Plasma biomarkers associated with survival and thrombosis in hospitalized COVID-19 patients

Severe coronavirus disease-19 (COVID-19) has been associated with fibrin-mediated hypercoagulability and thromboembolic complications. To evaluate potential biomarkers of coagulopathy and disease severity in COVID-19, we measured plasma levels of eight biomarkers potentially associated with coagulation, fibrinolysis, and platelet function in 43 controls and 63 COVID-19 patients, including 47 patients admitted to the intensive care unit (ICU) and 16 non-ICU patients. COVID-19 patients showed significantly elevated levels of fibrinogen, tissue plasminogen activator (t-PA), and its inhibitor plasminogen activation inhibitor 1 (PAI-1), as well as ST2 (the receptor for interleukin 33) and von Willebrand factor (vWF) compared to the control group. We found that higher levels of t-PA, ST2, and vWF at the time of admission were associated with lower survival rates, and that thrombotic events were more frequent in patients with initial higher levels of vWF. These results support a predictive role of specific biomarkers such as t-PA and vWF in the pathophysiology of COVID-19. The data provide support for the case that hypercoagulability in COVID-19 is fibrin-mediated, but also highlights the important role that vWF may play in the genesis of thromboses in the pathophysiology of COVID-19. Interventions designed to enhance fibrinolysis and reduce platelet aggregation might prove to be useful adjuncts in the treatment of coagulopathy in a subset of COVID-19 patients.

TMAO: a potential mediator of clopidogrel resistance

Trimethylamine-N-oxide (TMAO) can activate platelets and increase thrombosis risk in clinical and experimental models. Meanwhile, the patients with coronary artery disease have higher serum TMAO level. However, it remains unknown whether Clopidogrel Resistance (CR) could be attributed to TMAO. The present study aimed investigate the effects of TMAO on clopidogrel in ischemia and reperfusion (IR) model in rats. Clopidogrel could (1) promote the production of platelets, induce an increase in the platelet-larger cell ratio; (2) prolong the tail bleeding time; (3) reduce platelet aggregation function, induced by ADP, and alleviate myocardial thrombus burden. TMAO could partially offset the effects of clopidogrel and induce CR. Thus, the present study demonstrated that circulating TMAO could reduce the inhibitory effects of clopidogrel on platelet aggregation. TMAO may be a potential mediator of clopidogrel resistance.

Oxygen-ozone therapy in prevention and rehabilitation of myocardium infarct

In 1991, Prof. Lettieri (Naples, Federico II University) using Great Ozonated Blood Auto Infusion (GAE) treated patients having acute myocardium infarct, he had good results concerning pain and prognosis. Oxygen-ozone therapy is protective for ischemic cardiopathy. In 1996, oxygen-ozone therapy was used in relapse myocardium infarct prevention, showing an important factor against infarct relapse. Ozone has an important anti-inflammatory and rheological action, even if it is a strong oxidant. Paradoxically ozone activates cells antioxidant system, activates cells enzymatic function against free radicals and increases DNA antioxidant enzyme transcription. Ozone also activates redoxine system, reduce pro inflammatory cytokines II 1β, TNFX, modulate NFKB system, reduce platelet aggregation and stimulate different growth factor release. Because of the above skills, oxygen-ozone therapy helps to prevent ischemic cardiopathy and post infarcted rehabilitation. A mixture of ozone and oxygen administration has been evaluated on myocardium damaged tissues after an experimental ischemic event and myocardium reperfusion. Infarct damage can be counteract using pre- treatment with oxygen-ozone gaseous mixture. All our cardiopath patients treated with GAE have had an emo dynamic benefit, left ventricle ejection fraction improvement. Patients also improved aritmologic aspect with atrial fibrillation disappearance, enhance or disappearance of different comorbidity that often cardiopath/ischemic patients suffer.

Polyphenols: Inflammation

Background: Polyphenols widely distributed in plants, fruits and vegetables have received considerable attention on account of their physiological functions, including their antioxidant and anti-inflammatory properties. Some antioxidant components of cacao liquor prepared from fermented and roasted cacao beans, which is a major ingredient of cocoa and chocolate products, have been characterized as flavan-3-ols and procyanidin oligomers. Methods: This review focuses on a specific group of (-)-epicatechins and their oligomers, the procyanidins, in cacao products. Dietary polyphenols in cacao products have been shown to reduce hypertension, reduce platelet aggregation, improve serum lipids, and lower the incidence of atherosclerosis in animal studies and clinical trials. Conclusion: The intake of cacao products reduces hypertension and atherosclerosis on account of their physiological functions as antioxidants and anti-inflammation agents, indicating the mechanisms of prevention of hypertension and atherosclerosis by polyphenols.

The Influence of Diet and Nutrients on Platelet Function

Cardiovascular disease (CVD) is the leading cause of death worldwide. Platelet activation and aggregation play an integral role in hemostasis and thrombosis. Diets and nutrients play a potential role in modifying CVD progression, particularly in platelet function, and have the potential of altering platelet function tests. Diets such as Mediterranean diet, high in omega-3 polyunsaturated fatty acids (PUFA), and vegetarian diets have inverse relationships with CVD. Dark chocolate, foods with low glycemic index, garlic, ginger, omega-3 PUFA, onion, purple grape juice, tomato, and wine all reduce platelet aggregation. Dark chocolate and omega-3 PUFA also reduce P-selectin expression. In addition, dark chocolate reduces PAC-1 binding and platelet microparticle formation. Berries inhibit platelet function (PFA-100). Energy drinks have been shown to increase platelet aggregation and caffeine increases platelet microparticle formation. Therefore, repeat testing of platelet function may be required, not only after exclusion of known antiplatelet medications but also potentially after exclusion of dietary substances/nutrients that could have plausibly affected initial test data.