Factor IX concentrate therapy and thrombosis: relation to changes in plasma antithrombin III

Area of Science:

• Hematology
• Biochemistry
• Thrombosis Research

Background:

• Commercial factor IX (fIX) concentrates are linked to thrombotic complications.
• Previous studies indicated a decrease in antithrombin III (ATIII) functional activity post-fIX concentrate infusion.

Purpose of the Study:

• To extensively characterize changes in antithrombin III (ATIII) levels and function after factor IX (fIX) concentrate therapy.
• To investigate the cause of ATIII alterations and their relation to thrombotic events.

Main Methods:

• Functional assays, radial immunodiffusion (RID), and crossed immunoelectrophoresis (CIEP) were used to analyze plasma ATIII.
• ATIII levels were assessed pre- and post-infusion in patients receiving commercial or purified fIX concentrates.

Main Results:

• Commercial fIX concentrate therapy, especially at 100 U/Kg, caused dose-related and cumulative decreases in ATIII functional activity and antigen changes.
• Purified fIX concentrate therapy showed no significant changes in ATIII levels or function.
• ATIII alterations persisted for 24 hours in patients on daily commercial fIX therapy.

Conclusions:

• The observed antithrombin III (ATIII) changes are likely caused by a contaminant in commercial factor IX (fIX) concentrates, not fIX itself.
• These ATIII alterations are associated with the thrombotic complications of commercial fIX concentrates.