Increased thrombin generation in a child with a combined factor IX and
protein C deficiency
C Negrier, M Berruyer, A Durin, N Philippe and M Dechavanne
Laboratoire d'Hemobiologie, Institut Pasteur, INSERM U331, Faculte A.
Carrel, Lyon, France.
We report a quantitative protein C deficiency combined with a factor IX
deficiency in a one-year-old boy. The inheritance of the two deficiency
states was independent, the factor IX defect coming from the mother and the
protein C defect from the father. Both factor IX activity and antigen were
below 1%, and protein C activity as well as antigen were close to 27% of
normal values. This association raises a real therapeutic and prognostic
question. Protein C deficiency is indeed associated with a significant
thrombotic risk and some factor IX concentrates seem to carry a potential
thrombogenicity, particularly following infusion of repeated doses. We
evaluated in this patient the potential activation of the coagulation
system by measuring the levels of prothrombin fragment F1 + 2 at the basal
state and after a single administration of 20 U/kg of a high purity factor
IX concentrate. We found an unexpected basal activation of the hemostatic
system before infusion (F1 + 2 = 1.6 nmol/L), which further increased
during 8 hours. Despite the clinical predominant expression of the
hemophilic trait, our results seem to assess the biologic prevalence of the
protein C deficiency. This emphasizes the need for a careful follow-up
after infusions of repeated doses of factor IX, as used during a surgical
procedure. Furthermore, this raises the question of the prognosis because
the risk of thrombotic manifestations associated with a protein C
deficiency increases with age. Finally, these results highlight a part of
the in vivo activation process of prothrombin in case of failure of the
intrinsic pathway of coagulation. The protein C defect seems to be
responsible for an upregulation of the prothrombin activation through the
extrinsic pathway.
Volume 81,
Issue 3,
pp. 690-695,
02/01/1993
Copyright © 1993 by The American Society of Hematology
