Mona Salah El-Din Hamdy1, Aml Soliman Nasr1, Manal Mohamed Makhlouf2, Zainab Ali El-Saadany1, Magy Samir3, Dalia Saber Morgan4. 1. Department of Clinical and Chemical Pathology, Faculty of Medicine, El-Kasr El-Aini Hospital, Cairo University, El-Manial, Cairo, Egypt. 2. Department of Clinical and Chemical Pathology, Faculty of Medicine, El-Kasr El-Aini Hospital, Cairo University, El-Manial, Cairo, Egypt. manalmakhlouf2@yahoo.com. 3. Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt. 4. Department of Pediatrics, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt.
Abstract
INTRODUCTION: Hemophilias are a group of related bleeding disorders that show an X-linked pattern of inheritance. The clinical phenotype of severe hemophilia may vary markedly among patients as a result of many factors, including genetic prothrombotic risk factors. OBJECTIVES: Our objective was to study the incidence of the most common prothrombotic risk factors for additive effects among Egyptian patients with hemophilia A and their impact on clinical phenotype; annual bleeding frequency and severity of hemophilic arthropathy, as well as the effect of a single variation in these patients. METHODS: This study was carried out in 100 patients with hemophilia A. Genotyping for factor V Leiden (FVL) G1691A, prothrombin G20210A, MTHFR C677T, and A1298C mutations was conducted using a real time-polymerase chain reaction (RT-PCR) assay. RESULTS: Our study revealed mutations in hemophilia patients as follows: prothrombin G20210A (3 %), FVL (14 %), MTHFR C677T (42 %), and A1298C (59 %). Despite a lack of statistical significance when each gene was analysed separately, heterozygosity of prothrombin G20210A or FVL was always associated with either a mild or moderate, but never a severe, clinical presentation. The lowest bleeding frequency (less than once per month) was identified among patients with two heterozygous variants irrespective of the involved genes. In addition, the incidence of hemarthrosis was significantly higher among patients with a wild genotype of the prothrombin gene and FVL, and the average number of affected joints was significantly higher among patients with wild-type prothrombin and FVL genes than among heterozygous patients. CONCLUSION: These prothrombotic mutations have a cumulative effect in amelioration of the severity of bleeding in hemophiliacs. The most prominent effect is that of prothrombin G20210A and FVL, while MTHFR C677A and A1298C gene mutations are less conclusive.
INTRODUCTION:Hemophilias are a group of related bleeding disorders that show an X-linked pattern of inheritance. The clinical phenotype of severe hemophilia may vary markedly among patients as a result of many factors, including genetic prothrombotic risk factors. OBJECTIVES: Our objective was to study the incidence of the most common prothrombotic risk factors for additive effects among Egyptian patients with hemophilia A and their impact on clinical phenotype; annual bleeding frequency and severity of hemophilic arthropathy, as well as the effect of a single variation in these patients. METHODS: This study was carried out in 100 patients with hemophilia A. Genotyping for factor V Leiden (FVL) G1691A, prothrombinG20210A, MTHFRC677T, and A1298C mutations was conducted using a real time-polymerase chain reaction (RT-PCR) assay. RESULTS: Our study revealed mutations in hemophiliapatients as follows: prothrombinG20210A (3 %), FVL (14 %), MTHFRC677T (42 %), and A1298C (59 %). Despite a lack of statistical significance when each gene was analysed separately, heterozygosity of prothrombinG20210A or FVL was always associated with either a mild or moderate, but never a severe, clinical presentation. The lowest bleeding frequency (less than once per month) was identified among patients with two heterozygous variants irrespective of the involved genes. In addition, the incidence of hemarthrosis was significantly higher among patients with a wild genotype of the prothrombin gene and FVL, and the average number of affected joints was significantly higher among patients with wild-type prothrombin and FVL genes than among heterozygous patients. CONCLUSION: These prothrombotic mutations have a cumulative effect in amelioration of the severity of bleeding in hemophiliacs. The most prominent effect is that of prothrombinG20210A and FVL, while MTHFRC677A and A1298C gene mutations are less conclusive.
Authors: J J López-Jiménez; C P Beltrán-Miranda; J M Mantilla-Capacho; M A Esparza-Flores; L C López González; A R Jaloma-Cruz Journal: Haemophilia Date: 2009-07-10 Impact factor: 4.287
Authors: A Zivelin; N Rosenberg; S Faier; N Kornbrot; H Peretz; C Mannhalter; M H Horellou; U Seligsohn Journal: Blood Date: 1998-08-15 Impact factor: 22.113
Authors: Henrik Zetterberg; Björn Regland; Mona Palmér; Anne Ricksten; Lars Palmqvist; Lars Rymo; Demetrios A Arvanitis; Demetrios A Spandidos; Kaj Blennow Journal: Eur J Hum Genet Date: 2002-02 Impact factor: 4.246