Abstract
This study was conducted to determine the impact of thromboelastography (TEG) on blood transfusion policy regarding utilization and preparation of cryoprecipitate in adult cardiac surgery. The differences in total transfusion requirement, length of postoperative ICU stay and 24 h mortality were also studied after introduction of TEG in transfusion protocol. It was a retrospective, single-center, observational study conducted in adult patients underwent cardiac surgery from April 2008 to March 2016. Two thousand patients underwent surgery when TEG was used compared with 1000 control patients before availability of TEG. Significantly more patients in the TEG group versus the control group received cryoprecipitate (41 vs. 7%; p < 0.05), while fewer received a transfusion (60 vs. 87.5%; p < 0.05). Significant increase in cryoprecipitate preparation was observed after introduction of TEG. Patients underwent surgery in TEG group showed substantial reduction in administration of PRBC (2.1 vs. 3.5 U; p < 0.05); FFP (2.4 vs. 3.8 U; p < 0.05) and platelets (1.1 vs. 2.7 U; p < 0.05) compared to control group without compromising the length of ICU stay or postoperative mortality. A TEG-guided approach in adult patients undergoing cardiac surgery may increase the use of cryoprecipitate, while decreasing the overall requirement of blood transfusion.
Keywords: Thromboelastography, Cryoprecipitate, Cardiac surgery, Inventory, Transfusion
Introduction
Bleeding during or after cardiac surgery is common and associated with transfusion of blood products which enhances the risk of morbidity and mortality [1]. Majority of allogeneic blood products are utilized in cardiac surgery leading to a challenge to maintain adequate inventory in blood banks [2]. Bleeding occurs after cardiac surgery due to previous dual-antiplatelet therapy, oral anticoagulants, hypofibrinogenemia, residual heparin effects, prolonged cardiopulmonary bypass time and intra-operative hypothermia [3–8]. Fibrinogen has a central role in coagulation pathway [9] and cryoprecipitates are commonly transfused as a source of fibrinogen. The hemostasis and transfusion management during and after cardiac surgery is usually guided by conventional laboratory tests like platelet count, prothrombin time (PT), activated partial thromboplas-tin time (aPTT), and serum fibrinogen level. However, the utility of these tests has been questioned due to their poor ability to predict bleeding and prolonged turnaround time. [10]. On the contrary, viscoelastic test like TEG results are rapidly available at the patient’s bedside or during the OT and allow a global assessment of hemostasis, including fibrinolysis. A potential advantage of viscoelastic tests is that they can be performed during cardiopulmonary bypass (CPB), allowing blood products to be prepared for administration immediately after CPB when required [11].The aim of this study was to determine the impact of TEG on blood transfusion policy regarding utilization of cryoprecipitate during and within 24-h of adult cardiac surgery as well as its effect on inventory policy regarding preparation of cryoprecipitate in blood bank. The study was also aimed to determine the differences in total transfusion requirement, length of postoperative ICU stay and 24-h mortality in patients who underwent surgery after introduction of TEG in transfusion protocol.
Materials and Methods
Study Details
This study was a retrospective, single-center, observational study conducted in adult patients underwent cardiac surgery from April 2008 to March 2016 in a cardiac center based in eastern India. This study was done as a part of blood bank audit; hence, waiver was obtained from the local ethics committee.
Study Population
Inclusion criteria for this study were patients aged more than 18 years, undergoing elective, first-time coronary artery bypass grafting (CABG), valve surgery, or combination of both on cardiopulmonary bypass (CPB) pump. During the study period, total 3567 patients underwent cardiac surgery by the same team of cardiac surgeons and anesthesiologists. Of these, 2365 received intra-operative TEG analysis (January 2012 to March 2016) but 365 patients were excluded from this study because of age less than 18 years, re-exploration surgeries, surgeries other than CABG or valve surgery, off-pump surgery, emergency surgery, pre-existing coagulation abnormalities or anaemia or patients received autologous blood transfusion. Two thousand patients underwent surgery on CPB pump and received TEG monitoring were finally included. Total 1202 patients underwent surgery before availability of TEG (April 2008 to December 2011) among them 202 were excluded due the same exclusion criteria mentioned in the TEG group. Total 1000 patients were eligible for inclusion in the historical cohort or control group. In OT, a standard preoperative, anaesthetic, surgical and postoperative treatment was provided to all patients including moderately hypothermic (33–34 °C) CPB after a loading dose of 300 IU/kg of heparin. The adequacy of heparin anticoagulation during CPB was monitored by an activated clotting time (ACT) ≥ 450 s. Once the patient was weaned from CPB heparin reversal was done by injection protamine sulfate in the ratio of 1:1 for total heparin used. The adequacy of heparin reversal was again monitored by ACT, and it was ensured that it reached preheparinization value. Chest tube drain was recorded hourly till 24 h postoperatively to detect excessive blood loss in the first 24 postoperative hours of surgery. Excessive bleeding was defined as > 100 ml every hour in the first 3 h or 300 ml in any hour or > 1000 ml in 24 h as per institutional protocol.
Blood Sampling, Blood Tests and Thromboelastography Analysis
Conventional preoperative blood tests were performed in both groups before surgery. Thromboelastography assays were performed in the TEG group before heparin administration at the beginning of CPB and at its discontinuation after heparin reversal. Blood was collected in vacutainer (BD Medical Systems) containing 3.2% trisodium citrate and sent to the transfusion medicine laboratory from OT. TEG analysis was done by trained personnel using a kaolin-based thromboelastograph analyzer (TEG Haemoscope 5000, USA) immediately after receiving the blood sample. TEG parameters studied were reaction time (R): time to initial fibrin formation up to 2 mm, K time (K): time to clot formation up to 20 mm, alpha angle (α): speed of clot formation, maximum amplitude (MA): measurement of clot strength, lysis index (LY 30%): clot dissolution (percentage decrease in amplitude 30 min post-MA), and coagulation index (CI): an index representative of the entire coagulation process. The normal reference values of TEG parameters (as provided by the manufacturer) for kaolin-activated citrated samples were taken as R = 2–8 min, K = 1–3 min, alpha (α) angle = 55°–78°, MA = 51–69 mm, CI = − 3 to + 3 and LY 30% = 0–8. Heparin contaminated venous lines were avoided during postoperative sample collection and in unavoidable circumstances, venous line was flushed with normal saline and first few millilitres of blood were then discarded. The whole blood sample was collected then and tested in heparinase containing kaolin vials available with the TEG kit.
Definition of Coagulopathy
On the basis of conventional coagulation assays in absence of TEG, coagulopathy was defined as one of the following criteria: INR ≥ 1.6, thrombocytopenia defined by platelet count ≤ 100 × 109/L and/or feature of excessive bleeding by chest tube drain. On the basis of individual TEG parameters, hypocoagulability was defined as prolonged R and K times and/or decreased alpha and MA below the reference values. With respect to CI on TEG, hypocoagulability was defined as CI < − 3. The fibrinogen deficiency was suspected when alpha was decreased with or without reduction of MA in presence of a platelet count ≥ 100 × 109/L.
Transfusion Policies
Patients in both the groups received packed red cells in case of hemodynamically significant bleeding and/or to maintain Hb levels above 80 g/L. Platelet transfusion was given in case of pre-operative thrombocytopenia and/or clinically relevant excessive bleeding. Cryoprecipitate was administered when the fibrinogen deficiency was suspected on the basis of individual TEG result as mentioned before. The transfusion of fresh frozen plasma was given when hypocoagulability was observed by conventional coagulation assay or during TEG analysis and/or presence of excessive bleeding.
Statistical Analysis
Data were analyzed by using Excel statistics software package. Continuous variables were expressed as mean ± standard deviation with range and comparison of means was done by Student’s t-test. Categorical data were expressed as frequencies and percentages. Chi-square test was used to analyze relationships between categorical data. Significance was established with p-values level of 0.05 (p < 0.05).
Results
All baseline preoperative data were similar between two groups are listed in Table 1. Cryoprecipitate transfusion was compared between two groups after 2:1 matching and it was found significantly more in patients operated under TEG group versus the control group, while fewer patients received overall at least one unit of blood component transfusion in TEG group compared to control listed in Table 2. Patients underwent surgery in TEG group showed substantial reduction in utilization of blood components like PRBC (2.1 vs. 3.5 U; p < 0.05); FFP (2.4 vs. 3.8 U; p < 0.05) and platelets (1.1 vs. 2.7 U; p < 0.05) compared to control group (Table 2).The differences between postoperative ICU stay and mortality were not significant between two groups (Table 2). However, significant increase in cryoprecipitate preparation was observed after introduction of TEG in blood transfusion service (Fig. 1).
Table 1.
Baseline preoperative and operative data
| Baseline characteristics | Thromboelastography group (n = 2000) |
Control group (n = 1000) | p value |
|---|---|---|---|
| Age (years)a | 70.0 ± 12.3 | 66.8 ± 13.3 | p > 0.05 |
| Sex-male, n (%)b | 1396 (69.8) | 725 (72.5) | p > 0.05 |
| Body weight (kg)a | 55.8 ± 11 | 57.3 ± 10.5 | p > 0.05 |
| Hemoglobin (g/L)a | 117 ± 17 | 125 ± 19 | p > 0.05 |
| Platelet count (× 109/L)a | 172 ± 79 | 180 ± 59 | p > 0.05 |
| INRa | 1.03 ± 0.1 | 1.09 ± 0.22 | p > 0.05 |
| APTT (s)a | 32.6 ± 4.6 | 33.5 ± 5.3 | p > 0.05 |
| Type of surgery-CABG, n (%)b | 1412 (70.6) | 682 (68.2) | p > 0.05 |
| CPB time (min)a | 132 ± 53.6 | 138 ± 56.3 | p > 0.05 |
aVariables are expressed as mean ± standard deviation
bVariables are expressed as frequency percentages (%)
Table 2.
Transfusion and postoperative outcome data
| Transfusion details | Thromboelastography group (n = 2000) | Control group (n = 1000) | p value |
|---|---|---|---|
| Patients received cryoprecipitate; n (%)a | 820 (41) | 70 (7) | p < 0.05 |
| Units of cryoprecipitate transfusedb | 5.2 ± 1.1 (0–8) | 1.55 ± 0.15 (0–2) | p < 0.05 |
| Patients received at least one transfusion; n (%)a | 1200 (60) | 875 (87.5) | p < 0.05 |
| Units of PRBC transfusedb | 2.1 ± 0.25 (0–4) | 3.5 ± 1.05 (0–6) | p < 0.05 |
| Units of FFP transfusedb | 2.4 ± 0.55 (0–4) | 3.8 ± 0.65 (0–6) | p < 0.05 |
| Units of platelets (RDP) transfusedb | 1.1 ± 0.25 (0–4) | 2.7 ± 0.55 (0–4) | p < 0.05 |
| ICU length of stay (h)b | 63.7 ± 5.6 (48–96) | 65.7 ± 7.6 (48–96) | p > 0.05 |
| 24 h mortality, n (%)a | 0 (0) | 0(0) | – |
aVariables are expressed as frequency percentages (%)
bVariables are expressed as mean ± standard deviation (range)
Fig. 1.
Preparation and utilization of cryoprecipitate units from April 2008 to March 2016
Discussion
In present study, the thromboelastography group was more likely to receive cryoprecipitate concentrates compared to control group to replenish the low fibrinogen level in blood as commercial preparation of fibrinogen concentrate was not available which is similar to the study conducted by Vasques et al. [12]. Multiple studies showed critical reduction of fibrinogen in CPB cardiac surgery patients with increased postoperative blood loss can be successfully managed by TEG/ROTEM [13–16]. In this study, the cryoprecipitate preparation in blood center was significantly increased to meet its demand after introduction of TEG in blood transfusion protocol which was not reported previously in literature. This study also demonstrated that TEG results could be used to control the bleeding with better transfusion management in terms of overall reduction of total transfusions in patients without compromising the length of ICU stay or postoperative mortality. Our findings are in agreement with those of others who have shown a beneficial effect of point-of-care coagulation management during cardiac surgery [12, 17–19]. Overall, patient blood management based on the TEG appears to be more restrictive than the one based on conventional laboratory testing. Therefore, TEG could be introduce as a cost-effective measure as it reduces the overall cost for transfusion [20]. The major limitation of our study is retrospective design. Furthermore, during this study we did not have provision of ROTEM which is technically a better tool compare to TEG to predict the fibrinogen depletion by its fibrinogen specific channel. Fibrinogen estimation in blood was not available pre and postoperative period during this study which could be considered as another limitation.
To conclude, TEG has significant impact on blood bank policy regarding preparation of cryoprecipitate to maintain adequate inventory in adult cardiac surgery. The results of this study suggest that a TEG-guided approach in adult patients undergoing CPB cardiac surgery may increase the use of cryoprecipitate, while decreasing the overall requirement of blood transfusion though further larger and possibly prospective multi-centric studies are necessary to provide more evidence on this strategy in different settings.
Acknowledgements
We are thankful to all the staffs of department of transfusion medicine for their support during audit and data collection.
Authors’ contributions
SSD designed the study; audited; collected data and prepared the draft.DD provided support during data analysis. SSD wrote the manuscript. Both the authors reviewed the manuscript before submission.
Funding
We did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors for this study.
Data transparency
All records were obtained from blood component issue register book and hospital electronic medical record system. The endpoint was transfusion details of allogeneic blood products during and within 24-hours of surgery. Blood component preparation book was audited to obtain the cryoprecipitate preparation details during this period as an inventory measurement process.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics Approval
Ethical approval was waived by the local Ethics Committee of The Mission Hospital in view of the retrospective nature of the study and all the procedures being performed were part of the blood bank audit.
Informed Consent
No clinical intervention was performed; only the retrospective data audit was done; individual consent was not obtained as each information was anonymized and the submission did not include any image of any person.
Footnotes
Publisher's Note
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Contributor Information
Suvro Sankha Datta, Email: suvro.datta@gmail.com.
Dibyendu De, Email: de.dibyendu@gmail.com.
References
- 1.Makar M, Taylor J, Zhao M, Farrohi A, Trimming M, D’Attellis N. Perioperative coagulopathy, bleeding, and hemostasis during cardiac surgery: a comprehensive review. ICU Dir. 2010;1:17–27. doi: 10.1177/1944451609357759. [DOI] [Google Scholar]
- 2.Görlinger K, Shore-Lesserson L, Dirkmann D, Hanke AA, Rahe- Meyer N, Tanaka KA. Management of hemorrhage in cardiothoracic surgery. J Cardiothorac Vasc Anesth. 2013;27:S20–S34. doi: 10.1053/j.jvca.2013.05.014. [DOI] [PubMed] [Google Scholar]
- 3.Ferraris VA, Saha SP, Oestreich JH, Song HK, Rosengart T, Reece TB, et al. Update to the society of thoracic surgeons guideline on use of antiplatelet drugs in patients having cardiac and noncardiac operations. Ann Thorac Surg. 2012;94:1761–1781. doi: 10.1016/j.athoracsur.2012.07.086. [DOI] [PubMed] [Google Scholar]
- 4.Carroll RC, Chavez JJ, Snider CC, Meyer DS, Muenchen RA. Correlation of perioperative platelet function and coagulation tests with bleeding after cardiopulmonary bypass surgery. J Lab Clin Med. 2006;147:197–204. doi: 10.1016/j.lab.2005.12.007. [DOI] [PubMed] [Google Scholar]
- 5.Crowther MA, Warkentin TE. Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents. Blood. 2008;111:4871–4879. doi: 10.1182/blood-2007-10-120543. [DOI] [PubMed] [Google Scholar]
- 6.Karlsson M, Ternstrom L, Hyllner M, Baghaei F, Flinck A, Skrtic S, et al. Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery. A prospective randomised pilot study. Thromb Haemost. 2009;102:137–144. doi: 10.1160/TH08-09-0587. [DOI] [PubMed] [Google Scholar]
- 7.Sniecinski RM, Chen EP, Makadia SS, Kikura M, Bolliger D, Tanaka KA. Changing from aprotinin to tranexamic acid results in increased use of blood products and recombinant factor VIIa for aortic surgery requiring hypothermic arrest. J Cardiothorac Vasc Anesth. 2010;24:959–963. doi: 10.1053/j.jvca.2010.02.018. [DOI] [PubMed] [Google Scholar]
- 8.Fassl J, Matt P, Eckstein F, Filipovic M, Gregor M, Zenklusen U, et al. Transfusion of allogeneic blood products in proximal aortic surgery with hyopthermic circulatory arrest: effects of thromboelastometry-guided transfusion management. J Cardiothorac Vasc Anesth. 2013;27(6):1181–1188. doi: 10.1053/j.jvca.2013.02.009. [DOI] [PubMed] [Google Scholar]
- 9.Kawashima S, Suzuki Y, Sato T, Kikura M, Katoh T, Sato S. Four-group classification based on fibrinogen level and fibrin polymerization associated with postoperative bleeding in cardiac surgery. Clin Appl Thromb Hemost. 2016;22:648–655. doi: 10.1177/1076029615597061. [DOI] [PubMed] [Google Scholar]
- 10.Nuttall GA, Oliver WC, Ereth MH, Santrach PJ. Coagulation tests predict bleeding after cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1997;11(7):815–823. doi: 10.1016/S1053-0770(97)90112-9. [DOI] [PubMed] [Google Scholar]
- 11.Segal JB, Dzik WH, Transfusion Medicine/Hemostasis Clinical Trials Network Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion. 2005;45(9):1413–1425. doi: 10.1111/j.1537-2995.2005.00546.x. [DOI] [PubMed] [Google Scholar]
- 12.Vasques F, Spiezia L, Manfrini A, et al. Thromboelastometry guided fibrinogen replacement therapy in cardiac surgery: a retrospective observational study. J Anesth. 2017;31(2):286–290. doi: 10.1007/s00540-016-2271-5. [DOI] [PubMed] [Google Scholar]
- 13.Hanna JM, Keenan JE, Wang H, Andersen ND, Gaca JG, Lombard FW, Welsby IJ, Hughes GC. Use of human fibrinogen concentrate during proximal aortic reconstruction with deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 2016;151:376–382. doi: 10.1016/j.jtcvs.2015.08.079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Ternström L, Radulovic V, Karlsson M, Baghaei F, Hyllner M, Bylock A, Hansson KM, Jeppsson A. Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: a prospective observational study. Thromb Res. 2010;126:e128–e133. doi: 10.1016/j.thromres.2010.05.028. [DOI] [PubMed] [Google Scholar]
- 15.Ranucci M, Baryshnikova E. Fibrinogen supplementation after cardiac surgery: insights from the zero-plasma trial (ZEPLAST) Br J Anaesth. 2016;116:618–623. doi: 10.1093/bja/aev539. [DOI] [PubMed] [Google Scholar]
- 16.Perez-Ferrer A, Vicente-Sanchez J, Carceles-Baron MD, Van der Linden P, Faraoni D. Early thromboelastometry variables predict maximum clot firmness in children undergoing cardiac and noncardiac surgery. Br J Anaesth. 2015;115:896–902. doi: 10.1093/bja/aev369. [DOI] [PubMed] [Google Scholar]
- 17.Rahe-Meyer N, Hanke A, Schmidt DS, Hagl C, Pichlmaier M. Fibrinogen concentrate reduces intraoperative bleeding when used as first-line hemostatic therapy during major aortic replacement surgery: results from a randomized, placebo-controlled trial. J Thorac Cardiovasc Surg. 2013;145:S178–S185. doi: 10.1016/j.jtcvs.2012.12.083. [DOI] [PubMed] [Google Scholar]
- 18.Rahe-Meyer N, Solomon C, Hanke A, Schmidt DS, Knoerzer D, Hochleitner G, Sørensen B, Hagl C, Pichlmaier M. Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial. Anesthesiology. 2013;118:40–50. doi: 10.1097/ALN.0b013e3182715d4d. [DOI] [PubMed] [Google Scholar]
- 19.Ichikawa J, Marubuchi T, Nishiyama K, Kodaka M, Görlinger K, Ozaki M, et al. Introduction of thromboelastometry guidance for the administration of fresh frozen plasma is associated with decreased allogeneic blood transfusions and postoperative blood loss in cardiopulmonary bypass surgery. Blood Transfus. 2018;16(3):244–252. doi: 10.2450/2017.0265-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Fleming K, Redfern RE, March RL, et al. TEG-directed transfusion in complex cardiac surgery: impact on blood product usage. J Extra Corpor Technol. 2017;49:283–290. [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All records were obtained from blood component issue register book and hospital electronic medical record system. The endpoint was transfusion details of allogeneic blood products during and within 24-hours of surgery. Blood component preparation book was audited to obtain the cryoprecipitate preparation details during this period as an inventory measurement process.