A general review of major global coagulation assays: thrombelastography, thrombin generation test and clot waveform analysis

Thrombosis Journal

Marcus D Lancé¹ 

[1] Department of Anesthesiology and Pain Treatment, Maastricht University Medical Center, P. Debyelaan 25, PO box 5800, 6202 AZ Maastricht, The Netherlands

关键词: Hemophilia;    Hemorrhage;    Thrombosis;    Global coagulation assays;   

Others  :  1135341
DOI  :  10.1186/1477-9560-13-1

 received in 2014-04-01, accepted in 2014-06-16,  发布年份 2015

【 摘 要 】

Thrombosis and hemorrhage are major contributors to morbidity and mortality. The traditional laboratory tests do not supply enough information to diagnose and treat patients timely and according to their phenotype. Global hemostasis tests might improve this circumstance. The viscoelastic tests (ROTEM/TEG) demonstrated to ameliorate treatment of acute hemorrhage in terms of decreased amount of transfusion and lowered costs. Thrombin generation measurement is indicative for thrombosis and might also become an important tool in managing hemorrhage. While the clot waveform analysis is less well known it could be of worth in staging sepsis patients, early detection of DIC and also in diagnosis and treatment monitoring of hemophiliac patients. Although in different degree all three methods still need more background, standardization and acceptance before a wide clinical application.

【 授权许可】

   
2015 Lancé; licensee BioMed Central.

【 参考文献 】

• [1]WHO: The top 10 causes of death. 2012. Assesed 2015 from [ http://www.who.int.mediacentre/factsheets/fs310/en/ webcite]
• [2]Kitchens CS: To bleed or not to bleed? Is that the question for the PTT? J Thromb Haemost 2005, 3:2607-2611.
• [3]Segal JB, Dzik WH: Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005, 45:1413-1425.
• [4]Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, De Robertis E, Filipescu DC, Fries D, Gorlinger K, Haas T, Imberger G, Jacob M, Lance M, Llau J, Mallett S, Meier J, Rahe-Meyer N, Samama CM, Smith A, Solomon C, Van der Linden P, Wikkelso AJ, Wouters P, Wyffels P: Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013, 30:270-382.
• [5]Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R: Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care 2013, 17:R76. BioMed Central Full Text
• [6]Hartert H: Blutgerinnungsstudien mit der Thromboelastographie: einem neuen Untersuchungsverfahren. Klin Wochenschr 1948, 26:577-583.
• [7]Macfarlane RG, Biggs R: A thrombin generation test; the application in haemophilia and thrombocytopenia. J Clin Pathol 1953, 6:3-8.
• [8]Holzknecht F: Die Auswertungen des Thromboelastogramms. Basel-New York: Karger, S.; 1962.
• [9]Strassner H: Die Entwicklung der Thromboelastographie ans Messverfahren. Book Die Entwicklung der Thromboelastographie ans Messverfahren 2002.
• [10]Raviv G, Cramer DB, Epstein M, Zuckerman L, Caprini JA: Electronic readout for three-channel thrombelastograph. J Med 1978, 9:17-31.
• [11]Kang YG, Martin DJ, Marquez J, Lewis JH, Bontempo FA, Shaw BW Jr, Starzl TE, Winter PM: Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg 1985, 64:888-896.
• [12]Tuman KJ, Spiess BD, McCarthy RJ, Ivankovich AD: Effects of progressive blood loss on coagulation as measured by thrombelastography. Anesth Analg 1987, 66:856-863.
• [13]Ganter MT, Hofer CK: Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg 2008, 106:1366-1375.
• [14]Schols SE, Heemskerk JW, van Pampus EC: Correction of coagulation in dilutional coagulopathy: use of kinetic and capacitive coagulation assays to improve hemostasis. Transfus Med Rev 2010, 24:44-52.
• [15]Afshari A, Wikkelso A, Brok J, Moller AM, Wetterslev J: Thrombelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion. Cochrane Database Syst Rev 2011, 16:CD007871.
• [16]Johansson PI, Stensballe J: Effect of Haemostatic Control Resuscitation on mortality in massively bleeding patients: a before and after study. Vox Sang 2009, 96:111-118.
• [17]Schochl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G, Kozek-Langenecker S, Solomon C: 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. BioMed Central Full Text
• [18]Gorlinger K, Dirkmann D, Hanke AA, Kamler M, Kottenberg E, Thielmann M, Jakob H, Peters J: 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, 115:1179-1191.
• [19]Perry DJ, Fitzmaurice DA, Kitchen S, Mackie IJ, Mallett S: Point-of-care testing in haemostasis. Br J Haematol 2010, 150:501-514.
• [20]Haas T, Goobie S, Spielmann N, Weiss M, Schmugge M: Improvements in patient blood management for pediatric craniosynostosis surgery using a ROTEM -assisted strategy - feasibility and costs. Paediatr Anaesth 2014, 24:774-80.
• [21]Lang T, von Depka M: Possibilities and limitations of thrombelastometry/-graphy. Hamostaseologie 2006, 26:S20-S29.
• [22]Jambor C, Reul V, Schnider TW, Degiacomi P, Metzner H, Korte WC: In vitro inhibition of factor XIII retards clot formation, reduces clot firmness, and increases fibrinolytic effects in whole blood. Anesth Analg 2009, 109:1023-1028.
• [23]Kitchen DP, Kitchen S, Jennings I, Woods T, Walker I: Quality assurance and quality control of thrombelastography and rotational Thromboelastometry: the UK NEQAS for blood coagulation experience. Semin Thromb Hemost 2010, 36:757-763.
• [24]Chitlur M, Sorensen B, Rivard GE, Young G, Ingerslev J, Othman M, Nugent D, Kenet G, Escobar M, Lusher J: Standardization of thromboelastography: a report from the TEG-ROTEM working group. Haemophilia 2011, 17:532-537.
• [25]Mauch J, Spielmann N, Hartnack S, Madjdpour C, Kutter AP, Bettschart-Wolfensberger R, Weiss M, Haas T: Intrarater and interrater variability of point of care coagulation testing using the ROTEM delta. Blood Coagul Fibrinolysis 2011, 22:662-666.
• [26]Theusinger OM, Nurnberg J, Asmis LM, Seifert B, Spahn DR: Rotation thromboelastometry (ROTEM) stability and reproducibility over time. Eur J Cardiothorac Surg 2010, 37:677-683.
• [27]Pitney WR, Dacie JV: A simple method of studying the generation of thrombin in recalcified plasma; application in the investigation of haemophilia. J Clin Pathol 1953, 6:9-14.
• [28]Hemker HC, Al Dieri R, De Smedt E, Beguin S: Thrombin generation, a function test of the haemostatic-thrombotic system. Thromb Haemost 2006, 96:553-561.
• [29]Dachary-Prigent J, Toti F, Satta N, Pasquet JM, Uzan A, Freyssinet JM: Physiopathological significance of catalytic phospholipids in the generation of thrombin. Semin Thromb Hemost 1996, 22:157-164.
• [30]Keularts IM, Zivelin A, Seligsohn U, Hemker HC, Beguin S: The role of factor XI in thrombin generation induced by low concentrations of tissue factor. Thromb Haemost 2001, 85:1060-1065.
• [31]Wielders S, Mukherjee M, Michiels J, Rijkers DT, Cambus JP, Knebel RW, Kakkar V, Hemker HC, Beguin S: The routine determination of the endogenous thrombin potential, first results in different forms of hyper- and hypocoagulability. Thromb Haemost 1997, 77:629-636.
• [32]Curvers J, Thomassen MC, Rimmer J, Hamulyak K, van der Meer J, Tans G, Preston FE, Rosing J: Effects of hereditary and acquired risk factors of venous thrombosis on a thrombin generation-based APC resistance test. Thromb Haemost 2002, 88:5-11.
• [33]Al Dieri R, de Laat B, Hemker HC: Thrombin generation: what have we learned? Blood Rev 2012, 26:197-203.
• [34]Campo G, Pavasini R, Pollina A, Fileti L, Marchesini J, Tebaldi M, Ferrari R: Thrombin generation assay: a new tool to predict and optimize clinical outcome in cardiovascular patients? Blood Coagul Fibrinolysis 2012, 23:680-687.
• [35]Schols SE, Lance MD, Feijge MA, Damoiseaux J, Marcus MA, Hamulyak K, Ten Cate H, Heemskerk JW, van Pampus EC: Impaired thrombin generation and fibrin clot formation in patients with dilutional coagulopathy during major surgery. Thromb Haemost 2010, 103:318-328.
• [36]Beltran-Miranda CP, Khan A, Jaloma-Cruz AR, Laffan MA: Thrombin generation and phenotypic correlation in haemophilia A. Haemophilia 2005, 11:326-334.
• [37]Salvagno GL, Astermark J, Lippi G, Ekman M, Franchini M, Guidi GC, Berntorp E: Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia? Haemophilia 2009, 15:290-296.
• [38]Young G, Sorensen B, Dargaud Y, Negrier C, Brummel-Ziedins K, Key NS: Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: current state of art and future perspectives. Blood 2013, 121:1944-1950.
• [39]Ay Y, Balkan C, Karapinar DY, Akin M, Bilenoglu B, Kavakli K: Feasibility of using thrombin generation assay (TGA) for monitoring bypassing agent therapy in patients with hemophilia having inhibitors. Clin Appl Thromb Hemost 2013, 19:389-394.
• [40]Lance MD, Ninivaggi M, Schols SE, Feijge MA, Oehrl SK, Kuiper GJ, Nikiforou M, Marcus MA, Hamulyak K, van Pampus EC, ten Cate H, Heemskerk JW: Perioperative dilutional coagulopathy treated with fresh frozen plasma and fibrinogen concentrate: a prospective randomized intervention trial. Vox Sang 2012, 103:25-34.
• [41]Bosch Y, Al Dieri R, ten Cate H, Nelemans P, Bloemen S, Hemker C, Weerwind P, Maessen J, Mochtar B: Preoperative thrombin generation is predictive for the risk of blood loss after cardiac surgery: a research article. J Cardiothorac Surg 2013, 8:154. BioMed Central Full Text
• [42]Ninivaggi M, Apitz-Castro R, Dargaud Y, de Laat B, Hemker HC, Lindhout T: Whole-blood thrombin generation monitored with a calibrated automated thrombogram-based assay. Clin Chem 2012, 58:1252-1259.
• [43]Loeffen R, Kleinegris MC, Loubele ST, Pluijmen PH, Fens D, van Oerle R, Ten Cate H, Spronk HM: Pre-analytical Variables of Thrombin Generation: Towards a standard procedure and validation of the method. J Thromb Haemost 2012.
• [44]Dargaud Y, Wolberg AS, Luddington R, Regnault V, Spronk H, Baglin T, Lecompte T, Ten Cate H, Negrier C: Evaluation of a standardized protocol for thrombin generation measurement using the calibrated automated thrombogram: an international multicentre study. Thromb Res 2012, 130:929-934.
• [45]Spronk HM, Dielis AW, De Smedt E, van Oerle R, Fens D, Prins MH, Hamulyak K, ten Cate H: Assessment of thrombin generation II: Validation of the Calibrated Automated Thrombogram in platelet-poor plasma in a clinical laboratory. Thromb Haemost 2008, 100:362-364.
• [46]Braun PJ, Givens TB, Stead AG, Beck LR, Gooch SA, Swan RJ, Fischer TJ: Properties of optical data from activated partial thromboplastin time and prothrombin time assays. Thromb Haemost 1997, 78:1079-1087.
• [47]Shima M, Thachil J, Nair SC, Srivastava A: Towards standardization of clot waveform analysis and recommendations for its clinical applications. J Thromb Haemost 2013, 11:1417-1420.
• [48]Toh CH, Giles AR: Waveform analysis of clotting test optical profiles in the diagnosis and management of disseminated intravascular coagulation (DIC). Clin Lab Haematol 2002, 24:321-327.
• [49]Downey C, Kazmi R, Toh CH: Early identification and prognostic implications in disseminated intravascular coagulation through transmittance waveform analysis. Thromb Haemost 1998, 80:65-69.
• [50]Bakhtiari K, Meijers JC, de Jonge E, Levi M: Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med 2004, 32:2416-2421.
• [51]Levi M, Toh CH, Thachil J, Watson HG: Guidelines for the diagnosis and management of disseminated intravascular coagulation: British Committee for Standards in Haematology. Br J Haematol 2009, 145:24-33.
• [52]Shima M: Understanding the hemostatic effects of recombinant factor VIIa by clot wave form analysis. Semin Hematol 2004, 41:125-131.
• [53]Chopin N, Floccard B, Sobas F, Illinger J, Boselli E, Benatir F, Levrat A, Guillaume C, Crozon J, Negrier C, Allaouchiche B: Activated partial thromboplastin time waveform analysis: a new tool to detect infection? Crit Care Med 2006, 34:1654-1660.
• [54]Dempfle CE, Lorenz S, Smolinski M, Wurst M, West S, Houdijk WP, Quintel M, Borggrefe M: Utility of activated partial thromboplastin time waveform analysis for identification of sepsis and overt disseminated intravascular coagulation in patients admitted to a surgical intensive care unit. Crit Care Med 2004, 32:520-524.
• [55]Vuilliez A, Floccard B, Sobas F, Chopin N, Allaouchiche B: [The abnormal activated partial thromboplastin time biphasic waveform: a red flag in the sepsis? Technique and interest as marker of the sepsis]. Ann Fr Anesth Reanim 2007, 26:259-262.
• [56]Paize F, Carrol E, Downey C, Parry CM, Green G, Diggle P, Newland P, Riordan FA, Thomson A, Hart CA, Toh CH: Diagnostic efficacy of activated partial thromboplastin time waveform and procalcitonin analysis in pediatric meningococcal sepsis. Pediatr Crit Care Med 2011, 12:e322-e329.