Severe Chronic Immune Thrombocytopenic Purpura Research Articles

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

What Level of Platelet Count and Symptoms Trigger Referral of Patients with Thrombocytopenia from Primary Care Physicians to Hematologists?

Introduction: Primary care physicians are typically the first physicians who see patients with thrombocytopenia. There are currently no data to document which patients who present with isolated thrombocytopenia or immune thrombocytopenic purpura (ITP) are referred to hematologists. The published ASH Practice Guideline on ITP (Blood 1996; 88:3) does not address the issue of referral to a hematologist; the British Committee for Standards in Haematology Guideline on ITP (Brit J Haematol 2003; 120:574) only recommends referral of children with severe chronic ITP. The goal of this study was to determine the level of thrombocytopenia or the combination of thrombocytopenia and bleeding symptoms that prompt family physicians to send patients to hematologists for further evaluation and management. Our a priori assumption was that this level would be less than or equal to 30,000/μL, regardless of bleeding symptoms.Methods: A survey was conducted in collaboration with the Oklahoma Physicians Resource-Research Network (OKPRN). The mission of the OKPRN is to provide community physicians with access to information and research opportunities to enhance their practices and to generate new knowledge through practice-based research. OKPRN family physicians (N=127) were asked to complete a short eight-item questionnaire consisting of five patient vignettes with varying degrees of thrombocytopenia and bleeding symptoms. For each vignette, the physician was to decide when or if he/she would send the patient to a hematologist for further management using a four point likert scale. The response categories were ‘very unlikely’, ‘unlikely’, ‘likely’, and ‘very likely’. The response scale was dichotomized (unlikely vs likely) to graphically display results across all five patient vignettes.Results: There was a 66% (84/127) response rate. Fifty-one percent (43/84) of the responders had been practicing family medicine between 6–20 years, 37% (31/84) for more than 20 years, and 12% (10/84) had been practicing between 1–5 years. Sixty-one percent (51/84) responded that there was a hematologist that they routinely called on the phone for advice and/or sent referrals, and 81% (68/84) practiced within 50 miles of a hematologist. Figure 1 shows as a patient's thrombocytopenia became more severe, the likelihood of referral to a hematologist increased. Seventy-five percent of the respondents surveyed were ‘likely’ to send a patient with moderate thrombocytopenia (platelet count 30,000/μL) without bleeding symptoms to a hematologist. The likelihood of referral increased to 85% when the moderate thrombocytopenia was associated with mild bleeding symptoms, and over 90% when a patient presented with severe thrombocytopenia (platelet count 10,000/μL) and bleeding symptoms. [Display omitted] Conclusion: Results from the OKPRN survey documented that patients with isolated thrombocytopenia and a platelet count of 80,000/μL would infrequently be referred to a hematologist while patients with platelet counts of ≤30,000/μL would almost always be referred, especially if there were bleeding symptoms. Results from this survey validate assumptions that ITP patients with moderate to severe thrombocytopenia are managed by hematologists, not primary care physicians. These data are important to define the scope of practice of hematology.

Severe chronic refractory immune thrombocytopenic purpura during childhood: A survey of physician management

Physician attitudes regarding management of children with severe chronic immune thrombocytopenic purpura (ITP) have not been recently characterized. We designed a survey of members of the American Society of Pediatric Hematology-Oncology (ASPHO) that described a 5-year-old female with ITP for 1 year who was unresponsive to steroids, IVIG, and anti-D immune globulin and having frequent epistaxis causing interference with her daily activities. A 13-item questionnaire evaluated physician decision-making in this setting. Two hundred and ninety-seven surveys (35% response rate) were returned, and 295 were evaluable. Thirty-three percent of respondents stated that they would recommend splenectomy for such a child. Of those who would not recommend splenectomy, 67% reported that they would instead treat with rituximab. If initial drug therapy failed, 47% would proceed with splenectomy. Those who reported treating with rituximab initially were more likely to recommend splenectomy following failure than those who preferred other drug therapy (P < 0.0001). Physician management of patients with chronic ITP is diverse. With the advent of new treatments such as rituximab and thrombopoetic agents it is critically important to compare their cost, adverse effects and efficacy with splenectomy in order to optimally guide treatment practices.

Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura

AbstractWe assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 × 109/L (50 000/mm3) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [CI], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included third-dose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP.

Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity.

In honour of Professor Rossi's 80th birthday we review the development of our understanding of the immune and auto-immune nature of the pathogenesis of immune thrombocytopenic purpura (ITP). The immune aspects have been documented by postviral alterations of the cellular and humoral immune system, by new methods of specific auto-antibody detection against platelet glycoproteins and by the therapeutic effect of administering immunoglobulin concentrate from healthy blood donors. The various possible mechanisms of action of immunoglobulin treatment have led to use of this treatment as an alternative for other immune-related disorders. The treatment of severe chronic ITP in children, however, remains unsatisfactory. With a new international clinical and laboratory study of children and adolescents with early chronic ITP we are continuing the investigation of the pathogenesis and treatment of ITP.

Treatment of chronic childhood immune thrombocytopenic purpura with intramuscular anti‐D immunoglobulins

Seven patients with chronic immune thrombocytopenic purpura (ITP) were treated with intramuscular anti-D (anti-D IgG) five times, on an alternate-day basis, or until a platelet count of 100 x 10(9)/l was achieved, and, subsequently, when necessary to maintain platelet counts above 50 x 10(9)/l. Five patients responded to therapy, two of whom entered long-term remission. Although signs of haemolysis were present in all patients, anaemia was never a problem. No patient developed haematomas at the site of injection. We suggest that intramuscular anti-D represents a safe and relatively inexpensive alternative to intravenous gamma globulins (IVGG) for children with severe chronic ITP.

Intravenous immunoglobulin administration in the treatment of severe chronic immune thrombocytopenic purpura

Human immunoglobulin was administered intravenously to nine adult patients having severe chronic immune thrombocytopenia purpura. The response in three patients was an increase in the platelet count to greater than 50,000/mm 3, a hemostaticly adequate level. Response was associated with a pretreatment platelet-associated immunoglobulin level of more than 5,000 molecules per platelet, and successful treatment resulted in a decrease in that level. In those patients with pretreatment platelet-associated immunoglobulin levels less than 5,000 molecules per platelet, there was neither a significant decrease in that level nor an increase in their platelet count. Immunoglobulin infusion may prove useful for selected patients with severe chronic Immune thrombocytopenia.

High-Dose Intravenous Immunoglobulin Therapy in Patients With Immune Thrombocytopenic Purpura

Four patients with severe chronic immune thrombocytopenic purpura who were refractory to all conventional therapy for that disorder were initially seen with either refractory bleeding or the necessity for an operation. We treated each of these patients with intravenous human serum immunoglobulin, and three of the four patients had a rapid and substantial increase in their platelet counts. This new method for ameliorating chronic immune thrombocytopenic purpura deserves further study and consideration.