Plasma Concentrations of Protein Z and Protein Z-Dependent Protease Inhibitor in Patients With Essential Thrombocythemia

Abstract

The pathological consequences of decreased protein Z (PZ) and/or Z-dependent protease inhibitor (ZPI) levels remain as yet unclear, despite a growing body of evidence which supports their involvement in an increased thrombotic risk. The purpose of the present study was 2-fold: to evaluate plasma concentrations of protein Z and ZPI in patients with essential thrombocythemia (ET) and to determine their significance in thrombotic complications. The median (range) plasma concentrations of PZ in our patients with ET were lower, but not significantly, than in healthy individuals: PZ (1.42 µg/mL, 0.36-3.14 µg/mL vs 1.6 µg/mL, 0.75-2.56 µg/mL, P = .08). On the other hand, the median (range) plasma concentrations of ZPI in the said patients with ET were meaningfully lower than in the reference group: ZPI (3.22 µg/mL, 0.85-6.97 µg/mL vs 4.41 µg/mL, 1.63-7.83 µg/mL, P = .0004). More importantly, the study revealed a statistically significant lower concentration of PZ and ZPI in patients with the presence of the JAK2V617F mutation relative to patients without the mutation, for PZ: 1.38 µg/mL, 0.36-2.6 µg/mL versus 1.63 µg/mL, 0.88-3.14 µg/mL, P = .03, and ZPI 2.89 µg/mL, 0.85-5.91 µg/mL versus 3.61 µg/mL, 1.53-6.97 µg/mL, P = .002. Additionally, significant differences between the concentrations of PZ and ZPI were found in patients with venous thrombotic episodes compared to healthy individuals, for PZ: 1.23 µg/mL, 0.82-1.99 µg/mL versus 1.6 µg/mL, 0.75-2.56 µg/mL, P = .043, and ZPI: 2.42 µg/mL, 0.85-4.21 µg/mL versus 4.41 µg/mL, 1.63-7.83 µg/mL, P < .0001. To recapitulate, our results suggest that the deficiency of PZ may increase tendency to thrombosis in patients with ET.

Assessment of the Procoagulant Activity of Microparticles and the Protein Z System in Patients Undergoing Off-Pump Coronary Artery Bypass Surgery

“…Moreover, all kits used in our study were extensively validated in preceding studies. 10,17,18 For the determination of MPs, MPs-TF, PZ, FX, and total TF, ELISAs by HYPHEN BioMed, SAS (Neuville-sur-Oise, France) were utilized. Microparticles procoagulant activity was determined using a ZYMUPHEN MP-Activity kit and expressed as phosphatidylserine (PS) equivalents (nanomolar PS).…”

Expression and Diagnostic Value of Serum Protein Z, Protein Z-dependent Protease Inhibitor and Coagulation-related Indicators in Foetal Growth Restriction.

“…PZ is vitamin K-dependent serum protein and commonly synthesized by vascular endothelial cells [17] . Its structure is similar to other K-dependent factors, such as VII, IX, and protein C [18] . Previous studies showed that PZ can acts an anticoagulant, like protein C and protein S. ZPI is a member of serpin superfamily and could rapidly inhibit activation of factor Xa with the requirement of PZ, calcium, and perocoagulant phospholipids, or suppress the activation of factor XI in the absence of the aforementioned cofactors [19] .…”

Expression and diagnostic value of serum protein Z and protein Z-dependent protease inhibitor in fetal growth restriction

“…PZ is a kind of vitamin K-dependent serum protein and commonly synthesized by vascular endothelial cells [17]. Its structure is similar to other Kdependent factors, such as VII, IX, and protein C [18]. ZPI is a member of serpin superfamily, which can rapidly inhibit activation of factor Xa when having PZ, calcium and procoagulant membranes.…”