed TTP.     

Catastrophic antiphospholipid antibody syndrome in systemic lupus erythematosus: an autopsy case report of a young woman

Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome (APS) characterized by disseminated microangiopathy that results in multiorgan failure. CAPS mainly occurs in association with systemic lupus erythematosus (SLE). Clinically, CAPS mimics disseminated SLE vasculitis, intravascular coagulation (DIC), and particularly thrombotic thrombocytopenic purpura (TTP). We describe an autopsy case of young woman with CAPS in SLE, which is difficult to differentiate from TTP secondary to SLE.     

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.     

Systemic lupus erythematosus presenting as fulminant thrombotic thrombocytopenic purpura]

A 20-year-old woman visited a nearby hospital because of sudden, severe, and unusual genital bleeding. She also exhibited severe anemia and thrombocytopenia. In transit to our hospital, the patient suddenly suffered cardiac arrest and died soon thereafter despite immediate blood transfusion and therapeutic intubation. Thrombotic thrombocytopenic purpura (TTP) was initially diagnosed at autopsy due to the observation of numerous fragmented erythrocytes in peripheral blood, evidence of hemolysis, and thrombotic microangiopathy in multiple organs. In addition, histopathologic and serologic findings disclosed an association with systemic lupus erythematosus (SLE). Test for anticardiolipin antibody was positive, and hemophagocytic findings were detected in lymph node specimens. Reports of TTP in association with SLE have been increasing in recent years. However, the mechanisms correlating these two illnesses have not been identified. We speculated that the rapid clinical course in this case was attributable to TTP that had been provoked by endothelial microangiopathy due to SLE, and moreover, the fact that the patient's general condition had been seriously complicated by excessive menstrual bleeding.     

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.     

Thrombotic thrombocytopenic purpura in systemic lupus erythematosus and antiphospholipid antibodies: effective treatment with plasma exchange and immunosuppression.

We describe 2 patients with systemic lupus erythematosus (SLE) with neurological complications and thrombocytopenia, who, upon further investigation, were found to have thrombotic thrombocytopenic purpura. While neither patient responded to treatment with corticosteroids, both responded to plasma exchange and intravenous cyclophosphamide. This highlights the need to carefully consider this diagnosis in patients with SLE presenting with neurological complications and thrombocytopenia.     

The frequency of thrombotic thrombocytopenic purpura in patients with systemic lupus erythematosus undergoing kidney biopsy

OBJECTIVE: To characterize the frequency of thrombotic thrombocytopenic purpura (TTP) among patients with systemic lupus erythematosus (SLE) undergoing kidney biopsy. METHODS: A retrospective review of all renal biopsies of patients with SLE at Rush-Presbyterian-St. Luke's Medical Center was performed for the years 1989 to 2001. RESULTS: Four cases of clinical and histopathological TTP were identified among the 257 patients with SLE who underwent renal biopsy during the 12 year study period. CONCLUSION: TTP appears to occur at higher than expected frequency among SLE patients undergoing biopsy for unexplained renal failure.     

Pathogenesis of thrombotic thrombocytopenic purpura

The recent discovery of important molecular and genetic mechanisms of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome provide an opportunity to reconstruct scientific and clinical paradigms. Acquired and congenital defects of the metalloprotease ADAMTS13 are a central feature in the pathogenesis of a major type of thrombotic microangiopathy. This and other pathogenic mechanisms can redefine the terminology of thrombotic microangiopathy. Deficient activity of ADAMTS13 suggests several possible models of microvascular thrombosis. The sporadic relationship between thrombotic microangiopathy and ADAMTS13 deficiency draws attention to other critical pathologic factors that are still poorly understood. Investigation of vascular injury and mechanisms of microvascular thrombosis remain the frontiers of investigation in thrombotic microangiopathy.     

Successful treatment of refractory thrombotic thrombocytopenic purpura with cyclosporine and corticosteroids in a patient with systemic lupus erythematosus and antibodies to ADAMTS13

A 46-year-old woman with systemic lupus erythematosus was hospitalized for purpura, hematochezia and hematuria. One week after admission, she developed grand mal seizures and coma and was diagnosed with thrombotic thrombocytopenic purpura (TTP) when fragmented red cells were found on the peripheral blood smear. Laboratory findings showed severe ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) deficiency and anti-ADAMTS13 antibodies, which in recent reports have indicated a poor prognosis. She was refractory to methylprednisolone pulse therapy and plasma exchange, but administration of cyclosporine induced remission without adverse effects. We propose that cyclosporine may be an effective treatment for cases of refractory TTP.