Treatment with liposome-encapsulated clodronate as a new strategic approach in the management of immune thrombocytopenic purpura in a mouse model.
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Immune thrombocytopenic purpura (ITP) is an autoimmune disease related to the presence of elevated levels of platelet-associated immunoglobulin, or autoantibodies. In recent years the importance of macrophage Fc gamma receptors in the uptake of platelets in ITP has been confirmed. Although in patients with ITP the platelet destruction occurs in liver and spleen, in this present experimental mouse model the liver was the principal organ of sequestration of sensitized platelets. The uptake in the spleen, bone marrow, lung, and kidneys was negligible and not different from that in control animals. In addition, the trapped platelets did not return to circulation, and new cells derived from the platelet-storage pool or new thrombocytogenesis were necessary to restore the platelet count. The depletion of splenic and hepatic murine macrophages by liposome-encapsulated clodronate (lip-clod) was studied as a new strategy for ITP treatment. Lip-clod inhibits, in a dose-dependent manner, the antibody-induced thrombocytopenia. Moreover, lip-clod treatment rapidly restored (24 hours) the platelet count in thrombocytopenic animals to hematologic safe values, and despite additional antiplatelet antiserum treatment, mice were able to maintain this level of platelets at least up to 48 hours. The bleeding times in lip-clod-treated animals was not different from those in controls, demonstrating that the hemostasis was well controlled in these animals. The results presented in this study demonstrate that lip-clod treatment can be effective in the management of experimental ITP. (Blood. 2000;96:2834-2840) (+info)
Factors predicting response to splenectomy in adult patients with idiopathic thrombocytopenic purpura.
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BACKGROUND AND OBJECTIVES: Splenectomy is the treatment of choice in the majority of patients affected by idiopathic thrombocytopenic purpura refractory to corticosteroid therapy, but it is not free from early and late complications. As the available literature does not seem to contain any precise indications concerning possible factors predicting the response to splenectomy, the aim of this retrospective study of 65 splenectomized patients was to attempt to identify potentially predictive clinical or laboratory parameters. DESIGN AND METHODS: For the purposes of statistical analysis, the patients were divided into two groups: the first included those with a complete (platelets > 100x10(9)/L) or partial response (platelets 50-100 x10(9)/L) to splenectomy; the second, the non-responders (platelets < 50x10(9)/L). The non-parametric tests were based on the Kruskal-Wallis method for independent samples, and the independent samples were compared using the Chi-square test according to Pearson. RESULTS: Univariate analysis did not reveal any significant correlation between successful splenectomy and age, sex, platelet count at diagnosis, anti-platelets antibody positivity, the site of platelet sequestration, the time between diagnosis and surgery, or the response to high intravenous immunoglobulin doses. However, the probability of success was greater in the patients with a complete or partial pre-operative response to steroid therapy (p<0.05). INTERPRETATION AND CONCLUSIONS: The factor most frequently associated with the success of splenectomy is the site of autologous platelet sequestration. Our study did not identify any clinical or laboratory parameter clearly predictive of post-splenectomy cure other than a transient response to steroid treatment. This finding needs further confirmation in larger patient populations. (+info)
Autoimmune thrombocytopenia following autologous hematopoietic cell transplantation: review of literature and treatment options.
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Autoimmune thrombocytopenia after high-dose chemotherapy and autologous bone marrow/peripheral blood stem cell transplantation occurs infrequently and only six cases meeting the criteria have been reported in the literature. All six of these patients had either acute myelogenous leukemia (AML) or lymphoblastic lymphoma (LBL). Immune thrombocytopenia following autologous transplantation in solid tumors has not been reported. We report the first case of autoimmune thrombocytopenia after high-dose chemotherapy and peripheral blood stem cell transplantation in a patient with breast cancer. A review of the literature has been conducted and treatment options are discussed. In two patients the condition resolved with treatment and in a third patient it improved. Immune-mediated thrombocytopenia in the post-transplant period is one of the causes of a low platelet count. It should be recognized promptly and treated. (+info)
Prenatal diagnosis of a subdural hematoma associated with reverse flow in the middle cerebral artery: case report and literature review.
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To our knowledge this is the first reported case of a subdural hematoma, related to fetal autoimmune thrombocytopenia, diagnosed prenatally by ultrasound. The underlying etiology was hidden maternal autoimmune thrombocytopenia. This disease, which is as serious as alloimmune thrombocytopenia, causes severe fetal thrombocytopenia, which carries with it a high risk of intracranial hemorrhage and recurrence in subsequent pregnancies. Only 14 cases of fetal subdural hematomas have been reported in the literature. The etiologies of these cases were principally traumatic, or due to disorders of hemostasis. Their prognoses were generally poor, with 50% resulting in fetal death in utero and the remaining 50% demonstrating post-natal sequelae. The presence of reverse flow in the middle cerebral artery is rare and its association with a subdural hematoma unusual. Abnormalities found on cerebral Doppler studies indicate an adaptive response to a fetal condition for which the prognosis is then very poor. Monitoring fetuses at risk for hemorrhage by ultrasound imaging and Doppler studies enables us to detect indicators of a worsening prognosis before the ultrasound appearance of morphological hemorrhage. The development of intracranial hemorrhage raises difficult management issues during the index pregnancy and in subsequent pregnancies. (+info)
Immune cytopenias as the presenting finding in primary Sjogren's syndrome.
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A diagnostic delay of several years in primary Sjogren's syndrome is common, even in patients who present with sicca symptoms. It is much more likely in cases with prominent symptomatic extraglandular involvement. We report on three such patients who presented as Coomb's positive haemolytic anaemia, systemic symptoms with agranulocytosis and gingival bleeding due to immune thrombocytopenia, to alert clinicians to the fact that primary Sjogren's syndrome may present as clinically significant immune-mediated cytopenia in the absence of sicca symptoms. Sjogren's syndrome, a common autoimmune disorder, should be considered in the differential diagnosis of apparently 'idiopathic' cytopenias and actively sought by directed history, Schirmer test and autoantibody screening. (+info)
An immunological syndrome featuring transverse myelitis, Evans syndrome and pulmonary infiltrates after unrelated bone marrow transplant in a patient with severe aplastic anemia.
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A patient with severe aplastic anemia underwent a matched unrelated bone marrow transplant, following which he developed a complex autoimmune syndrome. This featured transverse myelitis, immune mediated Coombs positive hemolytic anemia and immune thrombocytopenia (Evans syndrome), pulmonary infiltrates, eosinophilia, muscle pains and cramps and lichenoid dermatitis all of which may represent manifestations of graft-versus-host disease as they showed response to immunosuppression. Thus, although immune-mediated cytopenias after an allogeneic bone marrow transplant are rare, they should be considered as a possible cause of cytopenia in post-transplant patients. (+info)
Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura.
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Recent reports have suggested an association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP). The prevalence of H pylori infection and the effect of its eradication in a series of 30 ITP patients were investigated. H pylori infection has been documented in 13 patients (43.33%) by 13C urea breath test and confirmed by histologic examination. Bacterium eradication with antibiotics, obtained in 12 of 13 infected patients (92.3%), led to a complete response in 4 (33.33%) and to a partial response (platelets 90 x 10(9)/L-120 x 10(9)/L) in 2 (16.66%). The response was maintained for a median of 8.33 months, but 1 patient relapsed 7 months after eradication. Search for H pylori infection seems appropriate in ITP patients at diagnosis. Bacterium eradication provides a new good option for a nonimmunosuppressive treatment in some ITP patients. (+info)
Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor.
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The molecular basis for the anti-inflammatory property of intravenous gamma globulin (IVIG) was investigated in a murine model of immune thrombocytopenia. Administration of clinically protective doses of intact antibody or monomeric Fc fragments to wild-type or Fcgamma receptor-humanized mice prevented platelet consumption triggered by a pathogenic autoantibody. The inhibitory Fc receptor, FcgammaRIIB, was required for protection, because disruption either by genetic deletion or with a blocking monoclonal antibody reversed the therapeutic effect of IVIG. Protection was associated with the ability of IVIG administration to induce surface expression of FcgammaRIIB on splenic macrophages. Modulation of inhibitory signaling is thus a potent therapeutic strategy for attenuating autoantibody-triggered inflammatory diseases. (+info)