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Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia (review)

Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia (review)
Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia (review)
Pre-eclampsia (P-Ec) is a complex multisystem disorder of unknown aetiology reported to occur in about 6% to 8% of all pregnancies throughout the world. This disease is associated with fibrin deposition and occlusive lesions in placental vessels. Pro-thrombin activatable fibrinolysis inhibitor (pro-TAFI) is a relatively recently described glycoprotein that can be converted into its active form (TAFIa) by thrombin, thrombin–thrombomodulin and plasmin. TAFIa potentially inhibits fibrinolysis by removing C-terminal lysine and arginine residues from fibrin. These residues are required for adsorption of tissue-type plasminogen activator (t-PA) and plasminogen to fibrin. Therefore, TAFIa decreases plasmin formation and protects the fibrin clot against lysis. An increased of pro-TAFI/TAFIa levels has been reported in some clinical conditions associated with thrombotic tendency, as type II diabetes mellitus, deep vein thrombosis and symptomatic artery disease. Few studies have investigated pro-TAFI/TAFIa in normal or complicated pregnancy but contrasting results were reported. Understanding the role of pro-TAFI/TAFIa in the pathogenesis of P-Ec can hold great promise for improving P-Ec management. In this context, a large-scale study evaluating plasma TAFI antigen and activity, its synthesis and metabolism in pre-eclamptic women is required. Recently new selective TAFIa inhibitors have been developed. The design of a new therapy to treat and/or prevent P-Ec, based on successful use of TAFIa inhibitors, may have significant clinical ramifications
pro-TAFI, TAFIa, pre-eclampsia
0009-8981
1-6
Dusse, Luci Maria
3f8aa691-06d7-4d37-81d3-12719e292769
Cooper, Alan J.
65dcd1e1-3fcd-46b8-ad5f-f17e0d5b80a5
Lwaleed, Bashir A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Dusse, Luci Maria
3f8aa691-06d7-4d37-81d3-12719e292769
Cooper, Alan J.
65dcd1e1-3fcd-46b8-ad5f-f17e0d5b80a5
Lwaleed, Bashir A.
e7c59131-82ad-4a14-a227-7370e91e3f21

Dusse, Luci Maria, Cooper, Alan J. and Lwaleed, Bashir A. (2007) Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia (review). Clinica Chimica Acta, 378 (1-2), 1-6. (doi:10.1016/j.cca.2006.10.014).

Record type: Article

Abstract

Pre-eclampsia (P-Ec) is a complex multisystem disorder of unknown aetiology reported to occur in about 6% to 8% of all pregnancies throughout the world. This disease is associated with fibrin deposition and occlusive lesions in placental vessels. Pro-thrombin activatable fibrinolysis inhibitor (pro-TAFI) is a relatively recently described glycoprotein that can be converted into its active form (TAFIa) by thrombin, thrombin–thrombomodulin and plasmin. TAFIa potentially inhibits fibrinolysis by removing C-terminal lysine and arginine residues from fibrin. These residues are required for adsorption of tissue-type plasminogen activator (t-PA) and plasminogen to fibrin. Therefore, TAFIa decreases plasmin formation and protects the fibrin clot against lysis. An increased of pro-TAFI/TAFIa levels has been reported in some clinical conditions associated with thrombotic tendency, as type II diabetes mellitus, deep vein thrombosis and symptomatic artery disease. Few studies have investigated pro-TAFI/TAFIa in normal or complicated pregnancy but contrasting results were reported. Understanding the role of pro-TAFI/TAFIa in the pathogenesis of P-Ec can hold great promise for improving P-Ec management. In this context, a large-scale study evaluating plasma TAFI antigen and activity, its synthesis and metabolism in pre-eclamptic women is required. Recently new selective TAFIa inhibitors have been developed. The design of a new therapy to treat and/or prevent P-Ec, based on successful use of TAFIa inhibitors, may have significant clinical ramifications

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More information

Published date: March 2007
Additional Information: Invited critical review
Keywords: pro-TAFI, TAFIa, pre-eclampsia

Identifiers

Local EPrints ID: 73032
URI: http://eprints.soton.ac.uk/id/eprint/73032
ISSN: 0009-8981
PURE UUID: a1676881-fa6f-4583-81da-38e02dc4cd8b
ORCID for Bashir A. Lwaleed: ORCID iD orcid.org/0000-0001-5748-4892

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Date deposited: 26 Feb 2010
Last modified: 06 Aug 2024 01:39

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Author: Luci Maria Dusse
Author: Alan J. Cooper

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