Blood coagulation pathways

Figure 12.1 Schematic diagram of the initial steps of the extrinsic blood coagulation pathway. See text for details (TF tissue factor)...

Hanumanthaiah, R., Day, K., and Jagadeeswaran, P. (2002). Comprehensive analysis of blood coagulation pathways in teleostei Evolution of coagulation factor genes and identification of zebrafish factor VHi. Blood Cells 29, 57-68. 

An important step in the blood coagulation pathway is the formation of the prothrombinase complex. The latter is a mixture of factor V, factor Xa, Ca2+, and phospholipid. In this case, a phospholipid mixture with a net negative charge will allow the prothrombinase complex to form. This active enzyme is important in cleaving prothrombin to yield thrombin. The most active phospholipid mixture for in vitro studies has proven to be phosphatidylserine-phosphatidylcholine. Subsequently the hypothesis has developed that phosphatidylserine is key to the formation of prothrombinase. 

There is no doubt that phosphatidylserine is active in the above reactions. However, in neither of these two systems has the importance of this phosphoglyceride in an in vivo system been defined. Certainly in the protein kinase C studies, there appeared to be no real attempt to explore the effect of mixtures of phospholipids (which might be encountered in the cell) on the kinase activity. In the blood coagulation pathway, it is well established that phosphatidylserine-phosphatidylcholine mixtures with the proper net negative charge are key in the formation of the active prothrombinase. Consequently, there is a general assumption by many investigators in this field that phosphatidylserine is the key component. 

Following the recruitment and activation of platelets by injured capillaries, their soft clot aggregates provide a surface for plasma proteins to interact and activate thrombin, which transforms soluble fibrinogen to a fibrin clot. Thrombin is activated by two blood coagulation pathways, extrinsic and intrinsic. A defective extrinsic path is incompatible with life, whereas defects of the intrinsic path cause hemophilia. 

The answer is e. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 121—144. Wilson, pp 23—98.) Hemophilia A is caused by deficiency of factor VIII and hemophilia B by deficiency of factor IX. Both factors are involved in the intrinsic blood coagulation pathway that results in activation of factor X. Alternatively, factor X can be activated by tissue factors through the extrinsic blood coagulation pathway Activated factors X and V produce thromin from prothrombin, which in turn cleaves fibrinogen to produce fi-... 

Enzymes as Coagulant Eactors as in Human Blood Coagulation Pathways... 

EFFECTS ON HUMAN BLOOD COAGULATION PATHWAY 19.3.1 Human Blood Coagulation Pathway... 

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