The ITP syndrome: Pathogenic and clinical diversity

Department of Pathology and Laboratory Medicine, University of Pennsylvania, 513A Stellar-Chance, 422 Curie Blvd, Philadelphia, PA 19104, USA.
Blood (Impact Factor: 10.45). 05/2009; 113(26):6511-21. DOI: 10.1182/blood-2009-01-129155
Source: PubMed


Immune thrombocytopenia (ITP) is mediated by platelet autoantibodies that accelerate platelet destruction and inhibit their production. Most cases are considered idiopathic, whereas others are secondary to coexisting conditions. Insights from secondary forms suggest that the proclivity to develop platelet-reactive antibodies arises through diverse mechanisms. Variability in natural history and response to therapy suggests that primary ITP is also heterogeneous. Certain cases may be secondary to persistent, sometimes inapparent, infections, accompanied by coexisting antibodies that influence outcome. Alternatively, underlying immune deficiencies may emerge. In addition, environmental and genetic factors may impact platelet turnover, propensity to bleed, and response to ITP-directed therapy. We review the pathophysiology of several common secondary forms of ITP. We suggest that primary ITP is also best thought of as an autoimmune syndrome. Better understanding of pathogenesis and tolerance checkpoint defects leading to autoantibody formation may facilitate patient-specific approaches to diagnosis and management.

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Available from: Howard Liebman, Oct 09, 2015
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    • "Idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura (ITP) is a chronic disorder with thrombocytopenia that affects approximately 1 in 10,000 people. Primary ITP is a heterogeneous disease and underlying mechanisms include platelet autoantibody (detected only in 60% of cases [1]) directed against glycoproteins in the platelet membrane, activation of T cells, tolerance loss in T and B cells, and the development of cytotoxic T cells [2]. However, the initial inciting event in ITP is still unknown. "
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    ABSTRACT: Severe refractory ITP is clinically challenging and a variety of single or combination chemotherapies have been tried with limited outcome. We report a case of ITP that was unresponsive to multiple agents including high-dose steroid, IVIG, Rho(D) immune globulin, rituximab, cyclosporine, azathioprine, vincristine, mycophenolate mofetil, romiplostim, and eltrombopag; however, it achieved complete remission with combination treatment of cyclophosphamide and eltrombopag.
    07/2015; 2015:1-3. DOI:10.1155/2015/583451
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    • "Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder with a low platelet count characterized by premature platelet destruction and suppression of platelet production mediated by autoantibodies, which may predispose to bleeding.1) Since severe bleeding is uncommon when the platelet count exceeds 30000/uL, treatment is usually indicated when a platelet count is less.2) Considering the crucial role of platelets in thrombotic events, the prevalence of coronary artery disease (CAD) in patients with ITP seems to be uncommon, especially when the platelet count is low. "
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    ABSTRACT: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder with a low platelet count characterized by premature platelet destruction and suppression of platelet production mediated by autoantibodies, which may predispose to bleeding. Although the prevalence of coronary artery disease (CAD) in ITP seems to be rare, their co-occurrence is not unusual. Patients with ITP have increased risks for thrombosis and atherosclerosis associated with hemostatic factors, endothelial damage, and the negative effects of steroid and immunoglobulin therapies. Thus, the coexistence of ITP and CAD presents complex problems requiring a balance between hemorrhagic risk and prevention of thrombosis. Here, the authors present two patients with ITP, who were revascularized in different ways for CAD. Although the optimal management of thrombocytopenic patients with CAD is uncertain, individualized treatment modalities can be useful in patients with ITP and CAD.
    Korean Circulation Journal 07/2014; 44(4):264-7. DOI:10.4070/kcj.2014.44.4.264 · 0.75 Impact Factor
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    • "Similarly, platelet aggregation studies and platelet function analysis require even higher counts, i.e. PRP platelet count of 100 9 10 9 /l or at least a count of 50 9 10 9 /l respectively (Cines et al, 2009; W€ urtz et al, 2011). The only proposed solution thus far has been flow cytometric evaluation of platelet function, which was not clearly demonstrated to predict bleeding risk in ITP and is neither universally available nor a point of care test (Psaila et al, 2011). "
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    ABSTRACT: Platelet counts (PC) estimate bleeding risk in Immune Thrombocytopenia (ITP). We investigated whether measures of thromboelastometry and absolute immature platelet fraction (A-IPF) would correlate better with acute bleeding score (ABS) than PC or mean platelet volume (MPV). Simultaneous determination of ABS, complete blood count and thromboelastometry was performed in 141 ITP patients; 112 underwent A-IPF testing. Subgroup analyses were performed for paediatric subjects, PC <60 × 109/l and <30 × 109/l. PC significantly inversely correlated with ABS in all subjects, PC <30 × 109/l and total paediatric cohort. MPV did not correlate with ABS in any subgroup. Thromboelastometry measures of clot firmness, but not PC, significantly correlated with ABS in all subjects with PC <60 × 109/l, and children with PC <60 × 109/l and <30 × 109/l. A-IPF demonstrated stronger correlation with ABS than did PC among all subjects, those with PC <60 × 109/l, all children and children with PC <30 × 109/l (r = −0·37; r = −0·34; r = −0·44; r = −0·60) versus ABS with PC (r = −0·36; ns; r = −0·32; ns). Stronger correlations of both thromboelastometry measures of clot firmness and A-IPF than PC with ABS suggest factors beyond PC, i.e. related to platelet function, contribute to ITP bleeding pathophysiology. Thromboelastometry, A-IPF and ABS can be incorporated into routine or acute visits.
    British Journal of Haematology 05/2014; 166(4). DOI:10.1111/bjh.12929 · 4.71 Impact Factor
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