A case-control comparison within the framework of the prospective, multidisciplinary PLAT Study was performed to assess whether altered baseline fibrinolytic variables were associated with an elevated risk of ischemic thrombotic events in patients with documented coronary, cerebral, and/or peripheral atherosclerotic disease. Fibrinogen, D-dimer, tissue plasminogen activator (t-PA) antigen, and fibrinolytic activity before and after venous stasis (A=difference between the two values), t-PA inhibitor, and lipid levels in 60 atherosclerotic patients with a thrombotic event during the first year of follow-up were compared with those in 94 atherosclerotic patients without such events, who were matched for age, sex, and diagnosis at enrollment. Events were associated with a higher release of A t-PA antigen (P=.O47), higher D-dimer (P=.O24), and higher t-PA inhibitor (P=.001) levels. A Fibrinolytic activity was correlated inversely with t-PA inhibitor (P<.01) and triglycerides (J*<.05). D-Dimer was also correlated with systolic blood pressure (P<.01). Atherosclerotic patients at higher risk of thrombotic ischemic events are characterized by increased fibrin turnover and impaired fibrinolytic activity due to high t-PA inhibitor levels. This hemostatic disequilibrium may participate with conventional risk factors such as elevated triglyceride levels and systolic blood pressure in the multifactorial mechanism of ischemic sequelae in patients with preexisting vascular atherothrombotic disease. (ArUrioscler Thromb. 1993;13:1412-1417.) KEY WORDS • atherothrombosis • ischemic events • fibrinolytic variables • plasminogen activator inhibitor • D-dimerR ecent clinical studies have reported decreases in fibrinolytic activity in patients with coronary artery disease. 15 The major mechanisms involved in the type of fibrinolytic impairment seen in these patients are an increase in plasma tissue-type plasminogen activator (t-PA) inhibitor, particularly in subjects with hypertriglyceridemia, and a selective depression of t-PA activity in euglobulins. The t-PA inhibitor (PAI-1) has also been shown to be an independent risk factor for reinfarction in young survivors of myocardial infarction (MI). 6The prospective, multidisciplinary PLAT Study, which was performed to investigate the associations between hemostatic variables and ischemic events in 953 patients with documented atherosclerotic disease, 79 afforded the opportunity of carrying out a nested casecontrol study, with the aim of assessing whether altered baseline fibrinolytic variables characterize subjects at a higher risk of ischemic sequelae, and we now report the results. Fibrinogen, fibrinolytic activity, and t-PA anti-

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Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients.