Summary:
A new anticoagulant system involving a serpin has been recently characterized.
The protein Z/Z-dependent protease inhibitor (PZ/ZPI) system inhibits activated
factors X, XI and IX by different mechanisms. By homology with other
anticoagulant systems (antithrombin or the protein C/protein S), deficiency of
the serpin (ZPI) or its cofactor (PZ) might imbalance the haemostatic system
with thrombotic consequences. Evidence supports the in vivo anticoagulant role
of this complex and the thrombotic consequences of its deficiency. Non-sense
variations of the ZPI (W303X and R67X) have been associated with increased risk
of venous thrombosis. Moreover, PZ deficient mice carrying the FV Leiden have a
thrombotic phenotype. Finally, some reports suggest that PZ deficiency might
increase the risk of thrombosis. However, other studies question the thrombotic
relevance of both ZPI and PZ deficiencies and there is still insufficient
evidence with regard to protein Z levels and thrombotic events
Although protein Z was characterized already in the 1980s, its role in normal
and pathologic coagulation is still somewhat controversial. This system could
play a redundant role in haemostasis that explains the conflicting results on
its thrombotic potential, which might be exacerbated in combination with other
prothrombotic factors.
Keywords:
Thrombosis, Hereditary thrombosis, Acquired thrombosis, Arterial thrombosis, Protein Z
