Type: Oral
Session: 323. Disorders of Coagulation, Bleeding, or Fibrinolysis, Excluding Congenital Hemophilias: Clinical and Epidemiological: Novel Treatments and Outcomes
Hematology Disease Topics & Pathways:
Research, Bleeding and Clotting, Bleeding disorders, Hemophilia, Platelet disorders, Clinical Research, Health outcomes research, Pediatric, Diseases, VWD, Young adult , Study Population, Human
Our multi-center, retrospective, cohort study conducted at 5 Hemophilia Treatment Centers identified patients using an electronic medical record screening report with the inclusion criteria of female gender assigned at birth, ICD 9/10 codes for eligible bleeding disorder diagnoses, presence of at least one clinical encounter between 1/1/2015 to 4/1/2021, and age <21 years at time of initial encounter. We collected demographics, bleeding disorder diagnosis, characterization of HMB, treatment modalities, outcomes, and safety data. Treatment modalities were grouped as combined estrogen/progesterone therapy (oral, patch, or ring), progesterone therapy (oral, intrauterine device, implant, or injection), TXA therapy alone, or TXA plus estrogen/progesterone or plus progesterone. Statistical analysis was conducted by summarizing patient demographic variables, treatments, and outcomes with mean and standard deviation (SD) or median and quartiles for continuous variables and by frequency and percentage for categorical variables. The repeated outcomes of HMB control, AE, complications, and adherence were compared across treatments by generalized linear mixed-effects models.
221 patients were included. Mean age at diagnosis of HMB of 14.2 years (SD 1.7). Mean duration of HMB at time of initial HMB diagnosis was <3 months in 49%, 95% Confidence Interval (CI) [0.43, 0.56]; 28% [95% CI: 0.21, 0.35] had HMB >6 months at diagnosis. Seventy percent had von Willebrand disease, 20% with platelet function disorders, and 10% with factor deficiencies. At diagnosis of HMB, no patients were on treatment for HMB. During the study period, there were 1478 HMB-related health-care encounters, and most occurred at HTCs (40%) followed by OB-GYN clinics (19%). 474 treatment modalities were identified which consisted of combination estrogen/progesterone in 164 (35%), progesterone alone in 85 (18%), TXA in 64 (14%), estrogen/progesterone plus TXA in 26 (6%), progesterone plus TXA in 23 (5%), and other medications (factor, aminocaproic acid, or desmopressin acetate) in 112 (24%). Median number of treatment regimens per patient was 2 (1,3 for 1st,3rd quartiles, range):1-6). No thrombotic events occurred. Adherence was highest for progesterone therapy alone (84.5%), TXA (75%), combination estrogen/progesterone (65%), and least for estrogen/progesterone plus TXA (60%). At ≤3 months of treatment, effectiveness of HMB control occurred in 39% (95%CI: 0.3, 0.48)) on estrogen/progesterone; in 41% (95%CI: 0.28, 0.53) on progesterone, 49% (95%CI: 0.34, 0.63) on TXA, 44% ((95%CI: 0.19, 0.7) on progesterone plus TXA and 69% (95%CI: 0.41, 0.88) on estrogen/progesterone plus TXA. Patients on hormonal therapy (combination estrogen/progesterone or progesterone alone) plus TXA were 3.6 (95% CI 1.0-12.9 p=0.046) times more likely to report HMB control vs. hormonal therapy or TXA alone.
To our knowledge, this is the largest study examining HMB treatment in adolescents with bleeding disorders. Our study suggests that hormonal treatment in combination with TXA controls HMB more effectively than hormonal therapy or TXA alone. Yet hormonal therapy remains the predominant treatment. Despite limited numbers of patients on combination therapy with estrogen/progesterone and TXA, no thrombosis was reported. Larger prospective studies are needed to demonstrate effectiveness and safety seen in combining hormonal therapy and TXA to increase this treatment utilization in these patients.
Disclosures: Amos: Sanofi: Honoraria, Speakers Bureau; Genentech: Honoraria. Zia: Hema Biologics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Star Therapeutics: Consultancy, Honoraria; COR2ED: Consultancy, Honoraria. Chitlur: Genzyme: Honoraria; NHF: Consultancy; Novo Nordisk: Consultancy; Novo Nordisk: Honoraria; Takeda: Honoraria; CSL Behring: Honoraria; BPL Inc: Honoraria; Agios Pharmaceuticals: Research Funding. Malec: Sanofi: Honoraria, Speakers Bureau; Biomarin: Honoraria; Pfizer: Honoraria; Sobi: Honoraria; CSL Behring: Honoraria, Speakers Bureau; Takeda: Honoraria; Spark Therapeutics: Speakers Bureau; Novo Nordisk: Honoraria. Wheeler: Sanofi-Aventis USA: Honoraria; Bioverativ: Honoraria; BioMarin: Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding; Spark Therapeutics: Honoraria; Bayer: Honoraria; HEMA Biologics: Honoraria; Shire North America: Honoraria; Genentech: Honoraria; CSL Behring: Honoraria; Octapharma: Research Funding; Pfizer Inc: Honoraria; Octapharma USA: Honoraria; Takeda Pharmaceuticals: Honoraria.