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PubMed1999

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↗
PubMed1999

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↗
PubMed2000

Extreme hemodilution in rabbits: an in vitro and in vivo Thrombelastographic analysis.

UNLABELLED: Isovolemic hemodilution is used to decrease the incidence of blood transfusions. However, the effects of the degree of hemodilution and the fluid used on hemostasis are controversial. We tested the hypothesis that hemodilution and the fluid administered would adversely alter Thrombelastographic(R) (Haemoscope, Skokie, IL) variables (reaction time, alpha angle and maximal amplitude). Conscious rabbits had blood sampled from ear arteries and diluted 0% or 75% in vitro with one of four solutions: 6% hetastarch in 0.9% NaCl, 5% human albumin in 0.9% NaCl, or balanced electrolyte solutions containing either 6% pentastarch or 6% hetastarch. Isoflurane-anesthetized rabbits were randomly assigned to groups (n = 9 per group) that underwent in vivo isovolemic hemodilution (75% of estimated blood volume removed), with blood replaced with one of the four solutions mentioned previously. In vitro hemodilution resulted in a significant (P < 0.05) decrease in hemostatic function (increase in reaction time, decrease in alpha angle and maximal amplitude) that was largest after hemodilution with albumin. However, although in vivo hemodilution significantly (P < 0.05) decreased reaction time, increased the alpha angle, and decreased maximal amplitude, there were no significant fluid-dependent effects. IMPLICATIONS: The effects of hemodilution and the fluid used on Thrombelastographic(R) (Haemoscope, Skokie, IL) variables are markedly different between in vitro and in vivo hemodilution studies.

Animals↗
PubMed2000

The effect of In vitro hemodilution with gelatin, dextran, hydroxyethyl starch, or Ringer's solution on Thrombelastograph.

UNLABELLED: To determine the effects of progressive in vitro hemodilution with various plasma substitutes on whole blood coagulation, blood was obtained from six healthy volunteers. The Thrombelastograph((R)) (TEG; Haemoscope Corp., Morton Grove, IL) variables of reaction time, coagulation time, maximum amplitude, and growth angle were determined. The following plasma substitutes were tested: two gelatin solutions (4% gelatin polysuccinate and 5.5% oxypolygelatin); two dextrans (10% dextran 40 and 6% dextran 60); and five hydroxyethyl starch (HES) preparations (6% HES 70/0.5-0.55, 3% HES 200/0.5, 6% HES 200/0.5, 10% HES 200/0.5, and 6% HES 450/0.7). Ringer's solution was also tested to assist analyzing the intrinsic effect of colloid molecules on blood coagulation. The dilution ratios of citrated blood volume to plasma substitute volume were 10:2, 10:4, and 10:10. Blood coagulation was affected by plasma substitutes when the dilution ratios of citrated blood volume to colloid solution volume were 10:4 and 10:10. TEG variables did not change significantly after in vitro hemodilution with lactated Ringer's solution. The tested gelatin solutions showed less intrinsic effect on blood coagulation than other plasma substitutes. All HES preparations showed similar intrinsic effects as 6% dextran 60. The plasma substitute of 10% dextran 40 had the strongest effect on coagulation. Coagulation time was the most markedly affected TEG variable. Blood coagulation may be compromised when the dilution ratio of blood volume to colloid solution volume is >10:4. Whereas gelatin solutions have less intrinsic effect on blood coagulation, 10% dextran 40 has the strongest effect on coagulation. IMPLICATIONS: Blood coagulation may be compromised when the dilution ratio of blood volume to colloid solution volume is >10:4. Whereas gelatin solutions have less intrinsic effect on blood coagulation than hydroxyethyl starch or dextran, 10% dextran 40 has the strongest effect on coagulation.

Blood Coagulation↗
PubMed2000

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↗
PubMed2000

Evaluation of the contribution of platelets to clot strength by thromboelastography in rabbits: the role of tissue factor and cytochalasin D.

UNLABELLED: The contribution of platelets and soluble clotting components to clot strength has been the focus of several clinical studies using thromboelastography; it would, therefore, be beneficial to develop an animal model with which to mechanistically approach hemostatic disorders. Thus, we proposed to determine if the contribution of platelet function (G(P), dyne/cm(2)) and soluble components of the coagulation pathway to total clot strength (G(T)) in rabbits were similar to those in humans. Blood was sampled from the ear arteries of conscious rabbits (n = 12); 350 microL of the blood was placed in a thromboelastograph. Ten microliters of normal saline, cytochalasin D (an inhibitor of microtubule function, 10 microM final concentration), or tissue factor (a potent stimulator of platelet function, 0.00625% final concentration) was added to the blood sample, and thromboelastography performed for 1 h. The G(T) (mean +/- SD) was significantly (P < 0.001) different among samples exposed to normal saline, cytochalasin D, or tissue factor, with G(T) values of 7238 +/- 1432, 937 +/- 372, and 16,556 +/- 3314, respectively. G(P) was responsible for 87% and 94% of G(T) in the absence or presence of tissue factor, respectively. G(P) did not significantly correlate with platelet concentration in the absence or presence of tissue factor. The contribution of G(P) to G(T) is similar to that observed in humans. IMPLICATIONS: Rabbits may serve as a model of hemostasis that closely approximates human situations to mechanistically determine the etiology of coagulopathy. The contribution of platelet function to total clot strength is similar to that observed in humans.

Animals↗
PubMed2000

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↗
PubMed2000

The effect of hydroxyethyl starch 200 kD on platelet function.

We evaluated the effects of hydroxyethyl starch with a molecular weight of 200 kD (HES 200 kD) on platelets to gain insight into the potential mechanisms involved in the anticoagulant effects of HES 200 kD. Blood was obtained before and after an IV infusion (10 mL/kg) of either saline (n = 15) or HES 200 kD (n = 15) in otherwise healthy patients scheduled for minor elective surgery. Flow cytometry was used to assess the expression of glycoprotein (GP) IIb-IIIa, GP Ib, and P-selectin on agonist-activated platelets. Overall platelet function was evaluated by assessing thromboelastographic maximum amplitude (MA) in celite-activated blood and platelet function analyzer-closure times by using collagen/adenosine diphosphate cartridges. Saline infusion had no effects on platelet variables, whereas HES 200 kD reduced GP IIb-IIIa expression and MA and prolonged platelet function analyzer-closure times, without affecting the expression of P-selectin and GP Ib. In vitro experiments extended these observations by a concentration-related inhibiting effect of HES 200 kD on GP IIb-IIIa expression. This study demonstrates that cellular abnormalities with decreased availability of platelet GP IIb-IIIa are involved in the anticoagulant effects of HES 200 kD.

Adenosine Diphosphate↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

The effect of magnesium on coagulation in parturients with preeclampsia.

UNLABELLED: Preeclampsia is associated with complex coagulation abnormalities that include altered platelet function and consumption and activation of the fibrinolytic system. Magnesium sulfate, which is used as a therapeutic modality for the prevention of seizures in preeclamptic parturients, has anticoagulant and antiplatelet effects. We sought to determine the effects of magnesium on various components of the coagulation system in patients with preeclampsia. We assessed the coagulation status of 18 parturients with preeclampsia being treated with magnesium. The assessment was performed with the thromboelastograph test, which provides an overall assessment of blood coagulation via the coagulation index. Thromboelastography was performed before beginning magnesium therapy and 30 min and 2 h after a 6-g bolus of IV magnesium. The R value (time to first clot formation) was found to be significantly slower (P < 0.05) at 30 min after the magnesium bolus. This result suggests increased coagulant factor activity resulting from the magnesium bolus. However, there was no effect of magnesium on the overall coagulation, as evidenced by the lack of change in the coagulation index either at 30 min or at 2 h after the completion of the initial magnesium bolus. Therefore, this therapy should have no effect on the use of neuraxial techniques. IMPLICATIONS: On the basis of the thromboelastography assessment, we found that the current practice of administering magnesium did not influence overall coagulation in preeclamptic women. Therefore, magnesium administration should not affect the use of neuraxial techniques.

Adult↗
PubMed2001

Hemostatic changes in patients receiving hydroxyethyl starch: the influence of ABO blood group.

Hydroxyethyl starches (HES) interfere with coagulation because of their molecular structure and the amount infused during surgery. Coagulation defects include platelet dysfunction and a decrease of the VIII/von Willebrand factor complex (VIII/vWF). We examined the effects of 6% HES 200/0.6 on hemostasis by using an in vitro platelet function analyzer, the usual coagulation tests, the VIII/vWF complex assessment, and TEG analysis in patients undergoing abdominal surgery. The influence of the blood group was investigated. HES infusion induced primary hemostasis alterations, assessed by a prolonged platelet function analyzer closure time in the presence of epinephrine and adenosine diphosphate, which was not correlated with the platelet count. The decrease in VIII/vWF complex was proportional to the volume of infused HES (20 and 30 mL/kg) and was more pronounced in patients of the O blood group. The preoperative hypercoagulability status assessed by TEG analysis was reversed 24 h after HES infusion. In conclusion, 6% HES 200/0.6 induced immediate hemostasis alterations. Patients of the O blood group were likely to develop a von Willebrand-like syndrome after HES infusion. We conclude that intraoperative use of 6% HES 200/0.6 should be restricted in patients of the O blood group undergoing surgical procedures with high risk for bleeding.

ABO Blood-Group System↗
PubMed2001

The accuracy of coagulation tests during spinal fusion and instrumentation.

UNLABELLED: Patients undergoing major spine surgery may acquire a perioperative coagulopathy from dilution of coagulation factors and/or platelets or fibrinolysis. The mechanisms of the coagulopathy and role of coagulation testing during these procedures are poorly defined. Theoretically, coagulation tests could be used perioperatively to determine which patients are at risk for significant bleeding and guide transfusion therapy. We retrospectively evaluated the sensitivity, specificity, and accuracy of coagulation tests in predicting excessive surgical bleeding in 244 consecutive patients undergoing thoracic, lumbar, or sacral spinal fusion with or without instrumentation. Excessive bleeding was reported by the surgeon in 39 of the patients and was defined as recurrent microvascular bleeding despite adequate use of electrocautery and suture or decreased clot formation of blood pooled within the surgical field. Patients with excessive clinical bleeding sustained larger estimated blood losses than those with normal hemostasis. The total number of allogeneic red blood cells, platelets, and fresh frozen plasma units were also larger in patients with excessive bleeding noted during surgery. The intraoperative coagulation tests with the most sensitivity and specificity were the international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT). The INR had a sensitivity of 94%, a specificity of 88%, and an accuracy of 0.9 at a value of 1.4 (normal, 0.8-1.2). The PT had a sensitivity of 90%, a specificity of 64%, and an accuracy of 0.73 at a value of 13.5 s (normal, 8.4-12.0 s). The aPTT had a sensitivity of 85%, a specificity of 64%, and an accuracy of 0.71 at a value of 30.9 s (normal, 23-37 s). The thromboelastogram values were of marginal use. We conclude that the INR, PT, and aPTT may be helpful in guiding transfusion therapy in patients undergoing major spine surgery. IMPLICATIONS: Patients undergoing major surgery to the spine often acquire a perioperative coagulopathy. The prothrombin time and activated partial thromboplastin time had the greatest sensitivity and specificity for predicting bleeding in major surgery of the spine. The test values that differentiated normal from excessively bleeding patients could be used to guide transfusion therapy during surgery.

Adolescent↗