Thrombin generation is not increased in the blood of hemophilia B patients after the infusion of a purified factor IX concentrate

Pier Mannuccio Mannucci, Kenneth A. Bauer, Alessandro Gringeri, Samad Barzegar, Bianca Bottasso, Loredana Simoni, Robert D. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Prothrombin complex concentrates (PCC), licensed for the treatment of hemophilia B, are known to carry a significant risk of thromboembolic complications. Although the reasons for thrombogenicity are not completely understood, several manufacturers have developed purified factor IX concentrates that contain negligible amounts of the other vitamin K-dependent factors. To evaluate whether or not the infusion of such a factor IX concentrate is followed by lesser activation of the hemostatic system than by the infusion of a PCC, we performed a series of coagulation assays on 11 hemophilia B patients before and after the administration of these two types of concentrate using a randomized cross-over design. The levels of prothrombin fragment F1+2, a sensitive measure of the in vivo cleavage of prothrombin by factor Xa, was significantly increased in plasma after PCC, but not after factor IX concentrate. Plasma fibrinopeptide A, a sensitive index of the enzymatic activity of thrombin on fibrinogen, also increased significantly after PCC but not after factor IX concentrate. The fragment Bβ 15-42, a sensitive index of the enzymatic action of plasmin on fibrin II. did not change after either concentrate. There were also no differences in less sensitive coagulation measurements, such as plasma fibrinogen, antithrombin III, and fibrin monomers, nor in indices of platelet activation, such as β-thromboglobulin and platelet factor 4. These findings show that the infusion of a purified factor IX concentrate can result in substantially less activation of the coagulation cascade than may be seen with PCC.

Original languageEnglish
Pages (from-to)2540-2545
Number of pages6
JournalBlood
Volume76
Issue number12
Publication statusPublished - Dec 15 1990

ASJC Scopus subject areas

  • Hematology

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