That Promote Clotting

Laboratory Tests to Determine the State of the Blood Clotting System 

Laboratory tests can identify a faulty component of clotting or whether an elderly patient is required to alter coumarin drug or vitamin K dosages before a tooth is extracted. Samples of the patient s blood are taken and treated in various ways to allow the observation of the appropriate steps in the hemostasis pathways. For example, tissue factor is added to the blood sample for the prothrombin time (PT) test. Alternatively, certain clotting system components in the blood sample are removed or inactivated. These tests can be run quickly on small samples of blood. 

The activated partial thromboplastin time (APTT) measures the efficacy of the intrinsic and common pathways. Blood is collected and oxalate or citrate is added to arrest coagulation by binding calcium. In the laboratory, calcium is added to reverse the anticoagu- 

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Table 12.1 The coagulation factors that promote the blood clotting process. Note that the factor originally designated as VI was later shown to be factor Va...

Little intravascular coagulation of blood occurs in normal physiological conditions. Hemostasis involves the interplay of three procoagulant phases vascular, platelet, and coagulation) that promote blood clotting to prevent blood loss (Fig. 22.1). The fibrinolytic system prevents propagation of clotting beyond the site of vascular injury and is involved in clot dissolution, or lysis (Fig. 22.2). 

Mechanism of Action A fat-soluble vitamin that promotes hepatic formation of coagulation factors II, VII, IX, and X. Therapeutic Effect Essential for normal clotting of blood. 

Platelets not only tend to stick to one another, but to the walls of blood vessels as well. Obviously because they promote clotting, they have a key role in forming thrombi. Many attempts have been made to explain the process of atherogenesis, that is. the creation of plaque, which narrows arteries and, of particular concern, the coronary arteries. Recently, there has been increasing interest in the possible role of platelets in atherosclerosis. Evidence from experimentation with laboratory animals has provided some evidence of a lole foi platelets in this piocess. This is coveied in some detail by Zucker (1980). 

Structural features that promote biological activity are sometimes called biophores. They are divisible into pharmacophores and toxicophores. Pharmacophores impart desirable properties on a molecule (e.g., pharmacological activity or a particular fragrance). Toxicophores are responsible for undesirable effects such as toxicity (e.g., mutagenicity and skin sensitization). The same molecule can have more than one descriptor that can act as both a pharmacophore and a toxicophore in the same or different biological systems. Examples here are the toxic side effects of anti-cancer drugs and the use of Warfarin, a commercially available rat poison, to help reduce the formation of blood clots in human heart disease. 

Hypervitaminosis K. Although it is possible to overdose with this vitamin, the fact that it is available only over the counter in small doses in multivitamin preparations has resulted in little knowledge of any toxicities. Toxicities do not appear in animals administered large doses. It is known that excess intake of the vitamin does not promote clot formation. There is no Tolerable Upper Intake Level. 

A partially or completely occlusive clot forms on top of the raptured plaque. Exposure of collagen and tissue factor induce platelet adhesion and activation, which promote release of adenosine diphosphate and thromboxane A2 from platelets. These produce vasoconstriction and potentiate platelet activation. A change in the conformation of the glycoprotein (GP) Ilb/IIIa surface receptors of platelets occurs that cross-links platelets to each... 

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