Hemophilia and Other Bleeding Disorders: Genetics


Hemophilia is the term applied to a group of hereditary disorders characterized by excessive bleeding and which are due to lack or defective function of one or more blood coagulation factors.

Keywords: normal hemostasis; hemophilia; tissue factor; factor V; factor VII; factor VIII; factor IX; factor X; factor XI; prothrombin; fibrinogen

Figure 1.

Blood coagulation network. Coagulation factors are represented according to their protein domains, showing the high degree of duplication that has occurred during the evolution of this physiological system. Factors VII, IX and X have identical modular structure as do factors V and VIII. Domains: EG: epidermal growth factor; KR: kringle; F3: fibronectin type 3; FA58A: A domain of factors V and VIII; FA58C: C domain of factors V and VIII; Ser Pr: serine protease domain; AP: apple domain of factor XI and prekallikrein; γ: gamma‐carboxy glutamic acid domain. The inhibitors, which regulate this process, are not shown.

Figure 2.

Tissue factor (TF).

Figure 3.

Factor VII.

Figure 4.

Factor IX.

Figure 5.

Factor X.

Figure 6.


Figure 7.

Factor VIII.

Figure 8.

Factor V.

Figure 9.


Figure 10.

Factor XI.


Further Reading

Bolton‐Maggs PH (2000) Factor XI deficiency and its management. Haemophilia July 6 (supplement 1): 100–109.

Mannucci PM and Tuddenham EG (2001) The hemophilias – from royal genes to gene therapy. New England Journal of Medicine 344: 1773–1779.

McVey JH, Boswell E, Mumford AD, Kembell‐Cook G and Tuddenham EG (2001) Factor VII deficiency and the FVII mutation database. Human Mutation 17 (1): 3–17.

Neerman‐Arbez M, Johnson KM, Morris MA, et al. (1999) Molecular analysis of the ERGIC‐53 gene in 35 families with combined factor V‐factor VIII deficiency. Blood 93: 2253–2260.

Tuddenham EGD and Cooper DN (1994) The Molecular Genetics of Haemostasis and its Inherited Disorders. Oxford, UK: Oxford University Press.

Tuddenham EG and McVey JH (1998) The genetic basis of inhibitor development in haemophilia A. Haemophilia 4: 543–545.

Sciver CR, Beaudet AL, Valle D and Sly WS (eds.) (2001) The Metabolic and Molecular Basis of Inherited Disease, 8th edn, pp. 169–175. New York, NY: McGraw‐Hill.

Uprichard J and Perry DJ (2000) Factor X deficiency. Blood Reviews June 16 (2): 97–100.

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McVey, John H, and Tuddenham, Edward GD(Jan 2006) Hemophilia and Other Bleeding Disorders: Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005524]