Thromb Haemost 1986; 56(03): 353-359
DOI: 10.1055/s-0038-1661682
Original Article
Schattauer GmbH Stuttgart

Factor VIII: C (FVIII: C) Recovery and Half-Life After Infusion of Steam-Treated High Purity Factor VIII Concentrate in Severe Hemophilia A - Comparison of One-Stage Assay, Two-Stage Assay and a Chromogenic Substrate Assay

Peter Hellstern
*   The Dept, of Clinical Hemostaseology and Transfusion Medicine, University of Saarland, Homburg-Saar, F. R. G
,
Ralf Kiehl
*   The Dept, of Clinical Hemostaseology and Transfusion Medicine, University of Saarland, Homburg-Saar, F. R. G
,
Chieko Miyashita
*   The Dept, of Clinical Hemostaseology and Transfusion Medicine, University of Saarland, Homburg-Saar, F. R. G
,
Holger Schwerdt
+   The Dept, of Internal Medicine, University of Saarland, Homburg-Saar, F. R. G
,
Gerhard von Blohn
*   The Dept, of Clinical Hemostaseology and Transfusion Medicine, University of Saarland, Homburg-Saar, F. R. G
,
Michael Köhler
*   The Dept, of Clinical Hemostaseology and Transfusion Medicine, University of Saarland, Homburg-Saar, F. R. G
,
Maria Büttner
++   The Dept, of Pediatrics, University of Saarland, Homburg-Saar, F. R. G
,
Ernst Wenzel
*   The Dept, of Clinical Hemostaseology and Transfusion Medicine, University of Saarland, Homburg-Saar, F. R. G
› Author Affiliations
Further Information

Publication History

Received 01 April 1986

Accepted after revision 15 September 1986

Publication Date:
18 July 2018 (online)

Summary

Factor VIII :C recovery and half-life was measured in 16 hemophilia A patients under comprehensively standardized conditions. Each patient received the same lot of a steam-treated high purity FVIII concentrate at a dose of 19-33 U/kg body weight. A comparison was made between the one-stage assay, the two-stage assay and a chromogenic substrate test for FVIII :C determination using a FXa-sensitive chromogenic substrate. Factor VIII :C potency of the administered FVIII concentrate was measured using calibration curves derived from a concentrate standard and FVIII: C plasma levels were read from calibration curves derived from a plasma standard. The chromogenic assay showed a good reproducibility at FVIII: C levels between 0.015 and 0.50 U/ml. The FVIII :C recoveries calculated from the results of the one-stage assay, the two-stage assay and the chromogenic substrate test were 109 ± 20, 92 ± 14 and 81 ± 11% (x ± SD), respectively. The elimination half-lives of FVIII :C were calculated by non-linear least square analysis using a modified computerized Gauss-Newton algorithm. The half-lives calculated from the FVIII: C plasma levels measured by the one-stage assay, the two-stage assay and the chromogenic test were 23.8 ± 6.4, 22.2 ± 5.7 and 17.1 ± 4.8 h (x ± SD), respectively. No previous study has reported such long half-life values. Our findings indicate that measurements of recoveries and half-lives by the chromogenic FVIII :C assay and by computerized nonlinear least square analysis allow the possibility of individualized FVIII replacement therapy.

 
  • References

  • 1 Kasper CK, Dietrich SL. Comprehensive management of haemophilia. Clin Haematol 1985; 14: 489-512
  • 2 Kirkwood TB L, Barrowcliffe TW. Discrepancy between one-stage and two-stage assay of factor VIII :C. Brit J Haematol 1978; 40: 333-338
  • 3 Allain JP, Verroust F, Soulier JP. One or two stage assay for factor VIII?. Lancet 1979; 1: 1076-1077
  • 4 Barrowcliffe TW, Kirkwood T BL, Rizza CR. Aluminium hydroxide adsorption and factor VIII assays. Lancet 1980; 2: 820
  • 5 Barrowcliffe TW. Comparisons of one-stage and two-stage assays of factor VIII :C. Scand J Haematol 33 1984; (33) (Suppl. 41) 39-54
  • 6 Kjellman H. Calculations of factor VIII in vivo recovery and half-life. Scand J Haematol 1984; 33 (Suppl. 40) 165-174
  • 7 Rosen S. Assay of factor VIII: C with a chromogenic substrate. Scand J Haematol 1984; 33 (Suppl. 40) 139-145
  • 8 Mikaelsson M, Oswaldsson U. Standardization of VIII :C assays: a manufacturer’s view. Scand J Haematol 1984; 33 (Suppl. 41) 79-86
  • 9 Matucci M, Messori A, Donati-Cori G, Longo G, Vannini S, Morfini M, Tendi E, Rossi-Ferrini PL. Kinetic evaluation of four factor VIII concentrates by model-independent methods. Scand J Haematol 1985; 34: 22-28
  • 10 Rock G, Tittley P, Fuller V. An in vivo assessment of factor VIII concentrates. JAMA 1985; 254: 777-780
  • 11 Barrowcliffe TW, Tydeman MS, Kirkwood T BL, Thomas DP. Standardization of factor VIII - III. Establishment of a stable reference plasma for factor VUI-related activities. Thromb Haemostas 1983; 50: 690-696
  • 12 Barrowcliffe TW, Curtis AD, Thomas DP. Standardization of factor VIII - IV. Establishment of the 3rd international standard for factor VIII :C concentrate. Thromb Haemostas 1983; 50: 697-702
  • 13 Allain JP, Verroust F, Soulier JP. In vitro and in vivo characterization of factor VIII preparations. Vox Sang 1980; 38: 68-80
  • 14 Hartley HO. The modified Gauss-Newton method for the fitting of non-linear regression functions by least squares. Technometrics 1961; 3: 269-280
  • 15 Allain JP. Principles of in vivo recovery and survival study. Scand J Haematol 1984; 33 (Suppl. 41) 123-130
  • 16 Lee ML, Maglalang EA, Kingdon HS. An effect of predilution on potency assays of factor VIII concentrates. Thromb Res 1983; 30: 511-519
  • 17 Kasper CK. In vivo recovery of FVIII:C in hemophilic patients. Scand J Haematol 1984; 33 (Suppl. 41) 147-154
  • 18 Over J. Methodology of the one-stage assay of factor VIII (VIII :C). Scand J Haematol 1984; 33 (Suppl. 41) 13-24
  • 19 Seghatchian MJ, Miller-Andersson M. A colorimetric evaluation of factor VIII :C potency. Med Lab Sci 1978; 35: 347-354
  • 20 Mitchell GA, Abdullahad CM, Ruiz JA, Huseby RM, Alvarez DE, Geiger TM, Black FM, Heller ZH. Fluorogenic substrate assays for factors VIII and IX: introduction of a new solid phase fluorescent detection method. Thromb Res 1981; 21: 573-584
  • 21 Rosen S, Andersson M, Blomback M, Hagglund U, Larrieu MJ, Wolf M, Boyer C, Rothschild C, Nilsson IM, Sjorin E, Vinazzer H. Clinical application of a chromogenic substrate method for determination of factor VIII activity. Thromb Haemostas 1986; 54: 818-823
  • 22 Allain JP. Dose requirement for replacement therapy in hemophilia A. Thromb Haemostas 1979; 42: 825-831
  • 23 Aronstam A, McLellan DS, Wassef M, Mbatha PS. Effect of height and weight on the in vivo recovery of transfused factor VIII: C. J Clin Pathol 1982; 35: 289-291
  • 24 Blomback M, Nilsson IM. Treatment of hemophilia A with human antihemophilic globulin. Acta Med Scand 1958; 161: 301-321
  • 25 Abildgaard CF, Simone JV, Corrigan JJ, Seeler RA, Edelstein G, Vanderheiden J, Schulman J. Treatment of hemophilia with glycine-precipitated factor VIII. N Engl J Med 1966; 275: 471-475
  • 26 Abildgaard CF, Comet JA, Fort E, Schulman I. The in vivo longevity of antihaemophilic factor (factor VIII). Brit J Haematol 1964; 10: 225-237
  • 27 Weiss AE, Webster WP, Strike LE, Brinkhous KM. Survival of transfused factor VIII in hemophilic patients treated with epsilon aminocaproic acid. Transfusion 1976; 16: 209-214
  • 28 Nilsson IM, Hedner U. Characteristics of various factor VIII concentrates used in treatment of haemophilia A. Brit J Haematol 1977; 37: 543-557
  • 29 Verstraete M, Lust A, Vermylen J. In vitro and in vivo recovery of cryoprecipitated factor VIII. Proc 5th Cong W F Haemophilia, Montreal 1968
  • 30 Johnson AJ, Karpatkin MH, Newman J. Clinical investigation of intermediate - and high-purity antihemophilic factor (factor VIII) concentrates. Brit J Haematol 1971; 21: 21-41
  • 31 Allain JP. Etude de l’activite “in vivo” du facteur VIII ou du facteur IX apres injection de differents concentres: applications practiques. Nouv Rev Fr Hematol 1972; 12: 241-249
  • 32 Miyashita C, Hellstern P, Kohler M, von Blohn G, Wenzel E. In vitro characterization of commercial factor VIII concentrates: long-term follow-up. Blut 1984; 49: 53-59
  • 33 Schimpf K, Rothmann P, Schumacher K. Comparison of factor VIII concentrates in non-bleeding patients. Scand J Haematol 1984; 33 (Suppl. 41) 131-145
  • 34 Hathaway WE, Clarke SH, Upp J. Comparison of coagulation tests in surgical patients receiving high and intermediate purity concentrates. Blood 1981; 58 (Suppl. 01) 218a
  • 35 McLellan DS, Pelly C, McLellan HG, Jones P, Aronstam A. The “in vivo” characteristics of factor VIII procoagulant antigen (VIII: CAg) in haemophilia A subjects. Thromb Res 1982; 25: 33-39
  • 36 Van Loo R. Untersuchung fiber Recovery, Halbwertszeit und HalfDisappearance Time (HDT) bei einem Faktor VIII-Hochkonzentrat. Inauguraldissertation Rheinische Friedrich-Wilhelms-Universitat; Bonn: 1983
  • 37 Nilsson IM, Kirkwood TBL, Barrowcliffe TW. In vivo recovery of factor VIII: a comparison of one-stage and two-stage assay methods. Thromb Haemostas 1979; 42: 1230-1239
  • 38 Over J, Sixma JJ, Doucet-de Bruine M HM, Trieschnigg A MC, Vlooswijk R AA, Beeser-Visser NH, Bouma BN. Survival of iodine-labeled factor VIII in normals and patients with classic hemophilia. J Clin Invest 1978; 62: 223-234