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Influence of coagulation factors on intrinsic thrombin generation

Stief, Thomas W; Otto, Stefanie; Renz, Harald

Blood Coagulation & Fibrinolysis: January 2007 - Volume 18 - Issue 1 - p 67–71
doi: 10.1097/MBC.0b013e32801297cd

The intrinsic coagulation activity assay (INCA) is a new thrombin-generation test that imitates the intrinsic pathway of blood coagulation. The aim of the present study was to investigate the influence of the main coagulation factors on the INCA. The INCA was performed with citrated plasma samples supplemented with different amounts of fibrinogen. The INCA and activated partial thromboplastin time determination were performed with factor-depleted plasmas and with mixtures of depleted plasmas with normal plasma. Supplemented purified fibrinogen resulted in a decrease of intrinsic thrombin generation (50% inhibitory concentration = 0.8 g/l). The INCA depends on the intrinsic factors (factors VIII, IX, XI and XII) and on the factors of the common pathway (factors II, V and X): for normal thrombin generation, at least about 50% of normal factor II is necessary. For the majority of factors, the sensitivity of the INCA appears to be approximately one order of magnitude better than that of the activated partial thromboplastin time. The INCA allows one to diagnose defects in the intrinsic coagulation system and might be a useful test to support development and characterization of new drugs targeted at the intrinsic generation of thrombin.

Department of Clinical Chemistry, University Hospital Marburg, Germany

Received 13 June, 2006

Revised 23 October, 2006

Accepted 26 October, 2006

Correspondence and requests for reprints to T.W. Stief, MD, Priv.-Doz., Department of Clinical Chemistry, University Hospital, D-35033 Marburg, Germany Tel: +49 6421 286 4471; fax: +49 6421 286 5594; e-mail:

© 2007 Lippincott Williams & Wilkins, Inc.