Evaluation of Prothrombin Time with Use of Highly Diluted Tissue Factor Reagent

Abstract

Prothrombin time (PT) is an established screening method for hemorrhagic disorders. Recent progress of the biochemistry of tissue factor (TF)-dependent coagulation pathway revealed that TF/factor VIIa complex activated factor IX rather than factor X. However, PT does not reflect the activity of factors IX and VIII, because of excess amount of TF reagent in the assay system. In this study, we evaluated PT using highly diluted TF reagent (Dil-PT) and its clinical application. Coexistence of magnesium with calcium ion resulted in the shortening of Dil-PT. Dil-PT prolonged in accordance with the decrease of TF reagent, and prolongation was observed in factor VIII-and factor IX-deficient plasmas similarly to the factor X-, factor V-, factor VII-and factor II-deficient plasmas. On the contrary, prolonged clotting time of factor XI-, factor XII-, high molecular weight kininogen-and plasma prekallikrein-deficient plasmas were the same as that of normal pooled plasma in the Dil-PT system. In the clinical samples, significant shortenings of Dil-PT and PT were observed in the patients with rhabdomyolysis. On the other hand, Dil-PT showed significant shortning in gestational toxicosis, but PT did not. These results suggest that Dil-PT reflect the activity of factors IX and VIII besides factors VII, X, V and II, and Dil-PT is an useful screening method that does not require specific reagents and apparatus for the detection of hypercoagulable state.