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Thromb Haemost 1987; 58(04): 1049-1052
DOI: 10.1055/s-0038-1646054
Original Article
Schattauer GmbH Stuttgart

Continuous High-Dose Factor VIII for the Induction of Immune Tolerance in Haemophilia A Patients with High Responder State: A Description of Eleven Patients Treated

E Scheibel
*   The University Departments of Paediatrics and Clinical Chemistry, Rigshospitalet, Copenhagen, Denmark
,
J lngerslev
**   The University Department of Ciinical Immunology, Aarhus Kommunehospital, Aarhus, Denmark
,
J Dalsgaard-Nielsen
***   The University Department of Haematology, Hvidovre Hospital, Hvidovre, Denmark
,
S Stenbjerg
**   The University Department of Ciinical Immunology, Aarhus Kommunehospital, Aarhus, Denmark
,
J B Knudsen
*   The University Departments of Paediatrics and Clinical Chemistry, Rigshospitalet, Copenhagen, Denmark
,
The Danish Study Group › Author Affiliations
Further Information

Publication History

Received 06 January 1986

Accepted after revision 07 September 1987

Publication Date:
29 June 2018 (online)

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Summary

Eleven severely affected haemophilia A patients (aged 6-42 y) with F VIII : C inhibitor (high responders) were treated with highdose F VIII in order to eliminate the inhibitors. The patients comprise Danish high responder patients treated during the period 1977-1985.

In all patients the inhibitors decreased significantly. In six, the inhibitor apparently disappeared (detection limit 0.4 Bethesda Units per ml) (BU/ml), in four patients a low level inhibitor of 0.4-1.4 BU/ml persisted. One patient is still on high-dose ;schedule. The duration of high-dose treatments ranged from less than one month up to 18 months. In all patients the tendency to spontaneous bleedings vanished when a measurable VIII : C level appeared in the post-infusion sample. The inhibitor suppression has allowed for extensive physical training and rehabilitation orthopaedic surgery. The patients are now able to conduct a normal haemophilic life on self-administered prophylactic doses of F VIII.

Keywords

Haemophilia A - High-dose F VIII - VIII :C inhibitor - High responder VIII:C inhibitor
 

  • References

  • 1 Allain JP, Frommel D. Antibodies to factor VIII. V. Patterns of immune response to factor VIII in hemophilia A. Blood 1976; 47: 973-982
    PubMedSearch in Google Scholar
  • 2 Gill MF. The natural history of factor VIII inhibitors in patients with haemophilia A. In: Factor VIII inhibitors. Hoyer LW. (ed.). Vol. 150 pp. 19-29 Alan R Liss; New York: 1984
    Search in Google Scholar
  • 3 Samsjoedin L MJ, Heijnen L, Mauser-Bunchoten EP. et al. The effect of activated prothrombin-complex concentrate (FEIBA) on joint and muscle bleeding in patients with hemophilia A and antibodies to factor VIII: a double-blind clinical trial. N Engl J Med 1981; 305: 717-721
    CrossrefPubMedSearch in Google Scholar
  • 4 Lusher JM, Shapiro SS, Palascak JE. et al. Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII. A multicenter therapeutic trial. N Engl J Med 1980; 303: 421-425
    CrossrefPubMedSearch in Google Scholar
  • 5 Kernoff P BA, Thomas ND, Lilley PA, Matthews KB, Goldman E, Tuddenham E GD. Clinical experience with polyelectrolyte-fractionated porcine factor VIII concentrate in the treatment of hemophiliacs with antibodies to factor VIII. Blood 1984; 63: 31-41
    PubMedSearch in Google Scholar
  • 6 Hultin MB. Management of inhibitors by immunosuppression. In: Haemophilia. Seligsohn U, Rimuu A, Horoszowski H. (eds.). pp. 107-112 Castle House; London: 1981
    Search in Google Scholar
  • 7 Hedner U, Sundqvist S-B, Nilsson IM. Immunosuppressive treatment in hemophiliacs with inhibitors. In: Activated Prothrombin Complex Concentrates. Mariani G, Russo MA, Mandelli F. (eds.). pp. 45-54 Praeger; New York: 1982
    Search in Google Scholar
  • 8 Pintado T, Taswell HF, Bowie EJ. Treatment of lifethreatening hemorrhage due to acquired factor VIII inhibitor. Blood 1975; 46: 535-541
    PubMedSearch in Google Scholar
  • 9 Nilsson IM, Sundqvist S-B, Freiburghaus C. Extracorporeal protein A-sepharose and specific affinity chromatography fox lemoval of antibodies. In: Factor VIII inhibitors. Hoyer LW. (ed.). Vol. 150. Alan R Liss; New York: 1984: 225-241
    Search in Google Scholar
  • 10 Brackmann HH, Gormsen J. Massive factor Vlll infusion m haemophiliac with factor VIII inhibitor, high responder. Lancet 1977; II: 933
    PubMedSearch in Google Scholar
  • 11 Biackniaim HH. Induced immunotolerancc in factor VIII inhibitor patients. In: Factor VIII inhibitors. Hoyer LW. (ed.). Vol. 150. Alan R Liss; New York: 1984: 181-195
    Search in Google Scholar
  • 12 White GC, Taylor RE, Blatt PM, Roberts HR. Treatment of a high-titer anti-factor VIII antibody by continuous factor VIII administration: report of a case. Blood 1983; 62: 141-145
    PubMedSearch in Google Scholar
  • 13 Gomperts ED, Jordan S, Church JA, Sakai R, Lemire J. Induction of tolerance to factor VIII in a child with a high-titer inhibitor: In vitro and in vivo observations. J Pediatr 1984; 104: 70-75
    CrossrefPubMedSearch in Google Scholar
  • 14 Nilsson IM. Haemorrhagic and thrombotic diseases. John Wiley & Sons; London: 1974: 220-223
    Search in Google Scholar
  • 15 Kasper CK, Aledort LM, Counts RB. et al. A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorr 1975; 34: 869-872
    PubMedSearch in Google Scholar
  • 16 Allain J-P. Principles of in vivo recovery and survival studies. Scand J Haematol 1984; 33 suppl. (41) 123-130
    PubMedSearch in Google Scholar
  • 17 Stenbjerg S, Ingerslev J, Zachariae E. Factor VIII inhibitor treatment with high doses of factor VIII. Thromb Res 1984; 34: 533-539
    CrossrefPubMedSearch in Google Scholar
  • 18 Scheibel E, Feddersen C, Hertz H. Long-term high dose factor VIII treatment of 3 hemophiliacs with factor VIII inhibitor. Scand J Haematol 1985; 34: 378-384
    PubMedSearch in Google Scholar
  • 19 Stenbjerg S, Jprgensen J, Tauris P, Skottun T. Low dose factor VIII for the treatment of hemophilia with inhibitors. In: Mariani G, Russo MA, Manelli F. (eds.) Activated prothrombin complex concentrates. Praeger; New York: 1982: 206-212
    Search in Google Scholar
  • 20 van Leeuwen EF, Mauser-Bunschoten EP, van Dijken PJ, Kok AJ, Sjamsoedin-Visser E JM, Sixma JJ. Disappearance of factor VIII :C antibodies in patients with haemophilia A upon frequent administration of factor VIII in intermediate or low dose. Brit J Haematol 1986; 64: 291-297
    CrossrefPubMedSearch in Google Scholar
  • 21 Vehar GA, Keyt B, Eaton D. et al. Structure of human factor VIII. Nature 1984; 312: 337-342
    CrossrefPubMedSearch in Google Scholar
  • 22 Din N, Schwartz M, Kruse T, Vestergaard SR, Ahrens P, Scheibel E, Nordfang O, Esban M. Factor VIII gene-specific probes used to study heritage and molecular defects in hemophilia A. Resc Clin Lab 1986; 16: 182
    PubMedSearch in Google Scholar