Why Atherothrombosis is in Principle a Hematologic Disease: The Effect of Disorders and Drugs which Affect Thrombosis on the Development of Atherosclerotic Plaques

Abstract

The authors hypothesize that thrombosis causes both the complications of atherosclerosis as well as the underlying lesion, the atherosclerotic plaque. Atherosclerotic plaques develop from the organization of mural thrombi. In this process, circulating progenitor cells trapped within the thrombus differentiate into myofibroblasts which synthesize collagen, and endothelial cells which form granulation tissue. Eventually, all or most of the thrombus is replaced by collagen. Thus, conditions and drugs which affect thrombosis also affect the development of atherosclerotic plaques, i.e., atherogenesis. The authors review the process of organization and evidence showing that altered hemodynamics, increased blood viscosity, thrombophilias, coagulopathies, myeloproliferative disorders and drugs which modify the risk of thrombosis also affect atherogenesis. Accelerated atherogenesis is an underappreciated complication of many of these conditions. This paradigm explains how diverse risk factors, many of which have no association with inflammation or dyslipidemia, cause the same lesion. These data have implications for atherothrombosis theory and clinical practice.

The Role of Blood Viscosity in Infectious Diseases

“…This is also explained by the increased risk of thrombosis caused by inflammation. Fibrous remodeling or "organization" of a mural thrombus results in a lesion indistinguishable from an atherosclerotic plaque [3]. In a coronary artery, these lesions will increase the long-term risk of MI.…”

“…Increased blood viscosity is a risk factor for deep vein thrombosis [3,39]. Blood flow is slow in veins; therefore, blood viscosity becomes relatively high (viscosity = shear stress/shear rate).…”

“…The role of blood viscosity in pathophysiology has been neglected even though increased blood viscosity affects the presentation and complications of many diseases. Awareness of blood viscosity has provided insight into the anemias of heart failure, inflammation, renal failure, space flight, "hemolytic anemias", and most notably, the pathogenesis of atherothrombosis [1][2][3]. These insights should supplement or even supplant the current views of these conditions.…”