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PubMed1989

Biomembranes as models for polymer surfaces. V. Thrombelastographic studies of polymeric lipids and polyesters.

Our approach to the design of haemocompatible biomaterials is based upon the concept that coating a polymer or metal surface with phosphatidylcholine polar groups (corresponding to the major phospholipid of the human erythrocyte outer cell membrane) will improve their haemocompatibility. We have examined the effect on blood coagulation of a number of substrates: those normally used in prosthetic devices such as polyethylene terephthalate (Dacron), expanded polytetrafluoroethylene, silicone and new polymers which contain the phosphatidylcholine head group (phosphorylcholine). The effect on coagulation of blood exposed to these substrates was determined by the technique of material thrombelastography, a relatively new method for the in vitro screening of biomaterial thrombogenicity. The results obtained with Dacron, polytetrafluoroethylene and silicone are compared with those obtained with a phospholipid-dipalmitoyl-phosphatidylcholine, a polymerized phospholipid-diacetylenicphosphatidylcholine, and a range of recently synthesized polyesters, each of which contains the phosphorylcholine polar head group.

Biocompatible Materials↗
PubMed1985

Thrombelastographic diagnosis of blood coagulation in two freshwater fish species.

Blood coagulation in two freshwater fish species was investigated by thrombelastography. This indicated that the process in fish is similar to that of humans and mammals, involving the same three basic processes, i.e. extrinsic and/or intrinsic thromboplastin generation, the conversion of prothrombin in thrombin and the formation of fibrinogen to fibrin. Calcium is essential for these reactions to occur.

Animals↗
PubMed1985

A thrombelastographic study of the effect of stress on the blood coagulation in Cyprinus carpio (Cyprinidae) and Oreochromis mossambicus (Cichlidae).

The normal blood coagulation in Cyprinus carpio and Oreochromis mossambicus was investigated by thrombelastography and standard thrombelastographs were obtained for each species. The effect of stress on blood coagulation was thereafter determined. The thrombelastograms indicated hypercoagulability under stress conditions. A prominent observation is the differences in the elasticity of the clot under various conditions. Fibrinolysis occurred in all cases, except in the case of Cyprinus carpio after severe agitation for 30 min. Relevant values for various parameters are given.

Animals↗
PubMed2006

Aprotinin shows both hemostatic and antithrombotic effects during off-pump coronary artery bypass grafting.

BACKGROUND: Hemostatic drugs are widely thought to be unnecessary and potentially detrimental in off-pump coronary artery bypass graft surgery (OPCABG), despite well-established use in on-pump surgery. In a randomized, prospective OPCABG trial, we assessed efficacy and safety of aprotinin through a comprehensive assessment of graft patency and hematologic function. METHODS: Sixty patients were randomly assigned to full-dose aprotinin or placebo. Heparin was titrated to a kaolin-based activated clotting time of greater than 300 seconds. Exclusionary criteria included creatinine greater than 2 mg/dL, conversion to on-pump CABG, and preoperative GPIIb/IIIa inhibition. Hematologic assessments were obtained preoperatively, at the end of surgery, and on days 1 and 3: mean platelet volume, thrombin generation (prothrombin fragment 1.2 assay), and aspirin resistance using a modified thrombelastography, whole blood aggregometry, 11-dehydro-thromboxane B2 levels, and flow cytometry. Thrombotic events were defined as postoperative myocardial infarction by electrocardiography or elevated troponin I, clinical stroke by examination and head computed tomography, and bypass graft failure by multichannel computed tomography angiography on day 5. RESULTS: Aprotinin was associated with a significant reduction in intraoperative and postoperative blood loss compared with placebo but had no effect on transfusion rates. Patients treated with aprotinin had significantly fewer thrombotic events (3% versus 23%, p < 0.05, Fisher's exact test) and less postoperative aspirin resistance (20% versus 46%, respectively, p < 0.05, Fisher's exact test). Postoperative prothrombin fragment 1.2 level was reduced by aprotinin use. CONCLUSIONS: Aprotinin reduced perioperative bleeding after OPCABG. Preserved aspirin sensitivity in the aprotinin group may explain the observed reduction in thrombotic events and might be related to the suppression of perioperative and transmyocardial thrombin formation.

Aprotinin↗
PubMed2006

Contact activation prolongs clot lysis time in human plasma: role of thrombin-activatable fibrinolysis inhibitor and Factor XIII.

BACKGROUND: Contact activation system proteins (e.g., Factor XII, kallikrein) have been implicated as direct or indirect activators of plasminogen. However, contact activation and Factor XI have enhanced thrombin-activatable fibrinolysis inhibitor (TAFI) activation and decreased fibrinolysis, and Factor XIII (FXIII) also delays fibrinolysis via alpha(2)-anti-plasmin deposition on fibrin polymers. Thus, the goals of this study were to define how fibrinolysis is modulated in human plasma by contact or tissue factor (TF) activation, and what role TAFI and FXIII plays in this system. METHODS: Normal, TAFI-deficient and TAFI-deficient/FXIII-supplemented plasma was exposed to tissue-type plasminogen activator and activated with either celite or TF. Clot growth/disintegration kinetics were documented with thrombelastography. RESULTS: Normal plasma activated with celite had significantly prolonged onset and duration of clot lysis compared with samples activated with TF. TAFI-deficient plasma activated with celite was noted to have a duration of clot lysis not different from samples activated with TF, but a significant difference in time to onset of lysis persisted. Celite activation of TAFI-deficient/FXIII-supplemented plasma showed significantly prolonged onset and duration of clot lysis compared with samples activated with TF. CONCLUSIONS: Primarily TAFI, and to a lesser extent FXIII, contributed to contact system protein-mediated attenuation of fibrinolysis. Clinical investigation of these phenomena is warranted in clinical settings involving contact activation (e.g., intra-aortic balloon pumps and ventricular assist devices) to determine whether these devices modulate fibrinolysis and perhaps contribute to thromboembolic morbidity.

Carboxypeptidase B2↗
PubMed2005

Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation.

OBJECTIVES: This study sought to determine the prevalence of platelet aspirin resistance using methods that directly indicate the degree of platelet cyclooxygenase inhibition. BACKGROUND: Aspirin resistance in platelets may be overestimated by nonspecific laboratory measurements that do not isolate cyclooxygenase activity. METHODS: Arachidonic acid (AA)-induced light-transmittance platelet aggregation (LTA) and thrombelastography (TEG) platelet mapping were performed on the blood of healthy subjects (n = 6) before and 24 h after receiving 325 mg aspirin, and on 223 patients reporting compliance with long-term daily aspirin treatment (n = 203 undergoing percutaneous intervention [PCI] and n = 20 with a history of stent thrombosis). Aspirin resistance was defined as >20% aggregation by LTA or >50% aggregation by TEG. RESULTS: In healthy subjects, AA-induced aggregation by LTA was 82 +/- 10% before and 2 +/- 1% at 24 h after aspirin (p < 0.001), and aggregation by TEG was 86 +/- 14% before and 5 +/- 7% at 24 h after aspirin (p < 0.001). In compliant patients, AA-induced aggregation by LTA was 3 +/- 2% before PCI and 3 +/- 2% after PCI (p = NS), and aggregation by TEG was 5 +/- 9% before PCI and 6 +/- 14% after PCI (p = NS). Seven PCI patients were noncompliant, and all were aspirin sensitive after in-hospital aspirin treatment. Among 223 patients, only one patient ( approximately 0.4%) was resistant to aspirin treatment. CONCLUSIONS: Platelet aspirin resistance assessed by methods that directly indicate inhibition of cyclooxygenase is rare in compliant patients with coronary artery disease.

Adult↗
PubMed2004

A critical role for thrombin in platelet aggregation under high shear stress.

The serine protease, thrombin, plays a crucial role in both coagulation and platelet activation. Anhydrothrombin (AhT) is a catalytically inactive derivative of thrombin in which dehydroalanine replaces the active-site serine. AhT retains affinity for natural substrates of thrombin and may be a competitive inhibitor of thrombin-mediated coagulation and platelet reactions. In the present study, thrombelastography showed that AhT not only delayed the onset and the progress of the coagulation process but impaired clot strength, indicating that AhT may have both anticoagulant and antiplatelet activity. In addition, AhT prolonged the activated partial thromboplastin time dose-dependently, but had little effect on the prothrombin time, suggesting that its principal activity was mediated in the intrinsic coagulation pathway. AhT inhibited thrombin-induced aggregation of platelet-rich plasma. Complete inhibition of aggregation was evident at a concentration of 1.85 microM AhT. Furthermore, 3.7 microM of AhT almost completely abolished shear-induced platelet aggregation in PRP. Interpretation of this in vitro study requires confirmation in vivo, but the findings suggest that thrombin plays a critical role in shear related platelet mechanisms. AhT may be a useful tool for investigating platelet-based coagulation reactions and may provide the basis for a novel class of antithrombotic agents.

Anticoagulants↗
PubMed2006

Changes in blood coagulation of arm and leg veins during a simulated long-haul flight.

INTRODUCTION: Long-haul flights are associated with an increased incidence for venous thromboembolic events. At present, markers of coagulation and fibrinolysis were only analyzed from arm veins after long distance travel. Respective data from leg veins are missing. MATERIALS AND METHODS: Here, we measured these parameters in healthy volunteers (n=12) before and after 10 h sitting in modern aircraft chairs under normobaric hypoxia (corresponding to 2400 m altitude). Blood was collected from arm and leg veins before, immediately after and 1 day after sitting in the hypoxic chamber. RESULTS: We did not find any evidence for a significant intravasal thrombin and fibrin formation and a changed fibrinolytic activity, neither in arm nor in leg vein blood. TAT, PAP, and PAI-1 remained unchanged, and the increases of F1+2 in arm veins and of d-dimer in leg veins were within the upper reference limits. Moreover, there was no evidence of activation of coagulation as measured by thrombelastography (ROTEM(R)) and the new Thrombin Dynamic Test at both locations. There was no evidence of arm or leg hemoconcentration. CONCLUSIONS: In healthy volunteers, prolonged sitting in ergonomically superior aircraft seats does not induce significant changes in blood coagulation and fibrinolysis in venous blood of arm or leg. Since this study was performed under moderate hypoxia, reduction in oxygen pressure seems not to be a crucial factor for venous thrombosis at long-haul flights.

Adult↗
PubMed2002

Changes of biochemical markers and functional tests for clot formation during long-haul flights.

INTRODUCTION: Long-haul flights have been suggested to be associated with an increased risk for thromboembolic events. Until now, changes in the coagulation system during an actual flight have not been investigated. MATERIALS AND METHODS: To explore whether any changes occur in the coagulation system during a real long-haul flight molecular markers for coagulation and fibrinolysis were measured in 20 volunteers (10 subjects with a low and 10 with a moderate risk for venous thromboembolism (VTE)) during and after a return flight from Vienna to Washington. In addition, functional measurements of coagulation were performed using activated thrombelastography. RESULTS: Thrombelastographic measurements revealed activation of coagulation in all passengers, who showed an increased activity of FVII and FVIII as well as suppressed fibrinolysis. There was no evidence of a pronounced thrombin and fibrin formation. We did not find any differences between both groups concerning coagulation changes. CONCLUSION: Long-haul flights induce a certain activation of the coagulation system. This activated coagulation could be a risk factor for VTE during long-haul flights mainly when other risk factors are present.

Adult↗
PubMed2002

Perioperative assessment of coagulability in neurosurgical patients using thromboelastography.

BACKGROUND: Thrombelastography is a useful technique for evaluating coagulability. We hypothesized that it could be used to determine postoperative hematologic complications during and after neurologic surgery. METHODS: Forty-six neurosurgical patients were stratified by diagnosis: subarachnoid hemorrhage from ruptured intracranially aneurysms, intracranial-axial lesions, intracranial-extra-axial lesions, and degenerative spine disease. Thromboelastograms were performed before, during, and after surgery. Hematologic data were collected preoperatively and postoperatively; computed tomography scans and lower extremity Doppler sonography were performed postoperatively. A thrombosis index (TI) was used to assess coagulability. RESULTS: Coagulability increased over the course of surgery for all patients (p < 0.0001). In craniotomy patients, coagulability increased over the course of surgery (p < 0.05) with the most dramatic increase from intubation to skin incision (p < 0.05), and then after tumor removal or aneurysm clipping (p < 0.10). Univariate analysis among craniotomy patients showed that female gender (p < 0.0004) and smoking (p < 0.06) were associated with hypercoagulability. Among craniotomy patients, younger age was associated with hypercoagulability in the preoperative period (p < 0.01). There was no significant association between coagulability and aspirin or NSAID use, or intraoperative fluid volume. No patient developed a postoperative hematoma and one patient (2.2%) developed a lower extremity deep vein thrombosis. CONCLUSIONS: Increased coagulability begins between induction of anesthesia and skin incision, and continues to increase throughout surgery. These changes are more pronounced in patients undergoing craniotomy compared to patients undergoing spine procedures.

Adolescent↗
PubMed2002

Bacterial infection in cirrhosis impairs coagulation by a heparin effect: a prospective study.

BACKGROUND: Bacterial infections have been postulated as a trigger for variceal bleeding in cirrhotic patients, and impair coagulation evaluated by thrombelastography (TEG). Endogenous heparinoids have been detected after variceal bleeding and during liver transplantation in some cirrhotics using heparinase-modified-TEG. AIM: To assess if bacterial infection is associated with endogenous heparinoids in cirrhotics, thus impairing coagulation. METHODS: Native and heparinase-modified-TEG (cleavage of heparin and heparan-sulphate) was performed in 60 cirrhotics (Grade A, 2; B, 30; C, 28): 30 infected [septicaemia, 6 (culture positive); 6 (culture negative); spontaneous bacterial peritonitis, 10; chest infection, 4; others, 4], 30 not infected, and five infected patients without liver diseases, comparing TEG parameters r, alpha, and ma. Eight cirrhotics were studied before and after infection. The diagnosis of presence and type of infection was based on international standard criteria. RESULTS: A significant heparin effect was found only in infected cirrhotics (28 of 30) with significant changes in r (P=0.0003), alpha (P<0.0001), and ma (P<0.0001), but in none of those not infected. This effect completely reversed in the eight evaluated after resolution of infection. There was no heparin effect in infected non-cirrhotics. CONCLUSIONS: A heparin effect was only found in cirrhotic patients with infection, further confirming that infection significantly modifies coagulation in cirrhotic patients.

Adult↗
PubMed2002

Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease.

BACKGROUND/AIMS: As compared to other chronic liver diseases, cholestatic disorders are associated with a better outcome of variceal bleeding and less blood loss at transplantation, suggesting the presence of a hypercoagulable state. We have assessed plasmatic coagulation and platelet function in patients with cholestatic and non-cholestatic liver disease. METHODS: Thirty-seven patients with chronic cholestatic liver disease (primary biliary cirrhosis (PBC)/primary sclerosing cholangitis (PSC)), 53 patients with chronic hepatitis C (HCV) or alcoholic cirrhosis (C2), and 62 healthy controls were studied. RESULTS: Thrombelastography revealed a hypercoagulable state in non-cirrhotic patients with PBC/PSC, but not in those with HCV (ma-value: 6.54[6.25-6.92, 95%CI] vs. 5.39[5.11-5.58], P < 0.05) possibly due to higher fibrinogen levels in PBC/PSC patients (369[329-418]mg/dl vs. 263[250-275]mg/dl, P < 0.05). PFA-100 closure time was prolonged in HCV/C2 patients with advanced cirrhosis, but not in cirrhotic patients with PBC/PSC (Child B; epinephrine stimulation: 192[161-229]s vs. 132[105-158]s, P < 0.05). Flow cytometric studies of platelet receptors and granules revealed a higher surface expression of CD42b (112[105-119]% vs. 100[95-104]%, P < 0.05) and LIBS-1 (261[184-348]% vs. 121[92-145]%, P < 0.05) in patients with PBC/PSC than in those with HCV/C2. CONCLUSIONS: These results indicate that platelet function differs between patients with cholestatic and non-cholestatic liver disease and is stable or even hyperactive in patients with PBC and PSC.

Adolescent↗
PubMedDate not supplied

Bupivacaine inhibits whole blood coagulation in vitro.

BACKGROUND AND OBJECTIVES: Epidural anesthesia decreases the risk of postoperative deep venous thrombosis in selected patients. Intravascular local anesthetic levels resulting from epidural anesthesia may contribute to this effect by impacting coagulation. We studied the effects of bupivacaine (1-10 micromol/L) on whole blood coagulation measured by thrombelastography (TEG) and activated clotting time (ACT). METHODS: We incubated whole blood with bupivacaine (1, 2, and 10 micromol/L) or Tyrode's solution (control) for 60 minutes and measured TEG and ACT clotting parameters. RESULTS: Bupivacaine (1 or 10 micromol/L) prolonged ACT when compared with control. The thromboxane A2 (TX) receptor antagonist SQ29548 also prolonged ACT significantly. The combination of SQ29548 and bupivacaine was equally effective as bupivacaine alone, compatible with the hypothesis that bupivacaine at these concentrations blocks TX signaling. Because SQ29548 + bupivacaine prolonged ACT more than did SQ29548 alone, bupivacaine likely inhibits processes in addition to TX signaling. This was evaluated further using TEG. After incubation with 2 microm bupivacaine, TEG reaction time and clot growth time increased significantly, and maximal amplitude decreased. CONCLUSIONS: Bupivacaine in clinically relevant concentrations influences whole blood clotting characteristics as measured by TEG and ACT. Thromboxane receptor antagonism increases ACT, confirming a role for TX in coagulation. Bupivacaine may also inhibit TX signaling, but seems to block additional factors as well. These findings might partly explain the beneficial effects of epidural anesthesia on postoperative thrombotic events.

Anesthesia, Epidural↗
PubMed2003

Anticoagulant activity of M-LAO, L-amino acid oxidase purified from Agkistrodon halys blomhoffii, through selective inhibition of factor IX.

One of haemorrhagic toxins present in snake venoms is L-amino acid oxidase (LAO), which catalyzes the oxidative deamination of L-amino acids with the generation of hydrogen peroxide. Although it is widely accepted that LAO alters platelet function, the effects of LAO on human blood coagulation remain largely unknown. The present study demonstrated, for the first time, that M-LAO, LAO purified from the venom of Agkistrodon halys blomhoffii (Japanese mamushi), possesses an anticoagulant activity. Thrombelastography (TEG) showed that M-LAO significantly delayed the onset and the progress of the coagulation process. In addition, the enzyme prolonged the activated partial thromboplastin time (aPTT) dose-dependently, but had little effect on the prothrombin time (PT), suggesting that its principal activity was mediated in the intrinsic coagulation pathway. Furthermore, M-LAO reduced factor IX procoagulant activity in a dose-dependent manner and did not affect other coagulation factors. These results indicate that M-LAO has an anticoagulant activity that impairs the intrinsic clotting by inhibiting factor IX.

Agkistrodon↗
PubMed2006

A total balanced volume replacement strategy using a new balanced hydoxyethyl starch preparation (6% HES 130/0.42) in patients undergoing major abdominal surgery.

BACKGROUND AND OBJECTIVE: The kind of fluid for correcting hypovolaemia is still a focus of debate. In a prospective, randomized, controlled and double-blind study in patients undergoing major abdominal surgery, a total balanced volume replacement strategy including a new balanced hydroxyethyl starch (HES) solution was compared with a conventional, non-balanced fluid regimen. METHODS: In Group A (n = 15), a new balanced 6% HES 130/0.42 was given along with a balanced crystalloid solution; in Group B (n = 15), an unbalanced conventional HES 130/0.42 plus an unbalanced crystalloid (saline solution) were administered. Volume was given when mean arterial pressure (MAP) was <65 mmHg and central venous pressure (CVP) minus positive end-expiratoric pressure (PEEP) level was <10 mmHg. Haemodynamics, acid-base status, coagulation (thrombelastography (TEG)) and kidney function (including kidney-specific proteins, N-acetyl-beta-d-glucosaminidase (beta-NAG) and alpha-1-microglobulin) were measured after induction of anaesthesia, at the end of surgery, 5 and 24 h after surgery. RESULTS: Group A received 3533 +/- 1302 mL of HES and 5333 +/- 1063 mL of crystalloids, in Group B, 3866 +/- 1674 mL of HES and 5966 +/- 1202 mL of crystalloids were given. Haemodynamics, laboratory data, TEG data and kidney function were without significant differences between the groups. Cl- concentration and base excess (-5 +/- 2.4 mmol L-1 vs. 0.4 +/- 2.4 mmol L-1) were significantly higher in patients of Group B than of Group A. CONCLUSIONS: A complete balanced volume replacement strategy including a new balanced HES preparation resulted in significantly less derangement in acid-base status compared with a non-balanced volume replacement regimen. The new HES preparation showed no negative effects on coagulation and kidney function.

Abdomen↗
PubMed2000

Coagulation effects of a recently developed hydroxyethyl starch (HES 130/0.4) compared to hydroxyethyl starches with higher molecular weight.

BACKGROUND: Hydroxyethyl starches (HES) are known to interfere with blood coagulation according to molecular weight, the degree of substitution and the C2/C6 ratio. A recently developed low molecular hydroxyethyl starch (HES 130/0.4) was designed to reduce the blood compromising potency. METHODS: In this study, effects of a 30% in vitro haemodilution with the new HES preparation (HES 130/0.4) in comparison to HES 200/0.5, HES 450/0.7 and sodium chloride solution were investigated using intrinsic and extrinsic activated thrombelastography (TEG) and plasmatic coagulation tests. RESULTS: Whereas plasmatic tests revealed no prolongation of coagulation by HES in comparison to sodium chloride, the TEG variables clotting time, clot formation time and maximal clot firmness showed a significant (P<0.05) inhibition by all the HES preparations. The inhibition was most pronounced in HES 450 (P<0.05 vs HES 130) while HES 130 did not show a statistically significant difference in extrinsic activated maximal clot firmness when compared to sodium chloride. CONCLUSION: These in vitro results demonstrate that hydroxythyl starches especially compromise clot polymerisation. The new preparation HES 130/0.4 seems to inhibit platelet function to a lesser extent than hydroxyethyl starch preparations with a higher molecular weight and degree of substitution.

Blood Coagulation↗
PubMed2001

Coagulation assessment in healthy pigs undergoing single xenon anaesthesia and combinations with isoflurane and sevoflurane.

BACKGROUND: With the introduction of new anaesthetics into clinical practice possible side effects of these novel anaesthetics have to be evaluated. This study was performed to clarify whether xenon or combinations of xenon with isoflurane or sevoflurane modify blood coagulation. METHODS: The study was performed in 20 healthy pigs which first underwent xenon anaesthesia (65 Vol%) and were then randomly assigned to combinations of xenon and isoflurane or sevoflurane at varying concentrations. During anaesthesia the following parameters were controlled: aPTT, PT, fibrinogen concentrations and thrombelastographic measurements. RESULTS: Xenon monoanaesthesia did not alter significantly any coagulation parameter. When isoflurane was introduced the aPTT showed a significant increase while fibrinogen concentration decreased. The introduction of sevoflurane led also to a decrease in fibrinogen concentration, while the aPTT was unchanged. These decreases in fibrinogen concentration were not accompanied by reduced maximal clot strength or elevated fibrinolysis evaluated by thrombelastography. Although the above-described changes were statistically significant, none of the parameters throughout the experiment exceeded the limits of normal values. CONCLUSION: In our study, xenon monoanaesthesia and combinations of xenon with isoflurane and sevoflurane did not lead to pathologic alterations in the measured coagulation parameters.

Anesthesia, Inhalation↗
PubMed1998

The effect of potato starch derived and corn starch derived hydroxyethyl starch on in vitro blood coagulation.

We have compared the effects of progressive in vitro haemodilution (30% and 60%) with potato starch derived hydroxyethyl starch and corn starch derived hydroxyethyl starch on blood coagulation in 80 patients using thrombelastography. Both solutions significantly compromised blood coagulation as evidenced by an increase in coagulation time and decrease in angle alpha, maximum amplitude and coagulation index (p < 0.05). Blood coagulation was more compromised during haemodilution with potato starch derived hydroxyethyl starch as compared with corn starch derived hydroxyethyl starch (p < 0.05). When taking the effect of haemodilution with 0.9% saline into account, haemodilution with both hydroxyethyl starch solutions also augmented clot lysis (p < 0.05), with potato starch derived hydroxyethyl starch having a greater effect than corn starch derived hydroxyethyl starch (p < 0.05). We conclude that potato starch derived hydroxyethyl starch compromises in vitro blood coagulation more than corn starch derived hydroxyethyl starch.

Adult↗