How I treat refractory immune thrombocytopenia

Abstract

This article summarizes our approach to the management of children and adults with primary immune thrombocytopenia (ITP) who do not respond to, cannot tolerate, or are unwilling to undergo splenectomy. We begin with a critical reassessment of the diagnosis and a deliberate attempt to exclude nonautoimmune causes of thrombocytopenia and secondary ITP. For patients in whom the diagnosis is affirmed, we consider observation without treatment.Observation is appropriate for most asymptomatic patients with a platelet count of 20 to 30 3 10 9 /L or higher. We use a tiered approach to treat patients who require therapy to increase the platelet count. Tier 1 options (rituximab, thrombopoietin receptor agonists, low-dose corticosteroids) have a relatively favorable therapeutic index. We exhaust all Tier 1 options before proceeding to Tier 2, which comprises a host of immunosuppressive agents with relatively lower response rates and/or greater toxicity. We often prescribe Tier 2 drugs not alone but in combination with a Tier 1 or a second Tier 2 drug with a different mechanism of action. We reserve Tier 3 strategies, which are of uncertain benefit and/or high toxicity with little supporting evidence, for the rare patient with serious bleeding who does not respond to Tier 1 and Tier 2 therapies. (Blood. 2016;128(12): 1547-1554 Case 1A 10-year-old male was diagnosed with primary immune thrombocytopenia (ITP) 5 months ago when he presented with epistaxis, petechiae, bruising, and a platelet count of 5 3 10 9 /L. He responded transiently to intravenous immunoglobulin G (IgG), but epistaxis recurred 2 weeks later. He subsequently received a short course of oral corticosteroids to which he had a temporary response in platelet count and cessation of epistaxis. Since discontinuing corticosteroids, he has had only occasional bruising and petechiae. His platelet count is currently 13 3 10 9 /L. He states that ITP is not interfering with activities.

A Novel PF4-Dependent Platelet Activation Assay Identifies Patients Likely to Have Heparin-Induced Thrombocytopenia/Thrombosis

“…11,31 The present study was designed to assess the ability of the PEA to selectively identify patients considered to be HIT positive on the basis of both clinical presentation (intermediate to high 4Ts score of 4-8) and PF4 ELISA results (OD $ 2.0 or $ 1.0, depending on the 4Ts score) as recommended. 19,20,29 Using this classification, the diagnostic accuracy of the PEA was found to be significantly better than that of the SRA (AUC, 0.92 vs 0.82; P < .05) and the P-selectin expression level of 24% was found to be optimal as a threshold for defining a positive test result. A significant difference in accuracy between the PEA and SRA was maintained The greater sensitivity of the PEA for detection of platelet-activating antibodies in patients receiving heparin treatment appears to be the result of PF4-dependent priming of test platelets by a mechanism not yet fully defined, leading to enhanced antibody binding and activation via the platelet Fc receptor CD32.…”

“…17,18 Accordingly, experts in the field recommend use of PF4 ELISA OD $ 2.0 or $ 1.0 together with an intermediate or high 4Ts score (4-5 or 6-8, respectively) to optimize diagnosis. 19,20 However, a low 4Ts score, in itself, has a high negative predictive value for HIT.…”

Immune Thrombocytopenia - Current Diagnostics and Therapy: Recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH, and DGTI

“…ITP with recurrent clinically relevant bleedings that does not respond to multiple therapies is a serious disease with high morbidity and mortality [125,126]. In this situation, patients are usually offered a combination of ITP agents, e.g., rituximab plus steroids plus TRAs.…”

Dapsone therapy for refractory immune thrombocytopenia patients: a case series

“…The goals of ITP treatment are to maintain the platelet count to avoid the risk of serious bleeding and to limit drug toxicity [17]. Several retrospective studies demonstrated that dapsone provides an effective, inexpensive, and well-tolerated alternative for patients with refractory ITP (Table 2) [12131415181920].…”