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. 2020 Feb 28;4(3):377-385.
doi: 10.1002/rth2.12314. eCollection 2020 Mar.

Hemophilia management: Huge impact of a tiny difference

Fabienne Kloosterman  1 , Anne-Fleur Zwagemaker  1 , Amal Abdi  1 , Samantha Gouw  1   2 , Giancarlo Castaman  3 , Karin Fijnvandraat  1   4
Affiliations

Hemophilia management: Huge impact of a tiny difference

Fabienne Kloosterman et al. Res Pract Thromb Haemost. .

Abstract

Hemophilia A and B are inherited X-linked disorders of hemostasis, associated with an increased bleeding tendency. Patients with severe hemophilia have undetectable clotting factor levels and experience spontaneous bleeds. In patients with nonsevere hemophilia, the clotting factor levels are 2% to 40% of normal and bleeds predominantly occur after provocative events such as trauma and surgery. Despite this milder phenotype, patients with nonsevere hemophilia may suffer from considerable morbidity and have an increased mortality risk. However, many aspects of the course of disease and treatment remain unclear. Information on the factors influencing interindividual differences in bleeding phenotype is lacking, and misdiagnosis may occur due to assay discrepancies in the diagnostic workup. Desmopressin is the preferred treatment modality, but some patients and indications require treatment with clotting factor concentrates. This may elicit inhibitor formation, which is associated with an increased burden of disease and a higher mortality rate. It has been found that patients with nonsevere hemophilia A carry a lifelong risk for this serious complication. In this review, we provide an overview of the current knowledge of the diagnosis and management of nonsevere hemophilia. A report of science presented at the International Society on Thrombosis and Haemostasis 2019 Annual Congress is also provided.

Keywords: diagnosis; hemophilia A; hemophilia B; phenotype; treatment.

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Figures

Figure 1
Figure 1
Distribution of mutations in F8 and F9 gene for mild hemophilia A and B, respectively. Figure is based on data from the F8 and F9 international database (http://www.factorviii-db.org and http://www.factorix.org)
Figure 2
Figure 2
Cumulative inhibitor incidence in 1112 nonsevere hemophilia A patients, according to cumulative exposure days to factor VIII concentrates. This research was originally published in Blood Online. Eckhardt CL, van Velzen AS, Peters M, et al. Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A. Blood. 2013;122(11):1954‐62
Figure 3
Figure 3
Distribution of F8 missense mutations associated with inhibitor development. (A) Two‐dimensional and (B) 3‐dimensional structure of the factor VIII protein. This research was originally published in Blood Online. Eckhardt CL, van Velzen AS, Peters M, et al Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A. Blood. 2013;122(11):1954‐62
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