RESUMO
The purpose of this narrative review was to provide an overview that allows readers to improve their understanding of hemophilia A, which is considered a genetic disease with a high impact on the quality of life of people who suffer from it is considered one of the diseases with the highest cost for health systems (In Colombia it is part of the five diseases with the greatest economic impact). After this exhaustive review, we can see that the treatment of hemophilia is on the way to precision medicine, which involves genetic variables specific to each race and ethnicity, pharmacokinetics (PK), as well as environmental factors and lifestyle. Knowing the impact of each of these variables and their relationship with the efficacy of treatment (prophylaxis: regular infusion of the missing clotting factor VIII in order to prevent spontaneous bleeding) will allow for individualizing the medical behavior in a cost-effective way. For this is required to build more strong scientific evidence with statistical power that allows us to infer.
RESUMO
Hemophilia A is an X-linked bleeding disorder caused by mutations in the FVIII gene. Genetic factors have been shown to be a risk factor for the development of inhibitors. We aimed to identify the specific variations of the FVIII gene of patients with hemophilia A with inhibitors and their association with the inhibitor titer. Methods: Cross-sectional descriptive study. We included 12 Colombian patients from a health care provider, "Integral Solutions SD", who underwent analysis of genetic material (DNA), which was reported by the Molecular Hemostasis Laboratory in Bonn, Germany. Results: All of these patients were diagnosed with severe hemophilia A with inhibitors; ages ranged between 6 and 48 years, with a median age of 13.5 years. Molecular analysis showed the inversion of intron 22 in six patients (50.0%), a small duplication in two patients (16.7%), the inversion of intron 1 in one patient (8.3%), a large deletion (8.3%), a nonsense mutation (8.3%) and a splice-site (8.3%), findings similar to those of other studies. A total of 58.3% of the patients presented inversion mutations with a high risk of developing inhibitors A total of 83.3% of the evaluated patients presented null mutations; however the presence of high inhibitor titers was 66.7%. The most frequent mutation was the inversion intron 22. Knowing the type of mutation and its association as a risk factor for generating inhibitors invites us to delve into other outcomes such as residual values of coagulation FVIII as well as its impact on the half-life of the exogenous factor applied in prophylaxis.
RESUMO
In recent decades, hemophilia A treatment has been focused on body weight, without taking pharmacokinetic parameters into account. Previous research has shown that the individual pharmacokinetic response is more effective in predicting the required dose of clotting factor. We want to evaluate the impact on reducing the frequency of bleeding in patients treated with recombinant factor VIII, based on a personalized comprehensive management program. Our aim was to compare the results of a standard comprehensive treatment program (stage I) vs. a personalized pharmacokinetic - based treatment program (stage II) in a cohort of 60 patients with severe hemophilia without inhibitors. The median age was 15.5 years (3-68). The annual bleeding rate (ABR) was 1.03 (62 episodes) in the first stage and 0.58 (35 episodes) in the second one, (p=0.004). By type of bleeding, the impact of the intervention differs significantly in spontaneous bleeding (p=0.007) and a 73% reduction in the first stage. There were no significant differences in traumatic bleeding. The use of pharmacokinetics (PK) for personalized dosing of patients with severe hemophilia A, significantly reduces ABR and spontaneous bleeding, improving the patient's quality of life and costs for the health system.
