See effects of pro- and anticoagulant agents on thrombodynamics results.

Coagulation factor deficiencies



Factor VIII deficiency

In cases of hemophilia, i.e. deficiency of fVIII or IX, the intrinsic tenase does not work normally impairing propagation of the clot.

Comparison of thrombodynamics results for a patient with severe hemophilia A and healthy donor is shown below.
Clot formation is initiated normally, but resultant clot growth is slow. Numerical parameters are shown in the table. V is decreased while Tlag does not change. 

  


 Hemophilia A

Control


Fibrinogen deficiency

Formation of a fibrin clot is the final result of the coagulation cascade. If there is no fibrinogen present or the polimerization process is impaired, the density of the clot will change.

The thrombodynamics results for fibrinogen deficient plasma which was spiked with different concentrations of fibrinogen are shown below. In the case of deficiency no clot is observed, increases of fibrinogen concentration result in increases of clot density.

        
   Fg  deficiency
                
          30% of Fg
       
        100% of Fg

 








           

Procoagulant  agents   

Activated coagulation factors in plasma lead to activation of the whole system which results in the increase of clot growth rate and spontaneous clot formation.

For further information refer to: Circulating Contact-Pathway-Activating Microparticles Together with Factors IXa and XIa Induce Spontaneous Clotting in Plasma of Hematology and Cardiologic Patients


Tissue Factor 


The presence of TF in plasma increases clot growth rate and can result in the formation of spontaneous clots in the plasma.


[TF]=0,25 pM
     
        Control

 

Factor VIIa


Factor VIIa is used as a bypassing agent in hemophilia treatment. It causes changes in clot formation similar to TF.

   
[VIIa] = 30 nM
     
      Control 
  
 
   

Factor XIa


If fXIa is present the clot growth rate is increased and spontaneous clot formation is observed.

  
      130 pM of fXIa
               
Control 


 

Phospholipid surface and platelets


Most of the reactions of the coagulation cascade occur on phospholipid surfaces. In the thrombodynamics assay platelet free plasma is used with no phospholipids added. But for some application it is possible to introduce additional phospholipid surfaces. For example artificial phospholipid vesicles or platelets.

If phospholipid vesicles are present, rate of fX and prothrombin cleavage is increased. This results in an increase of the rate of clot growth.

               
        4 μ of PLS
        
     Control
  
 
The vesicle composition is:
PS:PC:PE = 20:20:60 molar ratio
 

The assay can also be performed in platelet rich plasma. Platelets slightly increase the rate of clot propagation and can induce spontaneous clot formation.
   
       
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Anticoagulant drugs 


Heparin

Heparins in complex with antithrombin III inhibit activated factors II, X and IX.

Plasma results shown below are from a patient undergoing hip replacement surgery spiked in-vitro with heparin. The rate of clot growth decreases, while Tlag does not change. Spontaneous clotting is suppressed.

           
        0,06 ME/ml of
              heparin
 
Before heparin
  
  


   

Warfarin

Warfarin is vitamin K antagonist, which leads to decreased activity of factors VII, IX, X and II.

     
        Warfarin
     
     Control
  
  
 
 

Dabigatran

Dabigatran is a direct inhibitor of thrombin. Intake of 220 mg of dabigatran leads to an increase of lag time, and a decrease of initial rate of clot growth.

3h after
220 mg of Dabi
 
          Before dabi
  

  

   

Rivaroxaban

Rivaroxaban is a direct inhibitor of FXa. Intake of 10 mg of rivaroxaban leads to increase of lag time and a decrease of both the initial and stationary rates of clot growth.

        
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