Analysis of bleeding outcomes in patients with hypoproliferative thrombocytopenia in the A‐TREAT clinical trial

Background: Despite prophylactic platelet transfusions, hypoproliferative thrombocytopenia is associated with bleeding; historical risk factors include hematocrit (HCT) ≤25%, activated partial thromboplastin time ≥30 s, international normalized ratio ≥1.2, and platelets ≤5000/μL. Methods: We performed a post hoc analysis of bleeding outcomes and risk factors in participants with hematologic malignancy and hypoproliferative thrombocytopenia enrolled in the American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A-TREAT) and randomized to receive either tranexamic acid (TXA) or placebo. Results: World Health Organization (WHO) grade 2+ bleeding occurred in 46% of 330 participants, with no difference between the TXA (44%) and placebo (47%) groups (p = 0.66). Overall, the most common sites of bleeding were oronasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%). Among participants of childbearing potential, 28% experienced vaginal bleeding. Platelets ≤5000/μL and HCT < 21% (after adjusting for severe thrombocytopenia) were independently associated with increased bleeding risk (HR 3.78, 95% CI 2.16–6.61; HR 2.67, 95% CI 1.35–5.27, respectively). Allogeneic stem cell transplant was associated with nonsignificant increased risk of bleeding versus chemotherapy alone (HR 1.34, 95% CI 0.94–1.91). Discussion: The overall rate of WHO grade 2+ bleeding was similar to previous reports, albeit with lower rates of gastrointestinal bleeding. Vaginal bleeding was common in participants of childbearing potential. Platelets ≤5000/μL remained a risk factor for bleeding. Regardless of platelet count, bleeding risk increased with HCT < 21%, suggesting a red blood cell transfusion threshold above 21% should be considered to mitigate bleeding. More investigation is needed on strategies to reduce bleeding in this population.