Viscoelastic hemostatic fibrinogen assays detect fibrinolysis early

  • J. N. Harr
  • E. E. Moore
  • T. L. Chin
  • M. P. Chapman
  • A. Ghasabyan
  • J. R. Stringham
  • A. Banerjee
  • C. C. Silliman
Original Article

Abstract

Purpose

Viscoelastic hemostatic assays are emerging as the standard-of-care in the early detection of post-injury coagulopathy. TEG and ROTEM are most commonly used. Although similar in technique, each uses different reagents, which may affect their sensitivity to detect fibrinolysis. Therefore, the purpose of this study is to determine the ability of each device to detect fibrinolysis.

Methods

TEG (Rapid, Kaolin, Functional Fibrinogen) and ROTEM (EXTEM, INTEM, FIBTEM) were run simultaneously on normal blood as well as blood containing tPA from healthy volunteers (n = 10). A two-tailed, paired t-test and ANOVA were used to determine the significance between parameters obtained from normal blood and blood with tPA, and individual TEG and ROTEM assays, respectively.

Results

TEG detected significant changes in clot strength and 30-min lysis after the addition of tPA (p < 0.0001). All ROTEM assays detected changes in the 30-min lysis (p < 0.0001), but only INTEM detected changes in clot strength (p < 0.05). Kaolin and Rapid TEG assays detected greater changes in clot strength and lysis, but INTEM and EXTEM had decreased lysis onset times compared to TEG (p < 0.001). Functional Fibrinogen and FIBTEM assays detected lysis sooner than other TEG/ROTEM assays, and were comparable.

Conclusions

TEG assays detect greater changes in clot strength compared to ROTEM. Despite this, Functional Fibrinogen and FIBTEM assays detect fibrinolysis sooner than their corresponding intrinsic and extrinsic assays. Therefore, fibrinogen assays should be employed in actively bleeding trauma patients in order to provide timely antifibrinolytic therapy.

Keywords

Thrombelastography Thromboelastometry Fibrinogen Trauma-induced coagulopathy Fibrinolysis 

References

  1. 1.
    Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54(6):1127–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Plotkin AJ, Wade CE, Jenkins DH, Smith KA, Noe JC, Park MS, Perkins JG, Holcomb JB. A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries. J Trauma. 2008;64(2 Suppl):S64–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Maegele M, Lefering R, Yucel N, Tjardes T, Rixen D, Paffrath T, Simanski C, Neugebauer E, Bouillon B; AG Polytrauma of the German Trauma Society (DGU). Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury. 2007;38:298–304.PubMedCrossRefGoogle Scholar
  4. 4.
    MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003;55:39–44.PubMedCrossRefGoogle Scholar
  5. 5.
    Brohi K, Cohen MJ, Ganter MT, Schultz MJ, Levi M, Mackersie RC, Pittet JF. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma. 2008;64(5):1211–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Wohlauer MV, Moore EE, Thomas S, Sauaia A, Evans E, Harr J, Silliman CC, Ploplis V, Castellino FJ, Walsh M. Early platelet dysfunction: an unrecognized role in the acute coagulopathy of trauma. J Am Coll Surg. 2012;214(5):739–46.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Cotton BA, Harvin JA, Kostousouv V, Minei KM, Radwan ZA, Schöchl H, Wade CE, Holcomb JB, Matijevic N. Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration. J Trauma Acute Care Surg. 2012;73(2):365–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Ives C, Inaba K, Branco BC, Okoye O, Schochl H, Talving P, Lam L, Shulman I, Nelson J, Demetriades D. Hyperfibrinolysis elicited via thromboelastography predicts mortality in trauma. J Am Coll Surg. 2012;215(4):496–502.PubMedCrossRefGoogle Scholar
  9. 9.
    Schöchl H, Cotton B, Inaba K, Nienaber U, Fischer H, Voelckel W, Solomon C. FIBTEM provides early prediction of massive transfusion in trauma. Crit Care. 2011;15(6):R265.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Chapman MP, Moore EE, Ramos CR, Ghasabyan A, Harr JN, Chin TL, Stringham JR, Sauaia A, Silliman CC, Banerjee A. Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy. J Trauma Acute Care Surg. 2013;75(6):961–7.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejía-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23–32.PubMedCrossRefGoogle Scholar
  12. 12.
    Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) study. Arch Surg. 2012;147(2):113–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Holcomb JB, Minei KM, Scerbo ML, Radwan ZA, Wade CE, Kozar RA, Gill BS, Albarado R, McNutt MK, Khan S, Adams PR, McCarthy JJ, Cotton BA. Admission rapid thrombelastography can replace conventional coagulation tests in the emergency department: experience with 1974 consecutive trauma patients. Ann Surg. 2012;256(3):476–86.PubMedCrossRefGoogle Scholar
  14. 14.
    Kashuk JL, Moore EE, Wohlauer M, Johnson JL, Pezold M, Lawrence J, Biffl WL, Burlew CC, Barnett C, Sawyer M, Sauaia A. Initial experiences with point-of-care rapid thrombelastography for management of life-threatening postinjury coagulopathy. Transfusion. 2012;52(1):23–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Haemonetics. TEG 5000 System User Manual. P/N 06-510-US, Manual revision: AC. Niles, IL: Haemonetics Corporation, Haemoscope Division; 2010.Google Scholar
  16. 16.
    Tem Innovations GmbH. ROTEM (delta whole blood haemostasis system using thromboelastometry) US operating manual. REF 200120-USA. Manual Version:1.6.1.02.US. Munich, Germany: Tem Innovations GmbH; 2011.Google Scholar
  17. 17.
    Hardisty RM, Hutton RA. The kaolin clotting time of platelet-rich plasma: a test of platelet factor-3 availability. Br J Haematol. 1965;11:258–68.PubMedCrossRefGoogle Scholar
  18. 18.
    Owens MR. The role of platelet microparticles in hemostasis. Transfus Med Rev. 1994;8(1):37–44.PubMedCrossRefGoogle Scholar
  19. 19.
    Attilio P, Merritt C, Sims J, Kane N, O’Sullivan J. The effect of ellagic acid on platelet activation as measured by the quantification of P-selectin using flow cytometry. AANA J. 2010;78(6):453–9.PubMedGoogle Scholar
  20. 20.
    Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001;85(6):958–65.PubMedGoogle Scholar
  21. 21.
    Harr JN, Moore EE, Chin TL, Ghasabyan A, Gonzalez E, Wohlauer MV, Banerjee A, Silliman CC, Sauaia A. Platelets are dominant contributors to hypercoagulability after injury. J Trauma Acute Care Surg. 2013;74(3):756–62.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Levrat A, Gros A, Rugeri L, Inaba K, Floccard B, Negrier C, David JS. Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients. Br J Anaesth. 2008;100(6):792–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Harr JN, Moore EE, Ghasabyan A, Chin TL, Sauaia A, Banerjee A, Silliman CC. Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma. Shock. 2013;39(1):45–9.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Mangano DT, Tudor IC, Dietzel C; Multicenter Study of Perioperative Ischemia Research Group; Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006;354(4):353–65.PubMedCrossRefGoogle Scholar
  25. 25.
    Murkin JM, Falter F, Granton J, Young B, Burt C, Chu M. High-dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg. 2010;110(2):350–3.PubMedCrossRefGoogle Scholar
  26. 26.
    Martin K, Knorr J, Breuer T, Gertler R, Macguill M, Lange R, Tassani P, Wiesner G. Seizures after open heart surgery: comparison of epsilon-aminocaproic acid and tranexamic acid. J Cardiothorac Anesth. 2011;25(1):20–5.CrossRefGoogle Scholar
  27. 27.
    Yeh HM, Lau HP, Lin PL, Sun WZ, Mok MS. Convulsions and refractory ventricular fibrillation after intrathecal injection of a massive dose of tranexamic acid. Anesthesiology. 2003;98(1):270–2.PubMedCrossRefGoogle Scholar
  28. 28.
    CRASH-2 collaborators, Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096–101.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • J. N. Harr
    • 1
  • E. E. Moore
    • 1
    • 2
    • 3
  • T. L. Chin
    • 1
  • M. P. Chapman
    • 4
  • A. Ghasabyan
    • 2
    • 3
  • J. R. Stringham
    • 1
  • A. Banerjee
    • 3
  • C. C. Silliman
    • 3
    • 5
    • 6
  1. 1.Department of SurgeryUniversity of Colorado DenverAuroraUSA
  2. 2.Department of SurgeryDenver Health Medical CenterDenverUSA
  3. 3.Trauma Research CenterUniversity of Colorado DenverAuroraUSA
  4. 4.Department of SurgeryMedical College of GeorgiaAugustaUSA
  5. 5.Department of PediatricsUniversity of Colorado DenverAuroraUSA
  6. 6.Research DepartmentBonfils Blood CenterDenverUSA

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