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Effects of short-term fenofibrate treatment on circulating markers of inflammation and hemostasis in patients with impaired glucose tolerance.

CONTEXT: Apart from lowering lipid levels, peroxisome proliferator-activated receptor (PPAR) alpha activators (fibrates) produce many other favorable effects that may contribute to their clinical effectiveness in dyslipidemic and diabetic patients. OBJECTIVE: The objective of this study was to compare the impact of a short-term treatment with fenofibrate and the American Heart Association (AHA) step 1 diet on systemic inflammation, hemostasis, and monocyte secretory function in relationship with their metabolic actions. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: This was a prospective, randomized, placebo-controlled trial involving the group of 91 ambulatory patients with impaired glucose tolerance (IGT) (diagnosed on the basis of the American Diabetes Association criteria), randomly divided into three groups, simultaneously treated for 30 d with the AHA step 1 diet (n = 30), micronized fenofibrate (267 mg/d, n = 31), or placebo (n = 30). The control group included 34 age-, sex-, and weight-matched subjects with normal glucose tolerance. Eighty-six (95%) patients and all control subjects completed the study. MAIN OUTCOME MEASURES: Plasma markers of inflammation and hemostasis and monocyte release of proinflammatory cytokines were measured. RESULTS: Compared with subjects with normal glucose tolerance, IGT patients exhibited higher plasma levels/activities of fibrinogen, factor VII, plasminogen activator inhibitor-1, high-sensitivity C-reactive protein, and oxidized low-density lipoproteins. Lipopolysaccharide-activated monocytes from IGT patients released significantly more TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 in comparison with monocytes from control subjects. Thirty-day treatment with fenofibrate but not with the AHA step 1 diet: 1) improved lipid/lipoprotein profile and glucose metabolism, and 2) reversed or alleviated all the above-mentioned abnormalities. The favorable effects of fenofibrate on plasma high-sensitivity C-reactive protein and on monocyte release of TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 did not correlate with its action on plasma lipids but was related to the improvement in insulin sensitivity and weakly to free fatty acid-lowering action. CONCLUSIONS: Our study is the first to show that relatively small disturbances in glucose metabolism are associated with marked and multidirectional abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function. Moreover, fenofibrate may exhibit early pleiotropic effects in patients with IGT.

Adult↗

Zinc supplementation has no effect on lipoprotein metabolism, hemostasis, and putative indices of copper status in healthy men.

Pharmacological doses of zinc can adversely affect body copper status. The resulting copper deficiency can impact directly upon cholesterol metabolism and a suboptimal copper status has been observed to influence markers of hemostasis (specifically fibrinogen and the copper-containing coagulation factors V and VIII). The aim of this investigation was to examine the effect of a low level of zinc supplementation, to include dietary intake, at the United States tolerable upper intake level of 40 mg/d upon indicators of lipid metabolism, hemostasis, and copper. Thirty-eight subjects were recruited onto a double-blind placebo-controlled intervention trial and randomly selected to one of two groups. Group 1 took zinc supplements (30 mg/d) for 14 wk followed by copper supplements (3 mg/d) for 8 wk (to counteract adverse effects, if any, of zinc supplementation). A second group took placebo supplements for the full duration of the trial. Estimated dietary zinc intake approximated 10 mg/d. The effect of supplement was analyzed by repeated-measures analysis of variance (anova). Results indicate that no effect of zinc supplementation on putative indices of copper status, lipoprotein metabolism, and markers of hemostasis. These results indicate that short-term low-level zinc supplementation (total intake 40 mg/d) is not detrimental to health.

Adult↗

Regulation of hemostasis by singlet-oxygen (1DeltaO2*).

Hemostasis is the system of generation and destruction of thrombi. It consists of coagulation and thrombolysis and has a plasmatic part and a cellular one, the latter being the thrombocytes and endothelial cells for coagulation and the polymorphonuclear granulocytes (PMN) for thrombolysis. Main products of PMN are oxidants of the hypochlorite/chloramine-type that can generate the nonradical excited oxidant singlet molecular oxygen ((1)DeltaO(2)(*)). Physiologically, (1)DeltaO(2)(*) reacts with methionine and cysteine residues and with carbenic structures in lipids, generating dioxetanes, which upon disruption emit photons in the blue spectrum of light (380-450 nm). It modifies some important hemostasis components in blood: (1)DeltaO(2)(*) inactivates the factors I (fibrinogen), V, VIII, vWF, X, plasminogen activator inhibitor-1 (PAI-1), and alpha2-antiplasmin. (1)DeltaO(2)(*) oxidation of plasminogen and fibrin facilitates their specific cleavage by plasminogen activators and plasmin. Furthermore,(1)DeltaO(2)(*)downregulates thrombocyte-function and upregulates PMN-function. Chloramines seem to be the main physiologic generators of (1)DeltaO(2)(*): in concentrations of 0.1-2 mM in blood they strongly inhibit coagulation and enhance thrombolysis. The biogenesis and reaction pattern of (1)DeltaO(2)(*) is of importance to understand the PMN-physiology in hemostasis, giving rise to new therapy forms of thromboatherothrombosis in man.

Animals↗

Tourniquet release for hemostasis increases bleeding. A randomized study of 77 knee replacements.

We conducted a prospective, randomized study of 77 primary knee replacement operations on 75 patients (52 women), with a mean age of 71 years, to evaluate the effect of tourniquet release for hemostasis on blood loss and transfusion requirements. The operations were all done with spinal anesthesia and the use of a midline skin incision and medial parapatellar approach. In group I, the tourniquet was released for hemostasis before the wound was closed. In group 2, the tourniquet was first released after the wound was closed and a compressive dressing had been applied. The total intra- and postoperative blood losses were, on average, 858 mL (SD 443) in group I and 589 mL (347) in group 2 (p = 0.01). The median units of blood given and the postoperative decreases in hemoglobin values were similar in both groups. In a subgroup of 45 cementless prostheses, the 25 patients with prostheses allocated to group 1 lost 1022 mL (397) blood, compared to 646 mL (333) by the 20 patients with prostheses in group 2 (p = 0.01). Our findings speak against the efficacy of tourniquet release for hemostasis in knee replacement surgery.

Adult↗

Application of recombinant activated factor VII during surgery for a giant skull base hemangiopericytoma to achieve safe hemostasis. Case report.

The authors report on a 64-year-old woman with a huge recurrent skull base hemangiopericytoma, in whom they encountered severe difficulty in attaining intraoperative hemostasis. Standard surgical hemostatic methods and the administration of fresh-frozen plasma and prothrombin complex concentrates failed to stop diffuse bleeding from an inoperable tumor remnant. At a critical point during the operation, the intravenous administration of recombinant activated factor VII, combined with mechanical compression, finally led to satisfactory hemostasis. The rationale for using recombinant activated factor VII in situations of uncontrolled bleeding during neurosurgical procedures is discussed, along with the literature in which the use of recombinant activated factor VII as a maneuver of last resort is reported for hemostasis in other surgical fields.

Cerebral Angiography↗

[Platelet-vascular and red cell components of hemostasis in hemodialyzed patients suffering from sever hemorrhagic fever with renal syndrome].

AIM: To evaluate effect of hemodialysis on functional state of platelet-vascular and red cell components of hemostasis in patients suffering from severe hemorrhagic fever with renal syndrome (SHFRS). MATERIALS AND METHODS: Parameters of platelet-vascular and red cell hemostasis were studied in 51 patients with SHFRS who were divided into two groups. 27 patients of group 1 received conservative treatment, 24 patients of group 2 were put on dialysis. RESULTS: In oliguria, red cell deformity, spontaneous and induced aggregation was similar in both groups. There was a statistically significant anemia, platelet hyperreaction. CONCLUSION: The detected disorders in hemostasis are attributed to severity of the disease but not effects of hemodialysis.

Adult↗

A cell-based model of hemostasis.

Based on our work and that of many other workers, we have developed a model of coagulation in vivo. Many workers have demonstrated mechanisms by which cells can influence the coagulation process. Nonetheless, the prevailing view of hemostasis remains that the protein coagulation factors direct and control the process with cells serving primarily to provide a phosphatidylserine containing surface on which the procoagulant complexes are assembled. By contrast, we propose a model in which coagulation is regulated by properties of cell surfaces. This model emphasizes the importance of specific cellular receptors for the coagulation proteins. Thus, cells with similar phosphatidylserine content can play very different roles in hemostasis depending on their complement of surface receptors. We propose that coagulation occurs not as a "cascade", but in three overlapping stages: 1) initiation, which occurs on a tissue factor bearing cell; 2) amplification, in which platelets and cofactors are activated to set the stage for large scale thrombin generation; and 3) propagation, in which large amounts of thrombin are generated on the platelet surface. This cell based model explains some aspects of hemostasis that a protein-centric model does not.

Animals↗

[Primary hemostasis exploration].

Primary hemostasis exploration involves many tests, but most of them are highly specialized. Meanwhile, a few simple and reliable assays can make possible a first orientation of the diagnosis in a routine laboratory. This review is organized in four parts. It highlights the importance of pre-analytical steps when exploring hemostasis, especially a carefully conducted clinical history and blood collecting conditions. It first presents the tests involved in the global exploration: the platelet count, the bleeding time, the occlusion time and the prothrombin consumption test. Then, this review presents the tests essential for the diagnosis of thrombocytopenia, von Willebrand disease and platelet disorders. Finally, we discussed about the limits and the future of diagnosis in primary hemostasis, and more particularly about endothelial cells and the adhesion proteins that are implicated.

Blood Coagulation Disorders↗

[Microcirculation and hemostasis in influenza and acute viral respiratory infections complicated with pneumonia].

AIM: To study microcirculation (MC), hemostasis and blood viscosity (BV) in influenza and acute respiratory viral infections (ARVI) complicated by pneumonia. MATERIAL AND METHODS: Conjunctival biomicroscopy, hemostasis and BV were studied in 232 patients with influenza and ARVI. In 91 of them the disease complicated with acute pneumonia (AP), in 87--with obstructive bronchitis. RESULTS: Irrespectively of the disease course, patients with influenza and ARVI showed intravascular changes in MC system, hypercoagulation, deterioration of fibrinolysis. In convalescence platelet aggregation increased, fibrinolytic blood activity enhanced. In influenza and ARVI complicated with AP intravascular changes and hypercoagulation were most pronounced. In uncomplicated influenza and ARVI accompanied by bronchitis such changes are less severe. BV was the highest in development of AP. CONCLUSION: MC and hemostatic disorders arising in influenza and ARVI seem to be essential pathogenetic links provoking development of AP. In intravascular aggregation of platelets and red cells, activation of plasmic hemostasis differentiated treatment with desaggregants and anticoagulants are indicated.

Acute Disease↗

[Functional status of the intima and thrombocytic hemostasis in patients with symptoms of atherosclerosis of the cerebral and peripheral vessels].

The indices characterizing the state of lipid metabolism, endothelium of arteries and thrombocytic hemostasis were investigated. It was shown that in the zone of atherosclerotic stenosis of the arteries there were marked transformations of the endothelium followed by a decrease of their anticoagulatory properties. The cause and effect relationship between the disturbed thrombocytic hemostasis and lesions of the endothelium in atherosclerosis was confirmed. It is these factors which are the cause of frequent thromboembolic complications, especially in patients with lesions of the cerebral arteries. It is necessary to include methods of correction of the disturbed thrombocytic hemostasis in the complex treatment of patients with atherosclerosis.

Aged↗

[State of the hemostasis system in Poland's syndrome].

The results of a complex investigation of the system of hemostasis in 14 women with Poland's syndrome have shown combined thrombocytic-coagulational disorders, symptoms of hypocoagulation. The functional properties were impaired against the background of the normal or moderately reduced number of thrombocytes. The data of examination, case history and results of investigation of the hemostasis system show the Poland syndrome to be a variant of mesenchymal dysplasias. Changes in a number of the indices of the thrombocytic link of hemostasis depend on the degree of the deformity. The scheme of preoperative medicamental correction has been mastered. The results of a control hemostasiological investigation have shown an improvement of hemostatic properties of the clot, normalization of the adhesive and aggregational properties of thrombocytes. Minimal hemorrhage from soft tissues was noted in operative procedures after medicamental pretreatment.

Adolescent↗

[Problems of hemostasis and hermetic properties in liver resections with application of fibrin-collagen substance].

Forty-seven patients with various diseases of the liver were treated from 1992 to 2002. Patients had undergone liver resections of different scope. In 20 patients (study group) wound covering "Tachokomb" was used for final hemostasis and high hermetic properties of wound surface. Conventional suturing of the vessels and bile ducts was performed in 27 patients of the control group. Reliable hemostasis of the hepatic stump after anatomic resection was achieved in all the patients of the study group. Application of wound covering decreased time of final hemostasis, severity of hemorrhage and blood transfusion during surgery. Biliary complications after surgery were seen more often. Application of combined glue composition failed to reduce significantly rate of biliary complications after surgery, their rate increased proportionally to extension of liver resection.

Adolescent↗

Hemostasis in the era of the chronic anticoagulated patient.

The principal goal of this article is to develop an understanding of how poly-N-acetylglucosamine (pGlcNAc) helps to achieve hemostasis through mechanisms that involve vasoconstriction, red blood cell agglutination and platelet activation for fibrin clot formation. Several important features of these three mechanisms should be understood. The involvement of endothelin-1 in mediating vasoconstriction should be recognized, as well as the observation that red blood cell agglutination is mediated by direct contact of the cells with pGlcNAc fibers. Also, the ability of pGlcNAc to contact activate platelets through integrin-dependent mechanisms and the resulting ability of the platelet to activate thrombin for fibrin gel formation should be understood. It is also important to recognize that having three redundant (and synergistic) mechanisms for surface hemostasis with pGlcNAc imparts utility when patients have specific bleeding diapathies due to anticoagulation therapies, hemophilia, etc. It should also be realized that the hemostatic properties of pGlcNAc are dependent on the specific structure of the polymer as well as the small (fine) diameter of the polymer fibers. Finally, it is important to understand that the acceleration of hemostasis at the dermal opening of a track will accelerate fibrin clot formation in the entire track, because Virchow s three conditions for thrombus formation are satisfied: hypercoagulability (provided by the hemostatic mechanisms of the pGlcNAc), stagnant blood (when a clot forms on the surface of the pGlcNAc) and tissue damage from the procedure.

Acetylglucosamine↗

Hemostasis in endoscopic sinus surgery using a specific gelatin-thrombin based agent (FloSeal).

The safety and efficacy of a new hemostatic sealant, based on a gel with collagen derived particles and topical thrombin (FloSeal, Fusion Medical Technologies, Inc. Fremont, CA) were assessed as an alternative to nasal packing for hemostasis in functional endoscopic sinus surgery. In a prospective clinical study of 50 patients undergoing bilateral endoscopic anterior ethmoidectomy, 2 ml FloSeal was used after surgery to stop bleeding. The results were compared to a control group of 50 patients with Merocel packing and showed that intraoperative hemostasis was rapid and equal in both groups. The main advantages of the new hemostatic sealant included a higher degree of comfort during postoperative nasal breathing and absence of complaints due to pressure or pain. There was only one case of postoperative bleeding on the 6th day, which required nasal packing. There were no more cases of stenoses or synechia in the ostiomeatal complex than were found in the Merocel group. No systemic side effects due to FloSeal were observed. This specific hemostatic sealant was shown to be a safe and efficacious alternative method for hemostasis in endoscopic sinus surgery with high patient satisfaction and an easy and fast mode of application.

Blood Loss, Surgical↗

[Changes in the thrombocyte and procoagulant links in hemostasis in patients with arterial hypertension].

A study of 62 workers with arterial hypertension of the ore mining industry revealed significant and various changes of the thrombocytic and coagulation hemostasis in patients. Hyperfibrinemia, increase of adhesive-aggregation properties of cellular elements, depression of fibrinolysis creates a thrombogenic situation. For choice of treatment tactics in clinical conditions it is recommended to evaluate the thrombocytic and procoagulant links of hemostasis. Disorders in the system of primary hemostasis (increase of adhesive-aggregational properties of cellular elements) are an indication to the use of antiaggregants (tyclid, tyclopidin). In case of fibrinolysis depression, anticoagulants should be used in the therapy complex.

Adult↗

[Hemostasis and trophoblast-specific beta 1-glycoprotein in spontaneous abortion].

The relationship between the increase in maternal serum concentration of pregnancy-specific beta 1-glycoprotein (SP1) and levels of components of hemostasis system was investigated. The concentrations of SP1 were measured in the blood sera of 234 pregnant women with recurrent spontaneous abortions, in 115 somatically healthy pregnant women and 75 donors. A direct correlation between serum SP1 and levels of components of hemostasis system was shown. Results suggest that disturbances in hemostasis system influence synthesis of some placental proteins, including SP1.

Abortion, Spontaneous↗

[Impaired hemostasis as a cause of intensified bleeding after heart surgery with extracorporeal blood circulation].

The paper contains the results of a retrospective analysis of causes for an intensified bleeding in patients operated on the heart with artificial blood circulation. An affected hemostasis plasma chain, i.e. insufficiency of blood coagulation factors due to hemodelution, hypofibrinogenemia etc., provoked the above disorder in 39% of patients with a higher postoperative bleeding. Additional reasons for the impaired hemostasis chain included: the "heparin-rebound" phenomenon (3.4%), activation of the secondary fibrinolysis (3.4%) and disseminated intravascular coagulation (DIC) (0.14%). Finally, an undiagnosed inadequate surgical hemostasis provoked an intense bleeding in 19.5% of cases.

Blood Coagulation Disorders↗

[Hemostasis in patients with diseases of the retina and uveal tract].

Hemostasis studies of 152 patients with inflammatory dystrophic and circulatory diseases of the retina and the uveal tract have shown that the major hemostasis disorders consisted in the presence of soluble fibrin monomer complexes in the blood of 62-90.5% of patients and in retarded lysis of the blood euglobulin fraction. Patients with the above hemostasis disorders and central serous chorioretinopathies and abiotrophies develop delayed formation of the fibrin clot and its poor retraction, that is characteristic of latent imbalance of the coagulation and fibrinolysis processes and liability to DIC. Patients with retinal vein thrombosis develop, besides delayed fibrin polymerization in the clot and reduction of platelet contractility, a drastic depression of the blood and lacrimal fibrinolytic activity. Central choroiditis and uveitis was associated with a marked increase of lacrimal fibrinolysis and reduced blood plasma fibrinolysis, along with enhanced paracoagulation and prolonged lysis of the blood euglobulin fraction, this resulting in hypoproteolytic hypercoagulation. Local and systemic fibrinolysis test may help choose the drugs for local and general pathogenetic therapy.

Adolescent↗