Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1

Meltzer, Mirjam E. and Lisman, Ton and Groot de, Philip G. and Meijers, Joost C.M. and Cessie le, Saskia and Doggen, Carine J.M. and Rosendaal, Frits R. (2009) Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood, 116 (1). pp. 113-121. ISSN 0006-4971

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Abstract:	Elevated plasma clot lysis time (CLT) increases risk of venous and arterial thrombosis. It is unclear which fibrinolytic factors contribute to thrombosis risk. In 743 healthy control subjects we investigated determinants of CLT. By comparison with 770 thrombosis patients, we assessed plasma levels of fibrinolytic proteins as risk factors for a first thrombosis. Plasminogen activator inhibitor-1 (PAI-1) levels were the main determinants of CLT, followed by plasminogen, thrombin-activatable fibrinolysis inhibitor (TAFI), prothrombin, and α2-antiplasmin. Fibrinogen, factor VII, X, and XI contributed minimally. These proteins explained 77% of variation in CLT. Levels of the fibrinolytic factors were associated with thrombosis risk (odds ratios, highest quartile vs lowest, adjusted for age, sex, and body mass index: 1.6 for plasminogen, 1.2 for α2-antiplasmin, 1.6 for TAFI, 1.6 for PAI-1, and 1.8 for tissue plasminogen activator [t-PA]). Adjusting for acute-phase proteins attenuated the risk associated with elevated plasminogen levels. The risk associated with increased t-PA nearly disappeared after adjusting for acute-phase proteins and endothelial activation. TAFI and PAI-1 remained associated with thrombosis after extensive adjustment. In conclusion, CLT reflects levels of all fibrinolytic factors except t-PA. Plasminogen, TAFI, PAI-1, and t-PA are associated with venous thrombosis. However, plasminogen and t-PA levels may reflect underlying risk factors
Item Type:	Article
Copyright:	© 2010 by The American Society of Hematology
Faculty:	Management and Governance (SMG)
Research Group:	Health Technology & Services Research (HTSR)
Link to this item:	http://purl.utwente.nl/publications/76790
Official URL:	http://dx.doi.org/10.1182/blood-2010-02-267740
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