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Identification of patients at risk for excessive blood loss during coronary artery bypass surgery: thromboelastography versus coagulation screen.

In light of the potential morbidity associated with transfusion of blood products, a reliable preoperative screening test to identify cardiothoracic surgical patients who are at potential risk for increased intraoperative blood loss would be useful. Accordingly, we examined the efficacy of a variety of coagulation tests to predict intraoperative blood loss in 60 patients presenting for coronary artery bypass surgery (CABG). A complete coagulation screen, activated clotting time (ACT), and thromboelastograph (TEG) were performed before surgery. Intraoperative blood loss was determined by weighing sponges and measuring the quantity of blood in suction canisters. The duration of cardiopulmonary bypass was 100 +/- 4 min, and total surgery time was 5.0 +/- 0.1 h. Total crystalloid and colloid requirements were 5.5 +/- 0.2 and 1.4 +/- 0.1 L. Forty-eight percent of the patients required blood with an average requirement of 2.5 +/- 0.5 units. Total intraoperative blood loss averaged 1590 +/- 95 mL with a range from 640 to 3928 mL. Using multiple linear regression, all coagulation and TEG variables were used to model perioperative blood loss. Results showed that all components of the TEG failed to predict blood loss (r < 0.25, P > 0.78). However, three components of the routine coagulation assay, including bleeding time, prothrombin time, and platelet count could be modeled to predict perioperative blood loss (r = 0.75, P < 0.05). Although TEG has been shown to have potential in identifying postcardiopulmonary bypass coagulopathies, these results suggest that it does not appear to be useful in determining the coagulation status of CABG patients preoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The influence of induced hypothermia for hemostatic function on temperature-adjusted measurements in rabbits.

UNLABELLED: In hypothermic patients, a tendency to bleed may be observed even when hemostatic tests seem to be normal. Coagulation and platelet function tests are usually performed at 37 degrees C. We investigated the influence of induced hypothermia on temperature-adjusted hemostasis function testing using Sonoclot Analyzer (Sonoclot) and Thromboelastography (TEG). Anesthesia was induced and maintained with IV ketamine and fentanyl on 15 male New-Zealand White rabbits. A water blanket was used to induce hypothermia to 30 degrees C and to rewarm to 37 degrees C. Blood samples were obtained at four points: before hypothermia, at 34 degrees C, at 30 degrees C, and after rewarming. Standard coagulation tests were performed at 37 degrees C (C method), and simultaneously, real temperature hemostasis function tests (R method) were run. In Sonoclot(R), activated clotting time and time to peak increased and clot rate decreased significantly at 30 degrees C in the R method compared with those in the C method. In TEG(R), reaction time and clot formation time were prolonged and clot formation rate was diminished at 30 degrees C in the R method compared with those in the C method. Induced hypothermia delayed the coagulation cascade and reduced platelet function. During hypothermia, hemostatic measurements should be performed at real temperature to avoid overestimating patient hemostatic function based on results measured at the standard 37 degrees C. IMPLICATIONS: We investigated the influence of induced hypothermia on temperature-adjusted hemostasis function tests in rabbits using Sonoclot Analyzer and Thromboelastography. Induced hypothermia delayed the coagulation cascade and reduced platelet function. The conventional coagulation tests performed at 37 degrees C failed to detect these hypothermia-induced degradations in hemostasis performance.

Anesthesia↗

The effect of graded hypothermia (36 degrees C-32 degrees C) on hemostasis in anesthetized patients without surgical trauma.

UNLABELLED: The isolated effects of hypothermia on hemostasis have not been investigated in healthy humans. We cooled 16 anesthetized patients scheduled for elective intracranial surgery to 32 degrees C body core temperature and assessed prothrombin time (PT), activated partial thromboplastin time, thrombelastogram (TEG), closure time, and platelet count at 36 degrees C, 34 degrees C, and 32 degrees C body core temperature after the induction of anesthesia but before surgical intervention. Activated partial thromboplastin time, hematocrit, and closure time did not change, whereas PT and platelet count decreased during cooling. Platelet count decreased without a decrease in hematocrit; hence, a dilution by administered fluids seemed unlikely. The small decrease of platelet count is probably clinically irrelevant in patients with normal platelet count and function. The small decrease in PT indicates an alteration of the extrinsic pathway of coagulation. TEG measurements showed a delay of clot formation in temperature-adjusted measurements but showed no change if the test temperature was 37 degrees C. This indicates that hypothermia reduces plasmatic coagulation and platelet reactivity. However, the clot strength is not altered by hypothermia. All coagulation variables remained within the normal ranges. Our results may indicate that moderate short-term (4-h) hypothermia has only minor adverse effects in healthy humans. We can make no statement about the effects of hypothermia of longer duration. IMPLICATIONS: This study investigated the isolated effects of hypothermia in healthy anesthetized humans. We found only minor effects of body temperature reduction to 32 degrees C on assessed coagulation variables, indicating only minor effects in otherwise healthy humans.

Adult↗

Tissue factor-activated thromboelastograms in children undergoing cardiac surgery: baseline values and comparisons.

UNLABELLED: Activation of clotting with tissue factor (TF) allows rapid evaluation of thromboelastograms but alters the values of thromboelastogram variables. We have performed TF-activated thromboelastograms in 250 children <2 yr old undergoing cardiac surgery to establish baseline values. Five groups were distinguished to evaluate the effects of quantitative deficiencies in coagulation factor levels during infancy: <30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Activation of clotting (R and K values) was similar among groups. Infants 1-3 mo of age demonstrated increased clot strength compared with the other groups, a finding similar to previous evaluation of native thromboelastograms. The alpha and maximum amplitude values were numerically almost identical in each age group, a unique finding in activated thromboelastograms. Fibrinolysis was similar among groups. We believe that knowledge of baseline TF-activated thromboelastogram variables in young children will be useful in interpreting these thromboelastograms in clinical scenarios, in using these thromboelastograms as part of coagulopathy treatment algorithms, and during the application of more specific thromboelastogram modifiers. Additionally, the similarity of alpha and maximum amplitude values in each age group will allow even faster interpretation of thromboelastogram data. IMPLICATIONS: Baseline values for tissue factor-activated thromboelastograms in young children undergoing cardiac surgery have been established and will permit accurate use and interpretation of this thromboelastogram modification in evaluating and managing coagulopathies.

Algorithms↗

Hydroxyethyl starch as a priming solution for cardiopulmonary bypass impairs hemostasis after cardiac surgery.

UNLABELLED: We investigated the influence of hydroxyethyl starch (HES) as a priming solution for the cardiopulmonary bypass (CPB) circuit on postoperative hemostasis in 45 patients undergoing elective coronary artery bypass grafting. In a randomized sequence, 20 mL/kg of low-molecular-weight HES (HES 120; molecular weight 120,000 daltons), high-molecular-weight HES (HES 400; molecular weight 400,000 daltons), or 4% human albumin (ALB) was used as the main component of the CPB priming solution. The thromboelastographic values indicating the speed of solid clot formation (alpha-angle) and the strength of the fibrin clot (maximum amplitude and shear elastic modulus) were decreased up to 2 h after CPB in both HES groups. Four hours after the operation, blood loss through the chest tubes had increased in the HES groups: HES 120, mean 804 mL (range, 330-1390 mL); HES 400, mean 1008 mL (range, 505-1955 mL); and ALB, mean 681 mL (range, 295-1500 mL) (P < 0.05 between the HES 400 and ALB groups). We conclude that HES solutions, when given in doses of 20 mL/kg in connection with the CPB prime, compromise hemostasis after cardiac surgery. This effect appears related to formation of a less stable thrombus compared with that formed in the presence of ALB. IMPLICATIONS: The influence of hydroxyethyl starch (HES) on postoperative hemostasis was investigated in cardiac surgery. The thromboelastographic values indicated that HES solutions, when given in connection with the cardiopulmonary bypass prime, compromise hemostasis after cardiac surgery. This effect seems to occur through the formation of a less stable clot.

Adult↗

Diagnosis and treatment of intracardiac thrombosis during orthotopic liver transplantation.

Intracardiac thrombus formation during orthotopic liver transplantation can be a catastrophic event leading to death. Most often this devastating complication occurs after reperfusion and may be related to massive blood transfusion, marginal liver grafts, tendencies towards hypercoagulability, or the potential role of antifibrinolytics. We report a case of an intracardiac thrombus occurring during the hepatectomy stage (stage I) of orthotopic liver transplantation. Transesophageal echocardiography was used to quickly diagnose the thrombus, allowing rapid pharmacological intervention and later guide surgical evacuation of the intracardiac thrombus via the inferior vena cava.

Acute Kidney Injury↗

A novel thrombelastograph tissue factor/kaolin assay of activated clotting times for monitoring heparin anticoagulation during cardiopulmonary bypass.

We used a thrombelastograph (TEG) assay with tissue factor and kaolin (TEG TF/K) to measure activated clotting time (ACT) in 31 patients during cardiopulmonary bypass. For comparison, ACTs were also determined by a Hemochron Jr. Signature and a Hepcon HMS. The TEG TF/K correlated with both the Hepcon (r(2) = 0.789) and Hemochron (r(2) = 0.743) ACTs. The average ACT after heparin was 319 +/- 119 s (mean +/- sd) for the TEG TF/K compared with 624 +/- 118 s for the Hepcon instrument. To evaluate the effects of hemodilution on TEG TF/K and Hemochron assays, ACT assays were performed on blood diluted to 50% and titrated with heparin from 0 to 6 U/mL. Both instruments showed significant (P < 0.01) changes in the ACT-versus-heparin slope, but the 0 heparin intercept for the TEG TF/K ACTs was not significantly changed (P = 0.292), in contrast to that for the Hemochron device (P = 0.041). Both instruments also indicated the same 1.3:1 ratio of protamine to heparin for optimum heparin neutralization, with increasing ACTs at ratios >2.6:1. The TEG TF/K ACT assay rapidly monitors heparin anticoagulation, in addition to the capabilities of this instrument to monitor platelet function, clotting factors, and fibrinolysis.

Adult↗

Fibrinogen in children undergoing cardiac surgery: is it effective?

There is speculation based on laboratory tests and biochemical data regarding the functional integrity of the fibrinogen in young children. Recent investigations in adults have demonstrated that their fibrinogen level correlates with the thromboelastogram maximum amplitude (MA) after modification with a glycoprotein IIb/IIIa receptor blocker that uncouples platelet-fibrinogen interactions. We postulate that if the fibrinogen of young children is functionally intact then their fibrinogen levels should also correlate with modified thromboelastogram MA values as they do in adults. We compared modified and unmodified thromboelastogram variables of 250 children <2 yr old undergoing cardiac surgery with their fibrinogen levels and platelet counts. Five age groups were distinguished to determine if and when correlations become significant (<1 mo, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo). Fibrinogen levels correlated with modified thromboelastogram MAs only in the 12-24 mo group. In this 12-24 mo age group other correlations between fibrinogen levels and thromboelastogram variables influenced by fibrinogen also became significant, as did correlations noted in adults between platelet counts and thromboelastogram variables. We conclude that the fibrinogen of children <12 mo old with congenital heart disease is qualitatively dysfunctional.

Abciximab↗

The effect of hemopure on coagulation in clinically relevant concentrations.

Hemopure is a new colloidal blood substitute that may influence coagulation. We designed this study to examine the influence of this product on in vitro coagulation of whole blood by using the thrombelastograph (TEG). Blood samples from 20 volunteers were obtained. Hemopure was added to blood samples to obtain 0.5, 1, and 2 g/dL mixtures of Hemopure in blood. Control consisted of an undiluted sample and, for comparison, two samples diluted with volumes of lactated Ringer's solution (LR) equivalent to the two higher Hemopure dilutions. TEG with Hemopure at a concentration of 2 g/dL showed significantly shorter reaction and clot formation k times and an increased alpha angle compared with control. LR dilution with equivalent volume to 2 g/dL Hemopure solution also resulted in significantly shorter reaction and k times, as well as an increased alpha angle. Coagulation in samples with Hemopure at concentrations of 0.5 and 1 mg/dL did not vary significantly from control. Maximum amplitude did not vary significantly from control in any samples. The effect of Hemopure on TEG measures of coagulation is not significantly different from that of LR at clinically relevant concentrations.

Blood Circulation Time↗

A comparison of transfusion requirements between living donation and cadaveric donation liver transplantation: relationship to model of end-stage liver disease score and baseline coagulation status.

The use of living donation is an important option for patients in need of liver transplant. We retrospectively reviewed the preoperative Model for End-Stage Liver Disease (MELD) score, baseline coagulation laboratory results, and intraoperative transfusion of red blood cells and component therapy for 27 living donation transplants and 69 cadaveric donation transplants during a 3-yr period (2001-2004). Patients undergoing living donation transplantation had significantly lower MELD scores and preserved coagulation function compared with cadaveric donation transplantation recipients (P < 0.001). The living donation transplant patients also received significantly fewer transfusions of red blood cells and component therapy compared with the cadaveric donation transplant patients (P < 0.001). For the combined population of both cadaveric donation transplant and living donation transplant patients, there were significant associations between MELD score and preoperative coagulation tests (P < 0.001) and intraoperative transfusion of blood and component therapy. MELD score and preoperative fibrinogen concentration were identified as independent predictors of transfusion exposure. In conclusion, we detected significant differences in severity of disease at time of transplantation, degree of impairment of coagulation function, and need for transfusion of red blood cells and component therapy between patients undergoing living donation transplantation compared with patients undergoing cadaveric donation transplantation.

Blood Coagulation↗

Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction.

Postoperative thrombotic complications increase hospital length of stay and health care costs. Given the potential for thrombotic complications to result from hypercoagulable states, we sought to determine whether postoperative blood analysis using thromboelastography could predict the occurrence of thrombotic complications, including myocardial infarction (MI). We prospectively enrolled 240 patients undergoing a wide variety of surgical procedures. A cardiac risk score was assigned to each patient using the established revised Goldman risk index. Thromboelastography was performed immediately after surgery and maximum amplitude (MA), representing clot strength, was determined. Postoperative thrombotic complications requiring confirmation by a diagnostic test were assessed by a blinded observer. Ten patients (4.2%) suffered a total of 12 postoperative thrombotic complications. The incidence of thrombotic complications with increased MA (8 of 95 = 8.4%) was significantly (P = 0.0157) more frequent than that of patients with MA < or =68 (2 of 145 = 1.4%). Furthermore, the percentage suffering postoperative MI in the increased MA group (6 of 95 = 6.3%) was significantly larger than that in the MA < or =68 group (0 of 145 = 0%) (P = 0.0035). In a multivariate analysis, increased MA (P = 0.013; odds ratio, 1.16; 95% confidence interval, 1.03-1.20) and Goldman risk score (P = 0.046; odds ratio, 2.39; 95% confidence interval, 1.02-5.61) both independently predicted postoperative MI. A postoperative hypercoagulable state as determined by thromboelastography is associated with postoperative thrombotic complications, including MI, in a diverse group of surgical patients.

Adult↗

Measurement of patients' bivalirudin plasma levels by a thrombelastograph ecarin clotting time assay: a comparison to a standard activated clotting time.

Standard activated clotting time (ACT) tests have a poor correlation to bivalirudin levels, leading to uncertainty regarding adequate anticoagulation in percutaneous coronary intervention patients. We tested a Thrombelastograph (TEG) ecarin clotting time (ECT) assay for sensitivity to bivalirudin using blood from 80 patients undergoing interventional cardiology procedures with bivalirudin anticoagulation. This was compared to a standard Hemochron ACT assay using diatomaceous earth. With the TEG assay, the direct thrombin activator, ecarin, was used to initiate coagulation and measured as the reaction time. Plasma samples were evaluated for bivalirudin by a chromogenic assay at an independent hematological laboratory. Linear regression of the standard ACT versus bivalirudin level gave an r = 0.306 whereas the TEG ECT gave a much higher r2 = 0.746 (both P < 0.0001). The TEG ECT should prove more useful than the standard ACT for monitoring bivalirudin anticoagulation across the clinically therapeutic range.

Blood Coagulation↗

Sialic acid in fibrinogen: effects of sialic acid on fibrinogen-fibrin conversion by thrombin and properties of asialofibrin clot.

The final stage in a series of blood coagulating reactions is fibrinogen-fibrin conversion by thrombin. This reaction consists of fibrinopeptide A and fibrinopeptide B release, polymerization of fibrin monomer, and stabilized fibrin formation by factor XIII. The latter two reactions require calcium. In the present study there was no difference in the rate of thrombin-induced fibrinopeptide release between fibrinogen and asialofibrinogen where sialic acid in the terminal end of carbohydrate moiety of fibrinogen was removed by neuraminidase, but turbidity associated with asialofibrin clot formation was increased more rapidly. In asialo-derivatives, the dissolution time of the clots in high concentrated urea solution tended to be shortened and rigidity as a gel tended to be decreased. In measurement by thromboelastography there was no difference in the reaction time (r) between fibrinogen and asialofibrinogen, but the maximum amplitude (ma) was obviously decreased in asialofibrinogen. Furthermore, when the rate of cross-link formation between gamma chains by F-XIII was compared, the production of gamma-dimer in the same reaction time was found to be lower and formation of stabilized fibrin tended to be retarded in asialofibrinogen. Sialic acid in fibrinogen thus may clearly influence the polymerization of fibrin-monomer and the formation of cross-linked fibrin in a series of reactions for fibrinogen-fibrin conversion. This may be consistent with the theory that fibrinogen sialic acid residues are low affinity calcium-binding sites and influence fibrin assembly.

Asialoglycoproteins↗

[Effect of urinastatin on disseminated intravascular coagulation].

Effect of urinary enzyme inhibitor urinastatin (MTI) on disseminated intravascular coagulation (DIC) was investigated. The prolongation of PTT and increase in FDP in endotoxin-induced DIC in rats were restored by the intravenous infusion of MTI. The reduction in platelet counts, decrease in fibrinogen level and prolongation of PT were partially suppressed by the drug. Furthermore, in vitro addition of MTI prevented the decrease in r and k values and increase in ma and m epsilon values in the thromboelastogram of whole blood in endotoxin-induced DIC in rabbits. It is suggested that MTI might prevent DIC in vivo and in vitro through the inhibition of Factor XII activity and through the prevention of thromboplastin release caused by endotoxin.

Animals↗