The “platelet boilermaker”: A treatment protocol to rapidly increase platelets in patients with immune‐mediated thrombocytopenia
Authors: Sven R. Olson, Charles Chu, Joseph J. Shatzel, Thomas G. Deloughery
Journal: American Journal of Hematology (2016)

To the Editor: ITP is characterized by autoantibody-mediated destruction of platelets, often taking on a chronic, insidious course with periodic relapses 1. Corticosteroids and intravenous immunoglobulin (IVIG) are first-line therapies for ITP recommended by current guidelines, with initial response rates of approximately 70–85% and response times ranging from 24 h to more than 4 days 1, 2. While bleeding in ITP is typically mild, major hemorrhage or the need for urgent surgical procedures are not uncommon scenarios. More rapid hemostasis is necessary in these settings, which has prompted exploration of alternative strategies including the prolonged co-administration of IVIG and platelets 2-5. The largest review of this regimen to date showed a 62.7% success rate in achieving platelets >50,000/μL within 24 h of therapy 3. Data supporting particular emergency therapies, including concurrent IVIG and platelets, are lacking. We previously reported the efficacy of a variation of this regimen dubbed the “platelet boilermaker,” which consists of a 24-h continuous infusion of IVIG, 1 g/kg, and four units of apheresis platelets, each infused over 6 h. 70% of cases showed an excellent response in platelet counts 5. Here we report our outcomes with this protocol over the last 7 years, including data on previous and concurrent ITP therapies. Patients admitted to Oregon Health and Science University between September 2008 and December 2015 with a diagnosis of ITP, drug-induced ITP (DITP) or Evans syndrome who were treated with the boilermaker protocol were retrospectively identified, including those who received other ITP therapies previously or concurrently with the boilermaker. Prior and concurrent ITP treatments, daily post-treatment platelet counts over 4 days, and the incidence of bleeding or surgical complications were tabulated. 15 patients, 8 males and 7 females, with ITP, DITP or Evans syndrome received the boilermaker during the study period (Table 1). 17 distinct treatments were identified; one patient received the regimen three times. Age ranged from 23 to 89 (median 57, mean 48). All patients had pretreatment platelets <30,000/μL, bleeding signs and symptoms, or both. 13 of 15 (87%) patients had received prior ITP therapy. 12 of 17 (71%) cases received concurrent ITP treatments along with the boilermaker. 10 of 17 (59%) cases had previously been deemed refractory to IVIG alone. The average pretreatment platelet count was 9,000/μL. At 24, 48 and 72 hours after initiation of therapy, average platelet counts increased to 50,000/μL, 77,000/μL, and 79,000/μL, respectively. At 24 h, 11 of 17 (65%) cases and 9 of 17 (53%) cases increased platelets to >30,000/μL and >50,000/μl, respectively. Of the 10 cases that were previously refractory to IVIG, 6 (60%) achieved platelets >30,000/μL after 24 h, with four of these (40%) achieving counts >50,000/μL. Of the 12 cases that were treated concurrently with other ITP therapies, 6 (50%) mounted a platelet response >50,000/μL by 24 h; platelets remained <30,000/μL in the remaining 6 (50%) cases. All 5 (100%) cases that did not receive concurrent therapies achieved platelets >30,000/μL by 24 h, with three (60%) reaching 50,000/μL. No patients experienced worsening bleeding or surgical complications. Three patients underwent splenectomy and one pregnant patient delivered after 24 h of therapy. A second pregnant patient delivered via cesarean section after 4 days, and two patients underwent splenectomy greater than 1 week after therapy. In this retrospective review, 65% of patients showed a response after 24 h of therapy, defined as platelets >30,000/μL and a twofold increase in baseline levels 2. Over half the patients were also able to achieve the platelet threshold of >50,000/μL recommended for most non-neuraxial surgeries 6. The platelet boilermaker also showed favorable results for patients refractory to IVIG alone. No patient experienced worsening bleeding symptoms or surgical complications. Our review found similar efficacy of continuous IVIG and platelets compared with previous studies, including in patients who were IVIG refractory 3, 4. Chandramouli and Rodgers described favorable results with this treatment in two patients 4, while Spahr et al. reviewed 40 patients, finding a 62.7% success rate in achieving platelets >50,000/μL within 24 h 3. Of note, our protocol differs from that used in previous studies, which administered platelets every 8 h instead of every six 3, 4. Corticosteroids and IVIG are recommended first-line therapies for ITP with bleeding and/or platelets less than 30,000/μL, though response times can be delayed 1, 2. Prednisone can take up to 4 days to stimulate a platelet response, while dexamethasone generally takes at least 2 days 1. IVIG can stimulate a response within 24 h 1, 2. All of these response times can vary considerably 1, 2. Platelet transfusions alone often have no effect in ITP, though IVIG may counteract platelet destruction through its various immunomodulatory mechanisms. Hospitalizations for life-threatening hemorrhage are not uncommon in ITP. Patients may also require emergent surgery including therapeutic splenectomy. Both scenarios necessitate rapid hemostasis. Although guidelines advocate a variety of interventions for bleeding emergencies including antifibrinolytic agents, platelet transfusions, recombinant factor VIIa, or combinations of first and second-line therapies, these interventions have limitations including a lack of clear data on which offers the safest and quickest means to achieve hemostasis 1, 2. Concurrent infusion of IVIG and platelets is an alternative to these therapies, with increasing data suggesting efficacy and safety 3-5. Our review strengthens the rationale for this strategy. This retrospective review has several limitations, including a small number of cases and lack of response stratification based on concurrent ITP therapies, though only dexamethasone has an initial response time (48 h) rapid enough to confound early platelet increases 1. Although several patients underwent early splenectomy, our review was concerned with immediate (<24 h) effects of the platelet boilermaker. Despite these limitations, concurrent infusion of IVIG and platelets appears to be a viable strategy for rapidly increasing platelets in situations of life-threatening bleeding or imminent surgery. Sven R. Olson MD: Data accumulation and interpretation, manuscript drafting. Charles Chu: Data accumulation. Joseph J. Shatzel MD: Project conception and design, manuscript drafting. Thomas G. Deloughery MD, MACP, FAWM: Project conception and design, manuscript drafting, critical edits. Sven R. Olson,1* Charles Chu,2 Joseph J. Shatzel,3 and Thomas G. Deloughery3 1Department of Internal Medicine, Oregon Health and Science University, Portland, Oregon; 2School of Medicine, Oregon Health and Science University, Portland, Oregon; 3Division of Hematology and Medical Oncology, Oregon Health and Science University, Knight Cancer Institute, Portland, Oregon