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At least 433 records · Page 24Linked to original sources
PubMed2003

Effects of human mast cell tryptase and eosinophil granule proteins on the kinetics of blood clotting.

Hypereosinophilic syndromes are often associated with thrombosis through unclear mechanisms, and mastocytosis has been associated with a variety of bleeding disorders. The present studies were aimed at defining the roles and interactions of eosinophil and mast cell constituents on the kinetics of blood clotting as measured by thromboelastograms. Eosinophil granule proteins and purified eosinophil peroxidase markedly reduced the anticoagulant properties of the mast cell tryptase/heparin complex. Moreover, eosinophil peroxidase by itself functioned as a powerful procoagulant and also inhibited the anticoagulant actions of heparin in a chromogenic assay for antithrombin III/factor Xa activity. The anticoagulant activity of the tryptase/heparin complex was attributable exclusively to the associated heparin and not to the intrinsic enzymatic activity of tryptase. Eosinophil granule proteins also strongly inhibited the enzymatic activity of tryptase in the presence of hydrogen peroxide, thus implicating a critical role for eosinophil peroxidase. We conclude that eosinophil granule proteins and eosinophil peroxidase both function as powerful procoagulants and also inhibit the anticoagulant and enzymatic activities of mast cell tryptase. The present results thus provide a mechanistic rationale for the well-established link between certain eosinophilic inflammatory disorders and hypercoagulant states. They also suggest that eosinophils may play an important role in neutralizing the anticoagulant activity of mast cell tryptase/heparin in various diseases.

Antithrombin III↗
PubMed1987

Treatment of acute myocardial infarction with subcutaneous heparin at low doses.

Heparin has been used intensively in the treatment of acute myocardial infarction and preinfarction angina (PA) at full doses as a single drug by us. However, heparin may be used at smaller doses for similar purposes. These doses are not exactly anticoagulant, even though they reduce blood hypercoagulability, and act mainly in an antithrombotic capacity. We studied 529 patients with acute myocardial infarction, of whom 262 were treated with subcutaneous heparin at low doses (5000 IU every 12 h) and 267 received conventional therapy without antithrombotic drugs. Heparin used was Heparina (Abbott) and Liquemine (Roche), in vials with the equivalence 1 cm3 = 50 mg = 5000 IU. Blood rheologic factors (thromboelastography, platelet adhesiveness, total blood viscosity, and number of platelets) were determined in all patients, those treated with heparin at low doses and also the control group, before and after the 30-day treatment period. Diagnosis was based on clinical symptoms, laboratory studies, and electrocardiogram examination. In both the 262 patients treated with heparin at low doses and in the control group of 267 patients, baseline values of rheological factors were high. After 30 days (i.e., after study completion) these high values which are statistically significant compared with normal values, with p less than 0.0001 for both groups, remained constant in the control group who did not receive heparin. On the contrary, in the group treated with heparin at low doses, all these factors changed. Heparin provides protection against thrombosis by increasing the negative charge of the vessel wall and by other reactions at the endothelial surface. Heparin requires a plasmatic component called antithrombine III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

A novel recombinant soluble human thrombomodulin, ART-123, activates the protein C pathway in healthy male volunteers.

The effect of a novel recombinant soluble human thrombomodulin, ART-123, on protein C activation was investigated by measuring plasma prothrombinase activity in four healthy male volunteers. ART-123 at a dose of 0.3 mg was administered as a bolus intravenous injection for 1 minute. Plasma ART-123 concentration and prothrombinase activity were determined before and immediately, 24, and 48 hours after injection, and thromboelastography was recorded before and immediately and 24 hours after injection. The mean elimination half-life was 19.82 +/- 2.10 hours. Compared with pretreatment levels, ART-123 reduced prothrombinase activity by 44.2 +/- 11.7%, 52.1 +/- 10.8%, and 61.0 +/- 14.7%, respectively, immediately, 24, and 48 hours after injection, suggesting that ART-123 activated the protein C pathway. ART-123 did not affect thromboelastography values. There were no abnormal findings for objective signs or laboratory tests, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, coagulation and hemostatic parameters, blood chemistry, and urinalysis. Based on these observations, ART-123 at a dose of 0.3 mg can activate the protein C pathway in healthy volunteers.

Adult↗
PubMed2007

Hemostatic properties of glucosamine-based materials.

Glucosamine- and N-acetyl glucosamine-containing polymers are being used in an increasing number of biomedical applications, including in products for surface (topical) hemostasis. The studies presented here investigate the relationship between the structure (conformation) and function (activation of hemostasis) of glucosamine-based materials. Several polymer systems were studied, including fibers isolated from a microalgal source containing poly-N-acetyl glucosamine polymers that are organized in a parallel, hydrogen-bonded tertiary structure and can be chemically modified to an antiparallel orientation; and gel formulation derivatives of the microalgal fibers consisting of partially deacetylated (F2 gel) and fully deacetylated (F3 gel) polymers. Comparison of the properties of the poly-N-acetyl glucosamine fiber-derived materials with chitin, chitosan, and commercial chitosan-based products are presented. Several studies were performed with the glucosamine-based materials, including (1) an analysis of the ability of materials to activate platelets and turnover of the intrinsic coagulation cascade, (2) an examination of the viscoelastic properties of mixtures of platelet-rich plasma and the glucosamine-based materials via thromboelastography, and (3) scanning electron microscopic studies to examine the morphology of the glucosamine-based materials. The results presented demonstrate that hemostatic responses to the glucosamine-based materials studied are highly dependent on their chemical nature and tertiary/quaternary structure. The unique natural microalgal fibers were found to have strongly prohemostatic activity compared to the other materials studied.

Acetylglucosamine↗
PubMed2004

Thromboelastogram monitoring in the perioperative period of hepatectomy for adult living liver donation.

Living donor liver transplantation (LDLT) is becoming a widespread procedure. However, the risk of surgical and medical complications in healthy donors is still a major concern. Hypercoagulability contributes to thromboembolic complications after surgery, but alterations of hemostasis after liver resection are difficult to predict. This study aims to define the perioperative coagulation profile of living liver donors by the use of both routine tests and thromboelastogram (TEG). Ten subjects undergoing right hepatectomy for LDLT were studied. A complete coagulation screening was performed before operation. The coagulation profile was evaluated by platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), and TEG at the beginning and at the end of surgery, and on days 1, 3, 5, and 10 after operation, while the donors were under low molecular weight heparin (LMWH) prophylaxis. At preoperative screening, no subject showed evidence of a prothrombotic state. In all cases, TEG was normal at the beginning of surgery. In the postoperative period, despite decreased platelet counts, increased PT-INR, and normal aPTT values, TEG evidenced the progressive development of hypercoagulability in 4 subjects on day 5 and in 6 subjects on day 10. One donor with a definitely hypercoagulable TEG on day 5 experienced deep venous thrombosis (DVT) on day 8, which was resolved with therapeutic doses of LMWH. In conclusion, despite routine tests suggesting hypocoagulability and LMWH prophylaxis, TEG monitoring showed the unexpected occurrence of hypercoagulability in the majority of the subjects after hepatectomy for LDLT. TEG monitoring could be useful in the perioperative management of donors to guide antithrombotic treatment and increase the safety of the procedure.

Adult↗
PubMed2005

In vitro biological performances of phosphorylcholine-grafted ePTFE prostheses through RFGD plasma techniques.

Arterial prostheses made of microporous Teflon (ePTFE) are currently used in vascular surgery as bypasses for small and medium vessels. However, several clinical complications, such as thrombosis, frequently occur in these prostheses when implanted in humans. In this work, an original strategy was developed to improve the hemocompatibility of ePTFE prostheses, based on glow-discharge surface modification followed by chemical grafting of phosphorylcholine, known for its hemocompatible properties. This procedure leads to a covalent attachment of the molecules, therefore preventing their removal by shear stress induced by blood flow at the implant wall. The improvement of the blood compatibility properties of the modified ePTFE arterial prostheses have been investigated by in vitro tests such as thromboelastography, neutrophil adsorption, platelet aggregation, and cell cultures. These in vitro tests put in evidence that thrombogenicity index, platelet aggregation, and neutrophil adhesion were decreased by the molecule grafted on the prostheses. Moreover, the cell growth on the surface of the PRC-grafted prostheses was greatly enhanced in comparison to the virgin prosthesis. Based on these results, it could be concluded that PRC grafting on ePTFE prostheses permit to improve in vitro hemocompatibility and biocompatibility in comparison with their virgin counterpart.

Ammonia↗
PubMed2001

Analysis of coagulation changes associated with supraceliac aortic crossclamping using thromboelastography.

INTRODUCTION: The etiology of the coagulation changes seen with supraceliac (SC) aortic crossclamping (AXC) remains controversial; both primary fibrinolysis and clotting factor consumption have been implicated. The cause of these changes was investigated with thromboelastography (TEG), a test that measures the viscoelastic properties of thrombus to dynamically assess coagulation and fibrinolysis. METHODS: Eight pigs underwent SC AXC for 30 min; 5 pigs undergoing 30 min of infrarenal (IR) aortic clamping served as controls. Blood was drawn before AXC, before unclamping, and 5 and 60 min after unclamping. Thromboelastography and standard coagulation tests [prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and platelet count] were performed. Measured TEG parameters included fibrinolytic index (a measure of fibrinolysis), r value (a reflection of intrinsic coagulation cascade activity), and the alpha angle and K values (measures of the speed of solid clot formation). Repeated measures ANOVA and t test were used for statistical analysis. RESULTS: There was no difference in the fibrinolytic index at any time point between the two groups. Increased activity of the intrinsic coagulation cascade during SC clamping was reflected by a lower R value just before unclamping (12.6 +/- 3.0 vs 20.0 +/- 3.0, P = 0.048) compared to IR AXC. Decreased speed of solid clot formation was noted 5 min after unclamping in the SC group but not the IR group [as defined by an increased K value (ANOVA, P = 0.010) and a decreased alpha angle value (ANOVA, P = 0.005)]. Fibrinogen levels were lower in the SC than in the IR group 5 (P = 0.013) and 60 min after unclamping (P = 0.02), but PT, PTT, and platelets did not differ between the groups at any time points. CONCLUSIONS: Thirty minutes of SC AXC does not result in fibrinolysis. There is increased clotting activity during SC clamping followed by decreased speed of clot formation and decreased fibrinogen levels after unclamping. These changes are consistent with clotting factor consumption.

Animals↗