Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway

Hassan, Hamisa Jane; Leonardi, Antonio; Chelucci, Cristiana; Mattia, Gianfranco; Macioce, Giampiero; Guerriero, Raffaella; Russo, Giovanni; Pm, Mannucci; Peschle, Cesare

doi:10.1182/blood.v76.6.1158.1158

Cited by 52 publications

(24 citation statements)

References 35 publications

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“…Regulation of vitamin K-dependent proteins may be unique. Karpatkin et al (40,41) documented expression of fetal hepatic mRNA for rabbit prothrombin equal to or greater than expression in adult liver while plasma concentrations of prothrombin remained low, similar to our findings for PS and our perinatal results for PC as well as the FX results of Hassan et al (39). The discordance between relative abundance of mRNA for vitamin K-dependent proteins and plasma concentrations supports that regulation is not at the level of gene transcription.…”

Section: Discussionsupporting

confidence: 90%

“…Employing a methodology termed differential display reverse transcriptase-PCR, it has been shown that, in contrast to postnatal hepatic protein synthesis, approximately 99% of hepatic genes expressed during fetal development are not transcriptionally regulated, but most likely controlled at the level of translation (38). Hassan et al (39) demonstrated that by five weeks of gestation mRNA and intracellular proteins for coagulation factors VII, VIII, IX, X, fibrinogen, PC, and AT could be detected in hepatic cells of human embryos. Between 5 and 10 wk of fetal development, most coagulation mRNA increased from 30% to 50% of the normal adult level (39).…”

Section: Discussionmentioning

confidence: 99%

“…Hassan et al (39) demonstrated that by five weeks of gestation mRNA and intracellular proteins for coagulation factors VII, VIII, IX, X, fibrinogen, PC, and AT could be detected in hepatic cells of human embryos. Between 5 and 10 wk of fetal development, most coagulation mRNA increased from 30% to 50% of the normal adult level (39). In this study, mRNA abundance for FX was equal to abundance in adult liver during the first trimester of gestation; intracellular concentration of FX in the hepatocyte was greater than that found in adult livers at this same time.…”

Section: Discussionmentioning

confidence: 99%

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Development of Coagulation Regulatory Proteins in the Fetal and Neonatal Lamb

et al. 2002

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To investigate the development of coagulation regulatory proteins-protein C (PC), protein S (PS), and antithrombin (AT)-in relationship to the procoagulant protein factor X (FX), a chronically catheterized fetal ovine model was used. Infusion and sampling catheters were placed into pregnant ewes and their fetuses and maintained from mid-gestation. From a total of 110 fetuses, 17 lambs, and 63 ewes that were studied on one to 15 occasions, 212 fetal, 88 neonatal, and 157 maternal samples were obtained. Liver tissue was obtained from 31 fetuses and 15 ewes. Plasma levels of all proteins studied were higher in the ewe than in the fetus (p < 0.0001). Plasma levels of FX, PC, and PS achieved neonatal levels by mid-gestation with mild but significant decreases during mid- and late gestation. Fetal and early neonatal plasma concentrations of these vitamin K-dependent proteins fit a model with both quadratic (p < 0.01) and linear (p < 0.01) components. The discrepant levels in mRNA relative to plasma concentration were consistent with regulatory control beyond the level of transcription. In contrast, a simple linear increase in plasma protein levels was determined for the vitamin K-independent coagulation regulatory protein, AT (p for quadratic component > 0.05). This study suggests that fetal regulation of coagulation proteins follows characteristic patterns relative to the vitamin K dependence of the protein rather than its role as a procoagulant versus regulatory protein.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Development of Coagulation Regulatory Proteins in the Fetal and Neonatal Lamb

et al. 2002

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“…In the fetus the levels of factor IX mRNA and protein have been documented to be <10% that of the adult level up to 20 weeks gestation (Hassan et al, 1990). A similar pattern of expression has been documented in mice, where the levels of factor IX remain very low until day 17 post coitus and then abruptly increase in the final 4 d of gestation (Yao et al, 1991).…”

Section: Discussionmentioning

confidence: 63%

Androgen effects on factor IX expression: in‐vitro and in‐vivo studies in mice

et al. 1998

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Summary.A role for steroid hormones has been proposed for the post-pubertal factor IX increment of ϳ25% seen in both normal males and females, as well as in the postpubertal phenotypic recovery seen in haemophilia B Leyden. We have evaluated androgen receptor binding to the factor IX promoter and have assessed transcriptional activation of the factor IX gene in hepatocytes through transient transfection studies and through expression of factor IX in a murine model of androgen insensitivity. Whereas transfection of the androgen receptor alone did not activate expression from the factor IX promoter, co-transfection with the CCAAT enhancer binding protein resulted in a synergistic 17-fold enhancement of transcriptional activity. Using liver nuclear extracts and recombinant androgen receptor protein we have confirmed binding of this protein to the factor IX proximal promoter and disruption of binding with a mutation at nucleotide ¹26. Finally, studies in normal and testicular feminized male mice showed different developmental patterns of factor IX expression. In normal mice, expression recapitulates that seen in humans, with early post-natal levels being ϳ50% of the adult values and with a post-pubertal increment of ϳ25%. In contrast, testicular feminized animals did not show a significant post-pubertal increment of factor IX. These studies provide further support for the role of androgen receptor binding to the factor IX promoter in regulating the developmental expression of factor IX.

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“…2 Studies in humans and animals clearly indicate that coagulation factors in newborns are qualitatively similar, in terms of molecular weights and degree of glycosylation, to those in adults. 3,4 Therefore, the major diversity is likely to be quantitative, with plasma levels of many coagulation factors being different to those found in adults, throughout the pediatric age. 5 Within this perspective, a deep comprehension of developmental hemostasis is essential, in that it would provide the basis for the most appropriate evaluation of hemostatic disorders in pediatric patients.…”

mentioning

confidence: 99%

Coagulation Testing in Pediatric Patients: The Young Are Not Just Miniature Adults

Lippi

Franchini

Montagnana

et al. 2007

Semin Thromb Hemost

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During the past few decades, great progress has been made toward a better understanding of the development of the hemostatic system. It is now clear that the physiology of hemostasis in pediatric patients differs widely from that in adults, supporting the hypothesis that children might have natural protective mechanisms that justify such variations. However, the correct interpretation of hemostasis test results in young patients, along with a deep understanding of the normal postnatal development in the human coagulation system, are essential prerequisites to the proper investigation of thrombotic and hemorrhagic problems in pediatric patients. Because the hemostatic system is not fully mature by 3 to 6 months of age, it is important to recognize that interpretation of laboratory data in pediatric patients must be accompanied by appropriate age-dependent reference ranges, which should also be specific for the testing system used, to prevent misclassification of children as having defects of factors and inhibitors of the coagulation system.

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Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway

Cited by 52 publications

References 35 publications

Development of Coagulation Regulatory Proteins in the Fetal and Neonatal Lamb

Development of Coagulation Regulatory Proteins in the Fetal and Neonatal Lamb

Androgen effects on factor IX expression: in‐vitro and in‐vivo studies in mice

Coagulation Testing in Pediatric Patients: The Young Are Not Just Miniature Adults

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