Platelet biology of the rapidly failing lung.

Acute respiratory distress syndrome (ARDS) is characterized by a rapid-onset respiratory failure with a mortality rate of approximately 40%. This physiologic inflammatory process is mediated by disruption of the alveolar-vascular interface, leading to pulmonary oedema and impaired oxygen exchange, which often warrants mechanical ventilation to increase survival in the acute setting. One of the least understood aspects of ARDS is the role of the platelets in this process. Platelets, which protect vascular integrity, play a pivotal role in the progression and resolution of ARDS. The recent substantiation of the age-old theory that megakaryocytes are found in the lungs has rejuvenated interest in and raised new questions about the importance of platelets for pulmonary function. In addition to primary haemostasis, platelets provide a myriad of inflammatory functions that are poised to aid the innate immune system. This review focuses on the evidence for regulatory roles of platelets in pulmonary inflammation, with an emphasis on two receptors, CLEC-2 and TLT-1. Studies of these receptors identify novel pathways through which platelets may regulate vascular integrity and inflammation in the lungs, thereby influencing the development of ARDS.

International Union of Angiology Position Statement on perioperative drug and hemostasis management in vascular surgery.

This position paper, written by members of International Union of Angiology (IUA) Youth Committee, shows an overview of coagulation system and laboratory tests, analysis of medical therapies (older and newer), medication discontinuation/restart recommendations, bridging therapy recommendations, and an overview of hemostatic agents used in the operating room.

Daily Step Counts in Participants With and Without Peripheral Artery Disease.

PURPOSE: We compared the prevalence of participants with and without symptomatic peripheral artery disease (PAD) who met the goals of attaining >7000 and 10 000 steps/d, and we determined whether PAD status was significantly associated with meeting the daily step count goals before and after adjusting for demographic variables, comorbid conditions, and cardiovascular risk factors. METHODS: Participants with PAD (n = 396) and without PAD (n = 396) were assessed on their walking for 7 consecutive days with a step activity monitor. RESULTS: The PAD group took significantly fewer steps/d than the non-PAD control group (6722 ± 3393 vs. 9475 ± 4110 steps/d; P < .001). Only 37.6% and 15.7% of the PAD group attained the goals of walking >7000 and 10 000 steps/d, respectively, whereas 67.9% and 37.4% of the control group attained these goals (P < .001 for each goal). Having PAD was associated with a 62% lower chance of attaining 7000 steps/d than compared with the control group (OR = 0.383; 95% CI, 0.259-0.565; P < .001), and a 55% lower chance of attaining 10 000 steps/d (OR = 0.449; 95% CI, 0.282-0.709; P < .001). Significant covariates (P < .01) included age, current smoking, diabetes, and body mass index. CONCLUSIONS: Participants with symptomatic PAD had a 29% lower daily step count compared with age- and sex-matched controls, and were less likely to attain the 7000 and 10 000 steps/d goals. Additionally, participants who were least likely to meet the 7000 and 10 000 daily step count recommendations included those who were older, currently smoked, had diabetes, and had higher body mass index.

Clinical studies support a role for trem-like transcript-1 during the progression of sepsis.

Sepsis is a multi-factorial disease that kills an estimated 1,400 people a day worldwide. The Triggering Receptor Expressed in Myeloid (TREM) cells Like Transcript (TLT)-1 is a platelet receptor expressed on activated platelets. Translational studies of TLT-1 suggest that TLT-1 affects hemostatic and immunological parameters that lead to the formation of disseminated intravascular coagulation (DIC). Evaluation of mice suffering from endotoxic shock shows a dramatic increase of soluble TLT-1 (sTLT-1) in their blood. Accordingly, when we evaluated the blood of septic patients we find increased levels of sTLT-1 that correlate with the presence of DIC in humans. Based on current data we hypothesize that TLT-1 plays an important role in maintaining vascular integrity during sepsis; perhaps by modulation of both the immune and hemostatic systems, and that TLT-1 makes an attractive target not only for better understanding of sepsis, but also as a point of therapeutic intervention as well.

Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine.

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.

Treatment of superficial venous incompetence.

Superficial venous incompetence is a common lower limb vascular condition, with venous ulceration representing the most severe sequela of the disease. The treatment of superficial venous incompetence can aid in ulcer healing, and a variety of modalities are available. Successful treatment requires attention to appropriate patient selection and procedural technique.

Levels of soluble TREM-like transcript 1 in patients presenting to the emergency department with chest pain.

OBJECTIVE: Recent studies suggest that the soluble triggering receptor expressed on myeloid cells-like transcript 1 (sTLT-1) facilitate atherothrombosis. Therefore, we evaluated sTLT-1 as a functional measure of atherothrombosis in acute coronary syndrome (ACS). METHODS: Levels of sTLT-1 were determined by enzyme-linked immunosorbent assay on plasma from patients with potential ACS and compared with an age-matched control group with similar risk factors for cardiovascular disease. RESULTS: Of 53 patients enrolled, 19 patients were undergoing ACS (15 unstable angina, 2 non-ST-segment elevated myocardial infarction, and 2 ST-segment elevated myocardial infarction), 5 patients were found with noncardiac chest pain, and 29 were in the control group. The mean plasma sTLT-1 values in the ACS group were 4.644 ng/mL ± 1.277 standard error of the mean (SEM), in the noncardiac chest pain group were 0.708 ng/mL ± 0.427 SEM, and in the control group were 1.007 ng/mL ± 0.098 SEM. CONCLUSION: A statistically significant difference exists between patients experiencing cardiogenic chest pain versus controls (P < .05), suggesting sTLT-1 as a potential tool for understanding atherothrombosis in ACS.

Impaired vascular endothelial growth factor A and inflammation in patients with peripheral artery disease.

We compared apoptosis, cellular oxidative stress, and inflammation of cultured endothelial cells treated with sera from 130 patients with peripheral artery disease (PAD) and a control group of 36 patients with high burden of comorbid conditions and cardiovascular risk factors. Second, we compared circulating inflammatory, antioxidant capacity, and vascular biomarkers between the groups. The groups were not significantly different (P > .05) on apoptosis, hydrogen peroxide, hydroxyl radical antioxidant capacity, and nuclear factor κ-light-chain enhancer of activated B cells. Circulating tumor necrosis factor α (TNF-α; P = .016) and interleukin 8 (IL-8; P = .006) were higher in the PAD group, whereas vascular endothelial growth factor A (VEGF-A; P = .023) was lower. The PAD does not impair the endothelium beyond that which already occurs from comorbid conditions and cardiovascular risk factors in patients with claudication. However, patients with PAD have lower circulating VEGF-A than the control group and higher circulating inflammatory parameters of TNF-α and IL-8.

Management of pulmonary embolism: state of the art treatment and emerging research.

OPINION STATEMENT: Pulmonary embolism is one of the most important causes of morbidity and mortality in cardiovascular medicine and demands a circumscribed algorithmic treatment approach (Fig. 1). Anticoagulation should be triggered by a high clinical probability and continued based on urgent definitive imaging. Our assessment then continues with evaluation of the clinical severity of the pulmonary embolism to determine whether the patient will benefit from thrombolysis or not. We usually reserve this option for cases of massive pulmonary embolism (sustained hypotension, pulselessness, or persistent profound bradycardia) or patients with a low cardiopulmonary reserve and categorical signs of right ventricle failure. At this juncture, renal function, a diagnosis of active cancer, calculated bleeding risk, and estimated patient compliance will help us gravitate toward specific agent selection for subsequent anticoagulation management. While rivaroxaban is an attractive oral therapy option, it is not an appropriate choice for patients with significant renal disease; patients with cancer are better treated with low molecular weight heparin when possible. Warfarin anticoagulation continues to be a well-known, valid, and cost-effective treatment option. At the end of the primary treatment we assess each patient for the likelihood of thromboembolism recurrence, which will be highest among those patients with idiopathic events or those with cancer-associated thrombosis. We favor prolonged anticoagulation in these scenarios. In addition, we strongly advocate periodic scheduled follow up of patients on long-term anticoagulation for secondary prophylaxis to re-evaluate their bleeding and recurrence risk. We understand both of these extremes are in a dynamic balance, and likewise so should be the anticoagulation directives. As we learn more about recurrence and bleeding prediction, we foresee a personalized approach in which the anticoagulant agent for each patient will be narrowly chosen based on their specific performance.

Influence of peripheral artery disease and statin therapy on apolipoprotein profiles.

Apolipoprotein B is a stronger predictor of myocardial infarction than LDL cholesterol, and it is inversely related to physical activity and modifiable with exercise training. As such, apolipoprotein measures may be of particular relevance for subjects with PAD and claudication. We compared plasma apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD) and intermittent claudication and in 39 control subjects. Furthermore, we compared the plasma apolipoprotein profiles of subjects with PAD either treated (n = 17) or untreated (n = 12) with statin medications. For the apolipoprotein subparticle analyses, subjects with PAD had higher age-adjusted Lp-B:C (P < 0.05) and lower values of Lp-A-I:A-II (P < 0.05) than controls. The PAD group taking statins had lower age-adjusted values for apoB (P < 0.05), Lp-A-II:B:C:D:E (P < 0.05), Lp-B:E + Lp-B:C:E (P < 0.05), Lp-B:C (P < 0.05), and Lp-A-I (P < 0.05) than the untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD on statin medications have a more favorable risk profile, particularly noted in multiple apolipoprotein subparticles. The efficacy of statin therapy to improve cardiovascular risk appears more evident in the apolipoprotein sub-particle profile than in the more traditional lipid profile of subjects with PAD and claudication. This trial is registered with ClinicalTrials.gov NCT00618670.