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The effects of aprotinin on thromboelastography with three different activators.

BACKGROUND: Thromboelastography is used for assessment of hemostasis. Adherence to thromboelastography-guided algorithms and aprotinin administration each decrease bleeding and blood product usage after cardiac surgery. Aprotinin, through inhibition of kallikrein, causes prolongation of the celite-activated clotting time and the activated partial thromboplastin ratio. The aim of this study was to assess the effects of aprotinin on the thromboelastography trace. METHODS: Three activators were used in the thromboelastography: celite (which is widely established), kaolin, and tissue factor. Assessment was performed on blood from volunteers and from patients before and after cardiac surgery. RESULTS: The tissue factor-activated thromboelastography trace was unaffected by the addition of aprotinin. When celite and kaolin were used as activators in the presence of aprotinin, the reaction time (time to clot formation) of the thromboelastography trace was prolonged (P < 0.0001) and the maximum amplitude (clot strength) was decreased (P < 0.05). With celite as an activator, the addition of aprotinin decreased (P < 0.05) the thromboelastography alpha angle (rate of clot extension). The reaction time of the celite-activated trace correlated with the activated partial thromboplastin ratio (P < 0.01). The reaction time of the tissue factor-activated trace correlated with the international normalized ratio (P < 0.01). CONCLUSION: The thromboelastography trace is altered in the presence of aprotinin when celite and kaolin are used as activators but not when tissue factor is the activator.

Aprotinin↗

Thromboelastography with heparinase in orthotopic liver transplantation.

OBJECTIVE: To investigate the role of heparin in the postreperfusion coagulopathy during liver transplantation with heparinase-guided thromboelastography. DESIGN: A prospective, interventional study. SETTING: A university-affiliated hospital. PARTICIPANTS: Twenty-six patients undergoing orthotopic liver transplantation (OLT). INTERVENTIONS: Blood drawn at five intervals for thromboelastography assessment with native (12 patients) or celite blood (14 patients) compared with simultaneous thromboelastography traces with added heparinase. MAIN RESULTS: In the native samples, the prolonged R (reaction) and K (coagulation) time and decreased alpha angle were corrected in heparinase thromboelastograph traces immediately before reperfusion and 10 minutes postreperfusion. In the celite-accelerated samples, the heparinase traces showed correction of the R and K times and alpha angle only at the 10-minute postreperfusion stage. In seven patients who had thromboelastography performed after protamine administration, there were no differences between celite and heparinase-celite traces. CONCLUSIONS: Heparinase-treated thromboelastography offered compelling evidence for the presence of heparin-like activity after liver graft reperfusion. The objective evidence provided by this modification of thromboelastography-guided protamine administration and was useful in identifying one of the many potential causes of postreperfusion bleeding in patients undergoing OLT.

Blood Coagulation↗

Differences in arterial and venous thromboelastography parameters: potential roles of shear stress and oxygen content.

OBJECTIVE: To investigate potential mechanisms for the differences in thromboelastography variables observed between arterial blood samples and venous blood samples. DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: Patients undergoing cardiac surgery (n = 33). INTERVENTIONS: After the withdrawal of 10 mL of discarded blood (>3 deadspace volumes), 3 blood samples were withdrawn simultaneously from the central venous port of the pulmonary artery catheter (CVP), the radial arterial catheter (ART), and the side port of the 9F sheath introducer (SI). MEASUREMENTS AND MAIN RESULTS: Thromboelastography was done simultaneously on each sample. All thromboelastography analyses were performed with 1% celite and heparinase according to the manufacturer's guidelines. A total of 80 ART, SI, and CVP comparisons were obtained. Mean hematocrit values were not different between sampling sites (27 +/- 4 v 27 +/- 4 v 27 +/- 3). Thromboelastography R time values (mean +/- SD) were CVP, 8 +/- 3; ART, 10 +/- 3; and SI, 13 +/- 5 (p = 0.004). Thromboelastography maximal amplitude (MA) values (mean +/- SD) were CVP, 60.4 +/- 11.7; ART, 56.2 +/- 11.4; and SI, 50.5 +/- 13.2 (p = 0.008). Calculated maximal shear stresses were CVP, 48 dyne/cm(2); ART, 36 dyne/cm(2); and SI, 0.3 dyne/cm(2). Blood samples obtained from the CVP (highest shear stress) resulted in faster (shorter R) and stronger (larger MA) coagulation compared with the arterial site (intermediate shear stress) and sheath introducer (lowest shear stress). CONCLUSION: These data show that differences exist in thromboelastography values between arterial and venous blood samples and, more importantly, show that the differences observed are not related to differences in oxygen content. These differences seem to be related to differences in catheter lumen diameter and, presumably, shear forces.

Adult↗

Assessment of blood coagulation in severe liver disease using thromboelastography: use of citrate storage versus native blood.

Thromboelastography evaluates the viscoelastic properties of blood coagulation. Using native blood, measurement must start soon after sampling. With normal coagulation, native and citrated blood values correlate well. No data exists from cirrhotic patients. We compared native and citrate thromboelastography parameters in 30 cirrhotic patients (20 Child-Pugh C class, two liver failure). Thromboelastography was performed within 4 min using native blood and after recalcification within 1-2 h of citrate storage. Thromboelastography variables (, alpha, ) were compared using the Mann-Whitney test, correlation investigated with the Pearson method and the degree of agreement with the Bland-Altman method. There was no significant difference between citrated and native blood for all variables. Median values for native and citrated were, respectively, 16.4 (range 2.3-22.5) and 15.1 (range 9.8-29.9); 6.3 (range 3.5-11.3) and 6.2 (range 2.8-10.9); 48.3 (range 30.7-62.9) and 46.2 (range 30.4-60.4); angle alpha 30.8 (range 18.7-46.8) and 33.2 (range 19.9-55.8). Correlation for each variable was significant ( 0.01). There was a good degree of agreement for all but two patients (both bleeding) for all variables. Citrated blood can substitute native blood using thromboelastography in cirrhotic patients, allowing more time between sampling and the thromboelastography measurement.

Adult↗

Thromboelastography as an indicator of post-cardiopulmonary bypass coagulopathies.

Postoperative hemorrhage in patients undergoing open-heart surgery is a major cause of morbidity and mortality. Monitoring of coagulation in these patients has routinely involved the activated clotting time. Thromboelastography is currently used as a monitor of coagulation during liver transplantation. The thromboelastogram, by providing information on the interaction of all the coagulation precursors, gives more clinically useful information on coagulation than that available from the coagulation profile or the activated clotting time alone. This study was done to assess the usefulness of thromboelastography in open-heart surgery. Thirty-eight patients (29 undergoing coronary artery bypass grafting and 9 undergoing valve replacement) were studied with activated clotting time, thromboelastography, and coagulation profiles during three periods: before bypass, during bypass, and after protamine administration. Thromboelastography was a significantly better predictor (87% accuracy) of postoperative hemorrhage and need for reoperation than was the activated clotting time (30%) or coagulation profile (51%). Thromboelastography is easy to use and provides diagnostic data within 30 minutes of blood sampling.

Blood Coagulation Disorders↗

Prediction of excessive bleeding after coronary artery bypass graft surgery: the influence of timing and heparinase on thromboelastography.

OBJECTIVE: To compare the ability of thromboelastography, when done at either 10 or 60 minutes after protamine reversal of heparin, to predict excessive bleeding after coronary artery bypass graft (CABG) surgery and to investigate, with the use of heparinase, whether heparin contamination was responsible for the difference, if any. DESIGN: Prospective study. SETTING: University hospital, single institution. PARTICIPANTS: Patients undergoing elective CABG surgery (n = 40). INTERVENTIONS: Blood samples for thromboelastography and routine coagulation tests were collected before induction of anesthesia and at 10 and 60 minutes after protamine reversal of heparin. Blood loss and blood product use were recorded postoperatively. MEASUREMENTS AND MAIN RESULTS: Of 40 patients undergoing elective CABG surgery, 10 fulfilled the criteria for excessive postoperative bleeding. The sensitivity of thromboelastography to identify patients who bled was better at 60 minutes than at 10 minutes after protamine reversal of heparin (100% v 70%). There was greater specificity (83% v 40% at 10 minutes; 73% v 20% at 60 minutes) and positive predictive value (58% v 28% at 10 minutes; 55% v 29% at 60 minutes) when heparinase was added. At both times, thromboelastography showed only moderate correlation with total blood loss and the use of fresh frozen plasma or platelets or both. Conventional coagulation tests did not predict excessive postoperative bleeding. CONCLUSION: This study suggests that timing and the use of heparinase influence the predictive ability of thromboelastography, but its usefulness as a sole predictor of post-CABG surgery bleeding is limited.

Aged↗

Assessing platelet and fibrinogen contribution to clot strength using modified thromboelastography in pregnant women.

UNLABELLED: The monoclonal antibody fragment c7E3 Fab (ReoPro), by binding to platelet surface fibrinogen receptors (glycoprotein, GPIIb/IIIa), inhibits platelet aggregation and its interaction with fibrinogen. In this study, we used thromboelastography with ReoPro to evaluate the independent contribution of fibrinogen and platelets to clot strength. Thromboelastography was performed in 21 healthy, term parturients scheduled for elective cesarean delivery with 360 microL of celite-activated whole blood and with 5 microL of (2 mg/mL) ReoPro added to 355 microL of celite-activated whole blood. The contribution of platelets to clot strength (MAplt) was derived by subtracting MAfib (maximal amplitude with ReoPro) from MAwb (maximal amplitude with whole blood). Thus, MAwb - MAfib = MAplt. The value for MAwb (mean +/- SD) was 73+/-4 mm, for MAfib it was 33+/-5 mm, and for MAplt it was 40+/-3 mm. The contribution of fibrinogen and platelets to the MAplt was 45% and 55%, respectively. Modified thromboelastography using ReoPro in healthy parturients can be used to determine the contribution of fibrinogen and platelets to blood clot strength. IMPLICATIONS: Determining the independent contribution of platelets and fibrinogen to the maximal amplitude of thromboelastography using c7E3 Fab may further improve the use of thromboelastography in detecting and treating coagulation defects.

Abciximab↗

Rapid evaluation of coagulopathies after cardiopulmonary bypass in children using modified thromboelastography.

UNLABELLED: Complex coagulopathies follow cardiopulmonary bypass (CPB) in children. However, objective laboratory data that can be acquired rapidly to guide their management are lacking. Because thromboelastography has proven useful in this regard, we evaluated the use of celite or tissue factor (TF) activation and heparinase modification of blood samples to allow rapid determination of thromboelastogram data in children younger than 2 yr undergoing CPB. Celite or TF activation shortened the initiation of clotting and, thus, the time required for the important thromboelastogram alpha and maximum amplitude values to begin evolving. Although thromboelastogram alpha and maximum amplitude values were increased with these activators, correlations persisted between platelet count or fibrinogen level and each of these values. The additional use of heparinase allowed thromboelastograms to be obtained during CPB with values not different from those obtained without heparinase after protamine administration. Therefore, celite- or TF-activated, heparinase-modified thromboelastograms begun during CPB allow objective data to be available by the conclusion of protamine administration to help restore hemostasis after CPB in children. Thromboelastography identified transient fibrinolysis during CPB in some children that resolved by the conclusion of protamine administration. Future investigations of the effectiveness of modified thromboelastography-guided coagulopathy management after CPB in children are needed. IMPLICATIONS: Thromboelastography is useful in assessing the coagulopathies that follow cardiopulmonary bypass in children. Modifying blood samples with celite or tissue factor and heparinase allows thromboelastography begun before the termination of cardiopulmonary bypass to become a rapid point-of-care monitor to provide objective data for guiding blood component therapy to manage these coagulopathies.

Anticoagulants↗

Thromboelastography as a perioperative measure of anticoagulation resulting from low molecular weight heparin: a comparison with anti-Xa concentrations.

UNLABELLED: Low molecular weight heparin (LMWH) is commonly used to prevent postoperative thromboembolism. Currently, there is no convenient test to measure the degree of anticoagulation from LMWH. This prospective study examines the relationship of thromboelastography and serum anti-Xa concentration in patients treated with enoxaparin. Twenty-four adult patients scheduled for orthopedic surgery using epidural anesthesia were enrolled. Epidural catheters were removed the morning after surgery before the commencement of subcutaneous enoxaparin 30 mg twice daily. Venous blood samples were obtained at 1) the induction of anesthesia (baseline), 2) immediately before the third dose of enoxaparin postoperatively (Day 2-trough), 3) 4 h after the third dose postoperatively (Day 2-peak), and 4) immediately before the fifth dose postoperatively (Day 3-trough). Whole blood samples were obtained for thromboelastography, activated clotting time, and anti-Xa level analyses at each of the four time intervals. At the four sample intervals, the r time (mean +/- SEM). (20 +/- 1, 25 +/- 2, 51 +/- 6, 31 +/- 3 mm) and the k time (9 +/- 0. 7, 12 +/- 1, 27 +/- 5, 14 +/- 2 mm) of the thromboelastograph were significantly correlated with the expected peak and trough levels of LMWH and serum anti-Xa levels (P: < 0.05). At the Day 3-trough, thromboelastograph r times exceeded the normal range in 6 of 25 patients (25%). Prolongation of r time and k time on postoperative Day 3 may indicate an exaggerated response to LMWH. Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. IMPLICATIONS: Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. The r time from the thromboelastogram correlates with serum anti-Xa concentration.

Aged↗

Thromboelastography identifies sex-related differences in coagulation.

UNLABELLED: Thromboelastography is an in vitro, point-of-care monitor of whole blood coagulation. Thromboelastography studies have demonstrated a hypercoagulable state during pregnancy. Perhaps the hypercoagulability is attributable to female sex hormones. The aim of the study was to determine if sex, in addition to pregnancy, affected thromboelastography variables by studying male and female (pregnant and nonpregnant) volunteers. Thromboelastography showed significant (P:<0.01) differences in sex, with a significant (P: < 0. 0001) trend of increasing whole blood coagulability from men through nonpregnant to pregnant women. The thromboelastograph, used as a diagnostic tool, shows that women have more whole blood coagulability than men. IMPLICATIONS: The thromboelastograph, used as a diagnostic tool, shows that women have more whole blood coagulability than men.

Adult↗

Perioperative alterations of the thromboelastography in patients receiving one-stage bilateral total knee arthroplasty.

BACKGROUND: Total knee arthroplasty is associated with activation of coagulation and fibrinolytic system in the perioperative period. The coagulation and fibrinolytic activation in one-stage bilateral total knee arthroplasty has not been described before. Thromboelastography is a real-time aid in the monitoring of coagulation and is clinically valuable in the evaluation of whole blood hemostasis. We evaluated the coagulation and fibrinolysis system activation during and after one-stage bilateral total knee arthroplasty by thromboelastography. METHODS: Twenty patients, ASA class I-II, undergoing one stage bilateral total knee arthroplasty were included in this study. All patients received continuous spinal anesthesia with isobaric 0.2% bupivacaine. Arterial blood samples were obtained for thromboelastography in the following sequences (1) after induction of anesthesia (baseline), (2) 20 min after releasing tourniquet of the first leg (3) 20 min after releasing tourniquet of the second leg, (4) 2 h postoperatively, (5) 24 h postoperatively. RESULTS: There was a significant shortening of reaction time (R value) after deflation of the first leg tourniquet, and a further decrease of R value after deflation of the second leg tourniquet and two hours postoperatively. The perioperative change of coagulation time was similar to that of R value. The maximum amplitude decreased after releasing tourniquet of the second leg and two hours postoperatively. CONCLUSION: The activation of coagulation, as monitored by thromboelastography, is predominant in one-stage bilateral total knee arthroplasty after releasing tourniquet of the second leg and returns to baseline 24 h postoperatively.

Aged↗

Thromboelastography, whole-blood haemostasis and recurrent miscarriage.

BACKGROUND: Some cases of recurrent miscarriage have a thrombotic basis. Thromboelastography is a rapid, reproducible test of whole-blood haemostasis. METHODS: Thromboelastography was performed in 494 consecutive, non-pregnant women (median age 35 years; range 21-48) with a history of miscarriages at <12 weeks gestation (median 4; range 3-12) and 55 parous women (median age 33 years; range 20-41) with no history of pregnancy loss. The prospective outcome of untreated pregnancies amongst 108 women with recurrent miscarriage was studied. RESULTS: The maximum clot amplitude (MA) (median 66.0 mm; range 48.0-76.0) was significantly higher and the rate of clot lysis (LY30) (median 2.5%; range 0.5-7.8) significantly lower amongst women with recurrent miscarriage compared with controls (MA 61.5 mm; range 50.0-67.0; P = 0.01; LY30 4.9%; range 2.9-9.7; P = 0.01). The pre-pregnancy MA was significantly higher amongst women who subsequently miscarried (median 66.0 mm; range 54.0-73.0) compared with those whose had a live birth (median 61.7 mm; 48.0-71.5; P < 0.01). A pre-pregnancy MA >or=64 mm has a sensitivity of 68% and specificity of 82% to predict miscarriage. CONCLUSIONS: Thromboelastography identifies a subgroup of women with recurrent miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a state are at increased risk of miscarriage in future untreated pregnancies.

Abortion, Habitual↗

The effect of anesthetic techniques on blood coagulability in parturients as measured by thromboelastography.

Anesthetic techniques may affect blood coagulability and the subsequent incidence of thromboembolic events. The purpose of this study was to evaluate the effect of spinal and general anesthesia on blood coagulability in normal pregnant women undergoing cesarean section, using thromboelastography. In the spinal anesthesia group (n = 15), thromboelastography was performed after crystalloid preloading and during the immediate postanesthesia course. In the general anesthesia group (n = 15), thromboelastography was performed before induction and during the immediate postanesthesia course. Values for all thromboelastographic variables (reaction time [r], clot formation time [K], coagulation time [rK], maximum amplitude [MA], elastic shear modulus [G], clot formation rate [alpha angle], and coagulation index [CI]) in the preanesthesia period were similar in both the spinal and general anesthesia groups. However, in the postanesthesia period, r and K significantly decreased (P < 0.05), and alpha angle (P < 0.05) and CI significantly increased (P < 0.01) in the general anesthesia group when compared with the spinal anesthesia group. In the postanesthesia period, MA and G were similar in both groups. In the spinal anesthesia group, thromboelastographic variables did not change significantly in the postanesthesia compared with the preanesthesia period. We conclude that the use of general anesthesia for cesarean section is associated with accelerated coagulability when compared with spinal anesthesia.

Adult↗

Thromboelastography for monitoring prolonged hypercoagulability after major abdominal surgery.

UNLABELLED: Despite clinical and laboratory evidence of perioperative hypercoagulability, there are no consistent data evaluating the extent, duration, and specific contribution of platelets and procoagulatory proteins by in vitro testing. We tested the hypothesis that the parallel use of standard and abciximab-cytochalasin D-modified thromboelastography (TEG) can assess 7 days' postoperative hypercoagulability and can estimate the independent contribution of procoagulatory proteins and platelets. Thromboelastograms were performed before surgery, at the end of surgery, 6 h after surgery, and on postoperative days 1, 2, 3, and 7; they were analyzed for the reaction time and the maximal amplitude (MA). We calculated the elastic shear modulus of standard MA (G(t)) and modified MA (G(c)), which reflect total clot strength and procoagulatory protein component, respectively. The difference was an estimate of the platelet component (G(p)). There was a 10% perioperative increase of standard MA, corresponding to a 50% increase of G(t) (P < 0.0001) and an 86%-90% contribution of the calculated G(p) to G(t). We conclude that serial standard and modified thromboelastography may reveal prolonged postoperative hypercoagulability and the independent contribution of platelets and procoagulatory proteins to clot strength. IMPLICATIONS: Postoperative hypercoagulability, occurring for at least 1 wk after major abdominal surgery, may be demonstrated by standard and modified thromboelastography. This hypercoagulability is not reflected by standard coagulation monitoring and seems to be predominantly caused by increased platelet reactivity.

Abdomen↗

The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery.

UNLABELLED: Hemorrhage after cardiopulmonary bypass (CPB) remains a clinical problem. Point-of-care tests to identify hemostatic disturbances at the bedside are desirable. In the present study, we evaluated the predictive value of two point-of-care tests on postoperative bleeding after routine cardiac surgery. Prospectively, 255 consecutive patients were studied to compare the ability of modified thromboelastography (ROTEG) as well as a platelet function analyzer (PFA-100) to predict postoperative blood loss. Measurements were performed at three time points: preoperatively, during CPB, and after protamine administration with three modified thromboelastography and PFA tests. The best predictors of increased bleeding tendency were the tests performed after CPB. The angle alpha is the best predictor (area under the receiver operating characteristic curve 0.69) and, in combination with the adenosine diphosphate-PFA test, the predictive accuracy is enhanced (area under the receiver operating characteristic curve 0.73). The negative predictive value for the angle alpha is 82%, although the positive predictive value is small (41%). Thromboelastography is a better predictor than PFA. In routine cardiac surgery, impaired hemostasis as identified by point-of-care tests does not inevitably lead to hemorrhage postoperatively. However, patients with normal test results are unlikely to bleed for hemostatic reasons. Bleeding in these patients is probably caused surgically. The high negative predictive value supports early identification and targeted treatment of surgical bleeding by distinguishing it from a significant coagulopathy. IMPLICATIONS: Thrombelastography and platelet function analysis in routine cardiac surgery demonstrate high negative predictive values for postoperative bleeding, which supports early identification and targeted treatment of surgical bleeding by distinguishing it from a significant coagulopathy. The positive predictive values are small. The best predictors are thrombelastography values obtained after cardiopulmonary bypass.

Aged↗

Assessment of changes in coagulation in parturients with preeclampsia using thromboelastography.

BACKGROUND: Preeclampsia is associated with a risk of abnormal hemostasis that occurs most commonly secondary to thrombocytopenia. Thromboelastography measures whole blood coagulation and has been used to manage coagulation defects in obstetric patients. The authors conducted this investigation in a large number of preeclamptic women to assess changes in coagulation using thromboelastography. METHODS: Thromboelastography and platelet counts were performed in 52 healthy pregnant women, 140 mild preeclamptic women, and 114 severe preeclamptic women in active labor using disposable plastic cups and pins and native whole blood. In preeclamptic patients with a platelet count <100,000/mm3, conventional coagulation tests were also performed. Epidural analgesia was provided in some women when they requested pain relief. RESULTS: Fifteen percent of all preeclamptic women (38 of 254) and 2% (1 of 52) of healthy pregnant women had a platelet count <100,000/mm3. The incidence of thrombocytopenia <100,000/mm3 was 3% (4 of 140) and 30% (34 of 114) in mild preeclamptic patients and severe preeclamptic patients, respectively. Severe preeclamptic patients with a platelet count <100,000/mm3 were significantly hypocoagulable when compared to the other study groups. Ten severe preeclamptic women with a platelet count <100,000/mm3 had a maximum amplitude <54 mm (the lower limit of maximum amplitude in healthy pregnant women enrolled in this investigation). None of the mild preeclamptic women had a maximum amplitude <54 mm. Five severe preeclamptic women with a platelet count <100,000/mm3 had an abnormal coagulation profile, whereas all four mild preeclamptic women with a platelet count <100,000/mm3 had a normal coagulation profile. CONCLUSION: This study shows that severe preeclamptic women with a platelet count <100,000/mm3 are hypocoagulable when compared to healthy pregnant women and other preeclamptic women.

Adult↗

Essential thrombocythemia and epidural analgesia in the parturient. Does thromboelastography help?

BACKGROUND AND OBJECTIVES: It is often considered that essential thrombocythemia contraindicates placement of an epidural catheter because of the danger of epidural hematoma. Thromboelastography offers a possible means of determining the appropriateness of epidural analgesia in a patient with this disorder. METHODS: A pregnant woman with essential thrombocythemia and a history of spontaneous abortions was evaluated by thromboelastography at 38 weeks of gestation to determine the safety of using epidural analgesia for labor pain management. On the basis of the thermoelastography findings, the patient was given epidural analgesia with bupivacaine and fentanyl during her labor. RESULTS: The patient experienced good pain relief, delivered a healthy infant vaginally, and suffered no complications. CONCLUSIONS: Thromboelastography may be a useful diagnostic test in determining the suitability of regional techniques for labor analgesia in parturients with essential thrombocythemia. However, success in one patient does not prove the general safety of this approach.

Adult↗