Protein Z (PZ) is a
vitamin K-dependent plasma
glycoprotein that acts as a cofactor for PZ-dependent
protease inhibitor to inhibit
coagulation factor X(a). 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.