Bleeding Risk Factors in Thrombocytopenic Patients with Hematologic Malignancies

Introduction Despite prophylactic platelet transfusions, World Health Organization (WHO) grade ≥ 2 bleeding occurs in 50 to 70% of patients with hematologic malignancies and hypoproliferative thrombocytopenia secondary to therapy and/or underlying disease (Gernsheimer et al, Blood 2022). Anemia (hematocrit, HCT ≤ 25%), coagulopathy (activated partial thromboplastin time ≥ 30s, international normalized ratio ≥ 1.2), and platelet count ≤ 5000/µl were independently associated with increased risk of bleeding in the PLADO (platelet dose) trial of 1272 patients with hypoproliferative thrombocytopenia treated between 2004 to 2007 (Uhl et al, Blood 2017). Updated data on bleeding outcomes and risk of bleeding is lacking. Methods We performed a post-hoc analysis of bleeding outcomes and bleeding risk factors in 330 patients with hematologic malignancy and hypoproliferative thrombocytopenia from therapy and/or underlying disease randomized at 3 institutions to receive either tranexamic acid (TXA) or placebo in the double-blinded, multicenter American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A-TREAT) (Gernsheimer et al, Blood 2022). Patients received prophylactic platelet transfusions for a platelet count of ≤ 10,000/µl and WHO grade bleeding was assessed daily for 30 days after a platelet count ≤ 30,000/µl and study drug was started. Study drug was discontinued when platelet count was ≥ 30,000/ul for 46 hours without platelet transfusion support or until a maximum of 30 days after treatment activation, whichever came first. Red blood cell (RBC) transfusion was given according to local standard of care. Cox proportional hazards regression with time-varying covariates was used to assess the association of patient characteristics with the risk of a first major (grade 2+) bleeding event. HCT, platelet count, inpatient vs. outpatient status, steroid treatment, and fever were recorded daily. Patients were censored at the first of time of withdrawal, death, or day 30. Results WHO grade ≥ 2 bleeding occurred in 46% of patients overall with no difference between the TXA and placebo groups (TXA 44% versus placebo 47%, p=0.66). Bleeding rates were highest in allogeneic stem cell transplant patients, followed by chemotherapy, followed by autologous stem cell transplant. Overall bleeding rates by organ system showed oral and nasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%) bleeding (Table 1). WHO grade ≥ 2 vaginal bleeding occurred i