Preeclampsia is associated with low concentrations of protein Z

Erez, Offer; Hoppensteadt, Debra; Romero, Roberto; Espinoza, Jimmy; Gonçalves, Luís F.; Nien, Jyh Kae; Kusanovic, Juan Pedro; Fareed, Jawed; Gotsch, Francesca; Pineles, Beth L.; Chaiworapongsa, Tinnakorn

doi:10.1080/14767050701495011

Cited by 35 publications

(39 citation statements)

References 50 publications

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“…[34][35][36] In a previous study, PZ levels in pregnancies with fetal demise were found to be lower than those with healthy fetus. 26 Consistently, our study also support this findings. Because perinatal and maternal mortality is higher in more severe disease, suggested pathogenetic mechanisms for low PZ levels in HELLP syndrome would be expected to be more severe.…”

Section: Discussionsupporting

confidence: 93%

Low Levels of Protein Z Are Associated With HELLP Syndrome and its Severity

Kaygusuz

Fıratlı-Tuğlular

Toptaş

et al. 2010

Clin Appl Thromb Hemost

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Protein Z (PZ) was found to be associated with pregnancy complications. There are no data implying an association between hemolysis (H), elevated liver enzymes (EL), and low platelet counts (LP) (HELLP) syndrome and changes in plasma levels of PZ. The aim of this study is to investigate whether HELLP syndrome is associated with plasma concentrations of PZ. Protein Z levels in 29 women with HELLP syndrome were compared with 29 healthy, nulliparous and 25 normal pregnant women. The median PZ levels in patients with HELLP syndrome were found to be significantly lower than those of pregnant women. No significant difference was found between HELLP and healthy groups. Protein Z levels correlated with platelet counts, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) levels in patients with HELLP syndrome. Median PZ level was higher in partial HELLP than in complete HELLP. We calculated 1330 ng/mL as a cutoff value for PZ level to discriminate HELLP syndrome from normal pregnancy. Low PZ levels are associated with the pathobiology of HELLP syndrome.

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Section: Discussionsupporting

confidence: 93%

Low Levels of Protein Z Are Associated With HELLP Syndrome and its Severity

Kaygusuz

Fıratlı-Tuğlular

Toptaş

et al. 2010

Clin Appl Thromb Hemost

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“…1 Progressive rise of the median PZ level (lg/ml) in the first (n = 15), second (n = 97) and third (n = 66) trimester of pregnancy stable throughout pregnancy and the PZ deficiency could not be explained by gestational age. Erez et al found that the median concentration of PZ was reduced in pre eclampsia but not in women who delivered small for gestational age babies [9]. However, our results clearly show that the PZ levels rise progressively during the three trimesters and that this rise is blunted in patients with adverse pregnancy outcome or an associated pregnancy complication like preeclampsia or diabetes ( Fig.…”

Section: Discussioncontrasting

confidence: 51%

“…However, our results clearly show that the PZ levels rise progressively during the three trimesters and that this rise is blunted in patients with adverse pregnancy outcome or an associated pregnancy complication like preeclampsia or diabetes ( Fig. 1; Tables 3, 4) PZ is suggested to be a physiologic down regulator of blood coagulation and low PZ levels are associated with increased risk of ischemic stroke, particularly in males even in the absence of diabetes [9]. The levels of PZ in diabetic pregnant women has not been studied at all in the past and our results show that the median PZ levels in pregnant women with diabetes were comparatively the lowest amongst the subsets of pregnant subjects but did not reach statistical significance due to the small sample size (n = 18).…”

Section: Discussionmentioning

confidence: 59%

Protein Z levels in pregnant Omani women: correlation with pregnancy outcome

Gowri

Mathew

Gravell

et al. 2011

J Thromb Thrombolysis

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Placental insufficiency resulting in fetal loss has been recognized in women with thrombophilic predisposition. Recent studies indicate that there is a high prevalence of protein Z (PZ) deficiency in patients with unexplained fetal loss. The objective of this study was to measure the PZ levels in pregnant Omani women in the first, second and third trimesters and correlate with the pregnancy outcome. The study enrolled 126 consecutive pregnant women after an informed consent prospectively. PZ was estimated in the first, second and third trimester in 15, 97 and 66 pregnant women respectively and they were followed for pregnancy outcomes including live birth, still birth, spontaneous abortion/induced abortion, maternal complications, fetal complications and health risks/complications in the newborn. The median PZ level (Mean ± SD) in the first, second and third trimester were 0.98 (1.07 ± 0.46), 1.3 (1.36 ± 0.61) and 1.44 (1.43 ± 0.69) (P < 0.05, Student's t-test, between first vs. second and first vs. third trimester). PZ deficiency defined as PZ level below 0.54 μg/ml (below 10th centile in the Omani population) was observed in 4 (4.7%) women, but interestingly all had a normal pregnancy outcome. Amongst the 43 subjects in whom paired PZ estimations were available, reducing PZ levels were observed from baseline values in 8 (33%) with normal pregnancy outcome; 5 (55%), with diabetes; 3 (50%) with hypertension and 2 (50%) with low birth weight respectively (P < 0.05, chi square test). PZ values increased progressively during the three trimesters of pregnancy. However, this increase is blunted in patients with abnormal pregnancy outcome like low birth weight babies or pregnancies associated hypertension or diabetes. Isolated PZ deficiency alone did not result in an abnormal outcome in this cohort of subjects.

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“…While ZPI may inactivate Xa by itself, its binding to PZ increases its activity by 1,000-folds [18,19]. Reduction in PZ levels induces a procoagulant state and is associated with thrombotic diseases, including ischemic stroke, cardiovascular diseases [19], and pregnancy complications [14,20].…”

Section: Introductionmentioning

confidence: 99%

Protein Z polymorphisms associated with vaso-occlusive crisis in young sickle cell disease patients

Mahdi

Abu-Hijleh

et al. 2012

Ann Hematol

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We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) vaso-occlusive crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P=0.03), rs3024719 (P=0.02), rs3024731 (P<0.001), and rs3024735 (P<0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P=0.028) and rs3024735 (P=0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P=0.024), AGAA (P=0.011), and GGTG (P=0.002), and reduced frequency of AGTG haplotype (P=0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (P(c)=0.001) and GGTG (P(c)=0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.

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Preeclampsia is associated with low concentrations of protein Z

Cited by 35 publications

References 50 publications

Low Levels of Protein Z Are Associated With HELLP Syndrome and its Severity

Low Levels of Protein Z Are Associated With HELLP Syndrome and its Severity

Protein Z levels in pregnant Omani women: correlation with pregnancy outcome

Protein Z polymorphisms associated with vaso-occlusive crisis in young sickle cell disease patients

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