ITP in the 21st Century

Abstract

Ten years ago the American Society of Hematology published immune (or idiopathic) thrombocytopenic purpura (ITP) practice guidelines based upon a systematic and comprehensive review of the literature.1 The authors acknowledged that hematologists regularly faced clinical management decisions with too little published scientific information about the natural history of ITP. Many of the treatments employed in ITP had been discovered empirically, and therapeutic choices were often guided by published results in case series of selected patients without a control group. Today, a decade later, we benefit from work by many investigators addressing the natural history of ITP and the pathogenic mechanisms contributing to autoimmune platelet destruction. Practice guidelines and a number of expert and consensus opinions in the literature have better defined the field.2-6 The recent era has also brought reports of new prospective clinical trials including multicenter, randomized studies that promise better guidance for the clinical hematologist in the 21st century. Recent clinical investigations of ITP assess outcome measures in addition to platelet count increments including quality of life, 7 severity of bleeding, 8 and complications of therapy. In addition, there are published reports of systematic analyses that help interpret previous literature. Hypothesis-driven studies of ITP patients and experimental animal models have also improved our understanding of the basic cellular and molecular immune mechanisms that contribute to ITP and have thus revealed new therapeutic opportunities.The present contribution will cover some of the recent basic research that has advanced our understanding of the pathogenesis of ITP and will highlight some of the clinical trials that offer insights into the diagnosis, natural history, and management of ITP in adults and children. Promising new therapeutic modalities for chronic refractory ITP will be discussed. Emphasis is placed upon explicitly designed trials. Several important clinical topics could not be included: secondary ITP, immune thrombocytopenia in pregnancy and infancy, the role of viral infection in ITP, and drug-related thrombocytopenia. Space limitations and edi-

Predictors for splenectomy among patients with primary chronic immune thrombocytopenia: a population-based cohort study from Denmark

“…Two comorbidity levels were defined: 0, corresponding to no recorded underlying disease; and 1+, corresponding to one or more of the 19 diseases included in the Charlson Index being recorded in DNPR. Additionally, we categorised the patients according to 5 distinct comorbid categories: (1) cardiopulmonary disease, which included acute myocardial infarction, congestive heart disease, peripheral vascular disease and cerebrovascular disease, emphysema and chronic obstructive pulmonary disease; (2) connective tissue disease which included diffuse connective tissue disease, rheumatoid arthritis and other inflammatory polyarthropathies, and polymyalgia rheumatica; (3) moderate to severe renal disease which included glomerulonephritis, nephropathies, and end-stage renal disease; (4) hepatic disorder which included hepatitis acuta, cirrhosis hepatitis, cholelithiasis and cholangitis; and (5) diabetes (insulin-and noninsulin-dependent) (See Appendix for the relevant ICD-8 and ICD-10 codes).…”

“…Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased platelet destruction and inadequate platelet production [1]. It is presumed that the presence of antiplatelet auto-antibodies results in decreased platelet counts because of the clearance of platelets, typically by the reticuloendothelial system of the bone marrow, spleen, and/or liver [1].…”

“…It is presumed that the presence of antiplatelet auto-antibodies results in decreased platelet counts because of the clearance of platelets, typically by the reticuloendothelial system of the bone marrow, spleen, and/or liver [1].…”

The scintigraphic index spleen/liver at 30 minutes predicts the success of splenectomy in persistent and chronic primary immune thrombocytopenia

“…However, today, splenectomy is still considered the second-line of treatment when prednisone fails, when the doses required for maintaining a haemostatic platelet count is unacceptably high, or when the side effects are severe [1,[3][4][5][6]12]. Moreover, as the spleen is not only the main site of platelet destruction, but is an organ containing autoantibody-producing B-cells, splenectomy is also a curative treatment [1,3].…”

“…Bone marrow megakaryocytes generally respond generating a higher number of platelets, but sometimes, the antibodies inhibit their thrombopoietic function. The typical picture of acute primary ITP is the sudden presentation of cutaneous purpura and/or mucous bleeding and severe thrombocytopenia with a favorable outcome [1,3]. In the chronic form, the disease persists for more than 6 months [2,4].…”