Because protein Z helps inactivate factor Xa, deficiency or dysfunction of protein Z predisposes to venous thrombosis (mainly in patients with other clotting abnormalities).
Protein Z, a vitamin K–dependent protein, functions as a cofactor to down-regulate coagulation by forming a complex with the plasma protein, Z-dependent protease inhibitor (ZPI). The complex predominantly inactivates factor Xa on phospholipid surfaces. The consequence of protein Z or ZPI deficiency or of autoantibodies to protein Z in the pathophysiology of thrombosis and fetal loss is unresolved; however, either defect may make thrombosis more likely if an affected patient also has another congenital coagulation abnormality (eg, factor V Leiden). Quantification of protein Z ZPI, and protein Z autoantibodies is done in research laboratories by plasma electrophoresis, immunoblotting, and enzyme-linked immunosorbent assay. It is not yet known whether anticoagulant therapy or prophylaxis is indicated in protein Z or ZPI deficiency.
Last full review/revision January 2013 by Joel L. Moake, MD