Chimeric Factor VIII: The "Rosetta Stone" of the MSM
"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."--Arthur Schopenhauer
Chimeric factor VIII links nervous activity to blood enzymes to enable the capillary gate mechanism that regulates hemodynamic physiology in accord with autonomic balance.The peculiar pathophysiology of factor VIII served as a "Rosetta Stone" that enabled the identification of the mammalian stress mechanism.
Factor VIII consists of enzymatic factor VIIIC that is continuously released by the liver and enzymatically inert von Willebrand Factor (VWF) that is released from the vascular endothelium by sympathetic nervous activity. The two molecules bind together and circulate together in blood to form a gigantic protein complex called "factor VIII." VWF stabilizes labile VIIIC and enables its enzymatic activity, so that sympathetic tone and activity determines factor VIII activity.
Factor VIII enzymatically interacts with factors VII, IX and X to accelerate thrombin generation to energize its production of factor XIII that adds "cross links" of plasminogen, vitronectin and fibronectin to fibrillar soluble fibrin to generate insoluble fibrin that spontaneously polymerizes into strands that bind red cells into a clot.
The gigantic size of factor VIII prevents it from penetrating the viscoelastic clot of its own making, which limits clot propagation to the site of injury.
Factor IX complements factor VIII activity but does not affect factors VII and X. Defects in factor IX cause a mild clotting defect called "Christmas Disease."
Defects in factors VIII, IX, VWF and drugs such as heparin that inhibit their activity are generally survivable because they affect only hemostasis and do not disrupt embryological development, tissue maintenance, or tissue repair.
Defects in VIIIC cause classical hemophilia, which is a severe sex-linked clotting disorder that is transmitted by female carriers and primarily afflicts their male offspring. It undermines the capillary gate mechanism, causing exercise intolerance, but it prevents atherosclerosis via the turbulence mechanism.
Defects in VWF cause "von Willebrand Disease", a clotting disorder that is more common but usually less severe than true hemophilia. Its severity fluctuates with sympathetic tone and activity, but has little effect on exercise tolerance. In severe cases it is clinically indistinguishable from true hemophilia. It increases the risk of angiodysplasia, because VWF protects fragile capillaries from flow-related damage.