Ketorolac and thromboelastography.
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Analgesics↗
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Evaluation of laboratory coagulation and lytic parameters resulting from autologous whole blood transfusion during primary aortocoronary artery bypass grafting.
STUDY OBJECTIVE: To determine if autologous blood reinfusion influences overall hemostatic function following aortocoronary artery bypass graft (CABG) surgery, and if so, where the predominant area of this influence lies. DESIGN: Prospective, with control values on each patient. SETTING: Cardiac operating room of a major university-affiliated county hospital. PATIENTS: 20 patients undergoing elective CABG surgery. INTERVENTIONS: Following heparinization, and prior to cardiopulmonary bypass (CPB), venous blood (average 4.9 ml/kg) was removed via an indwelling internal jugular catheter into a preservative-free plastic transfer pack unit and stored without agitation at room temperature. This autologous whole blood was reinfused after systemic protamine reversal of heparin. Blood samples for analysis were drawn immediately before and 5 minutes after completion of the reinfusion. MEASUREMENTS AND MAIN RESULTS: Autologous blood reinfusion appears to be significantly related to increased hemoglobin, hematocrit, platelet count, fibrinogen, plasminogen, and antiplasmin levels. The prothrombin time and activated partial thromboplastin times decreased significantly, whereas activated clotting times and D-dimer levels were unchanged. Significant increases occurred in the following thromboelastography parameters: maximum amplitude, amplitude 60 minutes after the maximum amplitude, and whole blood clot lysis index. Reaction time and coagulation time were not statistically different from control values. CONCLUSIONS: Significant improvements in coagulation and lytic parameters occur following CPB after the infusion of autologous blood. These improvements in coagulation indices may be the result of the infused blood or hemoconcentration, which is also known to occur during this period. Additional control studies are needed to differentiate these effects.
Anticoagulants↗
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↗
Evaluation of coagulation during cardiopulmonary bypass with a heparinase-modified thromboelastographic assay.
Thromboelastography (TEG) is a useful method of assessing perioperative coagulation function in patients undergoing cardiac surgery. The presence of significant amounts of heparin in blood samples, however, prevents determination of changes in coagulation function by TEG or introduces artifactual error if samples contain heparin that is not present in vivo. For these reasons, whole blood coagulation function monitoring with TEG has not been feasible during cardiopulmonary bypass (CPB) with heparin anticoagulation. In this study, data obtained from 42 volunteers are presented to describe the effects of heparinase on TEG variables in the presence and absence of heparin. These data indicate that heparinase does not affect TEG parameters of whole blood not containing heparin and reverses the TEG effects of low levels of heparin contamination. Subsequently, 51 patients undergoing coronary artery surgery were studied using a modified TEG assay that incorporates in vitro application of heparinase to allow measurement of TEG parameters before, during, and after CPB. Heparinase-modified TEG assays facilitated diagnosis of heparin contamination in preoperative blood samples and permitted baseline TEG evaluation in patients receiving preoperative heparin infusions. Heparinase-modified TEG assays revealed declines in alpha and MA values during CPB, which persisted and significantly correlated with values after protamine infusion (alpha: r = 0.77, P = 0.001; MA: r = 0.78, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Systemic heparinization during peripheral vascular surgery: thromboelastographic, activated coagulation time, and heparin titration monitoring.
Fifteen patients (9 male, 6 female) undergoing peripheral vascular surgery were monitored during surgery for evidence of subclinical anticoagulation using the activated coagulation time (ACT), thromboelastography (TEG), and heparin titration monitoring. Assessments were made at 30-minute intervals before and after the occlusion clamp. Mean (+/- SD) ACT values preoperatively were 111 (17) seconds, and 10 minutes after 5,000 IU of heparin, the ACT was 264 (57) seconds (P < 0.001). Intraoperatively, there was a significant decline in ACT values at 30 minutes (ACT 228 [50] sec, P < 0.005) and 60 minutes (200 [46] sec, P < 0.001) postheparin. No significant difference in ACT was observed between samples drawn distally and proximally to the clamp. TEG profiles were abolished in all patients immediately following heparinization. However, in 2 patients nearly complete return of the TEG coagulation profile was observed prior to the termination of the procedure and was associated with ACT values less than 160 seconds. The heparin device was unable to accurately monitor heparin elimination at these low doses. Variability of patient response to heparinization necessitates the use of intraoperative monitoring of anticoagulation during peripheral vascular surgery.
Aged↗
[Manageability and potential for haemostasis monitoring by near-patient modified thromboelastometer (Rotem) in intensive care unit].
OBJECTIVE: Preliminary assessment of a rotary thromboelastometer (Rotem) in the haemostasis monitoring in ICU. STUDY DESIGN: Prospective, open. PATIENTS AND METHODS: The device: the Rotem is a rotary thromboelastometer, which measures continuously and retranscribes numerically viscoelastic properties of a clot after an in vitro haemostasis activation. 83 patients with various haemostasis disorders that 122 blood samples have been subjected to a double analysis: extemporaneous by Rotem and at the laboratory for conventional haemostasis tests (aPTT, PT, fibrinogen, platelets). We assessed Rotem's manipulation duration, time for the first results. We compared Rotem variables with conventional haemostasis parameters and haemostasis diagnosis with each method. RESULTS: Mean Rotem manipulation duration was measured at 2 minutes 51 seconds+/-1 minute 48 seconds and time for results at 13+/-6 minutes. Plasma fibrinogen level was strongly correlated with the kinetic of clot formation (CFT) and the maximun clot firmness (MCF) measured by Rotem (R>0.7, coefficient of Pearson). Platelets were strongly correlated with MCF. The PT and aPTT had a weak correlation with Rotem parameters (R< or =0.53). The diagnosis concordance between the two techniques was good with a pondered kappa coefficient measured at 0.68. Hypocoagulability thromboelastographic profile with Rotem was in agreement with conventional parameters diagnosis in 92 percent of cases. Hypercoagulability thromboelastographic profile was associated with a significant increase of conventional parameters (supranormal value in 78%). Normal thromboelastography profile was associated with normal conventional parameters in 49%. Different reagents used on several simultaneous tests specified the thromboelastographic diagnosis. A diagnostic algorithm showed the interest of the Rotem for the prediction of conventional test results. CONCLUSION: Rotem is an easy manipulation device whose concordant and rapid results allow its emergency use in the framework of haemorrhagic situations. It also allows an approach of hypercoagulability states so that the therapeutic implication remains to evaluate. The Rotem offers a dynamic multifactorial approach on total blood of haemostasis that is what makes it a prime aid of haemostasis monitoring, in complement of usual analytic haemostasis evaluation.
Adult↗
[Thromboelastography: one step forward?].
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Humans↗
Protamine enhances fibrinolysis by decreasing clot strength: role of tissue factor-initiated thrombin generation.
BACKGROUND: Excessive protamine administration to neutralize heparin after cardiopulmonary bypass has been implicated as a cause of postoperative hemorrhage. Protamine directly inhibits thrombin and tissue factor (TF)-mediated activation of factor VII. However, the half-life of protamine is only 4.5 minutes; thus the purpose of this study was to determine if protamine could enhance fibrinolysis, explaining the delayed, protamine-associated hemorrhage observed in the postoperative period. METHODS: Human plasma containing 0, 6.25, 12.5, or 25 microg/mL of protamine (n = 6 per condition) was exposed to 0.01% tissue factor and tissue-type plasminogen activator (tPA, 100 U/mL) for 30 minutes, with clot growth and disintegration measured by Thromboelastograph (Haemoscope Corp, Skokie, IL). The TF was increased to 0.1% in additional experiments with plasma containing protamine (25 microg/mL) and tPA. RESULTS: Protamine significantly (p < 0.05) delayed the time to clot initiation, decreased the speed of clot propagation, and diminished clot strength in a concentration-dependent fashion. The onset of fibrinolysis was significantly (p < 0.05) increased only in samples with 25 microg/mL of protamine, and the rate of clot lysis was not different among the conditions. The clot duration time (from initiation to disintegration) was significantly (p < 0.05) decreased in a concentration-dependent manner by protamine. Increased TF concentration (0.1%) significantly improved clot growth kinetics and prolonged clot duration in samples with 25 microg/mL of protamine compared with samples activated with 0.01% TF. CONCLUSIONS: Protamine enhanced fibrinolysis by decreasing clot strength by diminishing TF-initiated thrombin generation. Additional, clinical investigation is warranted to mechanistically implicate protamine-mediated enhancement of fibrinolysis to delayed bleeding after cardiopulmonary bypass.
Blood Coagulation↗
Thromboelastographic study of the effect of manipulation of central veins on coagulability of venous blood.
AIM: To measure whole blood coagulability in vitro using thromboelastography before and after direct and indirect manipulation of the internal jugular and subclavian veins. METHODS: We studied 10 patients (American Society of Anaesthesiologists (ASA) grades I or II) with malignant disease of the head and neck who were having selective neck dissections. We excluded patients with diabetes, those who were being given any anticoagulant, those who were actively infected, and those with known coagulopathy. We took 3 ml samples of venous blood during insertion of a peripheral cannula, after insertion of a central venous cannula, and after dissection of the internal jugular vein. Thromboelastography was done on recalcified citrated samples within 1h of sampling. The variables r, k, alpha angle, and maximum amplitude were recorded at each point and the values before and after manipulation were compared using t-tests. RESULTS: The only change was seen in the variable r, which showed an insignificant increase in coagulability.
Blood Coagulation↗
The ultrastructure of fibrinogen-420 and the fibrin-420 clot.
Fibrinogen-420 is a minor subclass of human fibrinogen that is so named because of its higher molecular weight compared to fibrinogen-340, the predominant form of circulating fibrinogen. Each of the two Aalpha chains of fibrinogen-340 is replaced in fibrinogen-420 by an Aalpha isoform termed alphaE. Such chains contain a globular C-terminal extension, alphaEC, that is homologous with the C-terminal regions of Bbeta and gamma chains in the fibrin D domain. The alphaEC domain lacks a functional fibrin polymerization pocket like those found in the D domain, but it does contain a binding site for beta2 integrins. Electron microscopy of fibrinogen-340 molecules showed the major core fibrinogen domains, D-E-D, plus globular portions of the C-terminal alphaC domains. Fibrinogen-420 molecules had two additional globular domains that were attributable to alphaEC. Turbidity measurements of thrombin-cleaved fibrinogen-420 revealed a reduced rate of fibrin polymerization and a lower maximum turbidity. Thromboelastographic measurements also showed a reduced rate of fibrin-420 polymerization (amplitude development) compared with fibrin-340. Nevertheless, the final amplitude (MA) and the calculated elastic modulus (G) for fibrin-420 were greater than those for fibrin-340. These results suggested a greater degree of fibrin-420 branching and thinner matrix fibers, and such structures were found in SEM images. In addition, fibrin-420 fibers were irregular and often showed nodular structures protruding from the fiber surface. These nodularities represented alphaEC domains, and possibly alphaC domains as well. TEM images of negatively shadowed fibrin-420 networks showed irregular fiber borders, but the fibers possessed the same 22.5-nm periodicity that characterizes all fibrin fibers. From this result, we conclude that fibrin-420 fiber assembly occurs through the same D-E interactions that drive the assembly of all fibrin fibrils, and therefore that the staggered overlapping molecular packing arrangement is the same in both types of fibrin. The alphaEC domains are arrayed on fiber surfaces, and in this location, they would very likely slow lateral fibril association, causing thinner, more branched fibers to form. However, their location on the fiber surface would facilitate cellular interactions through the integrin receptor binding site.
Blood Coagulation↗
Recombinant human antithrombin inhibits thrombin formation and interleukin 6 release in human endotoxemia.
We hypothesized that infusion of recombinant human antithrombin without concomitant heparin would have dose-dependent anticoagulant properties and potentially decrease endotoxin (lipopolysaccharide [LPS])-induced cytokine production. This was a randomized, double-blind, placebo-controlled study in parallel groups enrolling 30 healthy male volunteers. The active treatment groups received infusions of recombinant human antithrombin to increase antithrombin levels to 200% and 500% before infusion of 2 ng/kg endotoxin (LPS). Infusion of antithrombin dose-dependently decreased coagulation (P < .01 by repeated-measures ANOVA): peak levels of prothrombin fragment (1.8 nmol/L [95% confidence interval (CI), 1.3-2.3 nmol/L] in the 500% antithrombin group and 4.4 nmol/L [95% CI, 2.7-6.2 nmol/L] in the placebo group at 4 hours), thrombin antithrombin complexes (12 microg/L [95% CI, 8-16 microg/L] in the 500% antithrombin group and 34 microg/L [95% CI, 20-48 microg/L] in the placebo group at 4 hours), and D-dimer (0.2 microg/L [95% CI, 0.1-0.2 microg/L] in the 500% antithrombin group and 0.5 microg/L [95% CI, 0.4-0.7 microg/L] in the placebo group). Recombinant human antithrombin decreased peak interleukin-6 levels by 40% (222 pg/mL [95% CI, 148-295 pg/mL] and 216 pg/mL [95% CI, 112-320 pg/mL] in the 500% and 200% antithrombin groups, respectively, versus 357 pg/mL [95% CI, 241-474 pg/mL] in the placebo group; P < .001 by ANOVA). Finally, infusion of recombinant human antithrombin rapidly and transiently decreased neutrophil counts (by 19% [95% CI, 8%-30%] in the 500% antithrombin group versus 6% [95% CI, 1%-10%] in the placebo group, P = .002 by Kruskal-Wallis ANOVA) and monocyte counts (by 30% [95% CI, 16%-44%] in the 500% antithrombin group and 18% [95% CI, 9%-28%] in the 200% antithrombin group versus 8% [95% CI, 5%-20%] in the placebo group, P = .04) before LPS challenge, indicating that recombinant human antithrombin directly interacts with these leukocyte subsets. In summary, recombinant human antithrombin dose-dependently inhibited tissue factor-triggered coagulation. Effects on leukocytes and inhibition of interleukin-6 release seem to represent specific pharmacodynamic properties of recombinant human antithrombin.
Adult↗
Argatroban, bivalirudin, and lepirudin do not decrease clot propagation and strength as effectively as heparin-activated antithrombin in vitro.
BACKGROUND: Heparin-induced thrombocytopenia is a potentially limb- and life-threatening response to heparin exposure. Direct thrombin inhibitors (DTIs) have been reported to provide anti-coagulation for cardiopulmonary bypass; however, clot formation within the cardiopulmonary bypass circuit has been reported after the administration of DTIs. We present a case of thrombosis of the cardiopulmonary bypass circuit and, ultimately, death after argatroban administration. An in vitro thrombelastographic assessment of the effects of DTIs on clot kinetics was consequently performed to determine potential causes for this complication. METHODS: Normal human plasma was unmodified or exposed to heparin (1, 2, 3 U/ml), argatroban (5, 10, 50 microg/ml), bivalirudin (12, 20, 120 microg/ml), or lepirudin (3, 6, 10 microg/ml) before activation with tissue factor/kaolin in a thrombelastograph. Clot initiation (R, reaction time), propagation (MTG, maximum thrombus generation), and strength (MG, maximum elastic modulus) were determined. Analysis of variance was performed, with p < 0.05 considered significant. RESULTS: Compared with unmodified plasma, heparin significantly prolonged R and essentially reduced MTG and MG to the limits of detection in an activity-dependent fashion. In general, the DTIs tested prolonged R in a concentration-dependent fashion but did not diminish MTG or MG nearly as well as heparin. The only exception was 10 microg/ml lepirudin, which eliminated coagulation. CONCLUSIONS: DTIs demonstrated a significant prolongation of clot initiation but poor attenuation of propagation and strength. Further in vitro and clinical investigations to design a heparin-equivalent regimen to provide anti-coagulation for patients with heparin-induced thrombocytopenia are indicated.
Anticoagulants↗
In vitro evidence of gender-related heparin resistance.
Coagulability varies among men, women, and pregnant women, along a spectrum where the blood of men is the least and that of pregnant women the most coagulable. The effects of differences in coagulation status on the action of heparin cannot be measured by specific laboratory tests such as aPTT or anti-Factor Xa assay. Thromboelastography which measures whole blood coagulation can assess the effect of heparin against differing backgrounds of coagulation. The aim of this in vitro study was to explore differences in heparin effect between men, women and pregnant women. Fifteen male and female staff volunteers, and 15 pregnant women approaching term, donated venous blood, which was added to four cups in two TEG 5000 analysers. In the cups of the analysers was 0.03 mL of saline control, or heparin 0.4, 0.6 or 1 unit/mL. TEG variables r and k, angle and MA were compared across the groups using two way ANOVA. All subject groups demonstrated a significant heparin effect, which was least in the control group and greatest with 1 unit/mL (P < 0.0001). Across the subject groups, from men to pregnant women, increasing coagulability was seen, with shortening of r and k (P < 0.04), and increasing angle and MA (P < 0.0001). A relationship between gender and heparin was significant for r and k (P < 0.02) but not for angle and MA. This result assists the case against a one-size-fits-all approach to policies on heparinisation.
Adolescent↗
Evaluation of the platelet function analyzer (PFA-100) vs. the thromboelastogram (TEG) in the parturient.
BACKGROUND: The platelet function analyzer (PFA-100) is a bedside test of coagulation designed to evaluate platelet function. It measures the time required for whole blood to occlude a membrane impregnated with either epinephrine (EPI) or adenosine 5'diphosphate (ADP). The results are reported as closure time (CT-EPI or CT-ADP) in seconds. The thromboelastogram (TEG) measures whole blood clotting and the maximum amplitude (MA) correlates with platelet count and function. We wished to establish whether there is a correlation between the CT and platelet count, between the CT and MA, and between the MA and platelet count. METHODS: Platelet count, CT, and MA were measured in blood drawn from 172 healthy term parturients using the PFA-100. RESULTS: We were unable to detect a significant correlation between the CT-EPI and platelet count (r=-0.1, P=0.21), or the CT-ADP and platelet count (r=-0.02, P=0.83). We also did not find a correlation between the CT-EPI and MA (r=-0.13, P=0.12) or between the CT-ADP and MA (r=-0.11, P=0.19). However, we found a significant correlation between platelet count and MA (r=0.33, P<0.001). CONCLUSIONS: We conclude that the CT does not correlate with the platelet count or MA in the parturient, but the TEG does. Therefore the TEG may be a better tool to evaluate coagulation in the parturient with thrombocytopenia.
Adolescent↗
Thromboelastography should be available in every labour ward.
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Anesthesia, Obstetrical↗
Thromboelastography should be available in every labour ward.
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Anesthesia, Conduction↗
Thromboelastography assessment of coagulation status in parturients with lupus anticoagulant receiving heparin therapy.
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Adult↗