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A prospective, randomized, double-blind, placebo-controlled study of the platelet and global hemostatic effects of Ganoderma lucidum (Ling-Zhi) in healthy volunteers.

UNLABELLED: Ganoderma lucidum is a Chinese herbal medicine popular with cancer patients. Previous in vitro studies suggested that Ganoderma lucidum might impair hemostasis. In this prospective, randomized double-blind study, healthy volunteers received orally Ganoderma lucidum capsules 1.5 g (n = 20) or placebo (n = 20) daily for 4 wk. We monitored subjects before drug administration and at 4 and 8 wk thereafter by routine coagulation screen, fibrinogen concentration, von Willebrand ristocetin cofactor activity, platelet function analyzer PFA-100, and thrombelastography. There were no significant between-group differences and all measurements remained within the normal range. Ganoderma lucidum ingestion over 4 wk was not associated with impairment of hemostasis. IMPLICATIONS: Ingestion of Ganoderma lucidum does not cause impairment of hemostatic function in healthy volunteers, despite earlier in vitro reports that it may cause platelet inhibition and may have other antithrombotic and fibrinolytic activity. The use of Ganoderma lucidum preoperatively is unlikely to increase the risk of surgical bleeding in otherwise healthy patients.

Adult↗

The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery.

The value of human albumin (HA) for treating hypovolemia is controversial. Less expensive alternatives such as hydroxyethyl starch (HES) are sometimes refused because of unwanted side effects. We prospectively randomized 50 patients older than 70 years old undergoing major abdominal surgery to receive either 5% HA (n = 25) or a third generation HES preparation (6% HES 130/0.4; n = 25) when mean arterial blood pressure was <60 mm Hg and central venous pressure was <10 mm Hg. Hemodynamics, inflammation (interleukin-6), endothelial activation-integrity (adhesion molecules), coagulation (thrombelastography), and renal function (including kidney-specific proteins) were monitored after the induction of anesthesia, after surgery, 5 h in the intensive care unit, and on the first postoperative day. HA patients received 3960 +/- 590 mL of HA and 5070 +/- 1030 mL of Ringer's lactate solution, and HES patients received 3500 +/- 530 mL of HES and 4550 +/- 880 mL of Ringer's lactate solution. Total protein remained normal only in the HA-treated patients. No significant differences (P > 0.1) between the groups were seen with regard to hemodynamics, coagulation, and kidney function. Plasma levels of interleukin-6 and soluble adhesion molecules were significantly (P < 0.05) higher in the HA- than in the HES-treated patients. We conclude that HA in elderly patients undergoing major abdominal surgery can easily be replaced by a modern HES preparation. Because of the decreased inflammatory response and endothelial activation-injury, HES 130/0.4 seems to be the more appropriate fluid strategy for these patients.

Abdomen↗

[Physical mechanisms of solid-protein interactions in the interface between amorphous silicon carbide and fibrinogen].

State of the art in biomaterial research and implant design is a compromise between functionality and biocompatibility. Consequently the results often have disadvantages with respect to both aspects. In regard to biocompatibility the activation of the clotting system by alloplastic materials is of great significance, because it necessitates anticoagulant therapy. Further improvements of implant technology require an understanding of the interactions between blood and implants. Therefore a microscopic model of thrombogenesis at alloplastic surfaces will shortly be presented, which relates thrombogenicity of a material to the electronic structure of its surface. The requirements for high hemocompatibility, which result from this model--especially in regard to the density of states and the conductivity at the surface--are fulfilled by an amorphous alloy of silicon and carbon (a-SiC:H). The advantage of amorphous materials is that they do not obey stoichiometric rules. Thus they allow a continuous adjustment of the electronic parameters without fundamental changes of their mechanical and chemical properties. The theoretical results where checked by total internal reflection intrinsic fluorescence spectroscopy (TIRIF) as well as thrombelastography experiments (TEG). In comparison to conventional materials like titanium or LTI carbon the TEG-clotting time of a-SiC:H-coatings is prolonged in excess of 200%. As a consequence a-SiC:H is well suited as a hemocompatible coating material for hybrid structuring of cardiovascular implants.

Biocompatible Materials↗

Fibrin elasticity and coagulation.

Sudden increase of viscosity in former times indicated the start of coagulation. Yet its measurement destroyed the structure of coagulum. By the precursor method of thrombelastography the author 1944 found elasticity to be the essential physiological property of coagulum. In the production of elastic fibrin structure its early phase is the most efficient in this respect. The speed of prime structure formation is extremely fast in presence of enough phospholipid as well as of plasma factor XIII. Even high amounts of thrombin cannot replace one or both of these substances indispensable to grow rapidly a perfect fibrin web. This phase yet does not become effective if it is not accompanied by the orbital micro-flow of the new orbitometry method. Its shear is comparable to that in a coronary artery. The special resonance effect of the method in combination with the early phase of fibrin production is generating some kind of a physiological feed back: increasing fibrin will strengthen shear stress as long as less platelets are entangled which will reduce the elastic flexibility of fibrin web. Some kind of a "coagulation spin effect" in optimal combination of shear stress, phospholipid and factorXIII, will extremely fast originate a firm fibrin structure, a mechanism which may be of significance for a fast occlusion of arterial stenoses.

Blood Coagulation↗

Hematological assessment of patients undergoing plasmapheresis during cardiac surgery.

Methods of reducing patient exposure to homologous blood transfusions include the technique of intraoperative plasmapheresis for the production of platelet rich plasma (PRP). The present study was designed to determine the patient benefits of PRP by examining hemostatic changes in coagulation screens and viscoelastic whole blood monitoring (Thrombelastography, [TEG]). One hundred fifteen patients undergoing elective cardiac surgery were prospectively randomized into a blinded study. Sixty-three patients had 20 percent of the circulating plasma volume sequestered prior to heparinization and pheresed into PRP, which was reinfused 10 minutes following heparin reversal with protamine. The control (CTR) group of 52 patients were exposed to no sequestration procedure. Patients were followed to discharge and 112 parameters, including anthropometric, operative, and postoperative factors, were measured. There were no significant differences between patient groups in preoperative, cardiopulmonary bypass (CPB), or surgical parameters. Average PRP volume was 600+/-100 ml with a total platelet yield of 1.1 billion platelets per patient. TEG indices were determined at four distinct times during the surgical procedure. The CTR group had significantly higher pre-CPB TEG indices of 2.3+/-1.2 and 2.1+/-1.2 (mean+/-SD), vs. 1.8+/-1.5 and 1.4+/-1.7 in the PRP group (p less than .04). Following heparin reversal, pre-PRP reinfusion TEG values were similar between groups, although both groups had significantly decreased indices when compared to pre-CPB values. Thirty minutes post-PRP infusion the treatment group had significantly improved TEG recovery when compared to the CTR group, 1.0+/-1.2 vs. 0.3+/-1.7 (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Changes in blood coagulation in diabetic nephropathy].

Investigations on certain hemocoagulation indices are carried out of 52 diabetics, 32 of them with diabetic nephropathy. The following indices were determined: thrombocyte numer, thrombocyte adhesion and aggregation, recalcification and heparinrecalcification time, partial thromboplastin time (PTT) and prothrombin time, coagulation retraction and thrombelastography. Data for increased blood coagulation are established in diabetics and especially in the presence of nephropathy. Most manifested are the changes in thrombocyte adhesion, in PTT, recalcification and heparin-recalcification time. Changes in thrombelastogram and the rest of the indices are less manifested. In patients with more advanced forms of nephropathy--the increased hemocoagulation is more pronounced. The changes described are considered non diabetes specific and are associated with the accompanying atherosclerosis. Those changes might indicate inclusion of anticoagulants and antiaggregating medicines in the therapeutic program of patients with diabetic nephropathy with the respective indications.

Adult↗

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.

Animals↗

Acidic glycosaminoglycans in three layers of human aorta: their different constitution and anticoagulant function.

1) Constitutional difference of the acidic glycosaminoglycans (AGAG) in the three layers, the intima, media and adventitia, of normal human aorta was investigated by electrophoretic characterization and enzymatic analyses with other chemical determinations. The anticoagulant activity of the AGAG in the three layers of human aorta was compared by thrombelastography. 2) The analytical data indicated that the AGAG in the three layers out consisted of chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, heparan sulfates and hyaluronic acid. It was found that the proportion of dermatan sulfate and heparan sulfates was increased in order from the intima to the adventitia. 3) The predominant anticoagulant actihan in the inner layers referred to the concentration of glucuronic acid on thrombelastogram. The phenomenon was evidenced to be related with the constitutional difference of the AGAG in the three layers.

Adult↗

The Effect of Preoperative Aspirin and/or Heparin Therapy on Coagulation and Postoperative Blood Loss after Coronary Artery Bypass Surgery.

OBJECTIVE: To assess the effects of preoperative aspirin and/or intravenous heparin therapy on perioperative coagulation tests and postoperative blood loss for 24-hour after coronary artery bypass surgery. METHODS: Multiple conventional coagulation tests, activated clotting time, thrombelastograph, skin bleeding time and platelet aggregation were performed before induction of anaesthesia, following protamine administration and after skin closure in 45 patients. RESULTS: There was no significant difference in either coagulation tests or postoperative blood loss (median of 860 mL with a range of 275 to 2800 mL, versus 833 ml with a range of 500-1380 mL) between the aspirin and no-aspirin patients. Preoperative heparin therapy affected most coagulation tests (e.g. international normalised ratio, activated partial thromboplastin time, thrombin clotting time, prothrombin time, activated clotting time and coagulation time of thrombelastography) before anaesthesia. The effects disappeared following protamine administration and after skin closure. Post operative blood loss was not significantly increased for the heparin group compared with the no-heparin group (median of 850 mL with a range of 700-1400 mL, versus 856 mL with a range of 275-2800 mL, respectively). Similar results were seen in patients receiving preoperative co-administration of aspirin and heparin compared with patients receiving aspirin alone. There was no suppression of platelet activity in patients receiving preoperative heparin or co-administration of aspirin and heparin. However, such suppression was found in patients receiving aspirin only. CONCLUSION: This study suggests that preoperative aspirin ingestion and intravenous heparin therapy should be administered as indicated and that concerns about the risk of postoperative bleeding should not lead to modification or cessation of such therapy.

Journal Article↗

[Dilutional coagulopathy: development, diagnostic options and management].

When no fresh frozen plasma is available, acute major blood loss is compensated above all with crystalloids, colloids and red blood cell concentrates, meaning that all plasma clotting factors are diluted. Consumption coagulopathy is almost always accompanied by dilutional coagulopathy. Formulas for calculating critical blood loss and standard coagulation tests are often not helpful in the case of massive transfusion. On the other hand, systems suitable for point of care, such as thrombelastography, have important advantages. In the case of consumption and dilutional coagulopathy plasma coagulation is disturbed and critical values are first seen for fibrinogen. Not only is fibrin polymerization impaired by the bleeding-induced loss and dilution of fibrinogen, but also by interaction with artificial colloids, particularly hydroxyethyl starch preparations. Therapy of consumption and dilutional coagulopathy calls for fresh frozen plasma. If this is not available in sufficient quantity or within a reasonable time, coagulation factor concentrates must be used. Neither fresh frozen plasma therapy nor treatment with coagulation factor concentrates has been the subject of detailed clinical study. Further studies are needed to work out guidelines for coagulation management in the case of massive blood loss.

Blood Coagulation↗

[Use of phospholipids (Fibraccel) for hemostasis in thrombocytopenic-thrombocytopathic patients].

Eight thrombocytopenic/pathic patients received an intravenous infusion of phospholipids. In-vitro-bleeding test, thrombelastography and resonance thrombography were performed in order to show the hemostatic effect. There was no case in which phospholipids had an efficacy comparable to the transfusion of platelets. Two patients suffered from a severe anaphylactoid reaction after the administration of phospholipids.

Adolescent↗

Anticoagulant and antithrombotic action of the synthetic thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginine nitrile.

Anticoagulant and antithrombotic effects of a synthetic thrombin inhibitor of the tripeptide type, D-phenylalanyl-L-prolyl-L-arginine nitrile (1), were studied in vitro and in vivo. The anticoagulant action was investigated in common test assays such as thrombin time, activated partial thromboplastin time, prothrombin time and thrombelastography. In human plasma 1 caused a concentration-dependent prolongation of coagulation times and influenced the recalcification measured by thrombelastographic recording. In different models of experimental thrombosis in rats the antithrombotic effectiveness of 1 was shown. I.v. infusion of the thrombin inhibitor reduced or prevented the formation of stasis-induced venous thrombi and of arterial thrombi after electrically induced damage of the vessel wall as well as prolonged the time of a thrombotic occlusion of an extracorporeal arterio-venous shunt. At low doses 1 was also effective in thrombin-induced microthrombosis.

Animals↗

[Disseminated intravascular coagulation in eperythrozoonosis of swine].

Investigations were carried out on the influence of latent and clinically manifest Eperythrozoon suis infection upon haemostasis in swine. The study was carried out with 14 German Landrace pigs. Latent eperythrozoonosis was induced in 7 animals by experimental infection. Splenectomy of these 7 animals and 2 spontaneously infected pigs led to clinical manifestation of eperythrozoonosis. Five clinically healthy pigs were splenectomized and served as controls. In healthy pigs splenectomy was followed by a transient rise in fibrinogen and platelet count. Latent infection with Eperythrozoon suis did not cause an impairment of haemostasis. Acute eperythrozoonosis was associated with increased haemorrhagic tendency considered to be a consequence of intravascular coagulation and subsequent consumption coagulopathy. There was a prolongation of partial thromboplastin time and prothrombin time (Quick) and a decrease of platelet count. Thrombelastography showed prolongation of reaction and clot building time and a short-term decrease of maximum amplitude. Deviation from normal values was proportional to the number of red blood cells infected with Eperythrozoon suis. Anti-rickettsial therapy led to quick normalization of haemostasis. Various aspects of the cause and the consequences of the haemostatic defect are discussed with special regard to the underlying disease.

Anaplasmataceae Infections↗

Multiple uterine rupture and crushing injury of the fetal skull after blunt maternal trauma. A case report.

Multiple pelvic fractures and explosive-type uterine lacerations occurred in a previously healthy 17-year-old primigravida involved in a motor vehicle accident. The fetus suffered a crushed skull and was completely extruded with the placenta from the uterus. Treatment was complicated by severe disseminated intravascular coagulation with secondary fibrinolysis. Thrombelastography enabled us to rapidly evaluate the patient's coagulation status and to monitor her response to goal-directed therapeutic interventions (surgery, specific blood product therapy and epsilon-aminocaproic acid).

Accidents, Traffic↗

Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass.

Postoperative hemorrhage remains a major cause of morbidity after cardiopulmonary bypass (CPB). Treatment remains empiric because of the need for immediate correction and the lack of availability of rapid intraoperative coagulation monitoring (except for ACT) at most institutions. Thrombelastography (TEG) and Sonoclot analysis (SCT) are measures of viscoelastic properties of blood which allow rapid intraoperative evaluation of coagulation factor and platelet activity as well as overall clot integrity from a single blood sample. Routine coagulation tests (RCT) including activated clotting time (ACT), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level (FIB), and platelet count (PLT) were determined and compared to TEG and SCT to assess which best predicted clinical hemostasis after CPB. Forty-two patients prospectively felt to be at high risk for excessive post-CPB bleeding had blood obtained for RCT, TEG, and SCT analysis before systemic heparinization and 30 min after protamine administration. Nine of 42 patients had excessive chest tube drainage, but no reoperations were required. After CPB, mean values for RCT were normal, but there were abnormalities in TEG and SCT parameters that reflect platelet-fibrin interaction. Both TEG and SCT were 100% accurate in predicting bleeding in these nine patients and, overall, both tests were significantly better predictors of postoperative hemorrhage than RCT. We conclude that viscoelastic determinants of clot strength may be abnormal after CPB and that SCT and TEG are, therefore, more useful than RCT for the detection and management of coagulation defects associated with CPB.

Adult↗

[Short-lasting infusions of Fibraccel following aortocoronary bypass surgery. The effect on postoperative blood loss and hemostasis depending on the time of extracorporeal circulation].

Bleeding is a major problem in the post-operative period (p.o.) after aortocoronary bypass surgery. Harke et al. have investigated the beneficial effect of homologous phospholipid complex (Fibraccel) after mitral and/or aortic valve replacement. No actual data were available evaluating therapy with Fibraccel after aortocoronary bypass grafting. We were especially interested in the influence of Fibraccel on routine blood coagulation parameters: partial thromboplastin time (PTT), thrombin time (TT), prothrombin time = Quick fibrinogen, platelet count and activated clotting time, spontaneous platelet aggregation (alpha 2/Tr, platelet aggregation test II of Breddin), thrombelastography, blood loss from the chest drain, use of fresh frozen plasma, and side-effects of the substance after aortocoronary bypass grafting. Forty patients (6 female, 35 male, mean age 58 years, ASA III-IV) were studied in a randomized order. Patients who had acetylsalicylic acid (ASS) or anticoagulants during the last 7 days before operation were excluded. In 20 patients 50-ml Fibraccel infusions lasting 30 min each were started immediately after antagonism by protamine chloride. Subsequent 50-ml Fibraccel infusions were given every 4 h until 20 h after extracorporeal circulation (ECC). The other 20 patients received placebo infusions at corresponding times. Each patient had a routine ASS medication (0.5 gi.v) about 8 h p.o. Blood samples for immediate analysis were taken: I = before operation; II = after ECC, before protamine; III = 90 min after protamine; IV = on the first p.o. day (20.5 h after protamine).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗

[Thrombolytic therapy of deep venous thrombosis with rt-PA].

Recombinant human tissue-type plasminogen activator (rt-PA) was given to seven patients with phlebographically documented deep vein thrombosis at a dose of 60-120 mg/day (0.71-1.76 mg/kg body weight/24 h) for 2 to 4 days. rt-PA induced evident recanalization in 6 of 7 cases. The lowest here used dose of 0.71 mg/kg/24 h was thrombolytical highly effective, but a dose of 1.4 mg/kg/24 h and over was accompanied by bleeding from venous puncture sites. Coagulation analysis showed no obvious decrease of fibrinogen, while euglobulin clot lysis time and thrombelastography demonstrated the systemic fibrinolytic activity. Thus, therapy with rt-PA may represent an alternative and effective therapeutic procedure in treatment of venous thrombosis. The initial results make a case for expanded investigational use of rt-PA in patients with deep vein thrombosis to clarify conceivable advantages of therapy with this fibrin selective thrombolytic agent.

Blood Coagulation Tests↗

The influence of acetysalicylic acid on changes in platelet function due to physical exertion.

The influence of acetylsalicylic acid (ASA) on alterations of the platelets resulting from physical exertion was studied in 10 healthy volunteers. Before and 2 h after the administration of placebo or 1 g ASA, venous blood samples were taken for platelet counts, thrombelastography (TEG) and tests of ADP- and epinephrine-induced platelet aggregation. The blood in which the 2-h values were determined was sampled at the highest work-load during sub-maximum exercise on a bicycle ergometer (5 min each at 50, 100 and 150 watts). ASA had no effect on the alterations of the platelets due to physical effort: the increase in the first phase of epinephrine-induced aggregation, the elevation of the platelet count and the hypercoagulability demonstrable by TEG still persisted after the administration of ASA. Some effects were noted, however, that are also observed after the administration of ASA at rest: the second phase of epinephrine-induced aggregation was suppressed and disaggregation after induction with ADP was accelerated.

Adult↗