Accessible Requires Authentication Published by De Gruyter August 19, 2015

Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients – a retrospective study

Florian Prüller, Andreas Münch, Astrid Preininger, Reinhard Bernd Raggam, Yvonne Grinschgl, Jakub Krumnikl, Wolfgang Toller, Hellfried Metzler, Elisabeth Mahla and Harald Mangge

Abstract

Background: Fibrinogen-based clot firmness is reported as the maximum amplitude (MA) when using the citrated functional fibrinogen (CFF) assay in thrombelastography (TEG), and as the maximum clot firmness (MCF) together with several clot amplitude parameters when using the FIBTEM assay in thromboelastometry (ROTEM). Concern is currently being raised that these two tests have different platelet inhibiting performance and consequently provide different values. This is relevant for the clinical setting of fibrinogen replacement. We aim herein to compare the parameters of these two fibrinogen-based clot quality tests and their correlation with the plasma fibrinogen level as determined by the Clauss method.

Methods: In total 261 whole blood samples taken from 163 clinical routine surgical patients were analyzed with TEG 5000 and ROTEM tests, and correlation with Clauss fibrinogen level was assessed.

Results: Using TEG, the overall fibrin-based clot firmness measured in the CFF assay was significantly higher than the MCF measured by FIBTEM assay. Both assays showed significantly positive correlations with the fibrinogen levels measured using the Clauss method. However, individual values of Clauss fibrinogen concentration corresponded with different values for the two viscoelastometric tests; e.g. within the range of 1.9–2.1 g/L Clauss fibrinogen the median of CFF MA was 16.3 mm whereas FIBTEM MCF was 12.0 mm.

Conclusions: We showed herein by measurements of citrated whole blood samples from surgical patients that CFF MA values were different from FIBTEM MCF values measured in the same sample. Awareness that these whole blood assays provide different clot amplitude results is mandatory, particularly if they are being considered as tools for guiding fibrinogen supplementation. Thromboembolic side effects caused by a potentially too high fibrinogen substitution must also kept in mind in this context.


Corresponding authors: Dr. Florian Prüller, MD, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria, Phone: +43 316 385 82576 and 83340, Fax: +43 316 385 14024, E-mail: ; and Research Unit “Perioperative Platelet Function”, Medical University of Graz, Graz, Austria; and Prof. Dr. Harald Mangge, MD, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria, Phone: +43 316 385 82576 and 83340, Fax: +43 316 385 14024, E-mail: ; and BioTechMed-Graz, Graz, Austria

References

1. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. J Am Med Assoc 2010;304:1559–67. Search in Google Scholar

2. Kamel H, Johnston SC, Kirkham JC, Turner CG, Kizer JR, Devereux RB, et al. Association between major perioperative hemorrhage and stroke or Q-wave myocardial infarction. Circulation 2012;126:207–12. Search in Google Scholar

3. Levy JH, Szlam F, Tanaka KA, Sniecienski RM. Fibrinogen and hemostasis: a primary hemostatic target for the management of acquired bleeding. Anesth Analg 2012;114:261–74. Search in Google Scholar

4. Kamath S, Lip GY. Fibrinogen: biochemistry, epidemiology and determinants. Q J Med 2003;96:711–29. Search in Google Scholar

5. Gielen C, Dekkers O, Stijnen T, Schoones J, Brand A, Klautz R, et al. The effects of pre- and postoperative fibrinogen levels on blood loss after cardiac surgery: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg 2014;18:292–8. Search in Google Scholar

6. Karkouti K, Callum J, Crowther MA, McCluskey SA, Pendergrast J, Tait G, et al. The relationship between fibrinogen levels after cardiopulmonary bypass and large volume red cell transfusion in cardiac surgery: an observational study. Anesth Analg 2013;117:14–22. Search in Google Scholar

7. Walden K, Jeppsson A, Nasic S, Backlund E, Karlsson M. Low preoperative fibrinogen plasma concentration is associated with excessive bleeding after cardiac operations. Ann Thorac Surg 2014;97:1199–206. Search in Google Scholar

8. Kindo M, Hoang Minh T, Gerelli S, Perrier S, Meyer N, Schaeffer M, et al. Plasma fibrinogen level on admission to the intensive care unit is a powerful predictor of postoperative bleeding after cardiac surgery with cardiopulmonary bypass. Thromb Res 2014;134:360–8. Search in Google Scholar

9. Jans O, Jorgensen C, Kehlet H, Johansson PI, Lundbeck Foundation Centre for Fast-track H, Knee Replacement Collaborative G. Role of preoperative anemia for risk of transfusion and postoperative morbidity in fast-track hip and knee arthroplasty. Transfusion 2014;54:717–26. Search in Google Scholar

10. Rothwell PM, Howard SC, Power DA, Gutnikov SA, Algra A, van Gijn J, et al. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke. Stroke 2004;35:2300–5. Search in Google Scholar

11. Shenhar-Tsarfaty S, Ben Assayag E, Bova I, Shopin L, Cohen M, Berliner S, et al. Persistent hyperfibrinogenemia in acute ischemic stroke/transient ischemic attack (TIA). Thromb Haemost 2008;99:169–73. Search in Google Scholar

12. Rahe-Meyer N, Solomon C, Hanke A, Schmidt DS, Knoerzer D, Hochleitner G, et al. Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial. Anesthesiology 2013;118:40–50. Search in Google Scholar

13. Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion 2014;54:1389–405; quiz 8. Search in Google Scholar

14. Gorlinger K, Dirkmann D, Hanke AA, Kamler M, Kottenberg E, Thielmann M, et al. First-line therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study. Anesthesiology 2011;115:1179–91. Search in Google Scholar

15. Rourke C, Curry N, Khan S, Taylor R, Raza I, Davenport R, et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost 2012;10:1342–51. Search in Google Scholar

16. Weber CF, Gorlinger K, Meininger D, Herrmann E, Bingold T, Moritz A, et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology 2012;117:531–47. Search in Google Scholar

17. Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, De Robertis E, Filipescu DC, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013;30:270–382. Search in Google Scholar

18. ROTEM‐based algorithm for management of acute haemorrhage and coagulation disorders in trauma patients(A‐321): European Journal of Anaesthesiology (EJA). Available at: http://journals.lww.com/ejanaesthesiology/Fulltext/2006/06001/ROTEM_based_algorithm_for_management_of_acute.302.aspx. Accessed: 12 Apr 2015. Search in Google Scholar

19. Schöchl H, Maegele M, Solomon C, Görlinger K, Voelckel W. Early and individualized goal-directed therapy for trauma-induced coagulopathy. Scand J Trauma Resusc Emerg Med 2012;20:15. Search in Google Scholar

20. Schochl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G, et al. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care 2010;14:R55. Search in Google Scholar

21. Lang T, Bauters A, Braun SL, Potzsch B, von Pape KW, Kolde HJ, et al. Multi-centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagul Fibrinolysis 2005;16:301–10. Search in Google Scholar

22. Essener Gerinnungsrunde. Available at: http://www.essener-runde.de/publ/REMWG_Recommendations_Cardiac.pdf. Accessed: 12 Apr 2015. Search in Google Scholar

23. Levy JH, Goodnough LT. How I use fibrinogen replacement therapy in acquired bleeding. Blood 2015;125:1387–93. Search in Google Scholar

24. Lippi G, Favaloro EJ, Franchini M. Paradoxical thrombosis part 1: factor replacement therapy, inherited clotting factor deficiencies and prolonged APTT. J Thromb Thrombolysis 2012;34:360–6. Search in Google Scholar

25. Ang L, Thani KB, Ilapakurti M, Lee MS, Palakodeti V, Mahmud E. Elevated plasma fibrinogen rather than residual platelet reactivity after clopidogrel pre-treatment is associated with an increased ischemic risk during elective percutaneous coronary intervention. J Am Coll Cardiol 2013;61:23–34. Search in Google Scholar

26. physioklin.de: Fibrinogen-Marketing. Available at: http://www.physioklin.de/physiohaem/haemotherapie/fibrinogen-marketing.html. Accessed: 12 Apr 2015. Search in Google Scholar

27. Afshari A, Wikkelsø A, Brok J, Møller AM, Wetterslev J. Thrombelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion. Cochrane Database Syst Rev 2011:CD007871. Search in Google Scholar

28. Agren A, Wikman AT, Ostlund A, Edgren G. TEG® functional fibrinogen analysis may overestimate fibrinogen levels. Anesth Analg 2014;118:933–5. Search in Google Scholar

29. Franchini M, Lippi G. Fibrinogen replacement therapy: a critical review of the literature. Blood Transfus 2012;10:23–7. Search in Google Scholar

30. Harr JN, Moore EE, Ghasabyan A, Chin TL, Sauaia A, Banerjee A, et al. Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma. Shock 2013;39:45–9. Search in Google Scholar

31. Solomon C, Cadamuro J, Ziegler B, Schochl H, Varvenne M, Sorensen B, et al. A comparison of fibrinogen measurement methods with fibrin clot elasticity assessed by thromboelastometry, before and after administration of fibrinogen concentrate in cardiac surgery patients. Transfusion 2011;51:1695–706. Search in Google Scholar

32. Coakley M, Reddy K, Mackie I, Mallett S. Transfusion triggers in orthotopic liver transplantation: a comparison of the thromboelastometry analyzer, the thromboelastogram, and conventional coagulation tests. J Cardiothor Vasc Anesth 2006;20:548–53. Search in Google Scholar

33. Sankarankutty A, Nascimento B, Teodoro da Luz L, Rizoli S. TEG® and ROTEM® in trauma: similar test but different results? World J Emerg Surg 2012;7(Suppl. 1):S3. Search in Google Scholar

34. Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol 2014;89:228–32. Search in Google Scholar

35. Dontula P, Macosko CW, Scriven LE. Origins of concentric cylinders viscometry. J Rheol 2005;49:807–18. Search in Google Scholar

36. Venema LF, Post WJ, Hendriks HG, Huet RC, de Wolf JT, de Vries AJ. An assessment of clinical interchangeability of TEG and RoTEM thromboelastographic variables in cardiac surgical patients. Anesth Analg 2010;111:339–44. Search in Google Scholar

37. Jackson GN, Ashpole KJ, Yentis SM. The TEG vs the ROTEM thromboelastography/thromboelastometry systems. Anaesthesia 2009;64:212–5. Search in Google Scholar

38. Nielsen VG. A comparison of the thrombelastograph and the ROTEM. Blood Coagul Fibrinolysis 2007;18:247–52. Search in Google Scholar

39. Meyer MA, Ostrowski SR, Sorensen AM, Meyer AS, Holcomb JB, Wade CE, et al. Fibrinogen in trauma, an evaluation of thrombelastography and rotational thromboelastometry fibrinogen assays. J Surg Res 2015;194:581–90. Search in Google Scholar

40. Schlimp CJ, Solomon C, Ranucci M, Hochleitner G, Redl H, Schochl H. The effectiveness of different functional fibrinogen polymerization assays in eliminating platelet contribution to clot strength in thromboelastometry. Anesth Analg 2014;118:269–76. Search in Google Scholar

41. von Bormann B, Suksompong S, Zander R. Therapy with fibrinogen concentrate: clinical and ethical considerations. Transfusion 2013;53:1137–8. Search in Google Scholar

42. Ozier Y, Hunt BJ. Against: fibrinogen concentrate for management of bleeding: against indiscriminate use. J Thromb Haemost 2011;9:6–8. Search in Google Scholar

43. Spahn DR, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Gordini G, et al. Management of bleeding following major trauma: a European guideline. Crit Care 2007;11:R17. Search in Google Scholar

44. Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, et al. Management of bleeding following major trauma: an updated European guideline. Crit Care 2010;14:R52. Search in Google Scholar

45. Wikkelso A, Lunde J, Johansen M, Stensballe J, Wetterslev J, Moller AM, et al. Fibrinogen concentrate in bleeding patients. Cochrane Database Syst Rev 2013;8:CD008864. Search in Google Scholar

Received: 2015-4-13
Accepted: 2015-7-15
Published Online: 2015-8-19
Published in Print: 2016-3-1

©2016 by De Gruyter