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Influence of ketorolac tromethamine on clot elastic strength in humans as assessed by thromboelastography.

STUDY OBJECTIVE: To evaluate the effect of ketorolac tromethamine on coagulation using thromboelastography (TEG). DESIGN: TEGs were performed in each patient before and after ketorolac administration. Each patient's predrug results were used as control measurements for comparison with the postdrug results. SETTING: Medical center surgical unit. PATIENTS: Twenty ASA physical status I and II patients undergoing minor elective surgery; 12 healthy volunteers. INTERVENTIONS: TEGs were performed in all subjects before and 60 minutes after the intramuscular (IM) administration of ketorolac tromethamine 60 mg. Ten surgical patients were studied in the intraoperative period, and 10 surgical patients were studied in the postoperative period. The 12 healthy volunteers did not undergo a surgical procedure. MEASUREMENTS AND MAIN RESULTS: Specific parameters assessed from the TEGs were reaction time (R time), coagulation time (RK time), clot formation rate (angle of deflection), and maximum clot strength (maximum amplitude of deflection). Ketorolac administration did not cause statistically significant changes in these parameters in any of the three groups studied. CONCLUSIONS: IM administration of ketorolac tromethamine 60 mg did not significantly alter the speed of formation or viscoelastic strength of clots as measured by TEG. These results provide additional support for prior clinical studies confirming the safety of ketorolac administration in the perioperative period.

Adult↗

Thromboelastography and Sonoclot analysis in the healthy parturient.

STUDY OBJECTIVE: To compare values for two whole blood viscoelastic coagulation tests, thromboelastography (TEG) and Sonoclot analysis (Sonoclot R Coagulation Analyzer, Sienco, Inc., Morrison, CO), between healthy parturients and nonparturients. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: 41 healthy, nonpregnant females and full-term nonlaboring and laboring parturients. INTERVENTIONS: Blood samples for TEG and Sonoclot analysis were taken from all patients. TEG tracings were analyzed for reaction time (R), coagulation time (RK), the difference between RK and R (K), clot formation rate (alpha degree), and maximum amplitude (MA) values. Sonoclot tracings were analyzed for onset, rate increases, peak, and rate decreases values. MEASUREMENTS AND MAIN RESULTS: All TEG values were significantly different between nonpregnant females and parturients (p < 0.05). Sonoclot analysis showed that the parturients had a significantly decreased onset and increased primary slope (rate increases) in comparison to the nonpregnant females (p < 0.05). CONCLUSION: The differences found in the parturients reflect a hypercoagulable state. If these tests are to be used in evaluating obstetric patients, the results should be compared with values obtained for healthy parturients, not healthy nonparturients.

Blood Coagulation Tests↗

Comparison of thromboelastography to bleeding time and standard coagulation tests in patients after cardiopulmonary bypass.

This prospective study of 36 adult patients undergoing cardiopulmonary bypass (CPB) was conducted to determine the utility of thromboelastography (TEG) versus platelet studies (bleeding time, platelet count, mean platelet volume) and standard coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen) to more effectively discriminate patients likely to benefit from platelet or fresh frozen plasma (FFP) transfusion. Although the sensitivities of the bleeding time (71.4%) and platelet count (100%) were similar to the TEG (71.4%), the specificity (89.3%) of the TEG was greater than that of the bleeding time (78.5%) and platelet count (53.6%). Seven patients experienced clinically significant hemorrhage; 5 (71.4%) had an abnormal TEG. Three of 8 (38%) other patients with an abnormal TEG had no abnormal bleeding. Only 2 of 27 (7.4%) patients with a normal TEG had abnormal bleeding requiring platelet or FFP transfusion. Therefore, it is suggested that post-CPB patients with a normal TEG should not receive platelet or FFP transfusions empirically. If excessive bleeding is noted in a patient with a normal TEG, this suggests a surgically correctable etiology. Data from this series suggest that patients displaying an abnormal TEG appear to be at increased risk for hemorrhage; therefore, appropriate blood product support should be initiated at the first sign of accelerated bleeding.

Adolescent↗

An assessment of the duration of cephapirin-induced coagulation abnormalities as measured by thromboelastography.

Cephalosporin antibiotics are used prophylactically in cardiothoracic surgery to prevent postoperative infection. In 30 patients undergoing primary elective coronary artery bypass grafting, the whole blood coagulation system was prospectively evaluated before, and 10 and 30 minutes after administration of 1 g of cephapirin (Cefadyl, Bristol Laboratory, Evansville, IN). All patients had normal preoperative coagulation studies and had not received anticoagulant or antiplatelet therapy within 7 days of surgery. At 10 minutes after cephapirin administration, 23 of 30 patients had a significant change in all phases of whole blood coagulation as monitored by thromboelastography (TEG). Thirty minutes after cephapirin administration there was no statistical difference compared with the baseline TEG. It is concluded that cephapirin can cause a significant but transient change in the viscoelastic properties of blood. Coagulation parameters of the TEG should be measured prior to cephapirin administration to prevent errors in establishing baseline values prior to cardiopulmonary bypass.

Blood Coagulation↗

Monitoring platelet glycoprotein IIb/IIIa-fibrin interaction with tissue factor-activated thromboelastography.

Computerized thromboelastography (TEG) was used to study platelet glycoprotein IIb/IIIa function, characterize the consequences of the interaction between polymerizing fibrin and activated platelets, and establish a quantitative assay of platelet function. The ability of platelets to augment the shear elastic modulus of blood clots was measured by TEG under conditions of maximal platelet activation during ex vivo clot formation accelerated by recombinant human tissue factor (TF). Under these conditions, platelets significantly enhance clot strength eightfold (relative to platelet-free fibrin clots). This effect, inhibited by cytochalasin D and c7E3 Fab, appears to be dependent on the transmission of platelet contractile force to fibrin, through glycoprotein IIb/IIIa receptors. The c7E3 Fab dose response of TF-TEG clot strength is identical to results with platelet aggregation induced by the thrombin receptor agonist peptide (50% inhibitory concentration (IC50 = 3.6 microg/ml); adenosine diphosphate-induced aggregation is easier to inhibit (IC50 = 1.2 microg/ml). The results obtained with this system are reproducible (coefficient of variation for clot strength 4%; intraclass correlation coefficient 0.96). As a clinical assay, TF-triggered computerized TEG is easy to perform at the bedside, provides on-line results within 30 minutes, and may offer advantages over conventional measures of platelet function.

Abciximab↗

Comparison of the effect of different platelet GPIIb/IIa antagonists on the dynamics of platelet/fibrin-mediated clot strength induced using thromboelastography.

The effect of various platelet glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists on the dynamics of platelet-fibrin clot formation and strength induced by various stimuli was measured by thromboelastography (TEG). GPIIb/IIIa antagonists with high affinity for resting and activated platelets and with slow rates of dissociation from GPIIb/IIIa (Class I antagonists) demonstrated potent and comparable inhibition of platelet aggregation and tissue factor (TF), lipopolysaccharide (LPS), Factor Xa, and thrombin-induced clot strength, in contrast to antagonists that dissociate rapidly from GPIIb/IIIa (Class II antagonists). For example, the Class I antagonist XV459 (the free acid form of roxifiban) inhibited TF, endotoxin, Factor Xa, and thrombin-induced maximal clot strength and platelet aggregation with an IC(50)=30-70 nM, whereas the IC(50) of the Class II antagonist YZ211 (the free acid form of sibrafiban) for altering clot formation and strength was 0.3-4.7 microM. Moreover, the IC(50)'s of sibrafiban, and another Class II antagonist, orbofiban, for inhibiting platelet-fibrin clot formation and strength were substantially greater than their clinically achievable concentrations. Further, although aspirin treatment improved the efficacy of all GPIIb/IIIa antagonists, it did not alter the differences between Classes I and II antagonists. Thus, these data indicate that there are differences in the efficacy of various GPIIb/IIIa antagonists in inhibiting platelet-fibrin clot formation and strength. They also suggest that inhibiting platelet aggregation may not be the sole determinant for the in vivo efficacy of various GPIIb/IIIa antagonists.

Biomechanical Phenomena↗

[Monitoring of hemostasis during liver transplantation: contribution of thromboelastography].

Monitoring of coagulation is mandatory during liver transplantation (LT). Standard coagulation tests may be routinely used. However, they give static information and may be inadequate in case of severe coagulation defect. Interest has been recently focused on thromboelastography (TEG) which could give more suitable and rapid information in these cases. Few studies have evaluated the clinical interest of TEG compared to conventional tests. This comparison was the aim of the present study, performed in 89 patients scheduled for LT. The anaesthetic management as well as procedure of transfusion were similar in all patients. Before unclamping, 5000 KIU.kg-1 of aprotinin were injected. Routine tests and TEG were performed at the beginning and end of both pre-anhepatic and anhepatic phases, and 5, 30, 60, and 120 min after the revascularisation of the new liver. A phase of hypocoagulability was observed after unclamping. Biological signs included an increase in activated thromboplastin time, a reduction of alpha angle and maximum amplitude on TEG with a lengthening of its r + k component. A strong correlation existed between maximum amplitude and platelets, maximum amplitude and fibrinogen, alpha and fibrinogen at each time of the surgical procedure. Euglobulin lysis time decreased significantly after clamping, whereas fibrin degradation products increased at the same time. However, typical fibrinolysis with a clot lysis index (CLI) below 55% was only observed in 15 patients. Twelve of them had a CLI value reaching 0%, associated with severe generalized oozing. Aprotinin (200,000 to 600,000 KIU) corrected these abnormalities. These results show that TEG may not be very helpful to determine whether platelets or fibrinogen are involved in the phase of hypocoagulability detected after unclamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Coagulation status using thromboelastography in patients receiving warfarin prophylaxis and epidural analgesia.

To determine the coagulation status of patients receiving postoperative warfarin and epidural analgesia using thromboelastography (TEG(R)).Prospective, observational, clinical study.Orthopedic postoperative division at a university hospital.52 ASA physical status II and III patients undergoing knee arthroplasty and receiving prophylactic warfarin and epidural analgesia.Patients' preoperative and postoperative coagulation status was determined by TEG(R). Daily TEG(R) parameters were obtained until the epidural catheter was removed. TEG(R) parameters include reaction time (R-time or time until the first significant levels of detectable clot formation), K-time (clot firmness), maximum amplitude (MA-clot strength), alpha angle (clot development), and coagulation index (overall coagulation). In addition, daily international normalized ratios (INRs) were obtained as per our routine practice. On the day of catheter removal reaction time was significantly increased compared with preoperative values (p < 0.0001), but it remained within normal ranges. There was no change in the coagulation index. However, INR was abnormal and significantly increased (INR = 1.48+/-0.3; p < 0.0001), compared with preoperative values, on the day when the epidural catheter was removed. When the epidural catheters are removed, overall coagulation status, as measured by TEG(R), and despite an elevated INR (mean INR <1.5), remained within normal limits in patients receiving low-dose warfarin prophylaxis.

Aged↗

The effects of ropivacaine hydrochloride on coagulation and fibrinolysis. An assessment using thromboelastography.

Amide local anaesthetics impair coagulation by inhibition of platelet function and enhanced fibrinolysis. The potential therefore exists that the presence of amide local anaesthetics in the epidural space could contribute to the therapeutic failure of an epidural autologous blood patch. Ropivacaine is an aminoamide local anaesthetic increasingly used for epidural analgesia and anaesthesia, particularly in obstetric practice. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur clinically in the epidural space, alter coagulation or fibrinolysis. Thromboelastography was used to assess clotting and fibrinolysis of blood to which ropivacaine had been added. Although modest alterations in maximum amplitude, coagulation time and alpha angle were observed, the effect of ropivacaine on clotting and fibrinolysis was not clinically significant. We conclude that it is unlikely that the presence of ropivacaine in the epidural space would reduce the efficacy of an early or prophylactic epidural blood patch.

Adult↗

The effects of hypertonic saline solution (7.5%) on coagulation and fibrinolysis: an in vitro assessment using thromboelastography.

We studied the effects of hypertonic (7.5%) and normal saline on coagulation and fibrinolysis in an in vitro model using thromboelastography of human whole blood. Reaction times increased and alpha angles decreased with hypertonic saline replacement at 7.5% blood volume compared with similar dilution with normal saline. At 10% blood volume replacement with hypertonic saline, reaction and coagulation times were significantly increased and alpha angles were decreased. Clot lysis at 30 min was also significantly reduced. We conclude that 7.5% hypertonic saline solution has anticoagulant effects if it replaces 7.5% or more of blood volume.

Adult↗

Evaluation of the effects of levobupivacaine on clotting and fibrinolysis using thromboelastography.

Amide local anaesthetics inhibit platelet function. We hypothesized that residual anaesthetic in the epidural space could decrease efficacy of an epidural blood patch in preventing postdural puncture headache. Levobupivacaine has recently been approved for epidural anaesthesia. Its effects on coagulation have not previously been studied. The aim of this study was to determine the effects of levobupivacaine on clotting using thromboelastography. Ten ASA Class I volunteers were studied. Venous blood samples were analysed using a Haemoscope 2000D TEG analyser. Whole blood, a 50% saline control and two levobupivacaine solutions (2.5 mg mL(-1) and 2.5 microg mL(-1) in blood) were compared. The former reproduces that produced in the epidural space by blood (20 mL for an epidural blood patch) and levobupivacaine 0.5% (20 mL). The latter approximates plasma concentrations following epidural injection of levobupivacaine 0.5% (20 mL). P < 0.05 was considered significant. Maximum amplitude (MA), a measure of clot strength, is decreased by levobupivacaine 2.5 mg mL(-1). Levobupivacaine 2.5 mg mL(-1) decreases clot strength and may reduce efficacy of a prophylactic epidural blood patch.

Adult↗

Thromboelastography and recombinant factor VIIa-hemophilia and beyond.

Thromboelastography (TEG), which records the continuous profiles of whole blood (WB) coagulation, can be used to evaluate the effects of hemostatic agents, such as recombinant factor VII (rFVIIa). Our group has developed a revised TEG model, involving activation with minute amounts of tissue factor and subsequent signal processing, and has used this method to evaluate the effects of rFVIIa both in patients with hemophilia and in those receiving vitamin K antagonist (VKA) thromboprophylaxis. We review the early results of our investigations, which suggest that, in clinical situations where rFVIIa has shown benefit, the changes in the profiles obtained by TEG recording appear to correlate with the clinical outcome.

Adult↗

Influence of platelet count and activity on thromboelastography parameters.

It has been suggested that thromboelastography TEG) can help in limiting or directing the appropriate use of blood products during surgery. However, the contribution of platelets to the TEG profile has not been studied in detail. Blood was taken from eight healthy subjects and eight patients with peripheral arterial disease (PAD). Immunomagnetic separation was achieved by the addition of Dynabeads labeled with a CD41 murine antibody (to the GPIIb/IIIa receptor) to achieve 90-100% depletion of platelets from blood. This was then titrated with whole blood to achieve platelet counts of approximately 0, 25 and 50% of the original count to compare with whole blood using TEG. Platelet function was also assessed by spontaneous platelet aggregometry (SPA) at baseline and at the 50% dilution. SPA, maximum amplitude (MA) and K time were significantly different in PAD patients compared to controls (P < 0.05). In both controls and PAD patients there was a strong linear correlation between Log10 [platelet count] and MA (r = 0.97 for controls, r = 0.89 for PAD) and K time (r = -0.86 for controls, r = -0.68 for PAD). Correlation between Log10 [platelet count] and R time was poor in both groups. The MA and K TEG parameters may be most useful for assessing platelet transfusion requirements.

Aged↗

A prospective study of thromboelastography (TEG) and filter life during continuous veno-venous hemofiltration.

Anticoagulants are commonly used to prolong circuit life during continuous hemofiltration. However, a clear correlation between routinely performed blood coagulability tests and circuit life has not been demonstrated. This lack of correlation may derive from the limited ability of such tests to describe the likelihood of in vivo clotting. We hypothesized that thromboelastography (TEG), which derives its variables from a closer reproduction of in vivo coagulation, would significantly correlate with filter life. Accordingly, we conducted a prospective pilot study of the correlation between filter life and TEG-derived variables in 21 hemofilters used in 6 critically ill patients admitted to a tertiary intensive care unit. It involved the performance of TEG during steady state anticoagulation, measurement of circuit life, and of routine coagulation variables. The results showed that the mean circuit life was 20.7+/-4.0 h despite an average aPTT of 67.7+/-12.8 s and a mean heparin dose of 472.5+/-96.2 IU/h. The mean INR was 1.4+/-1 and the mean platelet count was 118+/-16 x 10(3)/mm3. Although several TEG variables correlated with heparin dose (p < 0.03), no correlation was found between any of the routine coagulation variables or any of the TEG variables and circuit life. In conclusion, no significant correlation between TEG derived variables or routinely measured coagulation variables and circuit life could be demonstrated. These findings suggest that such tests are not useful indicators of circuit anticoagulation adequacy and that factors other than blood coagulability may play a role in circuit failure.

Anticoagulants↗

Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery.

UNLABELLED: Transfusion therapy after cardiac surgery is empirically guided, partly due to a lack of specific point-of-care hemostasis monitors. In a randomized, blinded, prospective trial, we studied cardiac surgical patients at moderate to high risk of transfusion. Patients were randomly assigned to either a thromboelastography (TEG)-guided transfusion algorithm (n = 53) or routine transfusion therapy (n = 52) for intervention after cardiopulmonary bypass. Coagulation tests, TEG variables, mediastinal tube drainage, and transfusions were compared at multiple time points. There were no demographic or hemostatic test result differences between groups, and all patients were given prophylactic antifibrinolytic therapy. Intraoperative transfusion rates did not differ, but there were significantly fewer postoperative and total transfusions in the TEG group. The proportion of patients receiving fresh-frozen plasma (FFP) was 4 of 53 in the TEG group compared with 16 of 52 in the control group (P < 0.002). Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group (P < 0.05). Patients in the TEG group also received less volume of FFP (36 +/- 142 vs 217 +/- 463 mL; P < 0.04). Mediastinal tube drainage was not statistically different 6, 12, or 24 h postoperatively. Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period. We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy. These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery. IMPLICATIONS: Transfusion of allogeneic blood products is common during complex cardiac surgical procedures. In a prospective, randomized trial, we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing, and found the algorithm to be effective in reducing transfusion requirements.

Aged↗

Thoracic aorta occlusion-reperfusion decreases hemostasis as assessed by thromboelastography in rabbits.

UNLABELLED: Perioperative hemorrhage and thrombosis are serious complications associated with major vascular surgery. We hypothesized that thoracic aortic occlusion-reperfusion in rabbits would adversely affect hemostasis as assessed by thromboelastographic variables (reaction time, alpha angle and G [a measure of clot strength]). Isoflurane-anesthetized rabbits underwent either sham operation (n = 10) or 30 min of aortic occlusion followed by 90 min of reperfusion (n = 10). Blood samples (350 microL) were exposed to 10 microL of either 0.9% NaCl or cytochalasin D (a platelet inhibitor, 10 microM final concentration) and analyzed for 1 h by using thromboelastography after 30 min of postpreparation equilibration and at 30 and 90 min of reperfusion. Aortic occlusion-reperfusion resulted in a significant (P: < 0.05) increase in reaction time, decrease in alpha angle, and decrease in G at 30 and 90 min of reperfusion compared with the sham-operated group. The decrease in hemostatic function after aortic occlusion-reperfusion was observed to the same degree in samples with or without platelet inhibition. There were no significant differences in platelet concentration between the sham-operated and aortic occlusion-reperfusion groups. Aortic occlusion-reperfusion decreased hemostatic function in rabbits primarily by decreasing the coagulation factor-dependent, platelet-independent contribution to clotting. IMPLICATIONS: Thoracic aortic occlusion-reperfusion decreased hemostatic function in rabbits primarily by decreasing the coagulation factor-dependent, platelet-independent contribution to clotting. This decrease in hemostatic function may contribute to hemorrhagic complications associated with major vascular surgery.

Animals↗

Nitric oxide decreases coagulation protein function in rabbits as assessed by thromboelastography.

Nitric oxide (NO) is administered via infusion of donors such as nitroglycerin or in inhaled form for treatment of ischemia and pulmonary hypertension, respectively. In rabbits, the NO donor, DETANONOate, decreases whole blood clotting function as assessed by thromboelastographic variables (R, reaction time; alpha, angle; and G, a measure of clot strength). I hypothesized that DETANONOate-derived NO would adversely affect coagulation protein and platelet function. Blood obtained from ear arteries of conscious rabbits (n = 8) anticoagulated with sodium citrate. The blood was then incubated with 0 or 10mM DETANONOate for 30 min. After incubation and recalcification, thromboelastography was performed for 60 min under four conditions: 1) 0mM DETANONOate, 2) 0mM DETANONOate with platelet inhibition with cytochalasin D, 3) 10mM DETANONOate, and 4) 10mM DETANONOate with platelet inhibition. DETANONOate significantly (P < 0.05) increased R and decreased alpha and G in samples with or without platelet inhibition, compared with samples not exposed to DETANONOate. Lastly, the percentage of total G (G(T)) attributable to platelet function (G(P)) was significantly more in the absence of DETANONOate (G(P) = 92.3% +/- 1.6%; mean +/- SD) than after exposure to DETANONOate (G(P) = 90.2% +/- 2.3%). DETANONOate-derived NO significantly decreased coagulation protein function and platelet function. Coagulation protein function may be similarly affected in clinical situations involving the administration of NO or NO donors.

Animals↗

A thromboelastography study on the in vitro effects of L-arginine and L-NG-nitro arginine methyl ester on human whole blood coagulation and fibrinolysis.

The effects of L-arginine and L-NG-nitro arginine methyl ester (L-NAME) on human blood coagulation and fibrinolysis were studied in vitro using computerized thromboelastography and native whole blood. L-Arginine (8-80 microM) prolonged the split point (SP), reaction time (R) and biKoatugulierung time (K); and diminished the angle (alpha), maximum amplitude (MA) and TEG index. L-NAME (0.5-50 microM) shortened SP, R and K and increased alpha, MA and the TEG index in a concentration-dependent manner. Neither L-arginine nor L-NAME had any effect on clot lysis. SP and R indicated the initiation of fibrin-strand formation, therefore L-arginine delayed, while L-NAME promoted the processes leading to fibrin formation. K and alpha reflect the rate of clot formation and involve fibrin build-up and platelets. Thus, L-arginine inhibited and L-NAME enhanced the rate of clot formation. MA (clot strength) involves the integrity of fibrin strands and platelet aggregation, and again L-arginine was inhibitory, while L-NAME enhanced this interaction. The TEG index indicates the coagulability of the sample; L-arginine was anticoagulant while L-NAME had procoagulant effects. These results are consistent with the inhibitory effects of NO on platelet function and of the platelet-aggregating properties of NOS inhibitors. In addition, NO may play an inhibitory role in the process leading to fibrin formation and also on the interactions between platelets and fibrin. Such effects may be important when considering the clinical use of drugs that affect the NO-cGMP pathway.

Adult↗