PB1260 - Importance of molecular diagnostics to classify the severity of hemophilia A: a brief experience of Fundação Hemominas in Brazil

Background: Hemophilia A (HA) is a hereditary coagulopathy whose severity is classified by the plasmatic residual activity of FVIII (FVIII:C): Patients with FVIII:C >5% to 40% are classified as mild; FVIII:C between 1% and 5% are classified as moderate; and FVIII:C < 1% are classified as severe. The high intra-laboratory variability of coagulometric procedures and patient treatment prior to this diagnosis may affect the correct classification of the severity of HA in patients. To avoid misdiagnosis, molecular testing is presented as an important tool.

Aims: The aim of this study was to investigate the presence of introns 1 (INV1) and 22 (INV22) inversions in the F8 gene in patients with severe and moderate HA (FVIII:C < 3%). This study was approved by the local ethics committee and all patients signed an informed consent form.

Methods: Molecular tests were performed to detect INV1 and INV22 in 76 male patients with HA classified as severe (FVIII:C < 1%; n=50) or moderate (FVIII:C 1-3%; n=26) who were treated at Fundação Hemominas (Belo Horizonte, Minas Gerais, Brazil).

Results: Among the 50 severe patients included, 30 (60.0%) were identified with INV22 and four (8.0%) with INV1. In addition, among the 26 patients previously classified as moderate HA, 12 (46.2%) were reclassified as severe HA due to INV22 (n=9) or INV1 (n=3) diagnosis.

Conclusion(s): Molecular diagnostic is important for the correct diagnosis and classification of the severity of patients with HA, especially in patients with FVIII:C intermediate between severe and moderate forms. Correct diagnosis, in addition to monitoring the phenotypic profile, is crucial for managing patients and predicting coagulation factor consumption. This study was funded by Fapemig, Fundação Hemominas, and the Brazilian Ministry of Health.