Chronic Idiopathic Thrombocytopenia Purpura Research Articles

Combination immune-based therapy for chronic ITP

Idiopathic thrombocytopenia purpura (ITP) is a common pediatric disorder that often dramatically presents with sudden onset bruising, petechiae, and (typically quite severe) thrombocytopenia. While various therapies (glucocorticoids, intravenous gamma globulin, intravenous anti-D) can transiently increase the platelet count, serious bleeding from acute ITP is uncommon, with little evidence that preemptive treatment reduces either the risk of serious bleeding or the already low (10-15%) incidence of developing chronic ITP. Given the side effects commonly associated with these drugs, the pendulum has to some degree swung back toward observation without pharmacologic intervention for newly diagnosed patients. Chronic ITP is different. Over time bleeding manifestations can become more severe, lifestyle limitations become more burdensome, and bleeding from accidental trauma remains a constant concern. While splenectomy has long been used to treat chronic ITP, there remains a life-long increased risk of infection despite use of pre-splenectomy immunizations and prophylactic antibiotics. Various immunomodulatory therapies have also been used, joined more recently by thrombopoietin mimetic drugs. Unfortunately, many children with chronic ITP respond to these treatments either transiently, or not at all. In this volume of The Journal, Oved et al report a retrospective review of 33 children treated with a combination of 4 weekly doses of rituximab plus three 4-day pulses of dexamethasone. Each drug has been used individually for chronic childhood ITP, and prior studies in adults suggest that combination therapy may be more effective than either drug alone. All patients had received at least 1—and often many—prior treatments for chronic ITP. Approximately half of the patients who received combination therapy initially responded, and one-third maintained prolonged remissions 10-58 months after treatment; more interesting, almost all of the long-term responders were females who were treated <24 months from their initial diagnosis of ITP. Other than the expected GI upset from steroids and transient hypogammaglobulinemia from rituximab, treatment was generally well tolerated. These results suggest that this combination would be a reasonable early intervention for a female with chronic ITP, whereas alternative interventions should be pursued for male patients or those with prolonged duration of thrombocytopenia. Article page 225 ▶ Treatment of Children with Persistent and Chronic Idiopathic Thrombocytopenic Purpura: 4 Infusions of Rituximab and Three 4-Day Cycles of DexamethasoneThe Journal of PediatricsVol. 191PreviewTo assess initial and long-term outcome of children with persistent/chronic idiopathic thrombocytopenic purpura (ITP) treated with 4 infusions of rituximab and three 4-day cycles of dexamethasone (4R+3Dex) including cohorts with most benefit and/or treatment associated toxicity. Full-Text PDF

Dental extraction in a child with chronic idiopathic thrombocytopenia purpura: are preoperative platelet transfusions necessary?

Thresholds for platelet counts in patients at risk for bleeding are often used before surgery. We present a case report of a 13-year-old female with chronic idiopathic thrombocytopenia purpura for dental extraction with a platelet count of 4 × 10 L. Usually, therapies including platelet infusions, IV immunoglobulin, or corticosteroids would be used to increase platelet numbers. In this patient, rather than using any of these prophylactic therapies preoperatively, we used a "watchful waiting" strategy with a multidisciplinary team, the use of tranexamic acid and the aforementioned therapies available only as "rescue" agents.

Eltrombopag or Intravenous Immunoglobulin as a Bridge to Splenectomy in Adults With Chronic Idiopathic Thrombocytopenic Purpura: A Canadian Economic Analysis

Abstract Background Chronic idiopathic thrombocytopenia purpura (ITP) in adults is a potentially serious disorder affecting 6000 to 7000 Canadians. Initial treatment consisting of corticosteroids usually begins when the platelet count is persistently below 20 × 109/L or if the patient has bleeding complications. In cases in which corticosteroid resistance develops or in which they are contraindicated, splenectomy is the recommended second-line therapy. In many of these patients, intravenous immunoglobulin (IVIG; 1 g/kg/day for 2 days then 1 g/kg/day monthly) is often used as a bridge to surgery. Eltrombopag is a new orally administered agent that activates the thrombopoietic receptor and stimulates human megakaryocytes. Clinical trials have demonstrated that eltrombopag is safe and effective in the treatment of adults with chronic ITP. Therefore, it represents an attractive option to IVIG for use as a bridge to splenectomy. In this study, a cost-minimization analysis was conducted to test the hypothesis that eltrombopag is a cost-effective alternative to IVIG for this indication. Patients and Methods The economic analysis was conducted from the Canadian societal perspective using a 4-month time horizon. Estimates for direct medical costs in these patients were obtained from 6 hematologists from across Canada. The base case analysis considered direct costs for drug therapy, outpatient pharmacy fees, medical consultations and visits, laboratory and diagnostic procedures, as well as costs for secondary pharmacotherapy in cases in which the primary agent had to be discontinued because of side effects. For IVIG, the analysis also included visits to the infusion clinic, chair time to receive the infusion, nursing time, pharmacy preparation, as well as indirect costs (eg, time off work, patient travel). A 1-way sensitivity analysis was then undertaken on the key cost drivers to test the stability of the primary findings. Results Total direct and indirect costs for IVIG were $24,134 for 4 months of therapy with drug cost contributing to 84% of the total. In contrast, total costs for eltrombopag were approximately $14,651 for an overall savings of $9,543 per patient. The sensitivity analysis suggested that the base case findings were stable and were only modestly affected by variations in drug cost and duration of therapy. Conclusion Given its oral route of administration and cost-saving potential, eltrombopag would be an economically attractive alternative to IVIG when the intent of therapy is to create a bridge to surgery.

Danazol treatment of myelodysplastic syndromes

Peripheral cytopenias are common in patients with myelodysplastic syndromes. We previously successfully treated three such patients with improvement of some cytopenias with the impeded androgen danazol. To confirm this finding and elucidate the mechanism of response, we treated an additional 22 patients with myelodysplasia with oral danazol (600-800 mg daily) for 3-12 months. Eleven of 22 evaluable patients taking danazol met our criteria for improvement of peripheral counts, mainly thrombocytopenia. Chromosome analysis, marrow culture studies and serial bone marrow biopsies revealed no alteration of the abnormal clone or normal haematopoiesis in patients on danazol therapy. This suggested that improvement in blood counts was not related to modulation of ineffective haematopoiesis. Investigation of the thrombocytopenia in these patients revealed that most patients presented with markedly elevated platelet associated IgG (PAIgG), elevated plasma platelet-bindable IgG (PBIgG), and an elevated number of monocyte Fc gamma receptors. Treatment with danazol was associated with a decline in monocyte Fc gamma receptor number without significantly altering the elevated PAIgG or PBIgG levels. These results are similar to our observations in patients treated with danazol for chronic idiopathic thrombocytopenia purpura (ITP). Our data suggest that a component of the thrombocytopenia occurring in patients with myelodysplasia may be due to enhanced peripheral blood cell destruction by abnormal macrophages. Danazol may modulate cytopenia by decreasing the number of monocyte Fc gamma receptors. Danazol treatment was associated with minimal toxicity, but clinically meaningful responses were rare.

The spleen and splenectomy in immune (idiopathic) thrombocytopenic purpura

The benefits of surgical splenectomy in patients with immune (idiopathic) thrombocytopenia purpura (ITP) probably reflect the combined effects of eliminating a source of antiplatelet antibody synthesis as well as the primary site of platelet destruction. The recent availability of intravenous Rho(D) immune globulin (WinRho SDF ™; Nabi, Boca Raton, FL) presents an opportunity to extend the duration of nonsurgical (spleen-sparing) management of chronic ITP by inducing reversible Fc blockade. While new methods for laparoscopic splenectomy may offer improved surgical outcomes and reduced costs for ITP patients in the near-term, the long-term consequences of splenectomy remain to be determined. Partial splenectomy has been shown to be effective in the management of anemia in hereditary spherocytosis and elliptocytosis, while preserving vital splenic phagocytic and immune functions. The concept that cell destruction occurs in reticuloendothelial cells has been updated with recognition that the mononuclear phagocyte is neither a reticular nor an endothelial cell. Immune phagocytosis is now understood to be mediated by macrophage IgG Fc and complement receptors. A key factor for devising a strategy for selecting medical or surgical splenectomy, or postponing splenectomy, is an assessment of the relative importance of splenic immune versus phagocytic function in the pathogenesis of ITP.

Elevated levels of p53 protein in the neutrophils and monocytes of a patient with chronic idiopathic thrombocytopenic purpura or possible early myelodysplasia?

A 68 year old female who presented with long-term thrombocytopenia was clinically diagnosed as having chronic idiopathic thrombocytopenia purpura (ITP). Increased levels of the tumour suppressor p53 protein were detected by immunohistochemistry in the neutrophils and some monocytes of the peripheral blood preparation using the antibody DO-1, recognizing mutant and wild type p53 protein conformations. However, no positive staining in the peripheral blood samples from 41 myelodysplasias (MDS) and six normal individuals was observed. Single-stranded conformational polymorphism analysis performed on DNA extracted from the cytospin preparations from this patient indicated no mutations in exons 5–8 of the p53 gene. This report describes the unusual detection of elevated p53 protein in a non-neoplastic condition by immunohistochemistry using the antibody DO-1. This unexpected finding raises the possibility of classifying such patients as early MDS on the basis of their p53 status.

Chronic childhood idiopathic thrombocytopenia purpura: long‐term follow‐up

An understanding of the natural history of childhood chronic idiopathic thrombocytopenia purpura (ITP) could contribute to a rational therapeutic approach to its treatment, which remains controversial. In our retrospective study of 92 children with ITP, 22 had a chronic course and were followed for 3-14 years (median 8.6 years). Treatment, when indicated, was individualized: 4 patients (18.2%) did not receive any treatment, 14 (63.6%) received steroids only, while 4 (18.2%) were treated with steroids and one of the following: high-dose gamma globulin (4 patients), splenectomy (2 patients) or immunosuppressive therapy (2 patients). During follow-up, 14 patients (63.6%) achieved complete remission, 5 (22.7%) partial remission and only 3 (13.5%) remained severely thrombocytopenic, with minimal bleeding tendency. Eleven patients (50%) responded to the initial prednisone course (1-5 mg/kg/day), but showed a marked decrease in platelet count when steroids were tapered off. In view of the high rates of complete and partial remission and the mild course of the few non-responding patients, it is suggested that with adequate supportive therapy, follow-up problems and fatalities can be kept to a minimum. We believe that aggressive therapy, such as splenectomy, should be reserved for the rare symptomatic and severely thrombocytopenic patient.

Micromethod for demonstrating increased platelet surface immunoglobulin G: Findings in acute, chronic, and human immunodeficiency virus‐1‐related immunologic thrombocytopenias

A method has been developed for the demonstration of increased platelet surface IgG that uses 1 ml of blood regardless of the platelet count. Platelets are gel filtered to remove plasma and contaminating lymphocytes. They are then reacted with fluorescein-conjugated antihuman IgG and analysed by flow cytometry. Percent positive staining cells vary from 10% to 80% of total cells examined. A platelet antibody index is derived from the product of percent positive staining cells X mean fluorescence intensity of positive staining cells. All patients studied with chronic idiopathic thrombocytopenia purpura (ITP) or human immunodeficiency virus-1 (HIV-1)-related thrombocytopenia had increased platelet surface IgG. Twelve acute children and 11 chronic children had indices averaging 3.5- and 8.9-fold greater than 12 normal children, respectively. Five of 12 children with acute ITP had normal platelet IgG. There was no linear correlation between the platelet antibody index and platelet count. Platelets of patients with acute, chronic, or HIV-1-related ITP displayed autofluorescence. In chronic ITP, the percentage of platelets displaying autofluorescence had a significant negative correlation with the platelet count. This technique will be a valuable diagnostic tool in the pediatric population.

ASCORBATE FOR THE TREATMENT OF IDIOPATHIC THROMBOCYTOPENIC PURPURA

British Journal of HaematologyVolume 75, Issue 4 p. 626-627 Free Access ASCORBATE FOR THE TREATMENT OF IDIOPATHIC THROMBOCYTOPENIC PURPURA Kanjaksha Ghosh, Kanjaksha Ghosh Haematology Laboratory, Farwaniya Hospital, Kuwait, Arabian GulfSearch for more papers by this author Kanjaksha Ghosh, Kanjaksha Ghosh Haematology Laboratory, Farwaniya Hospital, Kuwait, Arabian GulfSearch for more papers by this author First published: August 1990 https://doi.org/10.1111/j.1365-2141.1990.tb07816.xCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES Brox, A.G., Howson-Jan, K. & Fauser, A.A. (1988) Treatment of ITP with ascorbate. British Journal of Haematology, 70, 341– 344. Quiquandon, I., Fenaux, P., Canlier, M.T. & Pagniez, D. (1990) Reevaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenia purpura: a report on 53 cases. British Journal of Haematology, 74, 223– 229. Verhoef, G.E.G., Boonen, S. & Boogaerts, M.A. (1990) Ascorbate for the treatment of refractory idiopathic thrombocytopenic purpura. British Journal of Haematology, 74, 234– 235. Citing Literature Volume75, Issue4August 1990Pages 626-627 ReferencesRelatedInformation

Overview of ITP treatment modalities in children.

Patients with idiopathic thrombocytopenia purpura (ITP) are frequently encountered by the pediatrician and pediatric hematologist. The clinical and laboratory features of ITP are quite uniform and facilitate prompt and accurate diagnosis. Bone marrow examination is not required in most cases since patients with alternative diagnoses (such as ALL) have greatly different presenting features. Acute ITP cannot be differentiated from the chronic form of the disease at presentation, nor can chronic disease be prevented by specific therapy administered for apparent acute ITP. Much controversy has revolved around whether an active interventionist (pharmacologic) or non-interventionist approach is preferred for management of ITP. The platelet count in both acute and chronic ITP often rises following treatment with prednisone and/or intravenous gamma globulin (IV GG), but such responses are transient and do not clearly provide protection against the rare complication of life-threatening hemorrhage. There are numerous disadvantages to an interventionist approach to therapy. Children with chronic ITP may require splenectomy if the disease is symptomatic enough to interfere with life-style, but the majority of these patients, too, require no specific therapy.