Clotting time factors affecting

Pharmacology Enoxaparin, tinzaparin, and dalteparin are LMWHs. These agents enhance the inhibition of Factor Xa and thrombin by binding to and accelerating antithrombin activity. They preferentially potentiate the inhibition of Factor Xa, while only slightly affecting thrombin and clotting time (activated partial thromboplastin time [APTT] or PT). 

Heparin inhibits reactions that lead to clotting, but does not significantly alter the concentration of the normal clotting factors of blood. Although clotting time is prolonged by full therapeutic doses, in most cases it is not measurably affected by low doses of heparin. Bleeding time is usually unaffected. 

Because many clotting factors are present in blood in small concentrations, direct chemical measurements often cannot be used to determine whether the factors are within normal concentration ranges or are deficient. Once a deficiency has been established, however, plasma from the affected person can be used to screen for the presence of the deficiency in other people. A rare deficiency in Factor XII leads to a prolongation of clotting time. Assuming that you have plasma from someone in which this deficiency has been estabfished, design a test that might help determine whether another person has a Factor XII deficiency. 

The complete 7 kb protein-coding sequence of human factor VIII was assembled from portions of overlapping cDNA and genomic clones and Introduced into appropriate mammalian expression vectors (9,10). Following transformation into either hamster kidney cells (9) or COS-1 monkey cells (11) factor VIII expression in transfected cell lines was characterized. The recombinant protein was shown to be biologically active, demonstrating the ability to activate factor IX and to reduce clotting time in plasma derived from patients affected with hemophilia A. Additionally, factor VIII activity of transfected cells was inhibited by a factor Vlll-specific antibody. 

To maintain hemostasis, blood must be retained in the vasculature as fluid. At the same time, blood components must be able to respond rapidly with a clot when a vascular injury occurs. To repair a vascular injury, platelets in blood first adhere as aggregates to the endothelial cells at the affected site and form an initial blood clot. Platelets then stimulate and activate coagulation factors found in plasma to form a more stable fibrin clot. As the injury is resolved and healed, the clot is degraded. Thrombosis is a pathological event wherein a blood clot occludes a blood vessel, resulting in ischemic necrosis of the tissue fed by the blood vessel. Ischemic necrosis involves local anemia and oxygen deprivation. Thrombosis of a coronary artery may lead to myocardial infarction or unstable angina [20]. 

Keys to toxicity Warfarin is a drug used to prevent blood clots in people who have had a stroke or heart attack. It is also an effective rat poison. How is this possible One key to toxicity is the dose— the amount of the chemical taken in by an organism. Exposure time can also be a factor even low-dose exposure to some chemicals over long periods of time can be hazardous. Toxicity is also affected by the presence of other chemicals in the body, the age and gender of the individual, and the chemical s ability to be absorbed and excreted. 

It seems probable that, as in rate, continuous heavy drinking stimulates the hepatic enzymes concerned with the metabolism of warfarin, leading to its more rapid elimination. As a result the half-life shortens. The fluctuations in prothrombin times in those with liver impairment may possibly occur because sudden large amounts of alcohol exacerbate the general dysfunction of the liver and this affects the way it metabolises warfarin. Alcohol may also change the ability of the liver to synthesise clotting factors. Constituents of beer other than alcohol may affect warfarin metabolism. ... 

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