The Pathogenesis of Chronic Immune Thrombocytopenic Purpura
Section snippets
Introduction and History
Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which, for reasons that remain unclear, platelet surface proteins become antigenic and stimulate the immune system to produce autoantibodies and cytotoxic T lymphocytes, which results in immune-induced platelet destruction and suppression of platelet production. There have been several previous reviews on the pathophysiology of ITP.1, 2, 3, 4 The present understanding of this topic is shown schematically in Fig 1.
The
Antigenic Response and Antibody Production
The fundamental abnormality leading to an autoimmune response in ITP is unknown and probably differs among patients. The immune system is carefully regulated since it must protect the body from outside invasion and, at the same time, not respond to self antigens. The response to antigens is modulated by two T-cell populations, CD4+ helper-inducer cells and CD8+ suppressor-cytotoxic cells. Immature T cells (CD4−CD8−) are produced in the bone marrow and migrate to the thymus. During thymic
Measurement of Autoantibody
Early attempts to measure anti-platelet antibody, using platelet agglutination, complement activation, and platelet lysis assays, were unsuccessful because of their lack of sensitivity and/or reproducibility. In the 1970s, the measurement of platelet-associated IgG showed a very high level of positivity in chronic ITP (∼90%); however, subsequent studies showed that these assays lacked specificity and were therefore not clinically useful. In 1982, Van Leeuwen et al38 reported that antibody
Platelet Destruction
There is no doubt that platelet destruction is an important mechanism in many ITP patients. As noted above, infusion of ITP blood or plasma into recipients with normal platelet counts resulted in thrombocytopenia in about two thirds of these individuals. In addition, the survival of both homologous and autologous radiolabeled platelets is reduced in essentially all ITP patients. In a survey of five large studies,62, 63, 64, 65, 66 117 of 119 patients with chronic ITP had shortened intravascular
Morphologic Studies
As noted earlier, early light microscopic studies of ITP bone marrow showed normal or increased numbers of megakaryocytes with a shift to younger forms that lacked cytoplasmic granularity or platelet formation and manifested nuclear and cytoplasmic degenerative changes.7, 9 Phase contrast studies confirmed these findings and showed that these megakaryocytic abnormalities could be produced in healthy control subjects by the infusion of ITP plasma.8 Early electron microscopic studies showed
Conclusions
The studies that have been reviewed in this article provide convincing evidence that thrombocytopenia in chronic ITP can be due to either immune-induced platelet destruction or suppression of platelet production. It seems likely that the relative importance of these two mechanisms will vary among patients with ITP.
Acknowledgments
The development of this manuscript was supported by an unrestricted educational grant from GlaxoSmithKline. Assistance in the development of this article was provided by Robert Coover and Brett Moskowitz, MA.
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2021, Scientific AfricanCitation Excerpt :The standard number of platelets in the blood is between 150,000 – 400,000 platelets per micro-liter [84]. The ITP can be the outcome of decreased thrombopoiesis in the bone marrow, amplified platelets exploitation in the liver, or platelet sequestration in the spleen [85–87]. This condition is also the second prevalent hematological problem in at least 10% of pregnant women as the result of physiological changes and obstetric conditions such as Low Platelet level syndrome, hemolytic uraemic syndrome, and amniotic embolism [88].
STATEMENT OF CONFLICT OF INTEREST: Dr McMillan has nothing to disclose.