Pathology Patterns Reviews Am J Clin Pathol 2005;123(Suppl 1):S96-S105 S96 DOI: 10.1309/113N8EUFXYUECCNA S1 © American Society for Clinical Pathology Abstract Several epidemiologic studies have shown that moderate intake of alcohol is associated with a lower risk of cardiovascular disease (CVD), but the mechanism is not fully elucidated. One of the proposed mechanisms of the protective effect of moderate alcohol intake is its beneficial effect on hemostasis. The aim of this review is to summarize the effect of ethanol intake on platelet aggregation and activation, coagulation factors including von Willebrand factor (vWF), and the fibrinolytic system. With regard to the effect of alcohol on platelet function, evidence in the literature suggests both platelet activation and platelet inhibition by ethanol. A unifying hypothesis is that platelets are partially activated by ethanol, with partial degranulation allowing for continued circulation of platelets with impaired function. Evidence also exists showing that ethanol intake decreases fibrinogen, factor VII, and vWF levels. In addition, alcohol intake has been found to increase fibrinolysis by increasing tissue plasminogen activator activity. The effect of ethanol on platelets, coagulation factors, and the fibrinolytic system is likely to contribute to the protective effect of CVD. The mechanisms by which alcohol affects the cardiovas- cular system, beneficially or detrimentally, have been the target of extensive research. Many epidemiologic studies have shown that moderate alcohol consumption (1-2 standard drinks per day or 10-20 g/d) can reduce the risk of heart disease and ischemic stroke by 20% to 60% and death of all causes by 10% to 20%. 1 The underlying factors contributing to the protective or pathophysiologic effects related to alcohol consumption are not well understood. Alcohol consumption affects plasma lipid profiles and has been shown to raise high-density lipoprotein levels. 2 A number of studies have indicated that ethanol also directly affects hemostasis via a number of mechanisms, including modulation of plasma coagulation factors, fibrinolysis, and platelet func- tion. 3-5 Thus, individuals without a history of alcoholism might benefit from moderate consumption of alcohol. Although the association between moderate drinking and a lower risk of coronary artery disease has been well documented, the mecha- nisms by which alcohol causes these effects remains just as elusive as those underlying alcohol-related diseases. Chronic alcohol consumption can predispose to bleeding. A study of patients in the United States and Sweden showed that the baseline incidence of acute upper gastrointestinal bleeding increased by 3-fold as alcohol consumption increased from 1 drink or fewer per week to more than 20 drinks per week. 6 There is also a linear association between the consump- tion of ethanol and the risk for hemorrhagic stroke. 7 In a study of a sample of Japanese men living in Hawaii, alcohol consumption reduced the incidence of myocardial infarction (MI) and cardiac death (ie, coronary thrombosis) but did not have the same protective effect against stable angina. 8 This finding suggests that the effect of alcohol on hemostasis is an important, possibly predominant, mecha- nism in protecting against cardiovascular disease (CVD). Effects of Alcohol on Hemostasis Raneem O. Salem, PhD, and Michael Laposata, MD, PhD Key Words: Cardiovascular disease; Ethanol; Platelet aggregation; Fibrinogen; von Willebrand factor; Fibrinolysis; Tissue plasminogen acti- vator; Tissue plasminogen activator inhibitor-1 DOI: 10.1309/113N8EUFXYUECCNA