Medical College of Wisconsin
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Combined tissue factor pathway inhibitor and thrombomodulin deficiency produces an augmented hypercoagulable state with tissue-specific fibrin deposition. J Thromb Haemost 2008 Jan;6(1):111-7

Date

11/02/2007

Pubmed ID

17973652

Pubmed Central ID

PMC3646640

DOI

10.1111/j.1538-7836.2007.02817.x

Scopus ID

2-s2.0-37548998987 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

BACKGROUND AND OBJECTIVE: Tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) are endothelial-associated anticoagulant proteins thought to control hemostasis in specific vascular beds. Here, we have examined the consequences of TFPI deficiency in the presence of a compounding procoagulant state caused by reduced TM function.

METHODS AND RESULTS: TFPI(+/-)/TM(pro/pro) mice are born at less than expected frequency in either TFPI(+/-)/TM(pro/+) or TM(pro/pro) mothers but are born at near the expected frequency in TM(pro/+) mothers. Adult TFPI(+/-)/TM(pro/pro) mice have elevated thrombin-antithrombin complex and increased thrombus volume in an electrical injury model of venous thrombosis. In striking contrast to mice with single deficiency of TFPI or TM, TFPI(+/-)/TM(pro/pro) mice exhibit augmented fibrin deposition not only in the liver, but also in the cerebral microvasculature.

CONCLUSIONS: TFPI(+/-)/TM(pro/pro) mice exhibit partial intrauterine lethality when carried by mothers with an underlying prothrombotic state, providing the first experimental evidence in an animal model that TFPI-dependent control of hemostasis in the vascular bed of the placenta fulfills a critical role for successful pregnancy outcome. In addition to the placenta, partial TFPI deficiency interacts with decreased TM function in an organ selective manner to produce fibrin deposition in other specific vascular beds, the liver and brain.

Author List

Maroney SA, Cooley BC, Sood R, Weiler H, Mast AE

Author

Rashmi Sood PhD Associate Professor in the Pathology department at Medical College of Wisconsin




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

Animals
Cerebrovascular Circulation
Female
Fibrin
Genotype
Lipoproteins
Liver
Mice
Microcirculation
Organ Specificity
Placenta
Pregnancy
Pregnancy Outcome
Thrombomodulin
Thrombophilia