# Factor VIII
**Factor VIII** (FVIII), also called antihemophilic factor, is a blood protein that acts as an essential cofactor in the activation of factor X, a step that leads ultimately to the formation of thrombin and fibrin and a stable clot. In the circulation it is bound to von Willebrand factor (VWF), which serves as its stabilizing carrier protein.[1](https://www.fda.gov/media/73587/download?attachment=) Inherited deficiency of factor VIII causes hemophilia A, the most common inherited, X-linked recessive coagulation factor deficiency, and replacement of the factor is the basis of treatment.[2](https://www.fda.gov/media/170579/download)
| Key fact | Detail |
|---|---|
| Function | Essential cofactor in activation of factor X, leading to thrombin and fibrin formation; carried and stabilized by von Willebrand factor[1](https://www.fda.gov/media/73587/download?attachment=) |
| Deficiency disease | Hemophilia A, an X-linked recessive disorder; severity graded as severe (<1 IU/dL), moderate (1 to <5 IU/dL), or mild (5 to <40 IU/dL) residual FVIII activity[2](https://www.fda.gov/media/170579/download) |
| Half-life | Natural and unmodified recombinant FVIII: 8 to 16 hours, with high interindividual variation influenced by age, VWF levels, ABO blood group, and assay method[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC13175579/) |
| Gene cloning | Factor VIII gene cloned in 1984, enabling recombinant production; first recombinant product licensed in 1992[4](https://www.hematology.org/about/history/50-years/hemophilia) |
| Extended half-life | rFVIII-Fc (Elocta/Eloctate) 19 hours; efanesoctocog alfa (ALTUVIIIO) approximately 48 hours, dosed 50 IU/kg weekly[5](https://www.ncbi.nlm.nih.gov/books/NBK570372/table/stcl0651.tab24/) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC13175579/) |
| Main complication | Inhibitor antibodies develop in approximately 30 to 35 percent of people with hemophilia A[4](https://www.hematology.org/about/history/50-years/hemophilia) |
## Role in coagulation
Factor VIII circulates as an inactive procofactor bound noncovalently to von Willebrand factor. After activation to FVIIIa, it serves as a cofactor in the activation of factor X, which proceeds to thrombin and fibrin formation.[1](https://www.fda.gov/media/73587/download?attachment=) VWF has a dual role: it promotes platelet adhesion and aggregation at sites of vascular injury, and it stabilizes factor VIII in the plasma.[1](https://www.fda.gov/media/73587/download?attachment=) This partnership explains why the pharmacokinetics of factor VIII depend on VWF: the half-life of natural and unmodified recombinant FVIII ranges from 8 to 16 hours and varies considerably between individuals with age, VWF levels, ABO blood groups, and the assay and sampling methods used to measure it.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC13175579/)
Because the genes for factor VIII and factor IX are on the [X chromosome](https://www.edgepedia.org/x-chromosome), hemophilia A usually affects males, while carrier females are rarely affected.[4](https://www.hematology.org/about/history/50-years/hemophilia) Patients with severe disease produce less than 1 percent of the normal amount of the factor and may use subcutaneous emicizumab for routine prophylaxis instead of relying on intravenous infusions, which may still be used for bleeding episodes.[4](https://www.hematology.org/about/history/50-years/hemophilia) • [15](https://www.ncbi.nlm.nih.gov/sites/books/NBK1404/)
## History of factor VIII therapy
The first "antihaemophilic factor" preparation dates to 1911, when Addis prepared a crude fraction by acidification of plasma.[6](https://www.sciencedirect.com/science/article/abs/pii/S0049384813004908) A major advance came in the mid-1960s with the discovery, described by Judith Graham Pool in 1965, of cryoprecipitated plasma, a factor VIII concentrate prepared by allowing fresh frozen plasma to thaw in the cold. Cryoprecipitate delivered more factor VIII in a smaller volume and made outpatient treatment of bleeds and elective surgery possible.[4](https://www.hematology.org/about/history/50-years/hemophilia) • [7](https://aob.amegroups.org/article/view/4328/html) By the late 1960s, lyophilized factor VIII concentrates made from pooled plasma allowed home treatment.[4](https://www.hematology.org/about/history/50-years/hemophilia)
**The contaminated plasma era.** Each batch of plasma-derived concentrate combined thousands of donations, and by the early 1980s plasma-derived products were transmitting hepatitis viruses and HIV. By 1985 most patients with hemophilia in the United States had been switched to heat-treated concentrates, but many had already been infected.[4](https://www.hematology.org/about/history/50-years/hemophilia) Factor VIII came into use by the [National Health Service](https://www.edgepedia.org/national-health-service) in the United Kingdom in the early 1970s, and because the country could not produce enough to meet need, supplies were brought in from the United States; testimony to the infected blood inquiry put the number of people who caught infections from tainted blood or blood products through transfusions or Factor VIII at over 30,000.[8](https://apnews.com/article/a01ca275febabf5b7d1d183b92857dbc)
**Recombinant factor VIII.** The successful cloning of the factor VIII gene in 1984, by groups including scientists at [Genentech](https://www.edgepedia.org/genentech), allowed production of recombinant human factor VIII; clinical trials began three years later, and by 1992 two pharmaceutical companies had licensed recombinant products.[4](https://www.hematology.org/about/history/50-years/hemophilia) • [9](https://discovery.ucl.ac.uk/id/eprint/10160680/) Recombinant products, made by transfecting factor VIII DNA into nonhuman mammalian cell lines, largely eliminated blood-borne pathogen transmission.[10](https://www.tandfonline.com/action/downloadTable?doi=10.1080%2F14712598.2018.1416088&downloadType=CSV&id=UT0001) Recombinant products are commonly grouped into generations by the amount of human or animal plasma-derived protein used in their manufacture, and deleting most of the B domain of the protein improved secretion from producer cells, giving rise to B-domain-deleted products.[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC5479262/)
## Standard and extended half-life products
Standard half-life (SHL) recombinant products have a circulating half-life of roughly 12 hours, which historically required intravenous injection two to three times per week for prophylaxis.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC13175579/) • [2](https://www.fda.gov/media/170579/download) In a network meta-analysis of hemophilia A treatments, the SHL products Kogenate (about 15 hours in adults, 10.7 hours in children), Kovaltry (13.3 to 14.8 hours), and Advate (9 to 12.9 hours) were grouped separately from extended half-life products such as Elocta/Eloctate.[5](https://www.ncbi.nlm.nih.gov/books/NBK570372/table/stcl0651.tab24/)
**Extended half-life (EHL) products** modify the molecule to prolong circulation. Approved approaches include Fc fusion (efmoroctocog alfa, Elocta/Eloctate, half-life 19 hours), [PEGylation](https://www.edgepedia.org/pegylation) (damoctocog alfa pegol, Jivi; rurioctocog alfa pegol, Adynovate; turoctocog alfa pegol, Esperoct), and single-chain structure ([lonoctocog alfa](https://www.edgepedia.org/lonoctocog-alfa), Afstyla).[5](https://www.ncbi.nlm.nih.gov/books/NBK570372/table/stcl0651.tab24/) • [12](https://experts.umn.edu/en/publications/clinical-studies-of-extended-half-life-recombinant-fviii-products/) • [13](https://www.pmda.go.jp/files/000231145.pdf)
Efanesoctocog alfa (ALTUVIIIO), approved by the FDA in February 2023, combines Fc fusion with XTEN half-life extension technology and is VWF-independent, giving a half-life of approximately 48 hours in adults (approximately 37.8 hours in children under 6 years) and supporting a dose of 50 IU/kg once weekly.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC13175579/) • [2](https://www.fda.gov/media/170579/download) The FDA's review notes that its half-life is more than twice that of the other long-acting recombinant products.[2](https://www.fda.gov/media/170579/download) For PEG-containing products, extensive clinical experience has not identified clear PEG-related organ toxicity in humans, but theoretical concerns about life-long exposure and potential tissue accumulation mean that pharmacovigilance and monitoring are still recommended, especially in young children.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC13175579/)
## Inhibitors and non-replacement alternatives
The main treatment complication is the development of inhibitors, antibodies that neutralize exogenous factor VIII; they develop in approximately 30 to 35 percent of people with hemophilia A, compared with 1 to 3 percent in hemophilia B.[4](https://www.hematology.org/about/history/50-years/hemophilia) Inhibitor development remains a major challenge alongside the short half-life of many products.[10](https://www.tandfonline.com/action/downloadTable?doi=10.1080%2F14712598.2018.1416088&downloadType=CSV&id=UT0001)
Treatment options beyond factor replacement have changed the landscape. Emicizumab (Hemlibra), approved in 2017, is a bispecific antibody (antibody binding two targets, here bridging clotting factors) that bridges factor IX and factor X, bypassing the need for factor VIII in the clotting cascade; it is given subcutaneously with a long half-life and works in patients with and without inhibitors.[2](https://www.fda.gov/media/170579/download) [Gene therapy](https://www.edgepedia.org/gene-therapy) offers another route: valoctocogene roxaparvovec (ROCTAVIAN) is an AAV5-based vector that delivers a functional copy of a B-domain-deleted factor VIII transgene to liver cells, and was approved in 2023 for adults with severe hemophilia A.[2](https://www.fda.gov/media/170579/download) A 2024 systematic literature review also found that no universally accepted definition of standard versus extended half-life classification exists, and that parameters other than half-life may matter for a clinically relevant product classification.[14](https://onlinelibrary.wiley.com/doi/full/10.1111/hae.15001)
## References
1. [Antihemophilic Factor/von Willebrand Factor Complex (Human), Dried, Pasteurized, FDA](https://www.fda.gov/media/73587/download?attachment=)
2. [Clinical Review Memorandum, ROCTAVIAN (valoctocogene roxaparvovec), FDA, June 28, 2023](https://www.fda.gov/media/170579/download)
3. [Extended Half-Life Factor Concentrates in Haemophilia Treatment, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC13175579/)
4. [Hemophilia: From Plasma to Recombinant Factors, American Society of Hematology](https://www.hematology.org/about/history/50-years/hemophilia)
5. [Table 24, Characteristics of Factor VIII Products Included in the NMA, Clinical Review Report: Emicizumab (Hemlibra), NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK570372/table/stcl0651.tab24/)
6. [The history of haemophilia – a short review, ScienceDirect](https://www.sciencedirect.com/science/article/abs/pii/S0049384813004908)
7. [Factor VIII manufactured from plasma: history of plasma-derived factor VIII therapies, Annals of Blood](https://aob.amegroups.org/article/view/4328/html)
8. [What happened in the UK's infected blood scandal from the 1970s to '90s?, AP News](https://apnews.com/article/a01ca275febabf5b7d1d183b92857dbc)
9. [Haemophilia, the journey in search of a cure. 1960–2020, UCL Discovery](https://discovery.ucl.ac.uk/id/eprint/10160680/)
10. [Recombinant factor VIII: past, present and future of treatment of hemophilia A, Taylor & Francis](https://www.tandfonline.com/action/downloadTable?doi=10.1080%2F14712598.2018.1416088&downloadType=CSV&id=UT0001)
11. [Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches?, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5479262/)
12. [Clinical studies of extended-half-life recombinant FVIII products for prophylaxis in adults and children, Experts@Minnesota](https://experts.umn.edu/en/publications/clinical-studies-of-extended-half-life-recombinant-fviii-products/)
13. [Report on the Deliberation Results: Afstyla (lonoctocog alfa), PMDA](https://www.pmda.go.jp/files/000231145.pdf)
14. [Classification of recombinant factor VIII products and implications for clinical practice: A systematic literature review, Haemophilia](https://onlinelibrary.wiley.com/doi/full/10.1111/hae.15001)
15. [Hemophilia A - GeneReviews® - NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/sites/books/NBK1404/)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Cardiovascular and blood conditions › Blood disorders (hematologic conditions) › Coagulation and bleeding disorders › Inherited coagulation-factor deficiencies › Hemophilia A (factor VIII deficiency)*
*Initially written Sep 17, 2026 · Reviewed: Sep 17, 2026; Sep 30, 2026; Oct 21, 2026 · Edited: Sep 30, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license