Thrombotic risk factors: Basic pathophysiology
Ida Martinelli, MD, PhD; Paolo Bucciarelli, MD; Pier Mannuccio Mannucci, MD
Although venous thrombosis has been traditionally associated with stasis and hypercoagulability, arterial thrombosis is mainly associated with heightened platelet reactivity and damage to the vessel wall. Accordingly, classic risk factors for venous andarterial thrombosis are usually considered distinct. Those for the former include cancer, surgery, pregnancy, and estrogens use, whereas risk factors of arterial thrombosis include smoking, hypertension, diabetes, the metabolic syndrome, and hyperlipidemia. However, a number of studies have recently challenged this dichotomy, and it is now recognized that venous and arterial thromboses shareseveral risk factors, suggesting a closer link between the two clinical conditions. Typical examples of shared risk factors are age and the metabolic syndrome. This review addresses the mechanism whereby established risk factors increase the risk of venous or arterial thrombosis, or both. (Crit Care Med 2010; 38[Suppl.]:S3–S9) KEY WORDS: venous thrombosis; arterial thrombosis; risk factors;coagulation; pathogenesis
lthough venous thromboembolism is a common disease, underlying pathogenic mechanisms are only partially known, particularly in comparison to those of atherothrombosis. During the past decades, progress has been made in the identiﬁcation and characterization of the cellular and molecular mechanisms that interdependently inﬂuence Virchow’s triad. It is now accepted that thecombination of stasis and hypercoagulability, much more than endothelial damage and activation, are crucial for the occurrence of venous thrombosis; venous thrombi are mainly constituted by ﬁbrin and red blood cell, and less by platelets. In contrast, platelets are essential for primary hemostasis, repair of damaged endothelium, and play a pivotal role in the development of atherosclerosis.Inﬂammation, lipids, and the immune system, through a complex interplay, are also important determinants of arterial and venous thrombosis, albeit to a lesser extent. This review considers the various risk factors for venous thrombosis and atherothrombosis, with the goal of de-
scribing the mechanisms by which they mediate disease. These considerations may prove useful when considering the thromboticrisk for patients admitted to the ICU.
The process of aging in humans is accompanied by modiﬁcations of the blood coagulation system that explain the heightened risk of thrombosis in the elderly. The plasma concentrations of some coagulation factors (factor V, factor VII, factor VIII, factor IX, ﬁbrinogen) increase progressively with age (1, 2). The same is true for von Willebrand factor, akey protein in platelet–vessel wall interactions (3). For instance, the Framingham study (4) has shown that plasma levels of ﬁbrinogen increase from a mean value of 280 mg/dL in individuals aged 47 to 54 yrs to 300 mg/dL in those aged 65 to 79 yrs, with an increase of 10 mg/dL for each age decade. High plasma levels of ﬁbrinogen may play a causative role in the high incidence of cardiovascularevents observed in elderly people, perhaps by enhancing the bridging of platelets via their glycoprotein IIb-IIIa receptor, by serving as a direct substrate of the clot, and/or by increasing blood viscosity (5). Alternatively, high ﬁbrinogen levels simply may be a marker of the chronic inﬂammatory state typical of aging, without directly contributing to the risk (5). A similar trend was shown foranother acute phase protein, coagulation factor VIII, which progressively increases with age, up to 200 U/dL in the seventh decade of life (6). Coagulation factor VII also increases
From A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, IRCCS Ospedale Maggiore Policlinico, Mangiagalli, and Regina Elena Foundation, Milan, Italy. The...