Coagulation factors half-lives

Coagulation factors are glycoproteins named by roman numbers (the numbers being ascribed at the time of the components definition, not sequence of activation) (Table 1). Besides von Willebrand factor (vWF), the coagulation factors are synthesized in the liver. They have very different half-lifes and different concentrations in the plasma. Several coagulation factors are stored in platelets and endothelial cells and can be released during activation of these cells, which can result in a much higher local concentration of the respective factor (e.g., vWF). 

Many of the coagulation factors measured by global coagulation tests have limited stability, and the time and temperature of storage of sample will affect their measurements. Concepts of analyte stability and half-life in plasma extend to markers measured by immunoassay. Markers of platelet activation are affected by artifactual activation in vitro upon collection of the blood specimen. This section will highlight some of the nonanalytical variables that, if uncontrolled, can lead to spurious results and thus affect the interpretation of laboratory data. 

Mechanism of Action A direct thrombin inhibitor that reversibly binds to thrombin-active sites. Inhibits thrombin-catalyzed or thrombin-induced reactions, including fibrin formation, activation of coagulant factors V, VIII, and XIII also inhibits protein C formation, and platelet aggregation. Therapeutic Effect Produces anticoagulation. Pharmacokinetics Following IV administration, distributed primarily in extracellular fluid. Protein binding 54%. Metabolized in the liver. Primarily excreted in the feces, presumably through biliary secretion. Half-life 39-51 min. 

This is an equation for a straight line, the slope of which is 2R /t, and describes the plots in Figure 8. From the experimental slopes one may calculate the half-life, T, and the Fuchs stability factor, W. These values are given in Table III. They confirm that coagulation is an important process in determining particle size and number from the outset. With no surfactant present the particles apparently have a net attraction for each other (W < 1), and disappear with a half-life on the order of four milliseconds. As surfactant concentration is increased it... 

Coagulation factors are proteins with varying but usually short half-lives, (s. tab. 5.12) Their determination allows the assessment of hepatic function. However, the respective half-life has to be considered. Disorders of coagulation factors are therefore important functional parameters in hepatic diseases - both in severe acute and in chronic cases. In liver diseases, there may be a lack of coagulation factors, which is predominantly and primarily caused by a disorder of the hepatocyte synthesis capacity. This lack can also be due to other causes (1.) accelerated catabolism, (2.) altered biosynthesis of inhibitors, (3.) production of abnormal factors, and (4.) increased demand due to intravasal coagulation. 

Tab. 5.12 Classification and synonyms of coagulation factors, their site of synthesis, vitamin K dependency and half-life (as far as is known)...

Antithrombin III is formed in the hepatocytes as an U2-globulin. It serves as a physiological inhibitor of serin proteases in the coagulation system and thus inhibits activating factors Ila, IXa, Xa, XIa and Xna. As the name implies, AT III is most effective as an inhibitor of thrombin. Half-life is 2-3 days. 

Fresh frozen plasma (FFP) 250 ml at six-hour intervals (10-20 ml/kg BW = 1,000-1,500 ml/day). Administration of 10 ml/kg BW (about 600-1,200 rnl) serves to elevate the concentrations of coagulation factors and inhibitors by 15—20%. The half-life of factor VII is only 6 hours, which is why dosage intervals of 6 to 12 hours must be maintained. IgA deficiency is a known contraindication. Adverse transfusion reactions may occur with a frequency of 1-5% of cases. Improvement in coagulopathy generally lasts 1 to 2 days. Caution is called for, since accentuated coagulation entails the danger of thrombosis (if necessary, AT III replacement of up to 60-80%), and an overload of the intra-... 

Quick s value A drop in the coagulation factors II, V, Vn, IX and X is a reliable indicator of the still remaining liver function. Factor VIII increases. With massive liver cell destruction, a dangerous decrease in factors V and VII is witnessed within 1 or 2 days (corresponding to the half-life of the factors) together with a reduction in Quick s value and Colombi s index (<60 - 80%). (45, 47, 71) (s. p. 105)... 

The prothrombin time, which is a measure of the activities of certain coagulation factors made by (he liver, is sometimes used as an indicator of hepatic synthetic function. Prothrombin has a very short half-life, and an increased prothrombin time may be the earliest indicator of hepatocellular damage. 

Flemophilia A and B coagulation defects, which are caused by deficiencies of Factor VIII and Factor IX, respectively, can be bypassed by administration of recombinant Factor Vila. Flowever, the short half-life of recombinant Factor Vila in vivo negates its routine clinical use. An in vivo method for the continnons generation of Factor Vila is reported which depends on tlie implantation of a porous chamber that contains Factor Xa or Xlla and continuously generates Factor Vila bypass activity from the subject s own Factor VII, which enters the chamber by diffusion. Once inside, the Factor VII is cleaved to Factor Vila by the immobilized Factor Xa or Xlla. Tlie newly created Factor Vila diffuses ont of the chamber and back into cuculation, where it can bypass the deficient Factors VIII or DC and enable coagulation to occur. In vitro, tliis method generates sufficient Factor Vila to sub-... 

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