The Enzymatic Interaction of Factors VII, VIII, IX and X
"The scientist is not a person who gives the right answers, he's one
who asks the right questions." -- Claude Lévi-Strauss
The elegant enzymatic interaction of blood-borne enzymatic factors VII, VIII, IX and X generates thrombin, soluble fibrin, and insoluble fibrin and determines their individual rates and locations of production.
Factor VII is the "trigger" of the enzymatic interaction. In the absence of its activity the other enzymes remain inert. It is extremely labile, and it exerts its enzymatic activities only when it is stabilized by tissue factor. When activated, it generates small amounts of thrombin that energize tissue maintenance, but by itself it does not generate enough thrombin to energize coagulation or tissue repair.
Factor VIIIC accelerates thrombin production to energize its conversion of factor X to Factor XIII to generate insoluble fibrin, which is essential for coagulation, capillary hemostasis, and capillary gate operation. Like factor VII, it is extremely labile and must be stabilized by von Willebrand Factor (VWF) to exert its enzymatic activities. VWF and VIIIC bind together and circulate in blood as a gigantic chimeric molecular complex known as "factor VIII" so that they circulate together and exert their effects in concert. Defects in VIIIC cause true hemophilia, a severe, sex-linked clotting disorder that primarily afflicts males. Defects in VWF cause von Willebrand Disease, a clotting defect that is usually less severe than hemophilia.
Factor IX is a "co-factor" of factor VIIIC. It enhances factor VIII activity but has no effect on the other enzymes. Defects in factor IX cause a mild clotting defect called "Christmas Disease." Unlike factors VII and VIIIC it is non-labile.
Factor X is also non-labile. It is the focus of the "final common pathway" of the classical coagulation cascade. It interacts with factor VIII to produce Factor XIII that generates insoluble fibrin. It also interacts with factor VII and tissue factor to amplify thrombin generation.
Factor XIII adds "cross-links" of plasminogen and fibronectin to molecular strands of soluble fibrin to generate insoluble fibrin to enable coagulation, capillary hemostasis, and capillary gate operation.
The interaction of factors VII and X with tissue factor is the engine of embryological development, and tissue repair. Defects in these factors are usually lethal. Medications such as warfarin and thalidomide that disrupt their interaction are teratogenic (i.e. they disrupt embryological development) and they also undermine tissue repair.
The interaction of factors VIII, IX and X is the engine of coagulation, capillary hemostasis, and capillary gate operation. Defects in factors VIII and IX disrupt coagulation but such defects are survivable because they do not disrupt embryological development or tissue repair. Heparin and its congeners disrupt factor VIII activity and paralyze coagulation, but this does not affect embryological development, so that these medications are safe during pregnancy.
The stable enzymatic activities of non-labile factors IX and X do not affect the enzymatic interaction, but the constantly fluctuating activities of factors VII and VIII alter the interaction to determine the rate, location, and magnitude of production of thrombin, soluble fibrin, and insoluble fibrin. Factor VII activity is increased by tissue disruption, and factor VIII activity is increased by nervous activity. Thus simultaneous increases in nervous activity and tissue disruption cause "positive feedback" that focuses MSM activity to energize tissue repair and induces MSM hyperactivity that causes disease manifestations.