Download PDF
Thromb Haemost 2000; 83(01): 65-69
DOI: 10.1055/s-0037-1613759
Commentary
Schattauer GmbH

The Half-life of Infused Factor VIII Is Shorter in Hemophiliac Patients with Blood Group 0 than in those with Blood Group A

André J. Vlot
1   From The van Creveldkliniek, University Medical Center Utrecht, Utrecht
2   From The Department of Haematology, Graduate School of Biomembranes, University Medical Center Utrecht, Utrecht
,
Evelien P. Mauser-Bunschoten
1   From The van Creveldkliniek, University Medical Center Utrecht, Utrecht
,
Antoanette G. Zarkova
3   The National Center of Haematology and Transfusiology, Sofia, Bulgaria, The Netherlands
,
Els Haan
1   From The van Creveldkliniek, University Medical Center Utrecht, Utrecht
,
Cas L. J. J. Kruitwagen
4   The Center for Biostatistics, University of Utrecht, The Netherlands
,
Jan J. Sixma
2   From The Department of Haematology, Graduate School of Biomembranes, University Medical Center Utrecht, Utrecht
,
H. Marijke van den Berg
1   From The van Creveldkliniek, University Medical Center Utrecht, Utrecht
› Author AffiliationsThis work was supported in part by the Van Creveld Foundation.
Further Information

Publication History

Received 08 June 1999

Accepted after revision 08 September 1999

Publication Date:
06 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

A considerable inter-individual variation in half-life of infused factor VIII is observed among patients with hemophilia A. The factors contributing to this wide range in factor VIII half-life are not known in detail. We analysed the pharmacokinetics of infused factor VIII in 32 patients with hemophilia A, comprising 20 brothers from 10 families, 3 and 4 brothers from 2 families, and 5 patients from 5 single families, respectively. Multiple linear regression analysis was used to asses the effect of several variables on factor VIII half-life. We found that the pre-infusion von Willebrand factor antigen levels (vWF:Ag) were positively correlated with factor VIII half-life (r = 0.52, p = 0.002), i. e., each variable was associated with about 27% of the variance of the other. In fraternal pairs, familial clustering was significant for AB0 blood group (p < 0.001), but could not be detected for factor VIII half-lives or pre-infusion vWF:Ag levels. vWF:Ag level (p = 0.001) and AB0 blood group (p = 0.003) significantly determined factor VIII half-life, whereas age, length, bodyweight, the presence or absence of a factor VIII gene inversion, and Rhesus phenotype did not. Patients with blood group 0 exhibited a statistically significant shorter factor VIII half-life than patients with blood group A (15.3 versus 19.7 h, respectively) (p = 0.003). Patients with blood group A and 0 differ in respect to the presence of anti-A antibodies in the latter. It is possible that these anti-A antibodies interact with endogenous vWF, thus affecting the half-life time of the factor VIII/vWF complex.

Key words

Hemophilia - factor VIII - von Willebrand factor - half-life - AB0 blood group system
 

  • References

  • 1 Noe DA, Bell WR, Ness PM, Levin J. Plasma clearance rates of coagulation factors VIII and IX in factor-deficient individuals. Blood 1986; 67: 969-72.
    PubMedSearch in Google Scholar
  • 2 Over J, Sixma JJ, Bruine MH, Trieschnigg MC, Vlooswijk RA, Beeser-Visser NH, Bouma BN. Survival of 125iodine-labeled Factor VIII in normals and patients with classic hemophilia. Observations on the heterogeneity of human Factor VIII. J Clin Invest 1978; 62: 223-34.
    CrossrefPubMedSearch in Google Scholar
  • 3 Kjellman H. Calculations of factor VIII in vivo recovery and half-life. Scand J Haematol Suppl 1984; 40: 165-74.
    PubMedSearch in Google Scholar
  • 4 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: 22-8.
    PubMedSearch in Google Scholar
  • 5 Messori A, Longo G, Matucci M, Morfini M, Ferrini PL. Clinical pharmacokinetics of factor VIII in patients with classic haemophilia. Clin Pharmacokinet 1987; 13: 365-80.
    CrossrefPubMedSearch in Google Scholar
  • 6 Fijnvandraat K, Peters M, ten Cate JW. Inter-individual variation in halflife of infused recombinant factor VIII is related to pre-infusion von Willebrand factor antigen levels. Br J Haematol 1995; 91: 474-6.
    CrossrefPubMedSearch in Google Scholar
  • 7 Fijnvandraat K, Berntorp E, ten Cate JW, Johnsson H, Peters M, Savidge G, Tengborn L, Spira J, Stahl C. Recombinant, B-domain deleted factor VIII (r-VIII SQ): pharmacokinetics and initial safety aspects in hemophilia A patients. Thromb Haemost 1997; 77: 298-302.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 White GC, Courter S, Bray GL, Lee M, Gomperts ED. A multicenter study of recombinant factor VIII (Recombinate TM) in previously treated patients with hemophilia A. Thromb Haemost 1997; 77: 660-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Allain JP. Principles of in vivo recovery and survival studies of VIII:C. Scand J Haematol Suppl 1984; 41: 123-30.
    PubMedSearch in Google Scholar
  • 10 Preston AE, Barr A. The plasma concentration of factor VIII in the normal population. The effects of age, sex, and blood groups. Br J Haematol 1965; 10: 238-45.
    PubMedSearch in Google Scholar
  • 11 Gill JC, Endres JBrooks, Bauer PJ, Marks Jr WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69: 1691-5.
    PubMedSearch in Google Scholar
  • 12 Morfini M, Lee M, Messori A. The design and analysis of half-life and recovery studies for factor VIII and factor IX. Factor VIII/Factor IX Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis. Thromb Haemost 1991; 66: 384-6.
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Kasper CK, Aledort LM, Counts RB, Edson JR, Fratantoni J, Green D, Hampton JW, Hilgartner MW, Lazerson J, Levine PH, McMillan CW, Pool JG, Shapiro SS, Shulman NR, van Eys J. A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34: 869-2.
    PubMedSearch in Google Scholar
  • 14 Lakich D, Kazazian HH, Antonarakis SE, Gitschier J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat Genet 1993; 05: 236-41.
    CrossrefPubMedSearch in Google Scholar
  • 15 Houwing-Duistermaat JJ, Derkx BH, Rosendaal FR, van Houwelingen HC. Testing familial aggregation. Biometrics 1995; 51: 1292-301.
    CrossrefPubMedSearch in Google Scholar
  • 16 Sodetz JM, Paulson JC, McKee PA. Carbohydrate composition and identification of blood group A, B, and H oligosaccharide structures on human Factor VIII/von Willebrand factor. J Biol Chem 1979; 254: 10754-60.
    PubMedSearch in Google Scholar
  • 17 Federici AB, Elder JH, De Marco L, Ruggeri ZM, Zimmerman TS. Carbohydrate moiety of von Willebrand factor is not necessary for maintaining multimeric structure and ristocetin cofactor activity but protects from proteolytic degradation. J Clin Invest 1984; 74: 2049-55.
    CrossrefPubMedSearch in Google Scholar
  • 18 Stoddart JH, Andersen J, Lynch DC. Clearance of normal and type 2A von Willebrand factor in the rat. Blood 1996; 88: 1692-9.
    PubMedSearch in Google Scholar
  • 19 Hironaka T, Furukawa K, Esmon PC, Fournel MA, Sawada S, Kato M, Minaga T, Kobata A. Comparative study of the sugar chains of factor VIII purified from human plasma and from the culture media of recombinant baby hamster kidney cells. J Biol Chem 1992; 267: 8012-20.
    PubMedSearch in Google Scholar
  • 20 Gill JC, Stephany K, Newton-Nash D, Foster PA. Apparent IgG anti-factor VIII antibodies in normal individuals are specific for AB0 blood group substances. Thromb Haemost 1995; 86: 611 (abstract).
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Gilles JG, Arnout J, Vermylen J, Saint RJ. Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction. Blood 1993; 82: 2452-61.
    PubMedSearch in Google Scholar
  • 22 Vlot AJ, Koppelman SJ, Meijers JC, Damas C, van den Berg HM, Bouma BN, Sixma JJ, Willems GM. Kinetics of factor VIII-von Willebrand factor association. Blood 1996; 87: 1809-16.
    PubMedSearch in Google Scholar
  • 23 Morfini M, Longo G, Messori A, Lee M, White G, Mannucci P. Pharmacokinetic properties of recombinant factor VIII compared with a monoclonally purified concentrate (Hemofil M). The Recombinate Study Group. Thromb Haemost 1992; 68: 433-5.
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Klein HG. Blood group and blood transfusion. In: Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL. Harrison’s principles of internal medicine. Thirteenth Ed.. McGraw-Hill, Inc; 1994: 1788-93.
    Search in Google Scholar
  • 25 Messori A, Longo G, Morfini M, Cinotti S, Filimberti E, Guistarini G, Rossi PFerrini. Multi-variate analysis of factors governing the pharmacokinetics of exogenous factor VIII in haemophiliacs. Eur J Clin Pharmacol 1988; 35: 663-8.
    CrossrefPubMedSearch in Google Scholar
  • 26 Koedam JA, Meijers JC, Sixma JJ, Bouma BN. Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor. J Clin Invest 1988; 82: 1236-43.
    CrossrefPubMedSearch in Google Scholar