Increased thrombin generation in a child with a combined factor IX and protein C deficiency.
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.
Negrier
C
C
Laboratoire d'Hémobiologie, Institut Pasteur, INSERM U331, Faculté A. Carrel, Lyon, France.
Berruyer
M
M
Durin
A
A
Philippe
N
N
Dechavanne
M
M
D005164:Factor IX / Q000032:analysis* / Q000627:therapeutic use; D005260:Female; D002836:Hemophilia B / Q000097:blood* / Q000150:complications / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D010446:Peptide Fragments / Q000032:analysis; D020151:Protein C Deficiency; D011516:Prothrombin / Q000032:analysis; D013917:Thrombin / Q000096:biosynthesis*
D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D005164:Factor IX; D013917:Thrombin