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PubMedDate not supplied

Coagulation and cytokine profile after major hepatobiliary surgery in Chinese patients.

BACKGROUND/AIMS: Hypercoagulability and increased circulating cytokine levels have been separately reported after surgical operations. We investigated whether the cytokine level and postoperative coagulation profile would change similarly in Chinese patients undergoing major hepatobiliary surgery. METHODOLOGY: Serial serum levels of IL-6, IL-1 beta and TNF-alpha were measured by colorimetric ELISA. Serial coagulation profile was measured by thrombelastography. Hemoglobin and white cell counts were also measured serially. RESULTS: Only mild hypercoagulability was found at the 12th and 144th hours, evidenced by shortening of r-time and k-time on thrombelastography (P < 0.05). IL-6 and IL-1 beta levels were significantly raised from the 12th hour (P < 0.01) while TNF-alpha level was unchanged. From the 3rd hour to the 48th hour, there was negative correlation between IL-6 levels and various thrombelastographic parameters such as coagulation index (r = -0.777, P < 0.001); k-time (r = 0.478, P < 0.05); maximum amplitude (r = -0.688, P < 0.01) and angle (r = -0.665, P < 0.01). CONCLUSIONS: We observed a much milder degree of hypercoagulability in Chinese patients after major hepatobiliary surgery as compared to those reported in other operations in non-Chinese patients. Unlike in sepsis where a close link between increased cytokine levels and hypercoagulability has been reported, increase in IL-6 was associated with less hypercoagulability in Chinese patients after major hepatobiliary surgery.

Adult↗
PubMed2005

Hextend attenuates hypercoagulability after severe liver injury in swine.

BACKGROUND: Hypercoagulability is a major source of morbidity and mortality after injury. A resuscitation regimen that modulates this coagulopathy may prove beneficial. We sought to evaluate the effects of lactated Ringer's (LR) solution and Hextend on the resuscitation of uncontrolled hemorrhagic shock. METHODS: Twenty swine underwent invasive line placement, midline celiotomy, and splenectomy. After a 15-minute stabilization period, we recorded a baseline mean arterial pressure and created a grade V liver injury. The animals bled freely for 30 minutes, after which we measured the initial blood loss (that after injury). We blindly randomized the swine to receive LR solution or Hextend to achieve and maintain the baseline mean arterial pressure for 90 minutes postinjury. Laboratory values were obtained at baseline and on completion of the 2-hour study period. RESULTS: The initial blood loss (before resuscitation) was 22 mL/kg in both treatment groups (p = 0.97). Animals required 119 +/- 78 mL/kg of fluid in the LR group and 40 +/- 21 mL/kg in the Hextend group (p = 0.01). After resuscitation, the secondary blood loss was 3.7 +/- 1.7 mL/kg in the LR group and 4.7 +/- 1.1 mL/kg in the Hextend group (p = 0.1). Thrombelastography revealed a hypercoagulable state in all animals after injury. This was less pronounced in those animals resuscitated with Hextend. Routine tests of coagulation did not reveal a hypercoagulable state. CONCLUSION: Modulation and restoration of normal coagulation is critical in the management of trauma patients. The patient's coagulation profile might determine the type of fluid to be used at various times during their course. Thrombelastography is superior to routine coagulation assays for the detection of a hypercoagulable state. Resuscitation with Hextend results in a decreased fluid requirement and attenuation of hypercoagulability after injury without increased blood loss.

Animals↗
PubMed2006

The relationship between coagulation and the extend of surgery and postoperative infection in surgical infants below 6 months of age.

AIM: First to assess coagulation changes after surgery in children below 6 months of age. Second to detect differences attributable to the extent of surgery and postoperative infection. MATERIALS AND METHODS: Blood counts, haemoglobin concentration (Hb), haematocrit (Ht), prothrombine time (PT), activated partial thromboplastine time (aPTT) and thrombelastography (TEG) were studied pre- and 2+/-1/2 d postoperatively. Patients were divided in 3 groups. I: minor surgery without access to the abdomen or thorax (n=51); II: abdominal or thoracic interventions (n=24); III: abdominal surgery with postoperative sepsis (n=11). RESULTS: Preoperative values of Hb, Ht and INR were related to the age of the infant. Postoperatively clot strength and formation rate increased in gr. I (p<0.05). In gr. II, clot formation was initiated earlier (p<0.05) even though PT decreased (p<0.05). In group III, patients postoperatively developed a tendency for hypocoagulability in all TEG-parameters, but not in plasmatic coagulation. Postoperative TEG measurements were significantly inferior in gr. III when compared to gr. I and II. CONCLUSION: Our findings suggest activation of whole blood coagulation in the uncomplicated postoperative period despite of a decrease in plasmatic coagulation. In sepsis, only thrombelastography, but not plasmatic coagulation was affected.

Age Factors↗
PubMed1985

Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation.

The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30-60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors.

Adult↗
PubMed2006

Effects of cardiac surgery on hemostasis.

Cardiac surgery affects both coagulation and platelet function. Revision of surgery due to bleeding has to be performed in 2% to 6% of patients undergoing cardiac surgery and is generally associated with a marked deterioration in prognosis. Factors contributing to acquired hemostatic abnormalities in cardiac surgery include the use of anticoagulants as well as the activation and consumption of coagulation factors and platelets induced by the extracorporeal circulation. Prophylactic use of antifibrinolytic agents such as aprotinin and tranexamic acid has been demonstrated to reduce the blood loss by half. Adequacy of heparin-induced anticoagulation in the perioperative setting is commonly controlled by the activated clotting time. This method also indicates the correct reversal of the heparin effect by protamine. In recent years, thrombelastography has proved to be valuable for diagnosis of coagulopathy associated with cardiac surgery. In addition, the use of thrombelastography-based algorithms has been shown to reduce transfusion requirements. In contrast to point of care methods, laboratory assessment of hemostasis is more time-consuming and, thus, often not as rapidly available as required. At this time, the therapy for perioperative hemostatic abnormalities is based mainly on the administration of blood components (fresh frozen plasma and platelet concentrates). In the future, recombinant activated factor VIIa might prove to be a therapeutic option in patients with otherwise untractable bleeding, but the efficacy of recombinant activated factor VIIa has yet to be defined for this indication.

Blood Coagulation Disorders↗
PubMed2003

Coagulation monitoring and management of anticoagulation during cardiac assist device support.

BACKGROUND: The incidence of clinically significant thromboembolic events due to the use of cardiac assist device systems remains high. Despite the considerable advances in cardiac assist device technology, the monitoring and management of the hypercoagulable coagulation status, resulting from foreign surfaces of the assist device system, altered rheologic conditions, and blood stasis in the recipient heart remain a challenge. Moreover septic complications and insufficient anticoagulation are responsible for thromboembolic events. METHODS: In addition to standard coagulation analysis, functional coagulation tests were performed including the use of a thrombelastographic monitoring system (ROTEG) and a platelet function analyzer (PFA-100). RESULTS: Severe biventricular ischemic heart failure developed in a 58-year-old man with acute myocardial infarction and he needed a biventricular assist device for a bridge to cardiac transplantation. Although the patient received acenocoumarol (Sintrom; Novartis Pharma, Vienna, Austria) and acetylsalicylic acid (Aspisol; Bayer AG, Leverkusen, Germany) as usual, ROTEG and the PFA-100 detected hypercoagulability while routine coagulation screening tests showed hypocoagulability. Moreover thrombus formation surrounding the canula of the left ventricular assist device was detected. Antithrombotic therapy with clopidogrel (Plavix) was initiated. Coagulation was closely monitored with modified thrombelastography and the PFA-100 to achieve sufficient but not overwhelming anticoagulation therapy. Three months after biventricular assist device implantation the patient underwent successful transplantation with no major blood loss. CONCLUSIONS: Thrombelastography should be the standard form of monitoring in such patients to decrease the risk of thromboembolic events and prevent bleeding complications.

Acenocoumarol↗
PubMed2004

[Monitoring of Perioperative Dilutional Coagulopathy Using the ROTEM Analyzer: Basic Principles and Clinical Examples].

Recent changes in quality of transfusion supply, transfusion triggers as well as fluid therapy promote the development of dilutional coagulopathy. Nevertheless, up to now guidelines generally assume presence of hypocoagulability when more than one individual circulating blood volume is lost. This might be true for some patients under some conditions but is not necessarily true for every patient. Routine coagulation tests are insufficient in predicting increased bleeding and, moreover, available after an unacceptable time delay. Therefore the occurrence of diffuse microvascular bleeding is often used as clinical sign to start hemostatic therapy. However, such severe derangement of hemostasis might lead to the development of secondary tissue damage and frequently is unresponsive to conventional treatment. Coagulopathy occurring during extensive surgery or after polytrauma can be detected and treated early when using the ROTEM monitoring. Recent data showing a direct beneficial effect of hemostatic therapy on blood loss and final outcome are scarce. However, evidence exists that the amount of blood loss, presence of coagulopathy and number of transfusions needed are associated with poor outcome in bleeding patients. Although manifold articles have been published already using thrombelastography for various indications (medline research "thrombelastography", 2022 articles), further data are needed to confirm the clinical experience that this technique is an excellent tool for safe patient management.

Autoanalysis↗
PubMed2002

Effect of taurine on platelets and the plasma coagulation system.

It is not yet clear what exact mechanisms are at work in hibernating animals that prevent clot formation and maintain tissue perfusion under conditions of very slow blood flow and increased blood viscosity brought about by the low temperatures. It has been shown that the total amino acid pool increases more then two fold in hibernating animals with taurine accounting for about 50% of this increase [Storey et al., Proc Natl Acad Sci USA 1988; 85(21): 8350-4]. This work investigates the effect of taurine on platelets and the plasma coagulation system. Taurine was added at different concentrations in the range between 5 and 25 mM to donor plasma. Using STA/STA Compact coagulation analyzer the following tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). At the highest concentration tested (25 mM) taurine prolonged TT by 9%. The prolongation was statistically significant but not clinically significant retaining TT within normal limits (16.7-20.7 s). PT and APTT remained unchanged by taurine. The effect of taurine on platelets was assessed by platelet aggregation by thrombin, extent of platelet shape change (ESC) induced by ADP, and thrombelastography. Taurine at 5 mM final concentration inhibited platelet aggregation by 10%. Increasing taurine concentration to 25 mM did not result in a further augmentation of the inhibitory effect. ESC was unaffected by taurine. Clot strength determined by thrombelastography also remained unchanged by taurine.

Adenosine Diphosphate↗
PubMedDate not supplied

Extensive coagulation monitoring in patients after implantation of the MicroMed Debakey continuous flow axial pump.

Ventricular assist device (VAD) implantation is associated with impaired primary hemostasis and thromboembolic complications. Recently, a new generation of implantable continuous flow axial pumps was introduced into clinical application. To study the potential thrombogenic properties of this type of pump, we applied extensive platelet monitoring was applied. In our institution, 13 patients received the MicroMed DeBakey VAD as a bridge to transplantation. Routine coagulation tests (platelet count, activated partial thromboplastin time, prothrombin time, antithrombin III activity) and platelet function tests (whole blood aggregometry, thrombelastography, flow cytometry) were performed. No clinically relevant thromboembolic events were detected. No correlation was found between global function tests, platelet aggregation, and thrombelastography. No correlation was detected between platelet activation and hemolysis parameters. Platelet aggregation and coagulation index were significantly suppressed early after operation. A subsequent phase of hyper-aggregability, starting around day 6, suggested the initiation of antiaggregation therapy. Platelet activation markers were upregulated in the postoperative period but were returned to preoperative levels after initiation of aspirin. In contrast to routine coagulation monitoring, platelet function tests reflect in detail the coagulation status of blood pump recipients and the efficiency of antiaggregation therapy. Aspirin and dipyridamole therapy in addition to oral anticoagulation using phenprocoumon may contribute to platelet function and clot mechanics restoration and is, therefore, recommended for patients after VAD implantation.

Adolescent↗
PubMed1995

Surfactant incorporation markedly alters mechanical properties of a fibrin clot.

Intra-alveolar clot formation is a common finding in acute and chronic inflammatory lung diseases. Incorporation of lipophilic surfactant components into a growing fibrin clot has recently been reported (Am. J. Respir. Cell Mol. Biol. 1993; 9:213-220). In the present study, we investigated the influence of such surfactant incorporation on the elastic properties and water permeability of the fibrin polymer. Thrombelastography and compaction experiments were employed for assessment of the elastic properties, and the permeability characteristics of the clot material were addressed in fibrin-packed columns. Two calf lung surfactant extracts (CLSE and Alveofact), Curosurf, and a synthetic phospholipid mixture (dipalmitoylphosphatidylcholine, phosphatidylglycerol, and palmitic acid at a ratio of 68.5:22.5:9 [wt/wt]) were used. The presence of surfactant did not affect the cleavage of fibrinopeptide A upon incubation of fibrinogen with thrombin (enzyme-linked immunosorbent assay technique). Similarly, kinetics and extent of factor XIII-induced covalent crosslinkage of the fibrin network remained unchanged in the presence of surfactant (sodium dodecyl sulfate polyacrylamide gel electrophoresis and D-Dimer quantification upon subsequent clot lysis). All surfactants, however, dose-dependently decreased the elastic modulus of the arising fibrin polymer. The maximal amplitude in thrombelastography was reduced, and the recovery of fluid after centrifugation of the fibrin clot increased. Fibrin clots embedding natural surfactant material displayed reduced permeability for saline as compared with control fibrin polymers. Subsequent washout of lipids from these clots with Triton X-100 resulted in increased hydraulic conductivity. This was accompanied by an increase in pore size, suggesting altered architecture of the fibrin matrix generated in the presence of surfactant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Global anticoagulant effects of a synthetic anti-factor Xa inhibitor (DX-9065a): implications for interventional use.

Heparin has been conventionally used as an anticoagulant for medical and surgical indications. Because factor Xa is an essential component of the prothrombinase complex and leads to the generation of thrombin, its inhibition has become a focus of newer antithrombotic drug development. The in vitro anticoagulant profile of DX-9065a, a synthetic direct factor Xa inhibitor, was studied using activated clotting time assay, thrombelastography, and global clotting tests, such as prothrombin time (PT), activated partial thromboplastin time (aPTT), diluted aPTT, Heptest, Heptest-HI, dilute Russell's viper venom time (dRVVT), thrombin time, ecarin clotting time, and amidolytic anti-Xa assay. In addition, the effect of DX-9065a on platelet aggregation and inhibition of thrombin generation markers (FPA, F1+2, and TAT) were studied. The pharmacokinetic and pharmacodynamic profiles of DX-9065a were also studied in a non-human primate (Macaca mulatta) model. DX-9065a produced a concentration-dependent increase in the Hemochron celite ACT and HemoTec ACT. Clotting times of 538 +/- 19 and 401 +/- 12, respectively, were reached at a concentration of 25 microg/mL signifying that DX-9065a may be useful in interventional cardiological procedures. DX-9065a prolonged the r-time on thrombelastography. DX-9065a did not show any effect on adenosine diphosphate (ADP)-, collagen-, epinephrine-, and arachidonic acid-induced platelet aggregation at concentrations up to 10 microgram/mL. DX-9065a exhibited a concentration-dependent prolongation of the PT, aPTT, diluted aPTT, Heptest, dRVVT, and reached the clotting times of 51.6, 132, 193, 47.9, 129.9 seconds, respectively, at a final concentration of 12.5 microgram/mL; compared to a control value of 10.6, 30.2, 41.9, 14, 32.2 seconds, respectively. DX-9065a did not affect the ecarin clotting time and thrombin time at concentrations up to 12.5 microgram/mL. Because DX-9065a prolonged the dRVVT, this may impact diagnostic screening of patients with systemic lupus erythematosus.

Adenosine Diphosphate↗
PubMed1989

The pharmacological profile of the low molecular weight heparin 21-23 in man: anticoagulant, lipolytic and protamine reversible effects.

The anticoagulant, lipolytic and protamine reversible effects of high doses of low molecular weight (LMW) heparin 21-23 and unfractionated heparin were compared in man. 7,500 units of each heparin were applied, which corresponds to 90 mg LMW heparin and 48 mg unfractionated heparin. The anticoagulant properties of the LMW heparin are characterized by a doubled half life of factor Xa activity, smaller influence on aPTT and thrombin after intravenous (i.v.) and subcutaneous (s.c.) injection, and higher bioavailability of factor Xa activity after s.c. administration (90% versus 15%). Protamine chloride completely neutralizes the effect on aPTT and thrombin and reduces the anti factor Xa activity by 60%. The bleeding time is prolonged by both normal and LMW heparin by 20%. This effect is normalized by protamine chloride, too. Thrombelastography with recalcified whole blood demonstrates that protamine chloride shortens but not completely normalizes the coagulation time in presence of either unfractionated or LMW heparin. The half life of lipoprotein lipase (LPL) activity is 60 min after i.v. administration of unfractionated heparin and 120 min with LMW heparin. Although the release of lipases (LPL and HTGL) is higher after i.v. and s.c. administration of the LMW heparin they do not induce higher releases of free fatty acids. This indicates that the lipolytic activity of this LMW heparin and unfractionated heparin is similar. The results show an improved anticoagulant pharmacological profile of this LMW heparin as compared to unfractionated heparin. Protamine normalizes the anticoagulant effects of LMW heparin with exception of a residual anti factor Xa activity and normalizes the changes of bleeding time and thrombelastography.

Adult↗
PubMed1996

[Anesthesiologic and intensive care requirements in liver transplantation].

The complex anaesthesia and intensive care of liver transplantation require special instruments beside expert's knowledge. We monitorize the haemodynamics invasively during the operation and immediately afterward. In the later period of intensive care we prefer the noninvasive haemodynamic monitoring techniques. The transoesophageal echocardiography has special role in the anaesthesia of liver transplantation. One of the most important equipment during the operation is the biopump that assures the shunt between the lower and the upper body. Controlling it also belongs to the tasks of anaesthesiologist. During the anaesthesia and early period of intensive care the most serious problem can be the disfunction of blood coagulation system of the recipient. To investigate it the thrombelastography is the most suitable technique which can show the in vivo processes. To analyze the curve of the thrombelastography requires special knowledge. Similarly, the analysis of the electroencephalogram during the anaesthesia is not the everyday task of an anaesthesiologist. To reduce the blood requirements during the operation we use the autotransfusion techniques. During the anaesthesia of the liver transplantation we use other equipment that belong to the everyday work of an anaesthesiologist i.e.: rapid blood infusion and patient warming and cooling systems, rapid laboratory and blood-gas analyzing methods. The anaesthesia and intensive care of liver transplantation claim wideranging knowledge of anaesthesiologist not only theoretically but also practically.

Anesthesia↗
PubMed1995

Postoperative hypercoagulability and deep-vein thrombosis after laparoscopic cholecystectomy.

Patients who undergo laparoscopic cholecystectomy (LC) are operated on under general anesthesia, in a reverse Trendelenburg position, with 12-15-mmHg pneumoperitoneum. All of these factors can induce venous stasis of the legs, which may lead to postoperative deep-vein thrombosis (DVT). The objectives of this study were to assess the degree of hypercoagulability and to determine the rate of postoperative DVT in a group of 100 patients in whom LC was completed. Whole-blood thrombelastography (TEG) and plasma-activated partial thromboplastin time (PTT) determination were carried out preoperatively and on the 1st postoperative day. All patients received pre-, intra-, and postoperative graduated compression stockings and sequential pneumatic compression devices until fully ambulatory. Twenty-six percent of the patients with a risk score > 4, or a post-operative TEG index > +5.0, received subcutaneous heparin (5,000 units b.i.d.), beginning in the postoperative period and continuing for 4 weeks as an outpatient. A complete venous duplex scan of both legs was performed on the 7th postoperative day, at the time of their office visit. Our results revealed significant postoperative hypercoagulability for the TEG index (P < 0.005) and for PTT (P < 0.05). One patient had an asymptomatic DVT (1%), and no side effects from the mechanical or pharmacological prophylaxis occurred in this series. These data suggest that the low incidence of thrombosis in the face of theoretical and laboratory evidence of postoperative hypercoagulability may reflect an effective prophylactic regime.(ABSTRACT TRUNCATED AT 250 WORDS)

Bandages↗
PubMed2005

[High dose fibrinogen administration for acute therapy of coagulopathy during massive perioperative transfusion].

During acute and severe perioperative bleeding a coagulopathy due to depletion, consumption and dilution of clotting factors and thrombocytes may occur. Diagnosis and therapy of such a coagulopathy should take place immediately. We report two cases of acute coagulopathy during perioperative bleeding and massive transfusion, which were treated successfully by administration of high dose fibrinogen concentrate. Diagnosis and treatment control were performed by thrombelastography.

Aged↗
PubMedDate not supplied

Distribution of acidic glycosaminoglycans in the intima, media and adventitia of bovine aorta and their anticoagulant properties.

SUMMARY: 1. The constituents of acidic glycosaminoglycans in the tunica intima, media and adventitia were studied by means of an enzymatic assay with chondroitinases and by electrophoretic characterization. 2. The content of the acidic glycosaminoglycans was higher in the intima than in the adventitia based on defatted dry tissue weight. The gel filtration pattern showed that, with chondroitinase-AC, the proportion of the intact glycosaminoglycans is greater in the adventitia than in the intima. 3. Electrophoresis before and after digestion with chondroitinases indicated that the three layers contain chondroitin-4- and -6-sulfates, dermatan sulfate, heparan sulfates and hyaluronic acid. In the case of the adventitia, bands migrating like the heparin standard were also detected. 4. Paper chromatographic separation of the unsaturated disaccharides after digestion with chondroitinases revealed that the proportion of chondroitin-6-sulfate is predominant in the intima, whereas the proportion of heparan sulfates, hyaluronic acid and dermatan sulfate is one and one-half-2 times higher in the adventitia than in the intima. 5. Anticoagulant activity, measured by thrombelastography, of the acidic glycosaminoglycans in the three layers clearly indicated that the glycosaminoglycans in the adventitia possess the highest potency among the three layers. It was considered that the higher activity of the glycosaminoglycans in the adventitia is due to the relatively greater proportion of heparan sulfates and dermatan sulfate.

Animals↗
PubMed1990

Anticoagulant properties of placenta protein 4 (annexin V).

A placenta protein, originally termed PP4, was found to inhibit the aPTT in a concentration-dependent manner. PP4 which turned out to be identical with a vascular anticoagulant of the annexin type, inhibits the blood clotting process by binding of the essential lipids in a reaction which is dependent on calcium ions. Also in the presence of calcium PP4 combines with platelet membranes neutralizing their procoagulant effect. By fluorescence-microscopy binding of PP4 to stimulated macrophages is shown. The antithrombotic effect of PP4 is demonstrated by means of thrombelastography of human blood. Coagulation triggered by the addition of thromboplastin/lipid-mixtures is extinguished by PP4.

Anticoagulants↗
PubMed1991

In-vivo antithrombotic potency of placenta protein 4 (annexin V).

The antithrombotic properties of Placenta Protein 4 (PP4) were investigated in laser or photochemically induced thrombus formation models in rats. In both in-vivo test-systems PP4 displayed a significant antithrombotic effect at dose levels as low as 0.3 and 1.0 mg/kg body weight. Bleeding times, surprisingly, were not prolonged significantly at these dose regimens. Maximal inhibition of thrombus formation in the laser-model was observed 15 min after intravenous administration of PP4, but was not recognizable in a clear-cut reaction in the second model. Determination of PP4 plasma levels in two monkeys revealed a half-life of 11.5 and 14.9 min, respectively. The maximal anticoagulant effect was observed between 15 and 30 min after administration of PP4 as determined functionally by means of thrombelastography.

Animals↗