Introduction

The incidence of venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism, and arterial thromboembolism, which can lead to myocardial infarction (MI) and stroke, increases with age, particularly after age 55. The comparatively low incidence of thrombotic events in women up to age 60 decreases over time; by age 60, incidence rates among men and women are essentially equal.

The predisposition to intravascular thrombosis among the elderly is difficult to explain but most likely reflects a multifactorial process with variable clinical expression. The predominant risk factors for arterial thrombosis may, in fact, originate within the vasculature itself in the form of atherosclerosis. However, the venous circulatory system is also affected, suggesting that one or more systemic factors are also involved.

Pathophysiology

Virchow's triad organizes the understanding of intravascular thrombosis and provides a platform for a comprehensive approach to its differential diagnosis. The three components of Virchow's triad are (1) abnormalities in the vessel wall, (2) abnormalities within the circulating blood, and (3) stasis of blood flow. Although many prothrombotic states are characterized by more than one defect, profound isolated defects may be sufficient to provoke thrombosis.

Vessel walls: The vascular (luminal) surface that is continuously exposed to circulating blood must be nonthrombogenic to avoid hypercoagulability. Yet, it must have prothrombotic capabilities in case protective clotting is needed. Profound structural abnormalities may be sufficient to stimulate thrombosis; however, usually an abnormality of clotting also exists.

Atherosclerosis plays an important role in stimulating unwanted clotting. It is considered the most common acquired hypercoagulable state. The atherosclerotic process may be influenced directly by abnormalities in platelet activation, coagulation, and fibrinolysis, each contributing to fibrin deposition and, ultimately, plaque growth. Rupture of plaque may stimulate abnormal clotting.

Atherosclerosis has an inflammatory aspect that represents a chronic inflammatory disease of the vasculature. Inflammation, in addition to producing a thrombogenic surface, is responsible for the release of mediators (eg, cytokines, chemokines) that may contribute to thrombosis directly or indirectly.

Vasculitis may also affect vessel walls and lead to abnormal clotting. It is characterized by various stages of inflammation, involving small-, medium-, or large-caliber vessels (depending on the disorder). Inflammation with accompanying structural and functional endothelial abnormalities and shear stress--increasing as a result of changes in luminal dimension--foster platelet adherence, activation, and fibrin deposition. Although some vasculitides may be associated with circulating procoagulant factors (eg, antiphospholipid antibodies), most increase thrombotic tendency primarily by creating focal abnormalities involving the vessel wall. Locally, active vasculitis can cause arterial thrombosis, including MI. In addition, healed vasculitis of the coronary arteries can accelerate atherosclerosis, itself a procoagulant state. Overall, the vasculitides most commonly associated with arterial thrombosis are polyarteritis nodosa and giant cell arteritis.

Circulating blood abnormalities: Under normal circumstances, blood circulates freely, and the plasma coagulation factors exist in a nonactivated state. Upon activation, intrinsic regulatory mechanisms prevent excess clotting (ie, more than is required for hemostasis). Abnormalities in either activation of the clotting cascade or deactivation once it has started can lead to hypercoagulability. Those abnormalities may develop as a result of abnormalities in clotting levels, intrinsic abnormalities of their protein structure, or circulating antibodies that abnormally activate the cascade.

Fibrinogen levels increase with age, with the greatest proportional increase occurring between ages 65 and 85. There is little difference between men and women. The relationship between fibrinogen level and cardiovascular risk appears to be independent of age. Whether factor VII activity and factor XII activity are independent risk factors for thrombotic events among the elderly remains open to debate. They may represent epiphenomena of disease activity (eg, atherosclerosis) rather than true prothrombotic risk factors.

Stasis of blood flow: Venous stasis occurs during prolonged periods of immobilization, such as following trauma, major surgery, or serious medical illnesses. Comparatively long periods of recovery and convalescence are common among the elderly, increasing their risk of stasis and venous thromboembolism.