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Spatial Dynamics of Contact-Activated Fibrin Clot Formation in vitro and in silicoin Haemophilia B: Effects of Severity and Ahemphil B Treatment

Published online by Cambridge University Press:  15 May 2008

A. A. Tokarev ,
Yu. V. Krasotkina ,
M. V. Ovanesov ,
M. A. Panteleev ,
M. A. Azhigirova ,
V. A. Volpert ,
F. I. Ataullakhanov  and
A. A. Butilin
A. A. Tokarev*
Affiliation:
Laboratory of Physical Biochemistry of Blood, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167
Yu. V. Krasotkina
Affiliation:
Laboratory of Physical Biochemistry of Blood, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167
M. V. Ovanesov
Affiliation:
Laboratory of Physical Biochemistry of Blood, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167 Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore MD 21287
M. A. Panteleev
Affiliation:
Laboratory of Physical Biochemistry of Blood, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167
M. A. Azhigirova
Affiliation:
Laboratory of Blood Plasma Protein Fractionation, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167
V. A. Volpert
Affiliation:
Institute of Mathematics, University Lyon 1, Villeurbanne, France 69622
F. I. Ataullakhanov
Affiliation:
Laboratory of Physical Biochemistry of Blood, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167 Faculty of Physics, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119992 Center for theoretical problems of physical-chemical pharmacology, Russian Academy of Sciences, 4 Kosygin Street, Moscow, Russia, 117977
A. A. Butilin
Affiliation:
Faculty of Physics, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119992
*
[email protected]
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Abstract

Spatial dynamics of fibrin clot formation in non-stirred system activated by glasssurface was studied as a function of FIX activity. Haemophilia B plasma was obtained fromuntreated patients with different levels of FIX deficiency and from severe haemophilia B patienttreated with FIX concentrate (Ahemphil B) during its clearance with half-life t1/2=12 hours. Asreported previously (Ataullakhanov et al. Biochim Biophys Acta 1998; 1425: 453-468), clotgrowth in space showed two distinct phases: activation and propagation. The activation phase ischaracterized by the time required to start clot growth from the activator, while the characteristicparameter of the propagation phase is the clot elongation rate. This rate reaches steady state inapproximately ten minutes after the beginning of growth. In haemophilia B plasma, clotformation is substantially impaired: clot starts to grow from the activating surface later than inhealthy donor plasma, and its propagation rate is considerably lower. The most significantabnormalities in clot growth kinetics are observed at FIX activity below 10% of normal.Simulation of these experiments was performed theoretically using a detailed biochemical model(Panteleev et al. Biophys J 2006; 90: 1489-1500) adapted for experimental conditions used.Suitability of the assumptions used to describe triggering contact activation was verified.

Keywords

blood coagulationintrinsic pathwayhaemophilia Bfactor IX concentratemathematical modellingautowave process
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 1 , Issue 2: Hematopoiesis and blood diseases , 2006 , pp. 124 - 137
Copyright
© EDP Sciences, 2006

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