Download PDF
Thromb Haemost 1981; 46(03): 597-601
DOI: 10.1055/s-0038-1653426
Original Article
Schattauer GmbH Stuttgart

Changes in Factor VIII Complex Activities During the Production of a Clinical Intermediate Purity Factor VIII Concentrate

C V Prowse
*   Edinburgh and South-East Scotland Blood Transfusion Service, Royal Infirmary, Edinburgh, U.K
,
B Griffin
+   Headquarters Unit Laboratory, Edinburgh, and Protein Fractionation Centre, Ellen’s Glen Road, Edinburgh, U.K
,
D S Pepper
+   Headquarters Unit Laboratory, Edinburgh, and Protein Fractionation Centre, Ellen’s Glen Road, Edinburgh, U.K
,
A J Dickson
The Scottish National Blood Transfusion Service, Protein Fractionation Centre, Ellen’s Glen Road, Edinburgh, U.K
,
T A McQuillan
The Scottish National Blood Transfusion Service, Protein Fractionation Centre, Ellen’s Glen Road, Edinburgh, U.K
,
I H Dickson
The Scottish National Blood Transfusion Service, Protein Fractionation Centre, Ellen’s Glen Road, Edinburgh, U.K
,
P R Foster
The Scottish National Blood Transfusion Service, Protein Fractionation Centre, Ellen’s Glen Road, Edinburgh, U.K
› Author Affiliations
Further Information

Publication History

Received 17 March 1981

Accepted 24 June 1981

Publication Date:
05 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Samples taken at various stages of preparation of intermediate purity factor VIII concentrate were assayed for factor VIII coagulant activity (VIII:C), factor VIII coagulant antigen (VIIIC: Ag) and factor VIII related antigen (VIIIR: Ag). The antigen results were used to assess mechanical loss during fractionation as these markers are relatively stable. In contrast VIII:C is sensitive to both mechanical and inactivation losses.

The major loss of factor VIII occurred during the cryoprecipitation and extraction step and was due to both mechanical loss and inactivation. Losses before and after this step were largely due to inactivation of the factor VIII.

Assay of VIIIR: Ag in concentrates presented problems and a modified technique is suggested.

Keywords

Factor VIII Concentrates - Plasma fractionation
 

  • References

  • 1 Bloom AL, Peake IR. Factor VIII and its inherited disorders. Br Med Bull 1977; 33: 219-224
    CrossrefPubMedSearch in Google Scholar
  • 2 Atichartakarn V, Marder VJ, Kirby EP, Budzynski AZ. Effects of enzymic degradation on the subunit composition and biologic properties of human factor VIII. Blood 1978; 51: 281-297
    PubMedSearch in Google Scholar
  • 3 Counts RB, Paskell SL, Elgee SK. Disulphide bonds and the quaternary structure of factor VIII- von Willebrand factor. J Clin Invest 1978; 62: 702-709
    CrossrefPubMedSearch in Google Scholar
  • 4 Smith JK, Bidwell E. Therapeutic materials used in the treatment of coagulation defects. Clinics Haematol 1979; 8: 183-206
    PubMedSearch in Google Scholar
  • 5 Yang HC, Duffy C. Factor VIII procoagulant and antigen content of antihaemophilic factor concentrates. Transfusion 1978; 18: 747-749
    CrossrefPubMedSearch in Google Scholar
  • 6 Jakob R, Pflugshaupt R, Furlan M, Beck EA. Variable degradation of factor VIII-related protein in lyophilised concentrates of anti-haemophilic factor. Vox Sang 1978; 35: 36-40
    CrossrefPubMedSearch in Google Scholar
  • 7 Nilsson IM, Hedner U. Characteristics of various factor VIII concentrates used in treatment of haemophilia A. Br J Haematol 1977; 37: 543-557
    CrossrefPubMedSearch in Google Scholar
  • 8 Allain JP, Verroust F, Soulier JP. In vitro and in vivo characterisation of factor VIII preparations. Vox Sang 1980; 38: 68-80
    CrossrefPubMedSearch in Google Scholar
  • 9 McCue MJ, Brossoit AD, Marmer DJ, Head DR. Von Willebrand factor (VIII :VWF) in lyophilized factor VIII concentrates. Am J Haematol 1980; 9: 39-42
    CrossrefPubMedSearch in Google Scholar
  • 10 Nilsson IM, Holmberg L, Stenberg P, Henriksson P. Characteristics of the factor VIII protein and factor XIII in various factor VIII concentrates. Scand J Haematol 1980; 24: 340-349
    PubMedSearch in Google Scholar
  • 11 Peake IR, Bloom AL, Giddings JC, Ludlam CA. An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand’s disease and fetal plasma and serum. Br J Haematol 1979; 42: 269-281
    CrossrefPubMedSearch in Google Scholar
  • 12 Newman J, Johnson AJ, Karpatkin MH, Puszkin S. Methods for the production of clinically effective intermediate- and high-purity factor VIII concentrates. Br J Haematol 1971; 21: 1-20
    CrossrefPubMedSearch in Google Scholar
  • 13 James HL, Wickerhauser M. Development of large-scale fractionation methods. II Preparation of a factor VIII concentrate of intermediate purity. Vox Sang 1972; 23: 402-412
    CrossrefPubMedSearch in Google Scholar
  • 14 Foster PR, White BJ. Thaw-siphon technique for factor VIII cryoprecipitate (Letter). Lancet 1978; 2: 574
    PubMedSearch in Google Scholar
  • 15 Foster PR, Hunter J, Dickson AJ, White BJ. Large scale plasma thawing for factor VIII recovery (Abstr). Thromb Haemostas 1979; 42: 64
    PubMedSearch in Google Scholar
  • 16 Smith JK, Snape TJ, Haddon ME, Gunson HH, Edwards R. Methods of assessing factor VIII content of stored fresh frozen plasma intended for preparation of factor VIII concentrates. Transfusion 1978; 18: 530-537
    CrossrefPubMedSearch in Google Scholar
  • 17 Hardisty RM, Macpherson JD. A one-stage factor VIII assay and its use on venous and capillary plasma. Thrombos Diathes Haemorrh 1962; 7: 215-229
    PubMedSearch in Google Scholar
  • 18 Macfarlane DE, Stibbe J, Kirby EP, Zucker MB, Grant RA, McPherson J. A method for assaying von Willebrand factor (ristocetin cofactor). Thrombos Diathes Haemorrh 1975; 34: 306-308
    PubMedSearch in Google Scholar
  • 19 Laurell CB. Electroimmunoassay. Scand J Clin Lab Invest 1972; 29 Suppl (Suppl. 124) 21-37
    CrossrefPubMedSearch in Google Scholar
  • 20 Ruggeri ZM, Mannucci PM, Jeffcoate SL, Ingram GI C. Immunoradiometric assay of factor VIII related antigen, with obser-vations on 32 patients with von Willebrand’s disease. Br J Haematol 1976; 33: 221-232
    CrossrefPubMedSearch in Google Scholar
  • 21 Howard MA, Hau L, Perkin J, Thomas KB, Firkin BG, Koutts J. Causes for the discrepandes in the measurements of factor VIII antigen. Thromb Res 1980; 19: 63-72
    CrossrefPubMedSearch in Google Scholar
  • 22 Hoyer LW, Trabold NC. Properties of human factor VIII procoagulant protein. Protides Biol Fluids Peeters H. ed 1980; 28: 289-294
    PubMedSearch in Google Scholar
  • 23 Wickershauser M, Mercer JE, Eckenrode JW. Development of large scale fractionation methods. VI. An improved method for preparation of antihaemophilic factor Vox Sang 1978; 35: 18-31
    PubMedSearch in Google Scholar
  • 24 Smith JK, Evans DR, Stone V, Snape TJ. A factor VIII concentrate of intermediate purity and higher potency. Transfusion 1979; 19: 299-306
    CrossrefPubMedSearch in Google Scholar
  • 25 Guisasola JA, Cockbum CG, Hardisty RM. Plasmin digestion of factor VIII: characterisation of the breakdown products with respect to antigenidty and von Willebrand activity. Thromb Haemostas 1978; 40: 302-315
    PubMedSearch in Google Scholar
  • 26 Kopec M, Bykowska K, Lopaciuk S, Jelenska M, Kaczanowska J, Sopata I, Wojtecka E. Effects of neutral proteases from human leukocytes on structure and biological properties of human factor VIII. Thromb Haemostas 1980; 43: 211-217
    PubMedSearch in Google Scholar
  • 27 Over J, Bouma BN, Sixma JJ, Bolhuis PA, Vlooswijk RA A. Heterogeneity of human factor VIII. III. Transitions between forms of factor VIII present in cryoprecipitate and in cryosupernatant plasma J Lab Clin Med 1980; 95: 323-334
    PubMedSearch in Google Scholar
  • 28 Weinstein M, Deykin D. Comparison of factor VIII related von Willebrand factor protein prepared from human cryopredpitate and factor VIII concentrate. Blood 1979; 53: 1095-1105
    PubMedSearch in Google Scholar
  • 29 Over J, Bouma BN, van MourikJ, Sixma JJ, Vlooswijk R, Bakker WoudenbergI. Characterisation of factor VIII present in the supernatant of cryopredpitate. J Lab Clin Med 1978; 91: 32-46
    PubMedSearch in Google Scholar
  • 30 Weisert O, Jeremic M. Preservation of coagulation factors V and VIII during collection and subsequent storage of bank blood in ACD-A and CPD solutions. Vox Sang 1973; 24: 126-133
    CrossrefPubMedSearch in Google Scholar
  • 31 Wensley RT, Snape TJ. Preparation of improved cryopredpitate factor VIII concentrate - a controlled study of three variables affecting the yield. Vox Sang 1980; 38: 222-228
    CrossrefPubMedSearch in Google Scholar