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Protein Z Deficiency


Michael B. Streiff

, MD, Johns Hopkins University School of Medicine

Reviewed/Revised Aug 2023

Because protein Z helps inactivate coagulation factor Xa, deficiency or dysfunction of protein Z predisposes to venous thrombosis (mainly in patients who also have 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 congenital deficiency, or of acquired autoantibodies to protein Z, in the pathophysiology of thrombosis, fetal loss, and cancer (ovarian or gastric) is not completely clear; however, a defect of either protein Z or ZPI may make thrombosis more likely if an affected patient also has another congenital coagulation abnormality (eg, factor V Leiden Factor V Resistance to Activated Protein C (APC) Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they also predispose to venous thrombosis. (See also Overview of Thrombotic Disorders... read more ) or an acquired autoantibody against a phospholipid-bound protein (an antiphospholipid antibody Antiphospholipid Syndrome (APS) Antiphospholipid syndrome is an autoimmune disorder characterized by venous and arterial thrombosis or pregnancy complications (eg, recurrent miscarriage) and persistent autoantibodies to phospholipid-bound... read more ).

Testing for protein Z deficiency is not part of routine thrombophilia testing. Quantification of protein Z, ZPI, and protein Z autoantibodies is done in specialized regional 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.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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