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Instead, PZ acts as a cofactor for the inhibition of factor Xa through the serpin PZ-dependent protease inhibitor (ZPI). PZ deficiency is associated with a procoagulant state, highlighted by excessive FXa secretion and thrombin production, and is linked with several thrombotic disorders, including arterial vascular and venous thromboembolic diseases. A role for the PZ\u2013ZPI complex in the regulation of physiological pregnancy has been demonstrated, highlighted by the progressive elevation in PZ levels in the first trimester of gestation, which then steadily decline toward delivery. An association between altered plasma PZ concentrations and adverse pregnancy outcomes (recurrent miscarriage, stillbirth, preeclampsia, intrauterine growth restriction, and placental abruption) has been reported. The mechanism by which PZ deficiency leads to adverse pregnancy outcomes is not clear, but it is multifactorial. It may be attributed to the anti-PZ IgG and IgM autoantibodies, which apparently act independently of classical antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-\u03b22-glycoprotein I antibodies). PZ deficiency has also been reported to be constitutional, and a number of variants in the PROZ (PZ) gene and SERPINA10 (ZPI) gene are linked with specific adverse pregnancy complications. This review summarizes the relationship between adverse pregnancy outcomes and acquired and constitutional PZ\u2013ZPI deficiency, in order to understand whether or not PZ deficiency could be considered as a risk factor for poor pregnancy outcomes.<\/jats:p>","DOI":"10.1530\/rep-13-0072","type":"journal-article","created":{"date-parts":[[2013,5,20]],"date-time":"2013-05-20T22:40:25Z","timestamp":1369089625000},"page":"R73-R80","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":34,"title":["Protein Z, an anticoagulant protein with expanding role in reproductive biology"],"prefix":"10.1093","volume":"146","author":[{"given":"Wassim Y","family":"Almawi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima S","family":"Al-Shaikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohannes K","family":"Melemedjian","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry \u00a0 College of Medicine and Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain 1 \u00a0 University of Arizona, Tucson, Arizona, USA 2 \u00a0 McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pharmacology \u00a0 College of Medicine and Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain 1 \u00a0 University of Arizona, Tucson, Arizona, USA 2 \u00a0 McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Biochemistry \u00a0 College of Medicine and Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain 1 \u00a0 University of Arizona, Tucson, Arizona, USA 2 \u00a0 McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad W","family":"Almawi","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry \u00a0 College of Medicine and Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain 1 \u00a0 University of Arizona, Tucson, Arizona, USA 2 \u00a0 McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pharmacology \u00a0 College of Medicine and Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain 1 \u00a0 University of Arizona, Tucson, Arizona, USA 2 \u00a0 McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Biochemistry \u00a0 College of Medicine and Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain 1 \u00a0 University of Arizona, Tucson, Arizona, USA 2 \u00a0 McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"key":"2026010712264490800_bib1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/S0301-2115(01)00496-1","article-title":"How strong is the association between maternal thrombophilia and adverse pregnancy outcome? 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