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Semin Thromb Hemost 2002; 28(S1): 063-074
DOI: 10.1055/s-2002-30198
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Sixteen Years of Treatment with Pasteurized Human Clotting Factor Concentrates in Children and Adolescents: A Pharmacosurveillance Investigation Comprising 727 Patient Years

Wolfgang Muntean1, 2 , Werner Zenz1, 2 , Jutta Falger3 , Christoph Male3 , Werner Streif4 , Johann Wank5 , Rudolf Schwarz6 , Klaus Schmitt6 , Peter Kurnik7 , Karl Zwiauer8
  • 1Department of Pediatrics, University of Graz, Austria
  • 2Ludwig Bolzmann Research Institute for Pediatric Hemostasis and Thrombosis, Graz, Austria
  • 3Department of Pediatrics, University of Vienna, Austria
  • 4Department of Pediatrics, University of Innsbruck, Austria
  • 5St. Anna Children Hospital, Vienna, Austria
  • 6Children Hospital, Linz, Austria
  • 7Children Hospital, Klagenfurt, Austria
  • 8Children Hospital, St. Pölten, Austria
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Publikationsdatum:
17. Mai 2002 (online)

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The main criteria for the quality of a clotting factor concentrate for treatment of congenital deficient patients are viral safety and low incidence of the development of inhibitors. Since the discovery of HIV, the viral safety of products has especially been dramatically improved, with the introduction of viral inactivation procedures. Many prospective studies show that plasma-derived products now can be regarded as safe in regard to HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). On the other hand, not all viruses are inactivated by all methods, as is demonstrated, for example, by the transmission of human parvovirus B19 by plasma-derived concentrates virus inactivated by various methods and even by recombinant products.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]

Incidence of inhibitors is reported with very different frequencies in different studies; in many studies, the number of patients is not large enough to allow definite conclusions about differences among studies. Whether the incidence is the same with plasma-derived and recombinant factor (F) VIII:C is not completely clear at this time; large differences have been reported even between plasma-derived products produced by similar methods.[11] [12] [13] [14] [15] [16] [17] [18] [19] [20]

Although acute allergic reactions pose no major problem in the use of clotting factor concentrates, with the close observation of patients triggered by the AIDS epidemic it became apparent that immunologic alterations can be found not only in patients infected with HIV or HBV and HCV but also in patients without infection but regular treatment with clotting factor concentrates.[21] [22] [23] [24] [25] [26] [27] [28] [29] [30]

Relatively small prospective trials of limited duration may not detect all possible rare side effects of a specific product. In addition, such trials cannot detect failures that may occur for a short period of time in the manufacturing process; a few such incidences have been reported in the past.[1] [2] [3]

For all the reasons just mentioned, it is important to closely monitor side effects of treatment with clotting factor concentrates to allow a quick response when known or possibly new side effects are recognized. Such pharmacosurveillance investigations also may add to our understanding of the development of inhibitors and immunologic alterations and serve as a base to compare with results of studies with new products. We report the results of a pharmacosurveilance investigation about pasteurized plasma-derived clotting factor concentrates comprising 727 patient years over a treatment period of up to 16 years in children and adolescents with congenital clotting factor deficiencies.

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