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Protein Z Deficiency


Joel L. Moake

, MD, Baylor College of Medicine

Last review/revision Jan 2021 | Modified Sep 2022
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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 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 Antibody Syndrome (APS) Antiphospholipid antibody syndrome is an autoimmune disorder in which patients have autoantibodies to phospholipid-bound proteins. Venous or arterial thrombi may occur. The pathophysiology is... read more ).

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.

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