The Experts below are selected from a list of 2310 Experts worldwide ranked by ideXlab platform
George J. Broze - One of the best experts on this subject based on the ideXlab platform.
-
Contribution of Protein Z and Protein Z-dependent protease inhibitor in generaliZed ShwartZman reaction.
Critical Care Medicine, 2013Co-Authors: Antje Butschkau, George J. Broze, Philipp Nagel, Eberhard Grambow, Dietmar Zechner, Brigitte VollmarAbstract:OBJECTIVE: Sepsis, a leading cause of mortality in critically ill patients, is closely linked to the excessive activation of coagulation and inflammation. Protein Z, a cofactor for the Protein Z-dependent protease inhibitor, enhances the inhibition of coagulation factor Xa, and Protein Z-dependent protease inhibitor inhibits factor XIa in a Protein Z-independent fashion. The functions of Protein Z and Protein Z-dependent protease inhibitor in the inflammatory and coagulant responses to septic illness have not been evaluated. DESIGN: For induction of generaliZed ShwartZman reaction, dorsal skinfold chamber-equipped mice were challenged twice with lipopolysaccharide (0.05 mg/kg on day -1 and 5 mg/kg body weight 24 hr later). Time-matched control animals received equal volumes of saline. SETTING: University research laboratory. SUBJECTS, INTERVENTIONS, AND MEASUREMENTS: Using intravital fluorescence microscopy in Protein Z-dependent protease inhibitor deficient (ZPI) and Protein Z deficient (PZ) mice, as well as their wild-type littermates (ZPI, PZ), kinetics of light/dye-induced thrombus formation and microhemodynamics were assessed in randomly chosen venules. Plasma concentrations of chemokine (C-X-C motif) ligand 1, interleukin-6, and interleukin-10 were measured. Liver and lung were harvested for quantitative analysis of leukocytic tissue infiltration and thrombus formation. MAIN RESULTS: After induction of generaliZed ShwartZman reaction, all mice showed significant impairment of microhemodynamics, including blood flow velocity, volumetric blood flow, and functional capillary density, as well as leukocytopenia and thrombocytopenia. Thrombus formation time was markedly prolonged after induction of generaliZed ShwartZman reaction in all mice, except of ZPI mice, which also had a significantly higher fraction of occluded vessels in liver sections. PZ mice developed the highest concentrations of interleukin-6 and interleukin-10 in response to generaliZed ShwartZman reaction and showed greater leukocytic tissue infiltration than their wild-type littermates. CONCLUSIONS: In this murine model of generaliZed ShwartZman reaction, Protein Z-dependent protease inhibitor deficiency enhanced the thrombotic response to vascular injury, whereas Protein Z deficiency increased inflammatory response.
-
structural basis for catalytic activation of Protein Z dependent protease inhibitor Zpi by Protein Z
Blood, 2012Co-Authors: Xin Huang, George J. Broze, Yizheng Tu, Jeffrey Gatti, Aiwu Zhou, Steven T OlsonAbstract:The anticoagulant serpin, Protein Z-dependent protease inhibitor (ZPI), is catalytically activated by its cofactor, Protein Z (PZ), to regulate the function of blood coagulation factor Xa on membrane surfaces. The X-ray structure of the ZPI-PZ complex has shown that PZ binds to a unique site on ZPI centered on helix G. In the present study, we show by Ala-scanning mutagenesis of the ZPI-binding interface, together with native PAGE and kinetic analyses of PZ binding to ZPI, that Tyr240 and Asp293 of ZPI are crucial hot spots for PZ binding. Complementary studies with Protein Z–Protein C chimeras show the importance of both pseudocatalytic and EGF2 domains of PZ for the critical ZPI interactions. To understand how PZ acts catalytically, we analyZed the interaction of reactive loop–cleaved ZPI (cZPI) with PZ and determined the cZPI X-ray structure. The cZPI structure revealed changes in helices A and G of the PZ-binding site relative to native ZPI that rationaliZed an observed 6-fold loss in PZ affinity and PZ catalytic action. These findings identify the key determinants of catalytic activation of ZPI by PZ and suggest novel strategies for ameliorating hemophilic states through drugs that disrupt the ZPI-PZ interaction.
-
heparin is a major activator of the anticoagulant serpin Protein Z dependent protease inhibitor
Journal of Biological Chemistry, 2011Co-Authors: Xin Huang, George J. Broze, Alireza R Rezaie, Steven T OlsonAbstract:Protein Z-dependent protease inhibitor (ZPI) is a recently identified member of the serpin superfamily that functions as a cofactor-dependent regulator of blood coagulation factors Xa and XIa. Here we provide evidence that, in addition to the established cofactors, Protein Z, lipid, and calcium, heparin is an important cofactor of ZPI anticoagulant function. Heparin produced 20–100-fold accelerations of ZPI reactions with factor Xa and factor XIa to yield second order rate constants approaching the physiologically significant diffusion limit (ka = 106 to 107 m−1 s−1). The dependence of heparin accelerating effects on heparin concentration was bell-shaped for ZPI reactions with both factors Xa and XIa, consistent with a template-bridging mechanism of heparin rate enhancement. Maximal accelerations of ZPI-factor Xa reactions required calcium, which augmented the heparin acceleration by relieving Gla domain inhibition as previously shown for heparin bridging of the antithrombin-factor Xa reaction. Heparin acceleration of both ZPI-protease reactions was optimal at heparin concentrations and heparin chain lengths comparable with those that produce physiologically significant rate enhancements of other serpin-protease reactions. Protein Z binding to ZPI minimally affected heparin rate enhancements, indicating that heparin binds to a distinct site on ZPI and activates ZPI in its physiologically relevant complex with Protein Z. Taken together, these results suggest that whereas Protein Z, lipid, and calcium cofactors promote ZPI inhibition of membrane-associated factor Xa, heparin activates ZPI to inhibit free factor Xa as well as factor XIa and therefore may play a physiologically and pharmacologically important role in ZPI anticoagulant function.
-
a meta analysis of potential risks of low levels of Protein Z for diseases related to vascular thrombosis
Thrombosis and Haemostasis, 2010Co-Authors: Francesco Sofi, Francesca Cesari, Gian Franco Gensini, Rosanna Abbate, George J. Broze, Sandra FediAbstract:The relationship between Protein Z levels and thrombosis is controversial. We performed a systematic review and meta-analysis of the available studies to assess the association between Protein Z and vascular thrombotic diseases. We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library, bibliographies of retrieved articles and abstracts of congresses up to October, 2009. Studies were included if they analysed Protein Z levels in patients with vascular thrombotic diseases. After the review process, 28 case-control studies (33 patient cohorts), including 4,218 patients with thrombotic diseases and 4,778 controls, were selected for analysis. The overall analysis using a random-effects model showed that low Protein Z levels were associated with an increased risk of thrombosis (odds ratio [OR] 2.90, 95% confidence interval [CI] 2.05–4.12; p<0.00001). On subgroup analysis, a significant association was found between low Protein Z levels and arterial vascular diseases (OR 2.67, 95%CI 1.60–4.48; p=0.0002), pregnancy complications (OR 4.17, 95%CI 2.31–7.52; p<0.00001), and venous thromboembolic diseases (OR 2.18, 95%CI 1.19–4.00; p=0.01). The results of this meta-analysis are consistent with a role for Protein Z deficiency in thrombotic diseases, including arterial thrombosis, pregnancy complications and venous thromboembolism.
-
A meta-analysis of potential risks of low levels of Protein Z for diseases related to vascular thrombosis.
Thrombosis and Haemostasis, 2010Co-Authors: Francesco Sofi, Francesca Cesari, Gian Franco Gensini, Rosanna Abbate, George J. Broze, Sandra FediAbstract:The relationship between Protein Z levels and thrombosis is controversial. We performed a systematic review and meta-analysis of the available studies to assess the association between Protein Z and vascular thrombotic diseases. We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library, bibliographies of retrieved articles and abstracts of congresses up to October, 2009. Studies were included if they analysed Protein Z levels in patients with vascular thrombotic diseases. After the review process, 28 case-control studies (33 patient cohorts), including 4,218 patients with thrombotic diseases and 4,778 controls, were selected for analysis. The overall analysis using a random-effects model showed that low Protein Z levels were associated with an increased risk of thrombosis (odds ratio [OR] 2.90, 95% confidence interval [CI] 2.05–4.12; p
Marc Vasse - One of the best experts on this subject based on the ideXlab platform.
-
Protein Z, a Protein seeking a pathology
Thrombosis and Haemostasis, 2020Co-Authors: Marc VasseAbstract:SummaryProtein Z (PZ) is a vitamin K-dependent factor identified in human plasma in 1984 characteriZed by an homology with other vitamin K-dependent factors (factor VII, IX, X, Protein C). In contrast to these factors, PZ does not possess any enZymatic activity but is involved as a cofactor in the down-regulation of coagulation by forming a complex with the Protein Z-dependent protease inhibitor (ZPI). ZPI inhibits the activated factor X (FXa) on phospholipid surface. In mice, the disruption of PZ gene is asymptomatic, but the association with the factor V Leiden mutation leads to a quasi complete mortality during the neonatal period with microvascular thrombosis. In humans, PZ is characteriZed by an unusual wide distribution in plasma, and a major decrease induced by warfarin. Isolated PZ deficiency does not seem to constitute a risk for venous thrombosis, but a severe PZ deficiency could increase the risk of well recogniZed venous thrombotic risk factors such as factor V Leiden, G20210A mutation or hyperhomocysteinemia. Unexpectedly, a relationship between PZ deficiency and ischemic arterial diseases such as stroke, acute coronary syndromes or peripheral arterial disease was described but not confirmed by all studies. PZ deficiency could be also a risk factor for early fetal losses, and increases the arterial risk in antiphospholipid syndrome. This review analyZes the different studies so far published and discusses the various results obtained in order to understand whether or not Protein Z deficiency could be considered as an arterial ischemic risk factor.
-
The Protein Z/Protein Z-dependent protease inhibitor complex. Systemic or local control of coagulation?
Hamostaseologie, 2011Co-Authors: Marc VasseAbstract:: Protein Z (PZ) is a vitamin K-dependent factor identified in human plasma in 1984 but it has no enZymatic activity. It is a cofactor of a serpin, the Protein Z-dependent protease inhibitor (ZPI), and the complex PZ/ZPI inhibits activated factor X on phospholipid surfaces. In mice, the disruption of PZ or ZPI gene is asymptomatic, but enhances the thrombotic phenotype and mortality of other thrombotic risk factors. Most of the clinical studies focused on PZ. Despite conflicting results, a recent meta-analysis indicated that PZ deficiency could be a risk for venous and arterial thrombosis and early fetal loss. However, these conclusions are drawn from case-control studies of small siZe, constituting an important limitation. Recently, it was shown that PZ and/or ZPI are synthesised by normal kidney and different cancer cells, suggesting that the complex PZ/ZPI could play a role in inhibiting the tissue deposition of fibrin. The physiopathological consequences of these observations remain to be established. At this time, the measurement of plasma PZ and ZPI or analysis of their gene polymorphisms should not be performed routinely for the exploration of thrombophilia.
-
Human endothelial cells synthesiZe Protein Z, but not the Protein Z dependent inhibitor.
Thrombosis and Haemostasis, 2006Co-Authors: Marc Vasse, Christophe Denoyelle, Cécile Corbière, Pierre-yves Litzler, Elisabeth Legrand, Jean-pierre VannierAbstract:Protein Z (PZ) is a vitamin K-dependent Protein isolated from human plasma, and acts as a cofactor for a serpin, called Protein Z-dependent protease inhibitor (ZPI).A prothrombotic phenotype has been reported in PZ deficient mice, and PZ deficiencies have been observed in patients with arterial thrombotic events. PZ was immunologically detected in the endothelium of atherosclerotic arteries,suggesting that endothelial cells could be involved in the production of PZ.In this study we analyZed the synthesis and release of PZ and ZPI by human umbilical vein endothelial cells (HUVEC), representative of the macrovasculature, and by HMEC-1, a microvascular endothelial cell line. PZ was quantified by a specific ELISA in the supernatant and in the lysates of both cellular types. Western blotting of the supernatants showed the presence of a band of 62 kDa,identical to PZ synthesiZed by the hepatoma cell line HepG2. mRNA of PZ was also detected in each cellular type. PZ biosynthesis was unaffected by inflammatory cytokines in HUVEC, whereas a slight decrease of mRNA and PZ antigen (53.5 ± 14.5% of Protein synthesis as compared to the control, p < 0.01) and a modest increase (126 ± 8.5 % as compared to the control, p< 0.05) were induced respectively byTumor Necrosis Factor (TNF)-alpha (25 ng/ml) and oncostatin M (5 ng/ml) in HMEC-1. Immunological studies showed the presence of PZ near the nucleus and a possible expression of PZ at the membrane.In addition,PZ was present in the endothelial cells of both normal arterial and venous vessel sections. In contrast, neither ZPI nor its mRNA was detected in endothelial cells.
-
High frequency of Protein Z deficiency in patients with unexplained early fetal loss.
Blood, 2002Co-Authors: J C Gris, Marc Vasse, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Caroline Pinçon, P MaresAbstract: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 (
-
high frequency of Protein Z deficiency in patients with unexplained early fetal loss
Blood, 2002Co-Authors: J C Gris, Marc Vasse, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Caroline Pinçon, P MaresAbstract: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.
P Mares - One of the best experts on this subject based on the ideXlab platform.
-
anti Protein Z antibodies in women with pathologic pregnancies
Blood, 2003Co-Authors: J C Gris, Cecile Amadio, Eric Mercier, Geraldine Lavignelissalde, Herve Dechaud, Mederic Hoffet, I Quere, Jean Amiral, M Dauzat, P MaresAbstract:Protein Z deficiencies have recently been described in women with unexplained early fetal loss. Using a new, specifically elaborated, commercially available enZyme-linked immunosorbent assay (ELISA), we performed a case-control study on anti–Protein Z immunoglobulin G (IgG) and IgM antibodies in 191 nonthrombotic, nonthrombophilic women with consecutive pathologic pregnancies. Levels of anti–Protein Z antibodies were categoriZed in 3 strata (percentiles 1 through 74, 75 through 97, 98 through 100 among controls). The 2 upper levels of IgG and IgM anti–Protein Z antibodies were associated with the risk of unexplained recurrent embryo loss or fetal death independently from habitual antiphospholipid/anticofactor antibodies, and a dose-effect relationship between antibody levels and the clinical risks was evidenced. In women, enhanced immune-complex formation with Protein Z may play a role in unexplained embryo losses and, from the 10th week of gestation, may favor hypercoagulability in the maternal placenta side.
-
Anti–Protein Z antibodies in women with pathologic pregnancies
Blood, 2003Co-Authors: J C Gris, Cecile Amadio, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Jean Amiral, M Dauzat, Géraldine Lavigne-lissalde, P MaresAbstract:Protein Z deficiencies have recently been described in women with unexplained early fetal loss. Using a new, specifically elaborated, commercially available enZyme-linked immunosorbent assay (ELISA), we performed a case-control study on anti–Protein Z immunoglobulin G (IgG) and IgM antibodies in 191 nonthrombotic, nonthrombophilic women with consecutive pathologic pregnancies. Levels of anti–Protein Z antibodies were categoriZed in 3 strata (percentiles 1 through 74, 75 through 97, 98 through 100 among controls). The 2 upper levels of IgG and IgM anti–Protein Z antibodies were associated with the risk of unexplained recurrent embryo loss or fetal death independently from habitual antiphospholipid/anticofactor antibodies, and a dose-effect relationship between antibody levels and the clinical risks was evidenced. In women, enhanced immune-complex formation with Protein Z may play a role in unexplained embryo losses and, from the 10th week of gestation, may favor hypercoagulability in the maternal placenta side.
-
High frequency of Protein Z deficiency in patients with unexplained early fetal loss.
Blood, 2002Co-Authors: J C Gris, Marc Vasse, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Caroline Pinçon, P MaresAbstract: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 (
Mederic Hoffet - One of the best experts on this subject based on the ideXlab platform.
-
anti Protein Z antibodies in women with pathologic pregnancies
Blood, 2003Co-Authors: J C Gris, Cecile Amadio, Eric Mercier, Geraldine Lavignelissalde, Herve Dechaud, Mederic Hoffet, I Quere, Jean Amiral, M Dauzat, P MaresAbstract:Protein Z deficiencies have recently been described in women with unexplained early fetal loss. Using a new, specifically elaborated, commercially available enZyme-linked immunosorbent assay (ELISA), we performed a case-control study on anti–Protein Z immunoglobulin G (IgG) and IgM antibodies in 191 nonthrombotic, nonthrombophilic women with consecutive pathologic pregnancies. Levels of anti–Protein Z antibodies were categoriZed in 3 strata (percentiles 1 through 74, 75 through 97, 98 through 100 among controls). The 2 upper levels of IgG and IgM anti–Protein Z antibodies were associated with the risk of unexplained recurrent embryo loss or fetal death independently from habitual antiphospholipid/anticofactor antibodies, and a dose-effect relationship between antibody levels and the clinical risks was evidenced. In women, enhanced immune-complex formation with Protein Z may play a role in unexplained embryo losses and, from the 10th week of gestation, may favor hypercoagulability in the maternal placenta side.
-
Anti–Protein Z antibodies in women with pathologic pregnancies
Blood, 2003Co-Authors: J C Gris, Cecile Amadio, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Jean Amiral, M Dauzat, Géraldine Lavigne-lissalde, P MaresAbstract:Protein Z deficiencies have recently been described in women with unexplained early fetal loss. Using a new, specifically elaborated, commercially available enZyme-linked immunosorbent assay (ELISA), we performed a case-control study on anti–Protein Z immunoglobulin G (IgG) and IgM antibodies in 191 nonthrombotic, nonthrombophilic women with consecutive pathologic pregnancies. Levels of anti–Protein Z antibodies were categoriZed in 3 strata (percentiles 1 through 74, 75 through 97, 98 through 100 among controls). The 2 upper levels of IgG and IgM anti–Protein Z antibodies were associated with the risk of unexplained recurrent embryo loss or fetal death independently from habitual antiphospholipid/anticofactor antibodies, and a dose-effect relationship between antibody levels and the clinical risks was evidenced. In women, enhanced immune-complex formation with Protein Z may play a role in unexplained embryo losses and, from the 10th week of gestation, may favor hypercoagulability in the maternal placenta side.
-
High frequency of Protein Z deficiency in patients with unexplained early fetal loss.
Blood, 2002Co-Authors: J C Gris, Marc Vasse, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Caroline Pinçon, P MaresAbstract: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 (
-
high frequency of Protein Z deficiency in patients with unexplained early fetal loss
Blood, 2002Co-Authors: J C Gris, Marc Vasse, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Caroline Pinçon, P MaresAbstract: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.
Eric Mercier - One of the best experts on this subject based on the ideXlab platform.
-
anti Protein Z antibodies in women with pathologic pregnancies
Blood, 2003Co-Authors: J C Gris, Cecile Amadio, Eric Mercier, Geraldine Lavignelissalde, Herve Dechaud, Mederic Hoffet, I Quere, Jean Amiral, M Dauzat, P MaresAbstract:Protein Z deficiencies have recently been described in women with unexplained early fetal loss. Using a new, specifically elaborated, commercially available enZyme-linked immunosorbent assay (ELISA), we performed a case-control study on anti–Protein Z immunoglobulin G (IgG) and IgM antibodies in 191 nonthrombotic, nonthrombophilic women with consecutive pathologic pregnancies. Levels of anti–Protein Z antibodies were categoriZed in 3 strata (percentiles 1 through 74, 75 through 97, 98 through 100 among controls). The 2 upper levels of IgG and IgM anti–Protein Z antibodies were associated with the risk of unexplained recurrent embryo loss or fetal death independently from habitual antiphospholipid/anticofactor antibodies, and a dose-effect relationship between antibody levels and the clinical risks was evidenced. In women, enhanced immune-complex formation with Protein Z may play a role in unexplained embryo losses and, from the 10th week of gestation, may favor hypercoagulability in the maternal placenta side.
-
Anti–Protein Z antibodies in women with pathologic pregnancies
Blood, 2003Co-Authors: J C Gris, Cecile Amadio, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Jean Amiral, M Dauzat, Géraldine Lavigne-lissalde, P MaresAbstract:Protein Z deficiencies have recently been described in women with unexplained early fetal loss. Using a new, specifically elaborated, commercially available enZyme-linked immunosorbent assay (ELISA), we performed a case-control study on anti–Protein Z immunoglobulin G (IgG) and IgM antibodies in 191 nonthrombotic, nonthrombophilic women with consecutive pathologic pregnancies. Levels of anti–Protein Z antibodies were categoriZed in 3 strata (percentiles 1 through 74, 75 through 97, 98 through 100 among controls). The 2 upper levels of IgG and IgM anti–Protein Z antibodies were associated with the risk of unexplained recurrent embryo loss or fetal death independently from habitual antiphospholipid/anticofactor antibodies, and a dose-effect relationship between antibody levels and the clinical risks was evidenced. In women, enhanced immune-complex formation with Protein Z may play a role in unexplained embryo losses and, from the 10th week of gestation, may favor hypercoagulability in the maternal placenta side.
-
High frequency of Protein Z deficiency in patients with unexplained early fetal loss.
Blood, 2002Co-Authors: J C Gris, Marc Vasse, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Caroline Pinçon, P MaresAbstract: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 (
-
high frequency of Protein Z deficiency in patients with unexplained early fetal loss
Blood, 2002Co-Authors: J C Gris, Marc Vasse, Eric Mercier, Herve Dechaud, Mederic Hoffet, I Quere, Caroline Pinçon, P MaresAbstract: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.
