Arnold, Donald M.

Background: Since publication of the American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia (ITP), new clinical trials have been completed and new treatments have become available. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are a focused update of the 2019 ASH ITP guidelines, centering on treatment of adults with primary ITP. Methods: ASH formed a multidisciplinary guideline panel including two patient representatives that was balanced to minimize potential bias from conflicts of interest. The University of Oklahoma supported the guideline development process, including updating or performing systematic evidence reviews (up to July 19, 2025). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and identification of areas with new data or where application of new methods would be of benefit. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks and the GRADE framework for multiple comparisons, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on recommendations in adults with primary ITP regarding initial therapy and second-line treatment in patients who failed first-line corticosteroids. The panel also issued good practice statements on thrombopoietic agent switching and splenectomy. Conclusions: Novel recommendations of these guidelines include: (1) initial therapy with a combination of rituximab plus corticosteroids or a thrombopoietic agent plus corticosteroids rather than corticosteroids alone (conditional recommendation) and (2) a thrombopoietic agent (strong recommendation) or rituximab (conditional recommendation) for patients who failed first-line corticosteroids.

AbstractPrior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5‐year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere—winter (December–February); spring (March–May); summer (June–August); autumn (September–November) and Southern Hemisphere—winter (June–August); spring (September–November); summer (December–February); autumn (March–May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%–31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization.

Background: Patients with immune thrombocytopenia (ITP) may require treatment to raise the platelet count before surgery. Intravenous immune globulin (IVIG) is commonly used for this purpose, but eltrombopag, an oral thrombopoietin receptor agonist, may be a good alternative. We compared perioperative eltrombopag or IVIG for the achievement of platelet count targets for major or minor surgery. Methods: We conducted a randomized, non-inferiority trial at 8 centers in Canada.ITP patients with a platelet count &lt;100 x109/L or &lt;50 x109/L before elective major or minor surgery, respectively, were assigned to receive daily oral eltrombopag starting 3 weeks preoperatively or IVIG 1 week preoperatively. Eltrombopag was discontinued 1 week after surgical hemostasis, and a repeat dose of IVIG was permitted up to 1 week after surgical hemostasis. The primary endpoint was the achievement of platelet count targets (90 x109/L for major surgery, or 45 x109/L for minor surgery) immediately before surgery and for 7 days after surgical hemostasis without rescue treatment. Intention-to-treat and per-protocol analyses were done using a one-sided test for the difference in rates of achieving perioperative platelet count targets with a non-inferiority margin of 10% at a significance level of 0.05. Patients were followed for 4 weeks postoperatively. Secondary outcomes were thrombosis, adverse events and treatment satisfaction as measured using a validated patient questionnaire. Results: From 2013 to 2019, 38 patients were assigned to received eltrombopag and 36 patients were assigned to receive IVIG before major (n= 31) or minor (n= 43) surgery. Five patients did not complete the study. By intention to treat, 30/38 (78.9%) patients on eltrombopag achieved perioperative platelet count targets compared with 22/36 (61.1%) on IVIG (absolute risk difference, 17.8%; one-sided lower limit of the 95% confidence interval, 0.4%; p=0.005 for non-inferiority). Results were similar in the per protocol analysis (absolute risk difference: 15.8%; one-sided lower limit of the 95% CI, -2.1%; p=0.009). Eltrombopag was superior to IVIG in the intention-to-treat analysis (p=0.047) but not in the per-protocol analysis (p =0.074). One patient developed pulmonary embolism 14 days after minor surgery (skin biopsy) and 7 days after stopping eltrombopag when the platelet count was 135 x109/L. Of 18 patients who underwent splenectomy on study, marked post-splenectomy thrombocytosis (platelets &gt;1,000 x109/L) occurred in 2 (11.1%) patients, both of whom were on eltrombopag. Global treatment satisfaction scores were higher for eltrombopag. Conclusion: Eltrombopag is non-inferior and may be superior to IVIG for achieving target platelet counts perioperatively for patients with ITP. Post-operative thromboprophylaxis should be considered with eltrombopag. Funding Source:This was an investigator-initiated trial funded by Novartis. Disclosures Arnold: Novartis: Honoraria, Research Funding; Rigel: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Principia: Consultancy. Heddle:Novartis: Research Funding. Hsia:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sholzberg:Novartis: Honoraria; Amgen: Honoraria, Research Funding. Lin:Pfizer: Consultancy; Novartis: Research Funding; Octapharma: Research Funding; Amgen: Consultancy. Larratt:Novartis: Honoraria. Amini:Amgen NL: Research Funding; Novartis NL: Research Funding. Schipperus:Novartis: Research Funding. Lim:Pfizer Canada: Consultancy, Honoraria; Portola Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Honoraria. OffLabel Disclosure: Eltrombopag is not licenced for perioperative treatment in patients with ITP.