Novel Classification of Thrombotic Disorders Based on Molecular Hemostasis and Thrombogenesis Producing Primary and Secondary Phenotypes of Thrombosis

Abstract

Thrombosis, the common and deadliest disorder among human diseases, develops as a result of the intravascular hemostasis following an intravascular injury, which can be caused by a variety of trauma, non-traumatic insults or clinical illnesses. Thrombosis can occur at any location of the vascular system supplied by blood from the heart to large and smallest arterial and venous systems and may affect the function and anatomy of the organ and tissue. It more commonly occurs in the smaller circulatory system of the vascular tree such as arterioles and capillaries, and venules of the organs, especially in the brain, lungs, heart, pancreas, muscle and kidneys, and sinusoids of the liver. Thrombosis has been referred as the disease of “blood clots”, which concept is incompletely defined, but represents many different hemostatic diseases from microthrombosis to fibrin clot disease, macrothrombosis, and combined micro-macrothrombosis. Thrombosis is produced following an intravascular injury via one or more combination of four different mechanisms of thrombogenesis: microthrombogenesis, fibrinogenesis, macrothrombogenesis and micro-macrothrombogenesis initiated by normal physiological hemostasis in vivo. The clinical phenotype expression of thrombosis is determined by: (1) depth of the intravascular wall injury, (2) extent of the injury affecting the vascular tree system, (3) physiological character of the involved vascular system, (4) locality of the vascular injury, and (5) underlying non-hemostatic conditions interacting with hemostasis. Recent acquisition of “two-path unifying theory” of hemostasis and “two-activation theory of the endothelium” has opened a new frontier in science of medicine by identifying the pathophysiological mechanism of different thrombotic disorders and also contributing to the better understanding of many poorly defined human diseases, including different phenotypes of stroke and cardiovascular disease, trauma, sepsis and septic shock, multiorgan dysfunction syndrome, and autoimmune disease, and others. Reviewed are the fundamentals in hemostasis, thrombogenesis and thrombosis based on hemostatic theories, and proposed is a novel classification of thrombotic disorders.