Factor VIII:C and VIII:CAg Response in Patients with Haemophilia A and von Willebrand's Disease after Administration of Different Factor VIII Concentrates or Plasma

Abstract

Factor VIII procoagulant activity (VIII:C) and factor VIII procoagulant antigen (VIII:CAg) were studied in seven patients with haemophilia A after administration of three different factor VIII concentrates or plasma. The in vivo recovery of VIII:CAg was less than that of VIII:C and the disappearance rate of VIII:CAg was much higher either when concentrates or plasma were given. The half-life of VIII:C was thus about 12 h but of VIII:CAg only about 3 h or less. Six patients with von Willebrand's disease were studied after administration of AHF-Kabi. In contrast to haemophilia A the discrepancy between VIII:C and VIII:CAg disappearance rates was not present in von Willebrand's disease, since both VIII:C and VIII:CAg showed a typical progressive increase. We conclude that factor VIII:C given to haemophilia patients does not behave like native VIII:C, not even when fresh plasma is used. Patients with von Willebrand's disease are capable of forming a normal VIII:C when appropriately stimulated.

Factor VIII Procoagulant Antigen Recovery Is a Dose-Related Response to Factor VIII Concentrate Infusions

“…This is consistent with previous findings [3,4] of lower recovery of VIIICAg relative to VIIIC following infusion of factor VIII con centrates having VIIICAg/VIIIC ratios «S 1.5. This would seem to imply the rapid removal (within 10 min) or masking of the immunoreactive sites of large amounts of VIIICAg protein which has no biological ac tivity, by a mechanism(s) as yet unknown.…”

“…Furthermore, results which have been obtained on the rate of disappearance of VIIICAg relative to VIIIC following the infusion of factor VIII concentrate are conflicting. Holmberg et al [3], using a solid-phase two-site immunoradiometric assay, showed a much reduced half-life of VIIICAg relative to VIIIC while two other reports [4,5], using one-site assays, found similar half-lives for VIIIC and VIII CAg. One of these [5] also reported increased recovery of VIIICAg compared to VIIIC.…”

“…Recent reports [3,4] have shown a lower in vivo recovery of VIIICAg as com pared to VIIIC following infusion of these concentrates into haemophiliacs at doses which yielded plasma VIIIC levels of approx imately 0.5 U/ml. This lower recovery of VIIICAg may reflect a selective clearance of inactivated coagulant protein.…”

Measurement of Factor VIII Procoagulant Antigen in Normal Subjects and in Hemophilia A Patients by an Immunoradiometric Assay and by an Enzyme-Linked Immunosorbent Assay

“…Similar observations were made by Holmberg et al [18] and Taylor et al [20] who also deter mined FVIILAg with solid-phase assays. In contrast.…”

“…These findings correspond to the ob servation of other authors, who generally found FVIILAg/FVIILC ratios greater than 1.0 [18][19][20], There are presently 4 studies that have concerned themselves with the assessment of FVIILAg recoveries after infusion of FVIII in a small number of hemophilia A patients [18][19][20][21]. In all cases, the FVIILAg recoveries were significantly lower than those of FVIILC when administered in dosages that lead to an FVIILC increase of less than 1 U/ml.…”