Comparison of the behavior of normal factor IX and the factor IX BM variant hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources

Abstract

A subset of hemophilia B patients have a prolonged bovine-brain prothrombin time. These CRM+ patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor X present in the sample. The prothrombin time changed as much as 20 seconds when the factor X concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor X concentrations are known.

Evaluation of Nonacog Beta Pegol Long-term Safety in the Immune-deficient Rowett Nude Rat (Crl:NIH-Foxn1rnu)

“…A dose-dependent shortening of an aPTT was observed in all 6 weeks of the dosing phase in the 6-week study but not in the 26-week study. A dosedependent prolongation of PT was observed in the 26-week study and is considered a result of PT assay interference by high rFIX concentrations as described previously by others (Lefkowitz et al 1993;Osterud et al 1981;Spitzer et al 1990). Shortening of aPTT and prolongation of PT is interpreted as an effect of unphysiologically high levels of rFIX on the assays and not a direct effect on the coagulation system.…”

Pulmonary Hemorrhage: An Unusual Life-Threatening Presentation of Factor IX Deficiency in a Monochorionic-Diamniotic Twin Neonate

“…The prolonged aPTT is due to a decrease in factor IX activity. Factor IX in the coagulation cascade is associated with platelet activation and the formation of thrombin, eventually leading to the development of a fibrin clot [3,4,5].…”