[13] Side effects include skin flushing, shortness of breath, fever, and red blood cell breakdown.

[16][17] Recombinant factor VIII was first made in 1984 and approved for medical use in the United States in 1992.

[21] This transfer of a plasma byproduct into the blood stream of a hemophiliac often led to the transmission of diseases such as HIV and hepatitis before purification methods were improved.

In the early 1990s, pharmaceutical companies began to produce recombinant synthesized factor products, which now prevent nearly all forms of disease transmission during replacement therapy.

[citation needed] von Willebrand Factor/Coagulation Factor VIII Complex (Human) (sold under the brand name Wilate) was approved for medical use in the United States in 2009.