Idiopathic thrombocytopenic purpura pathophysiology
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increased platelet destructionEditor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Auto-immune thrombocytopenic purpura is described by the increased platelet destruction due to production of auto-reactive antibodies against host platelets and suppression of platelet production in the bone marrow.
Pathophysiology
Pathogenesis
Acute ITP: Mainly affects children and usually follows a viral or bacterial infection
- Antigenic mimicry - Similar molecular structures on both host cells and infectious agents, inducing a self immune response which cross reacts with the host antigens.
- In acute ITP - anti-viral or anti-bacterial antibodies cross reacts against the patient's platelets.
- Mostly acute ITP is self resolving as infectious agents and antibodies are cleared from the body, causing the loss of anti-platelet reactivity.
- T cells are not involved in the parthenogenesis of acute ITP
Chronic ITP: (platelet counts < 150,000 x 109 per liter x 6 months) usually in adults
- Increased platelet destruction:
- Autoantibody‐induced platelet destruction
- Abnormal IgG auto-antibody recognizes glyco-protein IIb/IIIa, glyco-protein Ib/IX complex, GP Ia/IIa, and GP VI etc[1]
- Predominantly IgG auto-antibodies constitute the majority of antibodies but IgM and IgA antibodies can also be found in some of ITP patients.[2]
- Auto-antibodies binds to the circulating platelet membranes through glyco-proteins
- Auto-antibody-coated platelets induce Fcγ receptors and bind to antigen-presenting cells (Splenic macrophages or dendritic cells) in the reticulo-endothelial system[3][4]
- The auto-antibody-coated platelets undergo phagocytosis by splenic macrophages and peripheral blood neutrophils.[5]
- Autoreactive T lymphocyte‐mediated platelet lysis
- Abnormal cytotoxic T cells defect leads to differentiation of direct autoreactive B cells further leading to secretion of IgG auto-antibodies[6]
- Abnormal T cells includes cytotoxic T-lymphocyte (CD8+) and natural killer cells (CD3- CD16+ CD56+)[7]
- CD4-positive helper T cells react with platelet surface glycoproteins, through co-stimulation involving CD40:CD40L
- T cells act directly on the megakaryocytes in the bone marrow
- Autoantibody‐induced platelet destruction
- Autoantibody‐mediated suppression of platelet production:
Genetics
Associated Conditions
Conditions associated with
Gross Pathology
On gross pathology, characteristic findings of itp include:
- Acute
- Chronic
Microscopic Pathology
On microscopic histopathological analysis, characteristic findings of itp include:
- Acute
- Chronic
References
References
- ↑ McMillan R (March 2005). "The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura". Curr. Hematol. Rep. 4 (2): 160–5. PMID 15720967.
- ↑ McMillan R (March 2005). "The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura". Curr. Hematol. Rep. 4 (2): 160–5. PMID 15720967.
- ↑ Clarkson SB, Bussel JB, Kimberly RP, Valinsky JE, Nachman RL, Unkeless JC (May 1986). "Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody". N. Engl. J. Med. 314 (19): 1236–9. doi:10.1056/NEJM198605083141907. PMID 2939345.
- ↑ Shulman NR, Marder VJ, Weinrach RS (June 1965). "Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies". Ann. N. Y. Acad. Sci. 124 (2): 499–542. PMID 5214832.
- ↑ Firkin BG, Wright R, Miller S, Stokes E (February 1969). "Splenic macrophages in thrombocytopenia". Blood. 33 (2): 240–5. PMID 5812817.
- ↑ Olsson B, Andersson PO, Jernås M, Jacobsson S, Carlsson B, Carlsson LM, Wadenvik H (September 2003). "T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura". Nat. Med. 9 (9): 1123–4. doi:10.1038/nm921. PMID 12937414.
- ↑ Zhang F, Chu X, Wang L, Zhu Y, Li L, Ma D, Peng J, Hou M (May 2006). "Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura". Eur. J. Haematol. 76 (5): 427–31. doi:10.1111/j.1600-0609.2005.00622.x. PMID 16480433.
- ↑ Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ (July 1987). "Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance". J. Clin. Invest. 80 (1): 33–40. doi:10.1172/JCI113060. PMC 442198. PMID 3597777.
- ↑ Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, Nugent DJ (August 2003). "Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro". Blood. 102 (3): 887–95. doi:10.1182/blood-2002-05-1475. PMID 12676790.
- ↑ DAMESHEK W, MILLER EB (January 1946). "The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism". Blood. 1: 27–50. PMID 21013546.