Author, date and country | Patient group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
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Speiss et al, 1987, USA | 38 patients undergoing Cardiac Surgery (29 CABG, 9 valve replacements) Activated clotting times (ACT), Thromboelastography (TEG) and coagulation profiles performed pre-bypass, 45 min after institution of CPB and 30 min post-protamine Postoperative blood loss (1 ml/kg/h in first 8 h classed as abnormal) | Cohort Study (level 2b) | Postop blood loss | Significant correlation between aPTT & TEG | Small study 1 patient returned to theatre with arterial bleeding from aortotomy site and normal TEG and excluded from further analysis |
Correlation between TEG variables, ACT's and coagulation profiles, and comparison to postop blood loss to identify predictive capabilities of each test | All TEG's abnormal during CPB (no evidence coagulation) 29/37 (78%) TEG's normal post-Protamine - no single coagulation test consistently abnormal No correlation between abnormal TEG's and single abnormal coagulation test (moderate correlation between A60 and aPTT - r=–0.4708, P=0.01) TEG 87% accurate as predictor of postoperative bleeding (ACT 30% and coagulation profiles 51% accurate, P=0.004) | ||||
Ostrowsky et al, 2004, USA | 35 adults patients undergoing cardiac surgery with CPB Excluded if history of haemostatic disorder or requiring deep hypothermic circulatory arrest Plateletworks platelet function analyser (platelet count + platelet aggregation in presence of agonist) vs thromboelastography (TEG) Platelet assays - preincision, after removal of aortic cross-clamp, 1 h and 24 h postop using baseline, ADP and collagen reagent tubes TEG assays preop, post-protamine and 24 h postop | Cohort Study (level 2b) | Plateletworks data | No correlation between plateletworks and blood product usage | Wide range of procedures CABG, Valve or combination Valve or combination of CPB/cross-clamp times and lowest core temperatures |
TEG data | Significant change in alpha -angle from preop to postop TEG samples (p<0.035) | ||||
Blood product use | No significant difference in k-time and MA at the time intervals | ||||
Chest tube (CT) drainage | No correlation between TEG data and CT drainage Correlation between preop TEG MA and blood product usage (P=0.016) | ||||
Ereth et al, 1997, USA | 200 adult patients undergoing cardiac surgery with CPB Comparison of platelet-activated clotting test (PACT HemoSTATUS)- vs ACT and clotting studies (PT and APTT) vs TEG to predict blood loss and platelet dysfunction associated with CPB Coagulation studies, platelet tests and TEG taken pre and ost CPB; ACT samples taken post-heparin and on CPB; PACT performed pre-induction, after 40 min CPB and 20-40 min post-protamine Sensitivity, specificity of tests analysed using receiver operating characteristics (ROC) analysis of system using excessive blood loss as abnormal state | Cohort Study (level 2b) | Mediastinal blood loss (MBL) at 4 and 24 h | Post-protamine PACT correlated with 4-h MBL MBL (r=–0.30; P=0.014) | Design of study to assess PACT, HemoSTATUS test, not TEG Design of study specifically to correlate platelet function to bleeding Only small sub-group did not receive aprotinin |
Abnormal blood loss level set at: >100 ml/h in 1st 4 h | TEG MA correlated with 4 h MBL (r=–0.32; P=0.003) | ||||
Abnormal blood loss level set at: >200 ml/h in 1st 4 h | PACT sensitivity and specificity comparable to conventional coagulation tests in predicting blood loss | ||||
Platelet activated clotting test (PACT) | TEG MA more predictive than PACT and routine coagulation tests in predicting excessive blood loss post-CPB | ||||
Platelet count PT;aPTT TEG-R-Time;R+K-time; alpha-angle; MA; MA+30 | >100 ml/h blood loss in 4 h: – PACT 80% – sensitivity 80%; specificity 56%; – TEG-MA 48 mm – sensitivity 80%; specificity 75%; – Platelet count 110x10(to the power of 9)/l – sensitivity 64%; specificity 61%; – PT 14 s – sensitivity 68%; specificity 68%; – aPTT 40 s – sensitivity 50%; specificity 55%; | ||||
Essell et al, 1993, USA | 36 adult patients undergoing cardiopulmonary bypass Comparison of TEG to platelet function tests (bleeding time, platelet count, mean platelet volume) and standard coagulation tests (PT, aPTT, fibrinogen) Abnormal blood loss defined as loss >1500 ml blood in first 24 h postop or need to transfuse platelets of FFP to control haemorrhage (platelet of FFP ordered on basis of lab tests or clinical decision) | Cohort Study (level 2b) | Patients classed as 'bleeders' or 'non-bleeders' on basis of mediastinal tube (MT) or chest tube (CT) drainage Preop and postop bleeding time (BT) Preop and postop PT;aPTT: platelet count; MPV; Hb; Hct; fibrinogen; fibrinogen split products (FSP's); thrombin time TEG data – R-time; K-time; alpha-angle; MA; A60 (normal values derived from review of 'bleeders' and 'non-bleeders' on basis of mediastinal tube (MT) or chest tube (CT) drainage Preop and postop bleeding time(BT) Preop and postop PT; aPTT: platelet count; MPV; Hb; Hct; fibrinogen; fibrinogen split products (FSP's); thrombin time TEG data – R-time; K-time; alpha-angle; MA; A60 normal values derived from review of 'bleeders' and 'non-bleeders' | TEG – sensitivity 71.4%; specificity 89.3%; Bleeding time >9 min – sensitivity 71.4%; specificity 78.5%; Platelet count <130x10 (to the power of 9) – sensitivity 100%; specificity 53.6%; PT >13.55 s – sensitivity 85.7%; specificity 10.7%; APTT>30.85 s – sensitivity 85.7%; specificity 21.4%; Fibrinogen <175 – sensitivity 85.7%; specificity 32.1%; Thrombin time <9.95 s –sensitivity 28.6%; specificity 78.6%; Hb <12 g/dl – sensitivity 85.7%; specificity 7.1%; | Small study 61% of patients having CABG surgery. Remainder mix of valve, ASD repair, bundle ablations – wide range of procedures Assessing TEG as predictor of bleeding rather than to guide to therapy Unclear whether 'bleeders' and 'non-bleeders' used to define TEG normal values were from study or other population Blood loss seems excessive compared to other studies 1/36 died 8 h postop 35/36 completed study |
Cammerer et al, 2003, Germany | 255 consecutive patients Comparison of modified TEG (ROTEG) using activated blood samples ± Abciximab vs platelet function analyser (PFA-100) using epinephrine and ADP coated cartridges post-induction of anaesthesia, during CPB after rewarming and post-protamine administration to predict postop blood loss Data for blood loss >750 ml in 6 h compared to group with blood loss <750 ml in 6 h Data for blood loss above and below 75th percentile for 6 h blood - 'enhanced blood loss' - also compared ROC curves used to identify/compare best predictors Significant variables with univariate analysis subjected to binary logistic regression analysis | Cohort Study (level 2b) | Absolute blood loss | Blood loss >750 ml vs loss <750 ml | Bleeding threshold of 750 ml based on one other study and may be somewhat arbitary 75th percentile more useful Demonstrates low PPV and high NPV Low PPV means that coagulopathy identified by test may not necessarily cause bleeding – risk of over -treating if test result solely used to guide therapy |
Comparison of ROTEG and PFA-100 data for blood loss groups >750 ml and <750 ml in 6 h | – TEG data – no significant difference – PFA data – significant differences for preop ADP PFA vs postop ADP PFA and epinephrine PFA (P<0.05) | ||||
Comparison of ROTEG and PFA-100 data for blood loss groups more and less than 75th percentile in 6 h | Blood loss >500 ml vs. loss <500 ml – significant differences between ROTEG MA's on CPB and post-CPB (± Abciximab); ROTEG post-CPB; alpha-angle (± Abciximab); and post-CPB PFA's with ADP and epinephrine (P<0.05) Post-protamine post-CPB samples best predictors for bleeding with univariate analysis – MA <57 mm – PPV 37%; NPV 77% – alpha-angle <71° – PPV 41%; NPV 82%– Abciximab MA <17 mm – PPV 41%; NPV 85% – Abciximab -angle <26° – PPV 35%; NPV 84% – PFA ADP <118 s – PPV 34%; NPV 76% -angle of TEG best predictor of postop bleeding on logistic regression analysis with PFA-ADP post-CPB an additional significant factor | ||||
Ti et al, 2002, Singapore | 40 patients undergoing elective multivessel CABG surgery TEG samples (plain and heparinase-modified) taken pre-induction and at 10 min and 60 min post-protamine administration Subdivided into 'bleeders' (blood loss>1000 ml over 24 h, or 250 ml over 2 consecutive hours) and 'non-bleeders' | Cohort Study (level 2b) | Abnormal TEG values:– K-time >16 mm – {alpha}-angle <40° – MA<40 mm – LY60 >15% in MA | Moderate correlation between TEG parameters, total blood loss & requirement for FFP &/or platelets 60 min TEG better than 10 min TEG (sensitivity 100% vs. 70%) | Definition of degrees of postop bleeding somewhat arbitrary and based on 'local institutional modifications of definitions by previous authors' though no references cited 6/40 (15%) 10-min and 10/40 (25%) 60-min TEG's produced unreadable 'straight-line' traces and were excluded from analysis Small numbers in study |
Absolute blood loss Requirement for FFP and/or platelet transfusion | Use of heparinase- modified-TEG specificity (83% vs.40% @10 min, 73% vs. 20% @ 60 min); and PPV (58% vs. 28% @ 10 min, 55% vs. 29% @ 60 min) 'Bleeder' vs. 'non-bleeder' lab tests no significant difference | ||||
Nuttall et al, 1997, USA | 82 adult patients undergoing elective cardiac surgery Agreed subjective assessment by anaesthetist and surgeon into 'bleeders' and 'non-bleeders' 10 min post-protamine Quantitative assessment of bleeding post-CPB by collection of blood and irrigation fluid by suction from operative field Comparison of coagulation tests, bleeding times, platelet counts, TEG and sonoclot data as predictors of bleeding | Cohort Study (level 2b) | Identification of 'bleeders' | TEG data - – R time – 18 vs. 16 mm. (P=0.1475)) – sensitivity 47%; specificity 71%; | Diagnosis of bleeding subjective (but 'agreed' between surgeon and anaesthetist ROC analysis based on this subjective designation of 'bleeder' Lack of 'gold-standard' for diagnosis of bleeding may affect the ROC analysis |
Thromboelastography – post-Protamine R & K times; alpha-angle; MA; MA+30 (A30) Assessment of sensitivity, specificity, PPV and NPV achieved using Receiver Operator Characteristic (ROC) curves for bleeding | – R+K time – 29 vs. 23 mm P=0.0123) – sensitivity 53%; specificity 75%; – R+K time – 29 vs. 23 mm (P=0.0123) – sensitivity 53%; specificity 75%; alpha-angle – 40 vs. 46° (P=0.0138) – sensitivity 63%; specificity 71%; – MA – 47 vs. 53 mm (P=0.0006) – sensitivity 60%; specificity 79%; – MA+30 – 45 vs. 49 mm P=0.0614) – sensitivity 58%; specificity 67%; 30/82 36.6%) classed as 'bleeders' 10 min post-protamine Median blood loss ('bleeders vs 'non-bleeders'): – 775 vs. 200 ml intraoperative (P<0.001) – 949 vs. 547 ml first 24 h postop (P<0.001) Coagulation tests correlated best with intraoperative and postoperative blood loss (but predictive values outside normal ranges) | ||||
Dorman et al, 1993, USA | 60 patients presenting for CABG surgery Comparison of preoperative tests to predict blood loss: - Coagulation screen (aPTT, PT, platelet count, fibrinogen level; bleeding time) vs -ACT -TEG Blood/blood products given on basis of transfusion protocol | Cohort Study (level 2b) | Absolute intraoperative blood loss Packed cell and blood product requirements; Hb; Hct;Coag screen results –PT; aPTT; fibrinogen; platelet count; forearm bleeding time ACT results TEG results – R time; R+K time; MA; MA+30; MA+60; propto angle | PT; platelet count; bleeding time identified as significant contributing variables when blood loss considered dependant variable (r=0.75; P<0.05) No significant relationship between any TEG variable and blood loss by step-wise linear regression analysis (r<0.25, P>0.78) Significant linear relationship between propto-angle and MA(r=–0.54; P<0.05), propto-angle and R-time (r=–0.53; P<0.05),and propto-angle and R+K-time (r=–0.7; P<0.05) Significant correlation between propto-angle and PT (r=–0.58; P<0.05). Poor correlation between other coagulation screen parameters and TEG variables | Looked at preoperative coagulation studies; ACT and TEG data only as predictors of intraoperative blood loss 2/60 TEG's repeated post-induction in viewof unsatisfactory pre-induction traces |
Avidan et al, 2004, USA/UK | 102 patients undergoing elective CABG surgery with cardiopulmonary bypass 'Point of Care' (POC) - hepcon + Thromboelastography (TEG) + platelet function analyser (PFA-100) - vs 'laboratory algorithm group' (LAG) management - rapidly available ACT, INR, APTT - to direct treatment algorithm POC & LAG transfusion trigger 8 g/dl Comparison to retrospective case-control group (n=108) - 'clinician directed therapy' | PRCT with retrospective cohort control group (level 2b) | 24-h Blood loss | Median blood loss between two study and case-control and study groups not significant | Study assessed effects of combined POC monitors, not just TEG Variations in antifibrinolytic therapy between groups (tested groups given tranexamic acid; Case control group mostly given tranexamic acid or aprotinin at clinicians discretion Study questions accuracy of its own POC algorithm Time delays obtaining conventional clotting studies compared to rapidly available POC and LAG data might skew outcomes No transfusion trigger in case-control group |
Blood transfusion requirement Blood component requirement | Blood and component transfusion (Red cells, FFP and Platelets) in 'clinically directed' group > that in LAG or POCgroups (P<0.025) No significant difference between POC and LAG groups –therefore POC no better than rapidly available coag tests Abnormal TEG MA associated with increased postop bleeding. No results predicted increase in postop bleeding | ||||
Spiess et al, 1995, USA | 1079 sequential patients for revascularisation and/or open ventricle procedures 2 groups Group 1 - 488 pre introduction of TEG based guidelines Group 2 - 591 post introduction of TEG based guidelines Baseline and post-protamine TEG analysis performed | Cohort study (level 2b) | Number of pts transfused | – 13.7% pre-TEG vs.21.5% post-TEG received no transfusion (P=0.001) | Increased awareness of transfusion issues and philosophy and move towards less liberal transfusion and stricter transfusion triggers probably main contributor to decreased red cell transfusion during study. Introduction of TEG at the same time may have been coincidental Lack of rigid TEG protocol use and interpretation of TEG data not standardised and left up to individual clinicians Other coagulation data also available to clinical team if deemed necessary Much of study may show advantages of cooperative behaviour in monitoring changes rather than true experimental differences between groups |
Number receiving platelet transfusion | – 38.8% pre-TEG vs.42.1% post-TEG received no transfusion in operating room (P=0.005) | ||||
Number receiving FFP transfusion | – 83.2% pre-TEG vs. 73.9% post-TEG received red cell transfusion overall (P=0.0001) | ||||
Number receiving cryoprecipitate transfusion | – 59.2% pre-TEG vs. 48.2% post-TEG received Platelets (P=0.0001) – 36.1% pre-TEG vs. 26.4% post-TEG received FFP (P=0.001) | ||||
Incidence of massive transfusion | – 9.1% pre-TEG vs. 6.4% post-TEG received cryoprecipitate (P=0.091) – 10.2% pre-TEG vs. 9.5% transfusion (P=NS) | ||||
Re-exploration rate | – 5.7% pre-TEG vs. 1.5% TEG-monitored patients required re- exploration (P=0.0001) | ||||
Koster et al, 2001, USA | 30 adult patients undergoing surgery with cardiopulmonary bypass with prolonged ACT> 150 s after protamine reversal of heparin Treatment protocol based on analysis of data from multiple kaolin-activated TEG's: -Baseline -Heparinase -Heparinase/Abciximab -Heparinase/FFP-TEG ROTEG R-time <900 s and MA 40-50mm regarded as normal | Case series (level 3b) | experimental differences and MA variables Pre-treatment ACT Post treatment ACT | Therapy guided by ROTEG 2/30 (6.7%) given protamine 19/30 (63.3%) given FFP 2/30 (6.7%) given platelets 2/30 (6.7%) given platelets + FFP Mean pre treatment ACT 162.2±7.8 s Mean post-treatment ACT 127±8.3 s (P<0.05) | Small study No comparison to control group Mixed group of patients – CABG ± valve; multiple valves; aortic surgery; VAD implantation Mixed group of interventions Treatment algorithm more complicated than that used in other studies |
Shore-Lesserson et al, 1999, USA | 107 adult patients undergoing cardiac surgery utilising cardiopulmonary bypass (105 completed study) Conventional vs TEG protocol in presence of bleeding 53/105 TEG protocol – protamine, platelets, FFP, EACA, cryoprecipitate given according to TEG data (R-time, MA and LY30), plateletcount and fibrinogen levels 52/105 Conventional protocol – protamine, platelets, FFP, and cryoprecipitate given according to ACT, plateletcount, PT and fibrinogen levels | PRCT (level 1b) | Multiple time point analysis of: – Mediastinal tube drainage (MTD) -Blood component transfusion requirements -Lab coag tests (platelets, PT, aPTT, fibrinogen) -TEG variables (R-time, alpha-angle, MA and LY30) | 34/52 (65.4%) conventional group vs 22/53 (41.5%) of TEG group transfused (P=0.01) 17/52 (33%) Conventional group vs. 7/53 (13%) TEG group received non-RBC transfusion (P=0.02) 16/52 (31%) Conventional group received FFP vs. 4/53 (7.5%) of TEG group (P<0.002) FFP volume significantly more in conventional than TEG group (P<0.04) 15/52 (29%) Conventionalvs. 7/53 (13%) in TEG group received platelets (P<0.05). No significant difference in MTD between groups | Routine use of E-aminocaproic acid may modify TEG and make it more likely to trigger intervention Part of TEG protocol dependent on lab studies More options as part of TEG protocol Post-protamine lab tests used to guide 'Conventional protocol' vs. 'post-warm CPB heparinase modified samples' in TEG group. Ordering of component therapy based on this TEG sample but only actually given if patient bleeding therefore facilitated very early intervention for bleeding post-CPB |
Royston, 2001, UK | Series 1 60 patients undergoing complex cardiac surgery given haemostatic treatment at clinician's discretion/lab tests in presence of bleeding vs 'predicted' component requirements guided by heparinase modified celite activated TEG algorithm Series 2 60 patients randomised to 'clinician directed/lab tests' or TEG-directed component therapy using algorithm driven by R-time, MA and LY30 data. Products ordered as soon as clinicians judged necessary or test results available | Series 1 -retrospective cohort study (level 2b) Series 2 -PRCT (level 1b) | Mediastinal tube drainage (MTD) at 6 and 12 h post-op Red cell usage FFP usage Platelet usage | Series 1 - 22/60 (37%) given blood components vs 7/60 (12%) 'predicted' to require component therapy (P<0.05) 38 units FFP and 17 platelet pools given vs 6 units FFP and 2 units pooled platelets in 'predicted' group (P<0.05) Series 2 - 10/30 (33%) clinically managed patients received blood components vs 5/30 (17%) TEG patients (P<0.05) 16 units FFP and 9 platelet pools in clinically managed group vs 5 units FFP and 1 unit pooled platelets in TEG group (P<0.05) MTD no significant differences between groups | Patients who returned to theatre for bleeding discarded from study and replaced by additional patient TEG algorithm facilitated early intervention possibly before associated with excessive bleeding Could TEG give false positive results leading to unecessary treatment? Algorithm issues - study acknowledges that absolute values used in algorithm are derived from reference values in normal population and there is no evidence that they are optimal for study group |