Showing papers on "Protein Z published in 2014"

Changes in Plasma Levels of Natural Anticoagulants in Disseminated Intravascular Coagulation: High Prognostic Value of Antithrombin and Protein C in Patients with Underlying Sepsis or Severe Infection

Abstract: Results: Antithrombin and protein C showed higher areas under the ROC curve than protein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan–Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hematologic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high. Conclusions: Decreased plasma anticoagulant levels reflect florid consumption of the physiologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/ severe infection.

Is There a Role for MDR1, EPHX1 and Protein Z Gene Variants in Modulation of Warfarin Dosage? A Study on a Cohort of the Egyptian Population

Abstract: There is considerable inter-individual variability in warfarin dosages necessary to achieve target therapeutic anticoagulation. Polymorphisms in genes, which master warfarin pharmacokinetics and pharmacodynamics, might influence warfarin dose variation. Genes encoding drug transporters, such as human multidrug resistance (MDR1), as well as epoxide hydrolase 1 (EPHX1), which is a putative subunit of the vitamin K epoxide reductase, and Protein Z (PZ), which is a vitamin K-dependent plasma glycoprotein, are among those candidate genes. The purpose of this study was to investigate the contribution of MDR1 C3435T, EPHX1 H139R and PZ A-13G gene polymorphisms in warfarin dose variation in a cohort of the Egyptian population. Eighty-four patients whose international normalized ratio (INR) was in the range of 2–3, 41 males and 43 females, with a mean (±SD) age of 40.9 (13.3) years were recruited into this study. MDR1 C3435T, EPHX1 H139R and PZ A-13G gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Primarily, linear regression analysis, including the variables age, gender, MDR1 C3435T, EPHX1 H139R and combined MDR1 C3435T, EPHX1 H139R and PZ A-13G genotypes, was used to assess the effective factors for warfarin maintenance dose. Secondly, the previously examined cytochrome P450 (CYP) 2C9 A1075C and vitamin K epoxide reductase complex subunit 1 (VKORC1) C1173T were added to the regression analysis. Warfarin dose/week was not influenced by each of the MDR1 C3435T, EPHX1 H139R, and PZ A-13G gene polymorphisms when examined separately. However, when these single nucleotide polymorphisms (SNPs) were combined, MDR1 TT/EPHX1 RH,RR/PZ AA subjects showed statistically significant increase in warfarin dose/week when compared with MDR1 CC/EPHX1 RH,RR/PZ AA subjects [median (25th–75th percentiles): 49.0 (42.0–59.5) vs. 35.0 (24.5–42.0) mg/week, respectively] (p = 0.014). In contrast, in the presence of wild-type EPHX1 HH, there was a decrease in warfarin dose/week in MDR1 TT subjects when compared with CT and CC subjects [median (25th–75th percentiles): 22.0 (17.5–30.6), 42.0 (35.0–49.0) and 42.0 (28.0–54.3) mg/week, respectively] (p = 0.005 and 0.030, respectively). Age had a significant contribution (p = 0.048) to the overall variability in warfarin dose. Calculated weekly dose = 52.928 − (0.289 × age) + (9.709 × combined genotype). The multivariate linear regression equation of warfarin maintenance dose accounted for about 8 % of variation in dose (R 2 = 0.079), age accounted for 5 % of variation, while combined genotypes added the extra 3 %. However, the new regression equation accounted for 20.9 % of variation in dose. Age accounted for 5 %, while VKORC1 C1173T accounted for an extra 13 % of variation and MDR1 C3435T accounted for the remaining 3 % of variation. Calculated dose = 64.909 − (0.282 × age) − (13.390 × VKORC1) − (7.164 × MDR1). Correlation analysis showed a close and significant relationship between the calculated and actual warfarin dose (r = 0.457; p < 0.0005). Warfarin dose/week was significantly influenced by the combined MDR1 C3435T and EPHX1 H139R gene polymorphism since no polymorphism of PZ A-13G SNP was detected in our studied Egyptian population. Future studies with larger sample size will be needed to confirm our findings before definitive conclusions can be made.

Protein Z/protein Z-dependent protease inhibitor system in loco in human gastric cancer.

Abstract: In gastric cancer, hemostatic system components contribute to cancer progression, as activation of factor X (FX) was observed. The protein Z (PZ)/protein Z-dependent protease inhibitor (ZPI) complex inhibits factor Xa proteolytic activity. The purpose of this study was to determine the distribution of ZPI and PZ in relation to FX, and prothrombin fragment (F1 + 2), a standard marker for blood coagulation activation, in human gastric cancer tissue. ABC procedures and a double staining method employed polyclonal antibodies against PZ, FX, and F1 + 2 and a monoclonal antibody against ZPI. In situ hybridization (ISH) methods employed biotin-labeled 25-nucleotide single-stranded DNA probes directed to either PZ or ZPI mRNAs. FX and components of PZ/ZPI coagulation inhibitory system were observed in cancer cells. F1 + 2 was observed in gastric cancer cells as well. Double staining studies revealed FX/PZ, FX/ZPI, and PZ/ZPI co-localization on gastric cancer cells. ISH studies demonstrated the presence of PZ mRNA and ZPI mRNA in gastric cancer cells indicating induced synthesis of these proteins. The co-localization of PZ/ZPI and FX in gastric cancer cells indicates in loco that these proteins may play a role in anticoagulant events at the tumor tissue.

Plasma Protein Z Levels in Healthy and High-Risk Newborn Infants

Abstract: Objectives: To evaluate plasma protein Z (PZ) levels in healthy and high-risk newborn infants Background: Protein Z (PZ) is a vitamin K-dependent plasma protein , As is the case with other coagulation proteins and inhibitors, protein Z is consumed during disseminated intravascular coagulation (DIC), Functionally protein Z has been shown to be a direct requirement for the binding of thrombin to endothelial phospholipids , Protein Z also serves as a cofactor for the inhibition of coagulation factor Xa by a plasma serein called protein Z-dependent protease inhibitor (ZPI), The inhibitory function is exerted by the Protein Z- dependent protease inhibitor (ZPI), which circulates in the human plasma in a complex with PZ , The physiological function of protein Z is still rather ill-defined and may play role in high risk newborn Methods: This study was conducted on 85 newborns divided in 4 groups ,(group I newborns affected by respiratory distress syndrome (RDS) , group II newborns from mothers with pre-eclampsia, group III newborns small for gestational age (SGA) and group IV healthy term and preterm newborns normal for gestational age Newborns with sepsis, congenital malformation or hemorrhagic disorders were excluded, Plasma PZ levels was measured Results: In the neonates of the study groups, protein z level was significant lower in patient group than control group, in group I ( 079 ±032), group II (070± 030), group III (078 ±032) and group IV (144 ±043) (p value<0001) Conclusion: PZ deficiency occurs in newborns affected by severe RDS, in newborns from preeclampsic mothers and in SGA newborns, probably owing to activated coagulation in the first two conditions and to reduced PZ synthesis in the last one