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Role of fibrinogen- and platelet-mediated hemostasis in mouse embryogenesis and reproduction. J Thromb Haemost 2004 Aug;2(8):1368-79

Date

08/12/2004

Pubmed ID

15304043

DOI

10.1111/j.1538-7836.2004.00788.x

Scopus ID

2-s2.0-2942624713   30 Citations

Abstract

Studies of mice with genetic deficits in specific coagulation factors have shown that many, but not all, components of the hemostatic system serve an essential role in mouse embryogenesis and pregnancy. Although the developmental failures observed in these mice are typically associated with severe hemorrhage, it is uncertain whether the role of coagulation factors in embryogenesis and reproduction is specifically tied to their function in thrombus formation and prevention of blood loss (i.e. hemostasis). Here, we show (i) that a complete loss of fibrinogen- and platelet-dependent hemostatic capacity does not reproduce the developmental defects occurring in mice with either deficits in thrombin generation or unfettered thrombin consumption; (ii) that the essential role of fibrinogen in the maintenance of pregnancy does not involve interaction with platelets; and (iii) that the previously described in utero growth retardation of gene-targeted mice lacking NF-E2, a transcription factor critical for megakaryopoieis, is not caused by a loss of platelet-dependent hemostatic function. In addition, we demonstrate (iv) that fibrinogen can confer physiologically relevant hemostatic function in the absence of platelets, but that a complete loss of hemostatic capacity results if a combined absence of these components is genetically imposed. These findings support the notion that the function of coagulation factors for in utero development and pregnancy is mechanistically distinct from their ability to mediate the formation of hemostatic platelet-fibrin(ogen) aggregates.

Author List

Palumbo JS, Zogg M, Talmage KE, Degen JL, Weiler H, Isermann BH

Author

Hartmut Weiler PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate
Animals
Blood Platelets
Collagen
Crosses, Genetic
DNA-Binding Proteins
Embryo, Mammalian
Erythroid-Specific DNA-Binding Factors
Fibrinogen
GTP-Binding Protein alpha Subunits, Gq-G11
Genotype
Hemostasis
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-E2 Transcription Factor
NF-E2 Transcription Factor, p45 Subunit
Placenta
Polymerase Chain Reaction
Reproduction
Time Factors
Transcription Factors
Transgenes
Yolk Sac