Session: 322. Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Bleeding and Clotting, hemophilia, Clinical Practice (Health Services and Quality), Clinical Research, health outcomes research, pediatric, Diseases, Study Population, Human
Methods: Retrospective medical record review of Hemophilia A carriers <18 years of age was undertaken at our center. Inclusion criteria were family history of Hemophilia A and FVIII mutation or FVIII level <0.40 IU/ml in patients without genetic testing done. Patients with other co-existing bleeding disorders were excluded. Statistical analysis was done by Chi Square/Exact tests.
Results: Twenty-three pediatric Hemophilia A carriers were eligible, with median age of 12 years (range1-16). Fifteen were adolescents >10 years. Fourteen (60.9%) had FVIII level >0.40 IU/ml with 8 (57.1%) categorized as asymptomatic, and 6 (42.9%) symptomatic carriers in accordance with the new ISTH nomenclature. Nine (39.1%) patients had FVIII <0.40 IU/ml, with 8 (88.8%) categorized as mild (FVIII 0.05-0.40 IU/ml), 1 (11.1%) as moderate (FVIII 0.01-0.05 IU/ml), and none as severe (<0.01 IU/ml) Hemophilia A, as per the new nomenclature. Bleeding Scores (BS) were obtained in all patients using the ISTH Bleeding Assessment Tool (ISTH-BAT) with a median BS of 1 (range 0-7). A significant BS of >2 was present in 4/9 (44.4%) patients with FVIII <0.40 IU/ml, and 4/14 (28.6%) with FVIII >0.40 IU/ml, the difference was not statistically significant (p=0.40) (Table 1). Two symptomatic carriers with FVIII >0.4 IU/ml, had BS of 1 and 2. 5/15 adolescents (33.3%) had BS>2 (BS of 4 in 3; BS of 7 in 2). FVIII was measured with one stage assay (OSA) (N=17; 73.9%), chromogenic substrate assay (CSA) (N= 2; 8.7%) or both (N=4; 17.4%), with 1 patient’s (4.3%) CSA discrepantly lower than OSA by 0.62 IU/ml and none with inverse discrepancy. Genetic testing was done in 20/23 (86.9%) patients, with FVIII missense mutations in 14 (70%), intron inversions in 4 (20%), and deletions in 2 (10%), their association with BS did not show statistically significant difference (p=0.6) (Table 2).
Conclusion: Our study was done exclusively in pediatric Hemophilia A carriers, as it is important to identify children at risk of bleeding and institute preventive measures early. Unlike in adult women, higher number (one-third) of our patients experienced mucosal bleeding, and none reported joint or muscle bleeding. Our study showed lack of statistically significant association of FVIII levels with bleeding phenotype. According to the new ISTH nomenclature, 39.1% of our study patients have the diagnosis of Hemophilia A, of whom 55.6% did not have a significant BS. Of the 60.9% categorized as carriers, 28.6% had a significant BS. In addition, we found lack of statistically significant correlation of genetic mutation type with the bleeding phenotype, with none, 5% and 25% of the patients with deletion, intron inversion and missense mutation having a significant BS respectively. Follow-up/BS reassessment in our cohort is planned to monitor BS increase with age. Our study limitations include small cohort and retrospective analysis. Future pediatric studies are required to identify coagulation/genetic parameters that correlate better with bleeding phenotype, which may then help with early recognition and prompt institution of preventive therapy to pediatric Hemophilia A carriers at risk of bleeding, in order to avoid bleeding complications during adulthood.
Disclosures: Escobar: Genentech: Honoraria; CSL Behring: Honoraria; Bayer: Honoraria; Takeda: Honoraria; Novo Nordisk: Honoraria; UniQure: Honoraria; Sanofi: Honoraria; Kedrion: Honoraria; Hemobiologics/LFB: Honoraria; The National Hemophilia Foundation: Honoraria; Pfizer: Honoraria; BioMarin: Honoraria.
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