fibrin and Hyperlipidemias

Topics: Aging; Animals; Cholesterol; Fatty Acids; Fibrin; Heparin; Humans; Hyperlipidemias; Lipase; Lipid Metabolism; Lipidoses; Lipoprotein Lipase; Lung; Lung Diseases; Macrophages; Phagocytosis; Phospholipids; Silicosis

Topics: Blood Platelets; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Hyperlipidemias; Lipid Metabolism; Lipoproteins; Plasminogen; Thrombosis

This randomized, placebo-controlled, double-blind, crossover study on 25 free-living hyperlipidaemic volunteers aspired to prove the hypothesis that supplementation for 8 weeks with a FoodState Vitamin C complex (500 mg vitamin C, 160 mg bioflavonoids, 600 mg magnesium and 900 mg vitamin B complex) may improve haemostatic factors and fibrin network structures. Of the haemostatic factors measured, only median plasmin-antiplasmin complex (PAP) and thrombin-antithrombin complex (TAT) concentrations were both significantly decreased with FoodState Vitamin C complex compared with placebo [PAP, -4.05% (-23.39, -0.23) versus 1.81% (-8.95, 8.09); TAT, -5.81% (-18.47, 0.39) versus 0.12% (-8.03, 13.5)]. As for fibrin network structures, only compaction was significantly increased from baseline to end [49.95% (47.55, 53.70) to 51.85% (48.55, 56.65)] by FoodState Vitamin C complex supplementation. No significant changes were found in plasma fibrinogen, plasminogen activator inhibitor 1 activity, tissue plasminogen activator antigen, D-dimer, serum lipids or lipoprotein (a) concentrations. In conclusion, the decreases in TAT and PAP are possibly an indication that the FoodState Vitamin C complex decreased the initiation of haemostasis, which in turn led to a compensatory reduction in fibrinolysis. FoodState Vitamin C complex may therefore be protective of cardiovascular disease by causing a new reduced steady state of haemostatic balance and less rigid clots (increased compaction).

Topics: Adult; alpha-2-Antiplasmin; Antithrombin III; Ascorbic Acid; Biomarkers; Cross-Over Studies; Double-Blind Method; Female; Fibrin; Fibrinolysin; Hemostasis; Humans; Hyperlipidemias; Lipids; Male; Middle Aged; Peptide Hydrolases

A double-blind, placebo-controlled, cross-over study was conducted in 21 men with combined hyperlipoproteinaemia to examine if lipid-lowering treatment with gemfibrozil (10-12 weeks) affects blood coagulation and fibrin gel structure at rest or during mental stress. Gemfibrozil lowered plasma triglycerides by 57 +/- 4%, whereas high density lipoprotein (HDL) cholesterol increased by 22 +/- 5%. Gemfibrozil lowered the triglyceride content of low density lipoprotein (LDL). Gemfibrozil reduced the plasma concentrations of thrombin-antithrombin complex (TAT) and prothrombin fragment F1 + 2 (F1 + 2), both at rest and during mental stress. However, there were no effects of gemfibrozil treatment on the plasma concentrations of fibrinogen, factor VII antigen, activated factor VII (VIIa) or activated factor XII (XIIa), or on fibrin gel structure. Acute mental stress per se did not influence coagulation factors, reaction products or fibrin gel structure, or their responses to the study drug. Thus, gemfibrozil reduced thrombin generation in men with combined hyperlipoproteinaemia, without influencing the plasma levels of fibrinogen, VIIa and XIIa, or fibrin gel structure. Attenuation of thrombin generation may contribute to the primary-preventive effects of gemfibrozil on coronary heart disease.

Topics: Adult; Aged; Analysis of Variance; Cross-Over Studies; Double-Blind Method; Factor VII; Factor VIIa; Factor XIIa; Fibrin; Fibrinogen; Gels; Gemfibrozil; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Stress, Psychological; Thrombin

Standard biomarkers have been widely used for COVID-19 diagnosis and prognosis. We hypothesize that thrombogenicity metrics measured by thromboelastography will provide better diagnostic and prognostic utility versus standard biomarkers in COVID-19 positive patients. In this observational prospective study, we included 119 hospitalized COVID-19 positive patients and 15 COVID-19 negative patients. On admission, we measured standard biomarkers and thrombogenicity using a novel thromboelastography assay (TEG-6s). In-hospital all-cause death and thrombotic occurrences (thromboembolism, myocardial infarction and stroke) were recorded. Most COVID-19 patients were African--Americans (68%). COVID-19 patients versus COVID-19 negative patients had higher platelet-fibrin clot strength (P-FCS), fibrin clot strength (FCS) and functional fibrinogen level (FLEV) (P ≤ 0.003 for all). The presence of high TEG-6 s metrics better discriminated COVID-19 positive from negative patients. COVID-19 positive patients with sequential organ failure assessment (SOFA) score at least 3 had higher P-FCS, FCS and FLEV than patients with scores less than 3 (P ≤ 0.001 for all comparisons). By multivariate analysis, the in-hospital composite endpoint occurrence of death and thrombotic events was independently associated with SOFA score more than 3 [odds ratio (OR) = 2.9, P = 0.03], diabetes (OR = 3.3, P = 0.02) and FCS > 40 mm (OR = 3.4, P = 0.02). This largest observational study suggested the early diagnostic and prognostic utility of thromboelastography to identify COVID-19 and should be considered hypothesis generating. Our results also support the recent FDA guidance regarding the importance of measurement of whole blood viscoelastic properties in COVID-19 patients. Our findings are consistent with the observation of higher hospitalization rates and poorer outcomes for African--Americans with COVID-19.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Black or African American; Cardiovascular Diseases; Comorbidity; COVID-19; COVID-19 Testing; Diabetes Mellitus; Early Diagnosis; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinogen; Hospitalization; Humans; Hyperlipidemias; L-Lactate Dehydrogenase; Male; Middle Aged; Obesity; Organ Dysfunction Scores; Prognosis; Prospective Studies; SARS-CoV-2; Thrombelastography; Thrombophilia; Treatment Outcome; White People

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction-induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI-mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet-fed conditions comparable to that seen in chow diet-fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure.

Topics: Animals; Blood Platelets; Caspases; CD36 Antigens; Crotalid Venoms; Diet, High-Fat; Disease Models, Animal; Egtazic Acid; Fibrin; Humans; Hyperlipidemias; Lectins, C-Type; Lipoproteins, LDL; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 7; Phosphatidylserines; Platelet Activation; Signal Transduction; src-Family Kinases; Thrombosis

Topics: Acyclovir; Antiviral Agents; Blood Coagulation Disorders; Female; Fibrin; Herpes Zoster; Humans; Hyperlipidemias; Infarction, Middle Cerebral Artery; Lymphangiectasis, Intestinal; Middle Aged; Paraproteinemias; Protein S; Protein-Losing Enteropathies; Urinary Tract Infections

The anti-thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW), which is consisted of 11 herbs (indicated as concentrations) of Rehmanniae radix 24%, Hominis placenta 5%, Testudinis carapax 9%, Eucommiae cortex 9%, Asparagi radix 9%, Phellodendri cortex 9%, Achyranthis radix 7%, Liriopis tuber 7%, Angelicae sinensis radix 7%, Ginseng radix 6%, and Schizandrae fructus 3%, were investigated. The extracts of DJW and its 11 herbs, except G. radix, A. sinensis radix and S. Fructus, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. Also the extract inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In in vitro experiments, the extract was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin-induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. In conclusion, the protection of extracts of Korean herbs on the ischemic infarction induced artificially might be related to their inhibitory effects on DIC, platelet coagulation and thrombic action.

Topics: Adenosine Diphosphate; Animals; Cholesterol, Dietary; Collagen; Disseminated Intravascular Coagulation; Endotoxins; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolytic Agents; Heparin; Hyperlipidemias; Korea; Male; Plant Extracts; Plasminogen; Platelet Aggregation; Rats; Rats, Wistar; Thrombin

During episodes of dental bacteremia, viridans group streptococci encounter platelets. Among these microorganisms, certain Streptococcus sanguis induce human and rabbit platelets to aggregate in vitro. In experimental rabbits, circulating streptococci induced platelets to aggregate, triggering the accumulation of platelets and fibrin into the heart valve vegetations of endocarditis. At necropsy, affected rabbit hearts showed ischemic areas. We therefore hypothesized that circulating S. sanguis might cause coronary thrombosis and signs of myocardial infarction (MI). Signs of MI were monitored in rabbits after infusion with platelet-aggregating doses of 4 to 40 x 10(9) cells of S. sanguis 133-79. Infusion resulted in dose-dependent changes in electrocardiograms, blood pressure, heart rate, and cardiac contractility. These changes were consistent with the occurrence of MI. Platelets isolated from hyperlipidemic rabbits showed an accelerated in vitro aggregation response to strain 133-79. Cultured from immunosuppressed children with septic shock and signs of disseminated intravascular coagulation, more than 60% of isolates of viridans streptococci induced platelet aggregation when tested in vitro. The data are consistent with a thrombogenic role for S. sanguis in human disease, contributing to the development of the vegetative lesion in infective endocarditis and a thrombotic mechanism to explain the additional contributed risk of periodontitis to MI.

Topics: Animals; Bacteremia; Bacterial Physiological Phenomena; Blood Platelets; Blood Pressure; Cells, Cultured; Child; Coronary Thrombosis; Disseminated Intravascular Coagulation; Electrocardiography; Endocarditis, Bacterial; Fibrin; Heart Diseases; Heart Rate; Humans; Hyperlipidemias; Immunocompromised Host; Mouth; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Periodontitis; Platelet Aggregation; Rabbits; Shock, Septic; Streptococcus sanguis; Thrombosis

The application of OSO4 plus K3 [Fe(CN)6] as a secondary fixative following aldehyde fixation, permitted demonstration of the presence of 30-300 nm 'membrane-bound' particles in xanthomatous tissue. With the same fixation method, isolated low density lipoprotein particles in a fibrin matrix could be observed in the transmission electron microscope in a way permitting comparison with similarly fixed tissue. However, isolated particles of very low density lipoproteins treated in the same way as low density particles had an irregular appearance and a diameter varying between 30 and 80 nm.

Topics: Cholesterol; Fibrin; Hyperlipidemias; Lipoproteins, LDL; Lipoproteins, VLDL; Microscopy, Electron; Protein Conformation; Xanthomatosis

Topics: Animals; Capillaries; Diabetes Mellitus, Experimental; Disseminated Intravascular Coagulation; Fibrin; Hyperglycemia; Hyperlipidemias; Hyperplasia; Insulin; Rabbits; Triglycerides

Topics: Adult; Aged; Blood Coagulation; Factor XIII; Fibrin; Humans; Hypercholesterolemia; Hyperlipidemias; Lipoproteins; Lipoproteins, LDL; Middle Aged; Thrombelastography; Triglycerides

Topics: Blood Sedimentation; Fibrin; Fibrinogen; Humans; Hyperlipidemias; Platelet Adhesiveness

Topics: Arteriosclerosis; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Extracorporeal Circulation; Fibrin; Fibrinolysis; Hemorrhage; Heparin; Heparin Antagonists; Humans; Hyperlipidemias; Hypersensitivity; Natriuresis; Osteoporosis; Protamines; Prothrombin Time; Thromboembolism; Thrombophlebitis; Thromboplastin

Topics: Aminocaproates; Aminocaproic Acid; Animals; Aprotinin; Blood Coagulation; Carcinoma 256, Walker; Carcinoma, Brown-Pearce; Fibrin; Fibrinolysin; Heparin; Hyperlipidemias; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Rabbits; Radiation Effects; Rats; Research

Topics: Butter; Fibrin; Humans; Hyperlipidemias; Lipids; Male; Thrombosis

Topics: Arteriosclerosis; Coronary Disease; Fats; Fibrin; Fibrinolysis; Humans; Hyperlipidemias; Thrombosis