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Review
. 2023 Feb 16;15(1):130-150.
doi: 10.3390/hematolrep15010014.

Haemophilia A: A Review of Clinical Manifestations, Treatment, Mutations, and the Development of Inhibitors

Samuel Sarmiento Doncel  1   2 , Gina Alejandra Díaz Mosquera  1 , Javier Mauricio Cortes  1 , Carol Agudelo Rico  1 , Francisco Javier Meza Cadavid  1   3 , Ronald Guillermo Peláez  2
Affiliations
Review

Haemophilia A: A Review of Clinical Manifestations, Treatment, Mutations, and the Development of Inhibitors

Samuel Sarmiento Doncel et al. Hematol Rep. .

Abstract

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.

Keywords: Haemophilia A; inhibitors; mutations; treatment.

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Conflict of interest statement

The authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
Classical concept of the coagulation cascade. Note: This figure presents the classical theory of coagulation based on two pathways (intrinsic and extrinsic) that converge in a common pathway. Mann KG, et al. [4].
Figure 2
Figure 2
Current molecular model of coagulation. Note: This figure presents the current model of the coagulation cascade based on stages, created by the main author using the BioRender tool. Adapted from Sarmiento Doncel, S, et al.
Figure 3
Figure 3
Structure of the FVIII gene. Note: Location of coagulation factor VIII on the X chromosome, taken from the Molecular Basis of Haemophilia [23]. Adapted from Sarmiento Doncel, S, et al. using the BioRender tool.
Figure 4
Figure 4
Structure of coagulation FVIII. Note: This figure shows the structure of FVIII. After thrombin activation, this protein becomes a heterodimer with a heavy chain (A1-A2-B) and a light chain (A3-C1-C2). Figure created by the main author using the BioRender tool. Adapted from Hernandez C, et al. [25].
Figure 5
Figure 5
Development of inhibitors against exogenous FVIII. Note: Development of inhibitors against exogenous FVIII in patients with severe haemophilia A. Figure created by the main author using the BioRender tool.
See this image and copyright information in PMC

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