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Thromb Haemost 1995; 74(03): 868-873
DOI: 10.1055/s-0038-1649839
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

“In vitro” and in Animal Model Studies on a Double Virus- Inactivated Factor VIII Concentrate

Silvana Arrighi
The SCLAVO SpA, R/D Haemoderivatives, Siena, Italy
,
Roberta Rossi
The SCLAVO SpA, R/D Haemoderivatives, Siena, Italy
,
Maria Giuseppina Borri
The SCLAVO SpA, R/D Haemoderivatives, Siena, Italy
,
Vladimir Lesnikov
1   The Institute of Exp. Med., R.A.M.S., St. Petersburg, Russia
,
Marina Lesnikov
1   The Institute of Exp. Med., R.A.M.S., St. Petersburg, Russia
,
Elena Franco
2   The Dept. Public Health, Tor Vergata University, Rome, Italy
,
Maurizio Divizia
2   The Dept. Public Health, Tor Vergata University, Rome, Italy
,
Maria Elena De Santis
3   The AIMA Derivati, St. Rufina, Rieti, Italy
,
Enzo Bucci
3   The AIMA Derivati, St. Rufina, Rieti, Italy
› Institutsangaben
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Publikationsverlauf

Received 22. September 1994

Accepted after resubmission 02. Mai 1995

Publikationsdatum:
09. Juli 2018 (online)

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Summary

To improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.

The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.

 

  • References

  • 1 Peerlink K, Vermylen J. Acute Hepatitis A in patients with haemophilia A. Lancet 1993; 341: 179
    PubMedSuche in Google Scholar
  • 2 Mannucci PM, Gdovin S, Gringeri A, Colombo M, Mele A, Schinaia N, Ciavarella N, Emerson SU, Purcell RH. Transmission of hepatitis A to patients with hemophilia by factor VIII concentrates treated with organic solvent and detergent to inactivate viruses. Ann Intern Med 1994; 120 (01) 1-7
    CrossrefPubMedSuche in Google Scholar
  • 3 Morfini M, Mannucci PM, Ciavarella N, Schiavoni M. Prevalence of infection with the Hepatitis C virus among Italian hemophiliacs before and after the introduction of virally inactivated clotting factor concentrates: a retrospective evaluation. Vox Sang 1994; 67: 178-182
    CrossrefPubMedSuche in Google Scholar
  • 4 Ingerslev J. Safety of plasma derivatives. Haemostasis 1994; 24: 311-323
    PubMedSuche in Google Scholar
  • 5 Horowitz B, Wiebe ME, Lippin A, Stryker MH. Inactivation of viruses in labile blood derivatives I. Disruption of lipid enveloped viruses by tri(N- butyl) phosphate detergent combinations. Transfusion 1985; 25: 516-522
    CrossrefPubMedSuche in Google Scholar
  • 6 Horowitz MS, Rooks C, Horowitz B, Hilgartner M. Virus safety of solvent/detergent-treated antihaemophilic factor concentrate. Lancet 1988; 2: 186-189
    PubMedSuche in Google Scholar
  • 7 Schimpf K, Brackmann HH, Kreuz W, Kraus B, Haschke F, Scftritmm W, Moessler J, Auerswald G, Sutor AH, Koehler K, Hellstern P, Muntean W, Scharrer I. Absence of antihuman immunodeficiency virus types 1 and 2 seroconversion after treatment with hemophilia A and B or von Wille-brand’s disease with pasteurized factor concentrate. N Engl J Med 1989; 321: 1148-1152
    CrossrefPubMedSuche in Google Scholar
  • 8 Mannucci PM, Schimpf K, Brettler DB, Ciavarella N, Colombo M, Haschke F, Lechner K, Lusher J, Weissbach G. the International Study Group. Low risk for Hepatitis in hemophiliacs given a high purity, pasteurized factor VIII concentrate Ann Intern Med 1990; 113: 27-32
    CrossrefPubMedSuche in Google Scholar
  • 9 Shulman S, Lindgren A-Ch, Petrini P, Allander T. Transmission of Hepatitis C with pasteurized factor VIII. Lancet 1992; 340: 306-307
    PubMedSuche in Google Scholar
  • 10 Skidmore SJ, Pasi KJ, Mawson SJ, Williams MD, Hill FG H. Serological evidence that dry heating of clotting factor concentrates prevents transmission of non-A, non-U Hepatitis. J Med Virol 1990; 30: 50-52
    CrossrefPubMedSuche in Google Scholar
  • 11 Rizza CR, Fletcher ML, Kernoff PBA. Confirmation of viral safety of dry heated factor VIII concentrate (8Y) prepared by Bio Products Laboratory: A report on behalf of UK Haemophilia Centre Directors. Br J Haematol 1993; 84: 269-272
    CrossrefPubMedSuche in Google Scholar
  • 12 Mariani G, Di Paoloantonio T, Baklaya R, Morfini M, Mannucci PM. Ad Hoc Study Group of the Fondazione Dell’Emofilia. Prospective study of the evaluation of Hepatitis C virus infectivity in a high purity, solvent/ detergent-treated factor VIII concentrate: Parallel evaluation of other markers for lipid-enveloped and non-lipid-enveloped viruses Transfusion 1993; 33: 814-818
    CrossrefPubMedSuche in Google Scholar
  • 13 Gomperts ED. Procedures for the inactivation of viruses in clotting factor concentrates. Am J Hematol 1986; 23: 295-305
    CrossrefPubMedSuche in Google Scholar
  • 14 Prince AM, Horowitz MS, Zang E. The development of virus-free labile blood derivatives. Eur J Epidemiol 1987; 3: 103-118
    PubMedSuche in Google Scholar
  • 15 Bartolomei CorsiO, Azzi A, Morfini M, Fauci R, Rossi Ferrini P. Human parvovirus infection in haemophiliacs first infused with treated clotting factor concentrate. J Med Virol 1988; 25: 165-170
    CrossrefPubMedSuche in Google Scholar
  • 16 Lyon DJ, Chapman CS, Martin C, Brown KE, Clewley JP, Flower AJ, Mitchell VE. Symptomatic parvovirus B19 infection and heat-treated factor IX concentrate. Lancet 1989; 1: 1085
    PubMedSuche in Google Scholar
  • 17 Azzi A, Ciappi S, Zakvzeswska K, Morfini M, Mariani G, Mannucci PM. Human parvovirus B19 infection in hemophiliacs first infused with two high-purity virally attenuated factor VIII concentrates. J Hematol 1992; 39: 228-230
    PubMedSuche in Google Scholar
  • 18 Grobe-Bley A, Eis-Hübinger AM, Kaiser R, Oldenburg J, Brackmann HH, Schwarz TF, Schneweis KE. Serological and virological markers of human parvovirus B19 infection in sera of hemophiliacs. Thromb Haemost 1994; 72: 503-507
    Thieme ConnectPubMedSuche in Google Scholar
  • 19 Morfini M. In vitro characteristics of highly purified factor VIII concentrates. Ann Hemat 1991; 63: 123-125
    CrossrefPubMedSuche in Google Scholar
  • 20 Mannucci PM. Modern treatment of hemophilia: from the shadows towards the light. Thromb Haemost 1993; 70: 17-23
    Thieme ConnectPubMedSuche in Google Scholar
  • 21 Rubinstein AI, Rubinstein DB, Coughlin J. Combined solvent-detergent and 100° C (boiling) sterilizing dry-heat treatment of factor VIII concentrates to assure sterility. Vox Sang 1991; 60: 60
    PubMedSuche in Google Scholar
  • 22 Franco E, Divizia M, De Santis ME, Arrighi S, Borri MG. Inattivazione tramite calore secco del Poliovirus 1 in campioni di fattore VIII. 35th National Congress of Italian Society of Hygene (Std), Montecatini Terme. Italy: 1992: 180-183
    Suche in Google Scholar
  • 23 Jansen RW, Siegl G, Lemon SM. Molecular epidemiology of human Hepatitis A virus defined by an antigen-capture polymerase chain reaction method. Proe Natl Acad Sci USA 1990; 87: 2867-2871
    CrossrefPubMedSuche in Google Scholar
  • 24 Morace G, Pisani G, Divizia M, Paná A. Detection of Hepatitis A virus in concentrated river water by Polymerase chain reaction. Zentralblatt für Hygiene und Umweltmedizin 1993; 193: 521-527
    PubMedSuche in Google Scholar
  • 25 Bowie EJ W, Thompson JH, Didishcim P, Owen CA. Mayo Clinical Laboratory Manual of Hemostasis. Philadelphia: WB Saunders; 1971
    Suche in Google Scholar
  • 26 Hubbard AR, Curtis AD, Barrowelilfe TV, Edwards SJ, Jennings CA, Kemball-Cook G. Assay of factor VIII concentrates: comparison of the chromogenic and two stage clotting assay. Thromb Res 1986; 44: 887-891
    CrossrefPubMedSuche in Google Scholar
  • 27 Laemmli UK. Cleavage of structural proteins during the assembly of the bacteriophage T4. Nature 1970; 227: 680-685
    CrossrefPubMedSuche in Google Scholar
  • 28 Ouchterlony O. Diffusion in gel methods for immunological analysis. Progr Allergy. 1958 5. 1
    PubMedSuche in Google Scholar
  • 29 Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrilamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci 1970; 76: 1350-1354
    PubMedSuche in Google Scholar
  • 30 Grabar P, Williams CA. Métode permettante l’etude conjugée des propriété électrophoréiques et immunochimiqués d’une mélange de proteines: application au sérum sanguin. Biochim Biophys Acta (Amst) 1953; 10: 193
    CrossrefPubMedSuche in Google Scholar
  • 31 Cunningham AJ, Szenberg A. Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology 1968; 14: 599-601
    PubMedSuche in Google Scholar
  • 32 Nencioni L, Villa L, Tagliabue A, Antoni G, Presentini R, Perin F, Silvestri S, Boraschi D. In vivo immunostimulating activity of the 163-171 peptide of human IL-1ß. J Immunol 1987; 139: 800-804
    PubMedSuche in Google Scholar
  • 33 Voller A, Bartlett A, Bidwell DE. Enzyme immunoassay with special reference to ELISA tecniques. J Clin Pathol 1978; 31: 507-520
    CrossrefPubMedSuche in Google Scholar
  • 34 Sanchez-Cuenca JM, Carmona E, Villanueva MJ, Aznar JA. Immunological characterization of factor VIII inhibitors by a sensitive micro-ELISA method. Thromb Res 1990; 57: 897-908
    CrossrefPubMedSuche in Google Scholar
  • 35 Di Napoli G, Bucci E. Human parvovirus B19 after concentrates for haemophilia. Lancet 1994; 343: 1566
    PubMedSuche in Google Scholar
  • 36 Guillaume T. Parvovirus B19 and blood products. Lancet 1994; 343: 1101
    CrossrefPubMedSuche in Google Scholar