Description: Coagulation can be initiated either by the intrinsic or extrinsic pathway, but both mechanisms converge in the coagulation cascade. Both pathways are complex and involve numberous proteins known as coagulation factors.
Coagulation Factors that can be analysed with this kit:
Factor V (also known as Proaccelerin):
The factor V protein is made primarily by cells in the liver. The protein circulates in the bloodstream in an inactive form until the coagulation system is activated by an injury that damages blood vessels. When activated to factor Va it accelerates conversion of prothrombin to its active form thrombin. Thrombin then converts a protein called fibrinogen into fibrin, which is the material that forms the clot.
Beside this coagulation enhancing mechanism of Factor Va factor V seems to be involved in the coagulation inhibiting effect of activated protein C.
A hereditary Factor VIII deficiency is the most common type of haemophilia and also known as Haemophilia A.
In the circulating blood, it is mainly bound to von Willebrand factor to form a stable complex. Upon activation by thrombin, it dissociates from the complex to interact with Factor IXa in the coagulation cascade. It is a cofactor to Factor IXa in the activation of Factor X, which, in turn, with its cofactor Factor Va, activates more thrombin. No longer protected by vWF, activated FVIII is proteolytically inactivated in the process predominantly by activated Protein C and Factor IXa. Substitution therapy for Haemophilia A, autoimmune diseases, and various other diseases like granulopathies can lead to the formation of Factor VIII inhibitors. Factor VIII is an acute phase protein. Therefore raised levels can be found e.g. in liver diseases, cancer, stress situations and inflammation.
A hereditary Factor IX deficiency is known as Haemophilia B, the second most common type of hemophilia.
Factor IX is produced as an inactive precursor and when activated into factor IXa it can process factor X to its active form in the presence of serum Calcium and Factor VIII. FIX can also be activated directly by Tissue Factor - Factor VIIa complex in the extrinsic pathway.
An acquired factor IX deficiency can result from lack of vitamin K, liver diseases, asparaginase therapies and consumptive coagulopathies. Determination of factor IX levels is also of importance in monitoring Haemophilia B substitution therapies due to the fact that in some cases a production of factor IX inhibitor can occur.
Beside Antithrombin, Protein C is a key player in the inhibition of coagulation. Protein C is a zymogen of a serinportease and depends on vitamin K. APC normally inactivates coagulation factor V by cutting (cleaving) it at specific sites. When cleaving factor V at protein position 506, both proteins can than work together to inactivate factor VIIIa and hence increases fibrinolysis.
A lack (deficiency) of protein C can lead to excess clotting. These clots tend to form in veins, not arteries. Protein C deficiency can be passed down through families (inherited) or it can develop with other conditions, such as: Chemotherapy use, Disseminated intravascular coagulation (DIC), Liver disease, Long-term antibiotic use, Warfarin (Coumadin) use.
Protein C levels rise with age, but this does not cause any health problems.
Protein S depends on vitamin K and is the cofactor of activated protein C in inactivation of factor Va and factor VIIIa. In plasma there is equilibrium of protein S as free form and bound to C4b binding protein. Only the free form is active.
There are three different types of hereditary Protein S deficiency. An acquired protein S deficiency can result from vitamin K deficiency, coumarin therapy or oral contraceptives. Since protein S can be formed in the endothelium Protein S deficiencies in liver diseases are not very distinct.
Von Willebrand Factor:
vWF is part of the factor VIII complex. vWF plays an important role in primary haemostasis by inducing the adhesion of thrombocytes to injured vessel walls. vWF is not required for the processing of fibrin.
There are several variations of vWF disease and are mainly grouped into quantitative (type I+III) and/or qualitative (type II) defects in vWF. Elevated vWF levels can be seen in acute phase, stress, liver diseases, after surgery and after trauma.