Atherosclerosis and venous thromboembolism — similarities

Abstract

Copyright © Polskie Towarzystwo Kardiologiczne INTRODUCTION Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), and atherothrombosis have long been considered to be separate entities with distinct pathogenic mechanisms. The traditional rationale for this concept has been based on: (1) pathologic data showing platelet-rich thrombi in the arteries in contrast to ‘red clots’ observed in veins; (2) clinical data on a substantial efficacy of antiplatelet agents in the prevention of arterial thromboembolic events in contrast to negligible benefits from these drugs in patients with VTE; (3) experimental data demonstrating diffuse inflammatory infiltrates, extracellular cholesterol deposits, neovessel formation and calcification within advanced atherosclerotic lesions within the arterial wall in contrast to minor lesions largely within the endothelial layer of the thrombosed veins. A key component of this concept is the assumption that deranged local processes occurring inside the vessel wall account for arterial thrombosis with a minor contribution by blood-borne abnormalities, whereas a combination of extrinsic factors ranging from venous blood stasis to hypercoagulable blood that act on a normal wall of a vein determine the occurrence of venous thrombosis. Experimental data derived from biochemical laboratories, cell cultures and animal models has shown however many similarities in the pathophysiology of arterial and venous thrombosis [1]. Coagulation pathways and their regulation are in fact identical in arteries and veins. Blood circulating in the two types of vessels is the same in terms of coagulation proteins. All kinds of thrombosis are triggered with the same major physiological initiator of blood coagulation, i.e. tissue factor (TF) [2]. Finally, thrombus composition assessed following thrombectomy in patients with ST-segment elevation acute myocardial infarction (MI) is frequently hard to differentiate from that of thrombi obtained from thrombosed veins, as evidenced by the fact that fibrin represents the largest portion of the thrombotic mass in both types of vessels [3, 4]. Despite the key role of activated platelets as a driving factor of thrombus formation under high shear stress conditions, there is convincing evidence for a significant contribution of thrombin and blood coagulation proteins in arterial thrombosis, as well as for their expression in macrophages and other cells within atherosclerotic lesions [5]. Until the beginning of the current century, there was no clinical data to support basic science findings indicating that thrombus formation in most vessels follows the same pattern and once deranged haemostasis tilted toward thrombosis results in increased risk of thromboembolic events putting in danger both the arterial and venous beds. Within the last decade, accumulating evidence has indicated that patients following VTE are at risk of MI or ischaemic stroke and vice versa. However a lot of experimental and clinical questions are to be answered including those as to whether all affected patients are indeed prone to develop the other type of thrombosis and which diagnostic and therapeutic strategy should be adopted in such a clinical setting. This review summarises the most important clinical and experimental data on the association between arterial and venous thrombosis.