Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100 degrees C heat after lyophilization.
BACKGROUND
Double inactivation by solvent/detergent treatment plus heating at 100 degrees C for 30 minutes after lyophilization has been adopted to improve viral safety of factor VIII and factor IX concentrates, particularly with respect to non-lipid-enveloped viruses. The aim of this study was to evaluate the safety of concentrates exposed to these virucidal methods.


METHODS
Twenty-six previously untreated hemophiliacs, 19 with factor VIII deficiency and 7 with factor IX deficiency, were investigated in a prospective multicenter study over a 12-month follow-up period by the use of serologic and virologic markers for lipid- and non-lipid-enveloped viruses (human immunodeficiency virus types 1 and 2; hepatitis A, B, and C viruses; B19 parvovirus antibodies; and B19 DNA). Overall, 270,000 U of factor VIII and 102,000 U of factor IX concentrate were administered during the study period.


RESULTS
None of the 26 patients seroconverted for human immunodeficiency virus or hepatitis C virus. Hepatitis B virus markers remained negative in the 10 unvaccinated hemophiliacs. No hepatitis A virus seroconversion occurred among 17 susceptible patients. B19 seroconversion (IgM) and B19 viremia were observed within 2 weeks of the first concentrate infusion in 8 of 15 susceptible patients, 5 of 11 treated with factor VIII and 3 of 4 with factor IX concentrate.


CONCLUSIONS
This prospective study indicates that very high temperatures applied to lyophilized concentrates appear to prevent the transmission of hepatitis A virus to hemophiliacs. However, B19 parvovirus still contaminates concentrates despite the use of this robust virucidal method.
Santagostino
E
E
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Maggiore Hospital, Milan, Italy.
Mannucci
P M
PM
Gringeri
A
A
Azzi
A
A
Morfini
M
M
Musso
R
R
Santoro
R
R
Schiavoni
M
M
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003902:Detergents / Q000494:pharmacology; D005164:Factor IX / Q000032:analysis; D005169:Factor VIII / Q000032:analysis; D005260:Female; D006467:Hemophilia A / Q000628:therapy; D006358:Hot Temperature; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010322:Parvoviridae Infections / Q000635:transmission*; D016732:Parvovirus B19, Human; D012997:Solvents / Q000494:pharmacology; D013997:Time Factors
D000998:Antiviral Agents; D001779:Blood Coagulation Factors; D003902:Detergents; D012997:Solvents; D005169:Factor VIII; D005164:Factor IX; D000410:Alanine Transaminase