PB0551 - Girl with mild inherited hemophilia A and high-responding inhibitor associated with Melnick-Needles osteodysplasty syndrome: a case report of emicizumab prophylaxis effectiveness

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Ricardo Mesquita Camelo, MD, MBA, MSc, PhD, PostD

Professor
Department of Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
Belo Horizonte, Minas Gerais, Brazil

Co-Author(s)

LH

Luila Clicia Moura Henriques

Student
Faculty of Pharmacy, Universidade Federal de Minas Gerais (UFMG)
Belo Horizonte, Minas Gerais, Brazil
Maíse Moreira Dias

Hematologist
Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG)
Belo Horizonte, Minas Gerais, Brazil
LZ

Luciana Zuccherato

Geneticist
Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG)
Belo Horizonte, Minas Gerais, Brazil
SF

Sandra Sibele Figueiredo

Hematologist
Centro de Hematologia e Hemoterapia da Paraíba (HEMOÍBA)
João Pessoa, Paraiba, Brazil
EC

Edilma Silva Casaretto

Hematology Nurse
Centro de Hematologia e Hemoterapia da Paraíba (HEMOÍBA)
João Pessoa, Paraiba, Brazil
MT

Maria Daluz Freire Castro Tenório

Biochemistry
Centro de Hematologia e Hemoterapia da Paraíba (HEMOÍBA)
João Pessoa, Paraiba, Brazil
JA

Juliana Alvares-Teodoro

Professor of Pharmacy
Faculty of Pharmacy, Universidade Federal de Minas Gerais (UFMG)
Belo Horizonte, Minas Gerais, Brazil

Background: Associations of rare inherited disorders are an ultrarare event. Hemophilia A (HA) is a rare bleeding disorder due to a pathologic mutation in the F8 gene (encoding the clotting factor VIII [FVIII]). Melnick-Needles syndrome (MNs) is another rare osteodevelopmental disorder due to a pathologic mutation in the FLNA gene (encoding the filamin A). Both genes are located in the Xq28 position. Their association has never been reported and is intriguing because the impaired bone structure of MNs hampers the usual intravenous treatment of HA.

Aims: Herein we reported a girl diagnosed with mild hemophilia A and high-response inhibitor and MNs.

Methods: Medical files were revised.

Results: She was born in 1992 (karyotype 46,XX). MNs was diagnosed based on typical facies, s-like curvature of bones of legs, and irregular constrictions in the ribs. Since early in life, she presented petechiae and joint pain, treated with corticosteroids. In 2011, she was referred to our hemophilia treatment center due to FVIII plasmatic activity of 10.2% (inhibitor negative). Joint pain was treated as hemarthrosis with intravenous on-demand FVIII because her venous access was not feasible for regular prophylaxis, and she refused an intravenous catheter. A high-response inhibitor was diagnosed in 2014 (1,024 BU/mL). She refused immune tolerance induction due to the burden of frequent venous access. She switched to intravenous on-demand recombinant activated factor VII. The annualized bleeding rate for spontaneous treated bleeds (ABR-spo) increased from 1.5 (inhibitor-negative period) to 11.8 (inhibitor-positive period). Subcutaneous emicizumab prophylaxis was started in 2020. During emicizumab prophylaxis (3 years long), ABR-spo was 0.0 and Functional Independence Score in Hemophilia (FISH) increased from 21 (baseline) to 29 (year 3) points.

Conclusion(s): Emicizumab prophylaxis was related to reduced bleeding events and improved musculoskeletal functional health in a girl with HA and high-responding inhibitor and skeletal abnormalities resulting in difficult venous access.