Review of Therapies for Immune Thrombocytopenic Purpura

ArticleinSeminars in Hematology 43(3 Suppl 5):S1-2 · August 2006with1 Reads
DOI: 10.1053/j.seminhematol.2006.04.010 · Source: PubMed
  • [Show abstract] [Hide abstract] ABSTRACT: The period between isolation of HIV in the early 1980s and the development of effective viral inactivation procedures able to eradicate the virus from the blood supply was long and unfortunately many recipients of blood-derived products became infected; this translated into a devastating impact on their quality of life, quality of care as well as on their life expectancy. Some years later, hepatitis C virus infection was identified as another known blood-borne disease complicating the treatment of haemophilia. Nowadays, the potential threat of emerging new pathogens has stressed the need to provide effective but primarily safe products with regard to infectious agents, as well as to regularly update therapeutic guidelines for haemophilia. The aim of the present publication was to review some of the crucial aspects related to the choice of haemostatic concentrates for the treatment of haemophilia and other inherited bleeding disorders, to analyse the current situation in the United States, Canada and European Union countries and to report the most relevant aspects of the Spanish consensus opinion of haemophilia-treating doctors for the use of therapeutic products for haemophilia recently issued. Essentially, it suggests that a gradual switch to recombinant concentrates may be a beneficial decision for patients with haemophilia and for the National Health Service.
    Full-text · Article · Aug 2008
  • [Show abstract] [Hide abstract] ABSTRACT: Corticosteroid (CS) therapy is effective in many patients with immune thrombocytopenic purpura (ITP), although it is associated with adverse effects. This study was conducted to describe the CS-related symptom experience of adult patients with ITP and to compare the symptom experience of current users of CS, previous users of CS, and those who have never used CS. In 2006, adult members of the Platelet Disorder Support Association (PDSA) who were listed in the organization's database, resided in the United States, and had a diagnosis of ITP were invited to participate in a Web-based survey. Symptom experience was assessed using 33 CS-related symptoms derived from a scale developed for use in patients undergoing organ transplantation. Symptom experience over the past 4 weeks was measured in terms of the occurrence of symptoms (rated on a 5-point scale from 1 [never occurring] to 5 [always occurring]) and the distress associated with those symptoms (rated on a 5-point Likert scale from 0 [not at all distressing] to 4 [extremely distressing]). Respondents were categorized according to 4 patterns of CS use: current users, nonusers, previous users who stopped CS use <6 months earlier, and previous users who stopped CS use >or=6 months earlier. The survey was completed by 985 patients with ITP (8.2% of the PDSA membership). The median age of the sample was 47 years, and the ratio of women to men was 3:1. One hundred sixteen patients (11.8%) were current CS users, 171 (17.4%) were nonusers, 99 (10.1%) had stopped CS use <6 months earlier, and 599 (60.8%) had stopped CS use >or=6 months earlier. In all 4 groups, back pain, fatigue, sleep difficulties, muscle weakness, and difficulty seeing well were reported to be the most frequently occurring and most distressing symptoms. Current CS users and those who stopped CS treatment <6 months earlier also reported bruises to be among their most frequent and distressing symptoms. Twenty-five of the 33 symptoms occurred more frequently in current CS users than in nonusers, and 30 symptoms occurred more frequently in current users than in previous users who had stopped CS use >or=6 months earlier. Symptom occurrence was significantly greater for current users compared with those who stopped CS use <6 months earlier for puffy face (q = 0.003), excessive appetite (q = 0.002), changed facial features (q = 0.033), and buffalo hump (q = 0.048). Patients who had stopped CS use <6 months earlier reported 20 of the 33 symptoms significantly more often than those who had stopped CS use >or=6 months earlier (q < 0.05). The only symptoms reported significantly more often in patients who had stopped CS use >or=6 months earlier compared with nonusers were buffalo hump and bruises (q < 0.05). The distress associated with bruises was significantly higher in current users compared with nonusers and compared with previous users who had stopped CS use >or=6 months earlier (both, q = 0.047). Current users also reported significantly greater distress than nonusers for puffy face and excessive appetite (both, q = 0.047). Changed facial features was significantly more distressing in current users compared with those who had stopped CS use >or=6 months earlier (q = 0.047). Different symptom profiles emerged based on the pattern of CS use. Patients who were currently using CS or who had stopped CS treatment <6 months earlier reported more symptoms than did patients who had never received CS or who had stopped CS treatment =6 months earlier.
    Article · Sep 2008
  • [Show abstract] [Hide abstract] ABSTRACT: Thrombopoietin (TPO) is the major regulator of both megakaryopoiesis and platelet production. TPO is a glycoprotein primarily produced in the liver. TPO, when binding to its receptor (c-Mpl), triggers a signaling cascade that leads to the differentiation and proliferation of megakaryocytes, with a concomitant increase in platelets. The cloning and characterization of TPO in 1994 led to the production of a full length, glycosylated recombinant human TPO (rhTPO) and a pegylated, truncated protein (PEGrHuMGDF). These first-generation TPO drugs stimulated megakaryocyte production and increased platelet counts in healthy volunteers. Successful clinical trials followed in cancer patients, patients with immune thrombocytopenic purpura (ITP), and cancer patients receiving non-myeloablative chemotherapy. Neither rhTPO nor PEG-rHuMGDF raised platelet counts in myeloablated chemotherapy patients, probably due to a lack of megakaryocyte progenitor cells in their bone marrow. Unfortunately, neutralizing antibodies developed against TPO in 13 subjects who had received multiple injections of PEG-rHuMGDF. The resulting thrombocytopenia in these individuals ended all clinical trials with both drugs. A second generation of TPO growth factors have been developed and are in clinical trials. Researchers screened peptide libraries to find random, unrelated peptides that could stimulate TPO-dependent cell lines without also causing neutralizing antibody production. These peptides were then conjugated to various carrier molecules to increase their half-lives. This strategy led to the synthesis of romiplostim (AMG-531), with 2 sets of identical peptides linked to the Fc moiety of an Immunoglobulin G (IgG) antibody. This TPO peptide mimetic has shown success in clinical trials with healthy volunteers and individuals with ITP. No neutralizing antibodies have developed against AMG-531, however some thromboembolic events have occurred in high risk patients, and potentially reversible increases in bone marrow reticulin have been reported. Other TPO nonpeptide mimetics have been created by using a similar strategy with libraries of nonpeptide molecules that can stimulate TPO-dependent cell lines. Eltrombopag and AKR-501 are two drugs of this type that have shown positive results in clinical trials. In addition, antibodies that can stimulate the c-Mpl receptor are being engineered to act as potent TPO agonists. These and other drugs in preclinical development represent a new line of therapy for thrombocytopenic patients.
    Article · Apr 2009
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