High frequency of protein Z deficiency in patients with unexplained early fetal loss

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Abstract
The protein Z–protein Z-dependent inhibitor complex is a factor Xa inhibitor. Protein Z deficiencies have recently been described in patients with ischemic stroke. As placenta infarction leads to poor pregnancy outcome, we studied protein Z plasma concentrations in nonthrombotic, nonthrombophilic consecutive patients with unexplained pregnancy wastage. A significant amount of protein Z deficiencies was only found in the early fetal loss group (< 1 mg/L; 44 of 200,P < 10−4) and mainly in the case of fetal demise between the beginning of the 10th and the end of the 15th week of gestation (odds ratio, 6.7 [3.1-14.8],P < 10−3). These deficiencies were not due to partial vitamin K1 deficiency, and at least some of them were constitutional ones. In women, protein Z deficiency may induce an enhanced risk of severe placental insufficiency soon after the connection of maternal and fetal circulations.