Current safety of clotting factor concentrates

Area of Science:

• Hematology
• Virology
• Public Health

Background:

• Early clotting factor concentrates posed high risks for transmitting hepatitis viruses (100%) and human immunodeficiency virus (HIV) (60-80%) to hemophilia patients.
• Initial viral inactivation methods, like dry heating lyophilized concentrates since 1983, reduced HIV transmission but did not eliminate it entirely.
• Less extreme dry heating conditions (below 68°C for 72 hours) were insufficient to prevent all HIV transmissions.

Purpose of the Study:

• To review and evaluate various virus-inactivating procedures for clotting factor concentrates.
• To assess the effectiveness of newer methods in eliminating human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and non-A, non-B hepatitis virus.
• To determine the clinical efficacy of these procedures in preventing viral transmission in hemophilia patients.

Main Methods:

• Review of laboratory and clinical studies on virus-inactivation methods for clotting factor concentrates.
• Analysis of different "dry heating" protocols (e.g., 68°C vs. 80°C for 72 hours).
• Evaluation of alternative methods including modified heating (n-heptane, water vapor), heating in solution, solvent-detergent treatment, monoclonal affinity purification, and alkylation with beta-propiolactone.

Main Results:

• Newer methods like "dry heating" at 80°C for 72 hours, modified heating, solvent-detergent treatment, and others have shown significant reduction of HIV, HBV, and non-A, non-B hepatitis virus in laboratory studies.
• Clinical data indicate that "dry heating" at temperatures below 80°C and heating in n-heptane did not fully prevent non-A, non-B hepatitis transmission.
• Elimination of hepatitis B virus (HBV) transmission has been challenging to demonstrate conclusively across all methods.

Conclusions:

• While significant progress has been made in virus inactivation for clotting factor concentrates, particularly for HIV, complete elimination of hepatitis transmission remains a challenge.
• The efficacy of "dry heating" at 80°C for 72 hours is superior to lower temperatures for preventing non-A, non-B hepatitis transmission.
• Continued vigilance, including hepatitis B virus (HBV) immunization, is recommended for patients with hemophilia receiving clotting factor concentrates.