Background Previous studies relating increased thromboxane (TX) biosynthesis to cardiovascular risk factors do not answer the question whether platelet activation is merely a consequence of more prevalent atherosclerotic lesions or reflects the influence of metabolic and hemodynamic disturbances on platelet biochemistry and function. Methods and Results We examined 64 patients with large-vessel peripheral arterial disease and 64 age- and sex-matched control subjects. TXA ₂ biosynthesis was investigated in relation to cardiovascular risk factors by repeated measurements of the urinary excretion of its major enzymatic metabolite, 11-dehydro-TXB ₂ , by radioimmunoassay. Urinary 11-dehydro-TXB ₂ was significantly ( P =.0001) higher in patients with peripheral arterial disease (57±26 ng/h) than in control subjects (26±7 ng/h). Seventy percent of patients had metabolite excretion >2 SD above the normal mean. However, 11-dehydro-TXB ₂ excretion was enhanced only in association with cardiovascular risk factors. Multivariate analysis showed that diabetes, hypercholesterolemia, and hypertension were independently related to 11-dehydro-TXB ₂ excretion. During a median follow-up of 48 months, 8 patients experienced major vascular events. These patients had significantly ( P =.001) higher 11-dehydro-TXB ₂ excretion at baseline than patients who remained event free. Conclusions The occurrence of large-vessel peripheral arterial disease per se is not a trigger of platelet activation in vivo. Rather, the rate of TXA ₂ biosynthesis appears to reflect the influence of coexisting disorders such as diabetes mellitus, hypercholesterolemia, and hypertension on platelet biochemistry and function. Enhanced TXA ₂ biosynthesis may represent a common link between such diverse risk factors and the thrombotic complications of peripheral arterial disease.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

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 (delta = 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 delta t-PA antigen (P = .047), higher D-dimer (P = .024), and higher t-PA inhibitor (P = .001) levels. delta Fibrinolytic activity was correlated inversely with t-PA inhibitor (P < .01) and triglycerides (P < .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.

Article: Epidemiology of peripheral artery disease in Europe: VAS Educational Paper - International Angiology 2018 August;37(4):327-34 - Minerva Medica - Journals

The Progetto Lombardo Atero-Trombosi (PLAT) Study was a prospective, multicenter, multidisciplinary study of the association among hemostatic variables, conventional risk factors, and atherothrombotic events in four groups of patients with preexisting vascular ischemic disease (335 myocardial infarction survivors, 123 patients with stable angina pectoris, 160 with transient ischemic attacks, and 335 with peripheral vascular disease). In the myocardial infarction group, univariate analysis showed that atherothrombotic events were associated with high fibrinogen (p = 0.001), factor VIII:C (p less than 0.001), and von Willebrand factor antigen (vWF:Ag) (p = 0.004) levels and with low high density lipoprotein cholesterol (p = 0.043), factor VII (p = 0.019), and protein C (p = 0.044) levels; multivariate analysis produced associations with high fibrinogen and factor VIII:C levels and low protein C levels. By both univariate and multivariate analysis, events in the angina pectoris group were associated with high vWF:Ag (p = 0.026) and leukocyte (p = 0.033) levels and the presence of carotid arterial stenosis (p = 0.063); associations with high leukocyte (p = 0.037) and factor VIII:C (p = 0.186) levels, family history (p = 0.031), and diabetes (p = 0.061) were also found in the group with transient ischemic attacks. In those with peripheral vascular disease, events were associated with Fontaine stage greater than or equal to IIB (p = 0.024), high factor VIII:C levels (p = 0.073), and low protein C (p = 0.028), fibrinogen (p = 0.030), antithrombin III (p = 0.054), and factor VII (p = 0.057) levels by univariate analysis and with Fontaine stage and low fibrinogen levels by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)