Thrombodynamics parameters

 

  definition & description     influencing  factor   clinical meaning


Tlag, [min],
Lag-time

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Tlag is the time from the beginning of the measurement (contact of activator with plasma sample) until the beginning of the clot growth when the first significant levels of fibrin can be detected (when the light scattering value from the growing fibrin clot reaches half of the maximum light scattering value from the formed clot at the end of the measurement).

Tlag describes the initiation stage of coagulation process. It is analogous to clotting time (prothrombin time) in a routine laboratory coagulation assays.

 
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This parameter is sensitive to the initial stage of blood coagulation and reactions of the extrinsic pathway.

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  • Prolongation of this parameter is caused by hypocoagulation of differing nature:  deficiency of factors VII and X, (direct thrombin or factor Xa inhibitors, vitamin K antagonists).

  • Shortening of this parameter is rarely observed, and can be due to different causes of hypercoagulation.


V, [um/min],
Rate of clot growth

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V is the average rate of clot growth. If there is no strong spontaneous clotting, V is calculated on the interval 15-25 minutes after the beginning of clot growth [Tlag+15 min; Tlag+25 min]. If V cannot be calculated on this interval because of the presence of spontaneous clots, it is calculated on the 5-minute interval preceding spontaneous clots appearance– [Tsp-5 min, Tsp].

The V parameter characterizes the propagation stage of blood coagulation.

 
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V is sensitive to all coagulation cascade reactions, including the contact pathway and excluding the initiation reactions of the extrinsic pathway.

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V is the major parameter of the Thrombodynamics assay highly sensitive to a variety of stimuli, from hemophilia to hypercoagulation caused by different types of pathology (for example DIC).

  • Decreased V value indicates various different hypocoagulation states (hemophilia A, B C; factors V, X or thrombin deficiency; anticoagulant therapy – vitamin K antagonists, UFH and LMWH).

  • Increased V value indicates various different hypercoagulation states


Tsp [min],
Spontaneous clots
formation time

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Tsp is the time that spontaneous clots appear in the sample volume which had no initial contact with the activating insert. It is defined as the time from the beginning of the measurement until the average area of spontaneous clots reaches 5% of overall area of the measurement region.

The parameter characterizes clotting independent of the activator surface. Under normal condition, no spontaneous clotting is observed.

 
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Spontaneous clotting is induced by circulating activators, active coagulation factors and microparticles.

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Indicates a high pro-thrombotic tendency.


Vi, [um/min],
Initial rate of
clot growth

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Vi is the average rate of clot growth calculated on the interval 2-6 minutes after the beginning of clot growth.

The parameter also describes initial stages of clot growth but it is spatial elongation rather than local increase of thrombin concentration.

 
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The parameter is more sensitive to the reactions and components of the propagation stage than Tlag, but retains sensitivity to the initiation reactions. 

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  • A low Vi indicates differing hypocoagulation states (factors VII or X deficiency, anticoagulant therapy – factor Xa inhibitors, thrombin inhibitors, vitamin K antagonists, UFH and LMWH).

  • A high Vi indicates differing hypercoagulation states.


Vst, [um/min],
Stationary rate of
clot growth

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Vst is the average rate of clot growth calculated on the interval 15-25 minutes after the beginning of clot growth. If there are no spontaneous clots Vst and V are equal. In the presence of active spontaneous clotting Vst is not calculated.

 
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See V definition above

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See V definition above


CS, [um],
Clot size

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CS is the clot size at the 30th minute of measurement.

An integral parameter characterizing overall fibrin clot formation. CS is useful because of its «integral» nature (reflecting overall coagulation cascade performance): it can be used to compare differing results and also the effect of different drug.

 
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It is sensitive to all major components and processes of blood coagulation, because it is defined by both Tlag and rate of clot growth.

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  • A low CS indicates differing hypocoagulation states (hemophilia A, B, C, factors V, X or thrombin deficiency).

  • A high CS indicates differing hypercoagulation states.


D, [a.u.],
Clot density

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D is an optical parameter equal to the intensity of light scattering from a fibrin clot. It is proportional to the density of the fibrin clot mesh.

D parameter reflects firmness and structure of a formed clot. It reflects quantity and biological activity of fibrinogen, but cannot replace direct measurement of fibrinogen concentration.

 
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Sensitive to fibrinogen (concentration and polymerization ability) and factor XIII activity.

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  • A low D may indicate decreased fibrinogen levels and differing hypocoagulation states.

  • A high D may indicate increased fibrinogen levels. 

 Thrombodynamics-4D parameters


Ast, [Activity Unit/L], Stationary
amplitude of
thrombin peak

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Stationary amplitude of moving peak of thrombin concentration. As thrombin generation propagates in space as a moving peak (Dashkevich et al, Biophys J 2012), height of this peak is calculated as a maximal activity of thrombin in the fibrin formation zone which moves from the activator while clot is growing.

The parameter characterizes the propagation stage of blood coagulation.

 
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Ast is sensitive to all components and processes of blood coagulation.

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  • Increased Ast value indicates hypercoagulation states of various nature.

  • Decreased Ast value indicates hypocoagulation states of various nature (hemophilia A, B C; factors V, X or thrombin deficiency; anticoagulant therapy – vitamin K antagonists, UFH and LMWH, factor Xa and thrombin inhibitors).


Vt, [um/min],
Rate of
thrombin peak propagation

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The parameter characterizes the propagation stage of blood coagulation.

The parameter characterizes the propagation stage of blood coagulation.

 
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Vt is sensitive to changes in intrinsic pathway of blood coagulation; factors VIII, IX, XI, V, X and thrombin concentration.  This parameter is also sensitive to phospholipid vesicles concentration in plasma.

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  • Increased Vt value indicates hypercoagulation states of various nature.

  • Decreased Vt value indicates hypocoagulation states of various nature (hemophilia A, B C; factors V, X or thrombin deficiency; anticoagulant therapy – vitamin K antagonists, UFH and LMWH, factor Xa and thrombin inhibitors).

In addition several other parameters similar to homogeneous Thrombin Generation Test parameters are calculated on the activating surface - AMC concentration is averaged in the area 0.05-0.2 mm from the activator and then is transformed into thrombin generation curve

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ETP_ATG, [AU*min/L], Thrombin potential of activator thrombin generation

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The area under the curve of activator thrombin generation.

The parameter characterizes initial stage of blood coagulation.

 
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ETP_ATG is sensitive to changes both in the intrinsic and extrinsic pathway of blood coagulation.

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  • Increased ETP_ATG value indicates hypercoagulation states of various nature.

  • Decreased ETP_ATG value indicates hypocoagulation states of various nature including factor X, thrombin deficiency; anticoagulant therapy – vitamin K antagonists, factor Xa and thrombin inhibitors.


Cmax_ATG, [AU/L], Maximum
concentration of
activator thrombin generation

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Maximum concentration of thrombin generation at the near-activator area.

The parameter characterizes initial stage of blood coagulation.

 
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Cmax_ATG is sensitive to changes both in the intrinsic and extrinsic pathway of blood coagulation.

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  • Increased Cmax_ATG value indicates hypercoagulation states of various nature.

  • Decreased Cmax_ATG value indicates hypocoagulation states of various nature including factor X, thrombin deficiency; anticoagulant therapy – vitamin K antagonists, factor Xa and thrombin inhibitors.


Lag_ATG, [min],
Lag time of
activator thrombin generation

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Lag time of thrombin generation in the activator area. Lag_ATG is calculated as time when thrombin activity reaches 20 AU/L.

The parameter characterizes initial stage of blood coagulation.

 
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Lag_ATG is sensitive to the extrinsic pathway of blood coagulation.

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  • Increased Lag_ATG value indicates hypocoagulation states of various nature (factors V, VII, X and prothrombin deficiency; anticoagulant therapy – vitamin K antagonists, factor Xa and thrombin inhibitors, except heparins).


Tmax_ATG, [min],
Time to
thrombin peak in
activator thrombin generation

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Time to thrombin peak in thrombin generation at the near-activator area.

The parameter characterizes initial stage of blood coagulation.

 

 

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The parameter is sensitive to changes both in the intrinsic and extrinsic pathway of blood coagulation.

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  • Increased Tmax_ATG value indicates hypocoagulation states of various nature (factors V, VII, X and prothrombin deficiency; anticoagulant therapy – vitamin K antagonists, factor Xa and thrombin inhibitors, except heparins).

  • Decreased Tmax_ATG value indicates hypercoagulation states of various nature.

Reference ranges

Each laboratory should determine its own reference ranges using samples from healthy individuals that are typical for the local population. Users should take into account that individual pre-analytical factors in a given laboratory may influence the results. HemaCore provides a reference range representing a heterogeneous group of apparently healthy individuals for illustrative purposes only. The up to date normal reference ranges are provided in the T-2 Software and User Manual.