1/13. Renal involvement of thrombotic thrombocytopenic purpura: special reference to the glomeruloid structures.We report the case of a 9-year-old girl with biopsy-proven renal thrombotic microangiopathy in thrombotic thrombocytopenic purpura (TTP), with particular reference to the glomeruloid structures. The renal biopsy sample from this TTP patient revealed platelet thrombus deposition, a glomeruloid structure and aneurysm with relative sparing of the glomeruli. The glomeruloid structure displayed a proliferation of mainly capillary-sized channels lined by factor viii-related, antigen-positive plump endothelial cells embedded in the edematous connective tissue. These glomeruloid vessels communicated with the aneurysmal segment at the end portion of the arteriolar branch. We believe that the glomeruloid structures in TTP represent not merely organization or recanalization of thrombus but rather active angiogenesis through aneurysmal dilation in the arteriolized vessel, probably initiated by platelet agglutination.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/13. Specific von willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases.retrospective studies of patients with thrombotic microangiopathies (TMAs) have shown that a deficient activity of von willebrand factor (vWF)-cleaving protease is involved in thrombotic thrombocytopenic purpura (TTP) but not in the hemolytic-uremic syndrome (HUS). To further analyze the relevance of this enzymatic activity in TMA diagnosis, a 20-month multicenter study of vWF-cleaving protease activity was conducted in adult patients prospectively enrolled in the acute phase of TMA. patients with sporadic (n = 85), intermittent (n = 21), or familial recurrent (n = 5) forms of TMA (66 manifesting as TTP and 45 as HUS) were included. TMA was either idiopathic (n = 42) or secondary to an identified clinical context (n = 69). vWF-cleaving protease activity was normal in 46 cases (7 TTP and 39 HUS) and decreased in 65 cases (59 TTP and 6 HUS). A protease inhibitor was detected in 31 cases and was observed only in patients manifesting TTP with a total absence of protease activity. Among the 111 patients, mean vWF antigen levels were increased and the multimeric distribution of vWF was very heterogeneous, showing either a defect of the high-molecular-weight forms (n = 40), a normal pattern (n = 21), or the presence of unusually large multimers (n = 50). Statistical analysis showed that vWF-protease deficiency was associated with the severity of thrombocytopenia (P <.01). This study emphasizes that vWF-cleaving protease deficiency specifically concerns a subgroup of TMA corresponding to the TTP entity.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/13. Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab.The only established treatment for patients with thrombotic thrombocytopenic purpura (TTP) is plasma exchange against fresh frozen plasma. For cases refractory to plasma exchange, no generally treatment schedule exists. One option is immunosuppressive therapy with corticosteroids and vincristine. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen, and it has been successfully used in B-cell malignancies and is being investigated in autoimmune diseases. Its efficacy in TTP has not yet been determined. We report two female patients with severe TTP refractory to multiple courses of plasmapheresis, high-dose steroid treatment, and vincristine who responded after adding rituximab while continuing plasmapheresis.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/13. Cardiogenic shock complicates successful treatment of refractory thrombotic thrombocytopenia purpura with rituximab.BACKGROUND: Treatment of thrombotic thrombo-cytopenia purpura (TTP) with daily therapeutic plasma exchange (TPE) may be accompanied by a variety of adjunctive interventions including most recently rituximab. Rituximab, a murine and human monoclonal antibody directed against CD20 antigen on B lymphocytes, is primarily used for treatment of non-Hodgkin's lymphomas. Because of severe and fatal infusion reactions including heart failure, rituximab carries a boxed warning. CASE REPORT: A 20-year-old female presented with TTP. She underwent 17 daily (1 day skipped) TPE. Her platelet (PLT) count reached 150 x 10(9) per L and then gradually declined to 36 x 10(9) per L despite continuing TPE. Because of the refractory behavior of her disease, rituximab was administered. After the rituximab infusion, she developed a nonproductive cough which progressed to a productive cough, acute respiratory failure, chest pain, and hypotension and was moved to intensive care for management of biventricular cardiogenic shock (ejection fraction was 5%-10%). Once stable in the intensive care unit, TPE was resumed. Her PLT count reached 241 x 10(9) per L, and her lactate dehydrogenase decreased to normal after four TPEs. Her heart failure completely resolved and she was discharged. Rituximab was added to her medical record as a drug allergy. CONCLUSION: Refractory TTP has been reported to respond favorably to rituximab when used as an adjunct. Interventions, however, can also carry significant risk as illustrated by the cardiogenic shock in our patient. Use of rituximab for refractory TTP should follow a careful assessment of benefits.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/13. Two generations with familial thrombotic thrombocytopenic purpura.Thrombotic thrombocytopenic purpura (TTP) is a rare multi-system disease characterised by the pentad of microangiopathic haemolytic anaemia, thrombocytopenia, renal dysfunction, fever and neurologic changes. A hereditary form of recurrent familial TTP has been described, which usually presents in adolescence or early adulthood and can lead to recurrent or chronic relapsing TTP. Genetic analyses of patients with familial TTP have linked the disease to chromosome 9q34, and an increased incidence is seen in people with HLA-B40 group antigens. We describe here an 11-year-old Egyptian girl with no significant past medical history who presented with new onset of bruising, petechial rash, fatigue and fevers and was diagnosed with familial TTP. Further testing revealed that both the patient and her father had the HLA-B40 group antigen and also had ADAMTS-13 von willebrand factor-cleaving protease deficiency as well as factor-H deficiency.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
6/13. Immunologic thrombocytopenia followed by thrombotic thrombocytopenic purpura in two HIV1 patients.Two homosexual HIV1-positive male patients with thrombotic thrombopenic purpura (TTP) were found to have past history of immune thrombocytopenia (ITP). The first patient had ITP 10 months prior to TTP and was successfully treated by splenectomy. The second patient had ITP 32 months before TTP. No specific treatment was given for his asymptomatic ITP. association of hiv infection to TTP seems to be frequent. These two types of purpura have different pathogenic mechanisms but share a common altered immune response to antigenic challenge. The occurrence of ITP and TTP in hiv-positive patients may lead to errors in diagnosis and therapy.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
7/13. Thrombotic thrombocytopenic purpura as a complicating factor in a case of polymyositis and sjogren's syndrome.A 62-year-old woman was admitted for evaluation of muscular weakness, skin pigmentation, dry mouth, and interstitial pneumonia. During the course of her stay, adult respiratory distress syndrome, hemolytic anemia, renal failure, neurologic dysfunction, and thrombocytopenia appeared. A clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) accompanied by polymyositis and sjogren's syndrome was made. She died two weeks after the beginning of plasmapheresis, and an autopsy was performed. immunohistochemistry disclosed deposits of IgM, fibrinogen, and C1q in glomeruli and arterioles and deposits of C3 in small arteries. von Willebrand's factor antigen, which promotes the adhesion of platelets to the subendothelium, was positive in onion-peeled arteries of the kidney and the spleen. These results suggest that immune complexes may have triggered a sequence of events from vascular endothelial injury to TTP.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/13. Transient disappearance of immunologic disorders and remission after intercurrent measles infections in children with chronic idiopathic thrombocytopenic purpura.In two children with chronic idiopathic thrombocytopenic purpura (ITP) a transient remission of thrombocytopenia was observed after intercurrent measles infection. Both cases were girls who had a long history of thrombocytopenia. During acute measles infection, the delayed hypersensitivity response was suppressed. Total T lymphocytes, T-cell subsets, especially OKT4 cells, the lymphoproliferative response, and interleukin-2 (IL-2) and gamma-interferon production were decreased accompanying normalization of the OKT4/OKT8 ratio. However, OKT4 cells remained at a reasonably low level and the lymphoproliferative response stimulated with pokeweed mitogen was still in the lower normal range. Direct immunofluorescent study demonstrated that the measles antigen was present in the mononuclear cells, especially OKT4 cells. The levels of platelet-associated IgG antibody (PAIgG) and IgG circulating immune complex (CIC) were undetectable. One month later, the OKT4/OKT8 ratio lymphoproliferative response significantly increased, IL-2 and gamma-interferon production increased, and PAIgG and IgG CIC reappeared with the relapse of thrombocytopenia. There was also a significant increase in in vitro IgG production due to the presence of patient OKT8 cells and/or OKT4 cells. However, there was no enhancement in the presence of patient B cells. This suggests that the presence of specific OKT4 helper T cells and a defect in the suppressor function of suppressor OKT8 cells contribute to an overproduction of IgG and the appearance of PAIgG accompanied by thrombocytopenia. The transient remission associated with measles infection is probably related to the effect of the virus on the helper T cells, resulting in a decrease in specific OKT4 helper T cells and normalization of the OKT4/OKT8 ratio, suppression of IL-2 and gamma-interferon production, and platelet-associated IgG production.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
9/13. von willebrand factor abnormalities and endothelial cell perturbation in a patient with acute thrombotic thrombocytopenic purpura.The plasma of a 63-year-old patient with an initial acute, fatal episode of thrombotic thrombocytopenic purpura (TTP) contained agglutinated platelets and a factor viii-related von willebrand factor (vWF) antigen level that was elevated seven-fold above normal. Unusually large vWF multimers derived from endothelial cells were detected in her plasma at the onset of the TTP episode. This is the first patient in whom vWF abnormalities indicative of in vivo endothelial cell damage or perturbation have been found during an acute episode of TTP.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/13. Gastric carcinoma and thrombotic thrombocytopenic purpura: association with plasma immune complex concentrations.A patient with metastatic adenocarcinoma of the stomach developed microangiopathic haemolytic anaemia, thrombocytopenia, renal insufficiency, and fluctuating neurological abnormalities in association with appreciably raised plasma concentrations of immune complexes. This syndrome, similar to thrombotic thrombocytopenic purpura, occurred while the tumour was in sustained objective remission after successful treatment with fluorouracil, doxorubicin, and mitomycin. Reversal of the syndrome was achieved with plasmapheresis, azathioprine, corticosteroids, and antiplatelet treatment; this response was paralleled by a reduction in immune complex concentration, suggesting an immune aetiology for the syndrome. antibodies eluted from the immune complexes reacted with 50% of cells from the gastric cancer but less than 10% of cells from normal gastric mucosa. There was no reactivity with either carcinoembryonic antigen or mitomycin. A 17S immune complex reacted with a glycoprotein from the patient's autologous platelets and produced platelet aggregation. It is postulated that reducing the tumour and the pre-existing state of antigen excess by chemotherapy allowed soluble antigen-antibody complexes to form and the syndrome to develop.- - - - - - - - - - ranking = 3keywords = antigen (Clic here for more details about this article) |
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