Role of protein Z in stroke

Opinion statementProtein Z (PZ) is a vitamin K-dependent plasma glycoprotein that acts as a cofactor for PZ-dependent protease inhibitor to inhibit coagulation factor Xa. Studies in mice suggest that that decreased blood PZ levels lead to reduced inhibition of blood coagulation, thereby predisposing to thrombosis; however, clinical studies in humans have yielded conflicting results. Among patients with stroke, some epidemiologic studies have reported that reduced PZ levels increase the risk of stroke, whereas others have reported no association between PZ levels and stroke, or that elevated PZ levels increase stroke risk. Polymorphisms involving the gene for PZ can influence the PZ concentration and some polymorphisms (eg, intron G79A AA allele) may be protective against stroke, particularly among younger individuals. Although the association between PZ levels and stroke appears to be stronger in younger patients and in patients who do not have conventional vascular risk factors, it remains unclear whether the link between PZ levels and stroke is confounded or causal or whether blood levels of PZ are altered as a consequence of the acute stroke event.