Blood Physiology-Offline information
Coagulation pathways: The extrinsic pathway, with its tissue factor, is the usual way of initiating clotting in the body, and factor XII—the beginning of the full intrinsic pathway—normally plays little if any role (in contrast to its initiation of clotting in test tubes or within the body in several unusual situations). Thus, thrombin is initially generated only by the extrinsic pathway. The amount of thrombin is too small, however, to produce adequate, sustained coagulation. It is large enough, though, to trigger thrombin’s positive feedback effects on the intrinsic pathway (see figure) —activation of factors V, VIII, and XI and of platelets. This is all that is needed to trigger the intrinsic pathway independently of factor XII. This pathway then generates the large amounts of thrombin required for adequate coagulation. The extrinsic pathway, therefore, via its initial generation of small amounts of thrombin, provides the means for recruiting the more potent intrinsic pathway without the participation of factor XII. In essence, thrombin eliminates the need for factor XII. Moreover, thrombin not only recruits the intrinsic pathway but facilitates the prothrombin–thrombin step itself by activating factor V and platelets.
In summary:
In the body, the cascade usually begins via the extrinsic clotting pathway when tissue factor forms a complex with factor VIIa. This complex activates factor X, which then catalyzes the conversion of small amounts of prothrombin to thrombin. This thrombin then recruits the intrinsic pathway by activating factor XI and factor VIII, as well as platelets, and this pathway generates large amounts of thrombin.
Blood Substitutes: Researchers are currently investigating the use of blood substitutes to solve some of the problems inherent in blood transfusion. The most promising blood substitutes use the hemoglobin molecule as their basic component. Hemoglobin is the oxygentransporting molecule contained in red blood cells. Natural hemoglobin taken out of red blood cells cannot be introduced into the bloodstream. It breaks down immediately into smaller molecules that are toxic, especially to nerve cells, the liver, and the kidneys. However, hemoglobin that is first chemically altered to prevent it from breaking down can be safely transfused. Once in the cardiovascular system, the hemoglobin will transport oxygen in much the same way that it does inside an intact red blood cell. The modified hemoglobin is slowly broken down and eliminated from the body, without harming the patient’s liver or kidneys. What’s more, adequate supplies of hemoglobin are readily available, and don’t rely on human blood donors. One developer uses blood from cattle. Another uses human hemoglobin produced by genetically engineered bacteria (also the source of the human insulin injected by diabetics). Blood substitutes have additional benefits. Hemoglobinbased blood substitutes are better oxygen transporters than whole blood, although they remain in the patient’s body for only a few days. Unlike whole blood, blood substitutes are free of diseasecausing contaminants and can be stored for months at room temperature. Moreover, blood substitutes cannot cause a transfusion reaction because they lack the protein membrane of a red blood cell. This makes them the perfect "one-size-fits-all" substance for transfusion, and perhaps the ideal solution for critical-care emergencies. Blood substitutes are currently in widespread clinical trials in South Africa, where the AIDS outbreak has caused a critical shortage of available donors for whole blood. Other clinical trials are under way in the United States and Europe.