PB1151 - Mild Bleeding Phenotypes in Severe Hemophilia A with Transfusion Dependent Alpha-thalassemia

Background: Approximately 10-15% of patients with severe hemophilia A have paradoxically mild bleeding phenotypes. Prothrombotic gene mutations were found in 50% of those patients. Moreover, thalassemia disease is known to have a lifelong hypercoagulable state, but bleeding phenotypes in severe hemophilia A with thalassemia disease has never been reported.

Aims: To demonstrate bleeding phenotypes in severe hemophilia A with alpha-thalassemia disease.

Methods: Case description of severe hemophilia A with alpha-thalassemia disease.
DNA was sent for whole exome sequencing (WES). Then, the sequencing data was analyzed via the commercial software Sophia DDM v5.10.12 (Sophia Genetics™) and focused on genes based on the Human Phenotype Ontology HP:0001892 (abnormal bleeding) and HP:0001977 (abnormal thrombosis).

Results: A 6-year-old boy with alpha-thalassemia disease ((--SEA/αCSα), , hemoglobin H with Constant Spring) receiving regular transfusion every 4 weeks since the age of 3 years. He first presented to the clinic with easy bruising after trauma. There was no history of joint or muscle bleeding. The Thai Version of the Pediatric Bleeding Assessment Tool noted a positive score of 4 (N≤3). Physical examinations revealed thalassemic faces and hepatosplenomegaly without evidence of joint bleeding. Activated partial thromboplastin time was 126 seconds (N:22-33), and factor VIII activity by one stage and chromogenic assay < 1%. Additionally, ultrasound of both elbows, knees, and ankles showed no recent or remote joint bleeding features. Before transfusion and initiation of factor prophylaxis, thrombin generation using 5 pM of tissue factor demonstrated an endogenous thrombin potential of 1051.4 nM x min (N:1393.7, (1175.1-1612.3)) which was 75% of normal. WES could not identify any additional variant, including prothrombotic genes. Therefore, the alpha-thalassemia disease was the contributing factor to mild bleeding phenotypes in this patient. At present, the evaluation of the F8 inversion is being performed.

Conclusion(s): The hypercoagulable state caused by alpha-thalassemia may affect bleeding phenotypes of severe hemophilla A.