Preeclampsia is associated with low concentrations of protein Z

Abstract

Objective. Protein Z, a vitamin K-dependent plasma protein, has an important role in the regulation of the coagulation cascade. Protein Z deficiency has been associated with unexplained pregnancy loss and adverse pregnancy outcome in patients with thrombophilia. This study was conducted to determine if preeclampsia (PE), small for gestational age (SGA), and fetal demise are associated with changes in maternal plasma concentrations of protein Z.

Study design. This cross-sectional study included normal pregnant women (N = 71), patients with PE (N = 130), patients who delivered an SGA neonate (N = 58), and patients with fetal demise (N = 58). Maternal plasma protein Z concentrations were measured by a sensitive and specific immunoassay. Protein Z deficiency was defined as maternal plasma concentrations ≤5^th percentile of the normal pregnancy group (≤1.59 µg/mL). Non-parametric statistics were used for analysis.

Results. (1) Patients with PE had a lower median plasma concentration of protein Z than normal pregnant women (PE: median 1.6 µg/mL, range 0.2–3.3 µg/mL vs. normal pregnancy: median 2.4 µg/mL, range 1.1–3.4 µg/mL; p < 0.0001); (2) patients with an SGA neonate (median 2.3 µg/mL, range 0.2–3.8 µg/mL) and fetal demise (median 2.6 µg/mL, range 0.2–4.3 g/mL) did not have significantly different median protein Z concentrations from normal pregnant women (p > 0.05); and (3) women in the PE and fetal demise groups had significantly higher rates of protein Z deficiency than those with normal pregnancy outcome.

Conclusions. (1) PE, but not SGA or fetal demise, is associated with a significantly lower maternal median plasma concentration of protein Z than normal pregnancy, and (2) a high rate of protein Z deficiency is observed in patients with PE and fetal demise.

Keywords:

• SGA
• fetal demise
• factor X
• protein Z dependent protease inhibitor (ZPI)
• coagulation
• pregnancy