Measurement of procarboxypeptidase U (TAFI) in human plasma: a laboratory challenge.
BACKGROUND
The importance of carboxypeptidase U (CPU) as a novel regulator of the fibrinolytic rate has attracted much interest during recent years. CPU circulates in plasma as a zymogen, proCPU, that can be activated by thrombin, thrombin-thrombomodulin (T-Tm), or plasmin. Given that the proCPU concentration in plasma is far below its K(m) for activation by the T-Tm complex, the formation of CPU will be directly proportional to the proCPU concentration. A low or high proCPU plasma concentration might therefore tip the balance between profibrinolytic and antifibrinolytic pathways and thereby cause a predisposition to bleeding or thrombosis.


BACKGROUND
To measure plasma proCPU concentrations, different methods have been developed based on 2 different principles: antigen determination and measurement of CPU activity after quantitative conversion of the proenzyme to its active form by addition of T-Tm. The major drawbacks that should be kept in mind when analyzing clinical samples by both principles are reviewed.


CONCLUSIONS
proCPU is a potential prothrombotic risk factor. Evaluation of its relationship with thrombosis requires accurate assays. Many assays used in different clinical settings are inadequately validated, forcing reconsideration of conclusions made in these reports.
Willemse
Johan L
JL
Laboratory of Medical Biochemistry, University of Antwerp, B-2610 Wilrijk, Belgium.
Hendriks
Dirk F
DF
D025901:Carboxypeptidase B2 / Q000097:blood* / Q000378:metabolism; D004796:Clinical Enzyme Tests; D006801:Humans; D007118:Immunoassay; D007700:Kinetics; D010949:Plasma; D012307:Risk Factors; D013917:Thrombin; D018180:Thrombomodulin; D013927:Thrombosis / Q000175:diagnosis*
D018180:Thrombomodulin; D025901:Carboxypeptidase B2; D013917:Thrombin