Precision medicine in hemostasis: a review of prothrombin complex concentrates and the role of viscoelastic tests in tailoring therapy
https://doi.org/10.4081/ecj.2023.11500
Accepted: 21 September 2023
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This review explores the role of precision medicine in the management of bleeding disorders and anticoagulation therapy, with a focus on the use of visco-elastic tests such as Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM). These tests provide real-time, dynamic insight into a patient's coagulation status, guiding the choice between three-factor prothrombin complex concentrate (PCC3) and four-factor PCC (PCC4), as well as the use of activated four-factor PCC (FEIBA). The specific ROTEM tests, INTEM and EXTEM, further enhance our understanding of the intrinsic and extrinsic coagulation pathways. Moreover, the use of tranexamic acid (TXA) and fibrinogen, guided by these visco-elastic tests, has shown promise in trauma patients. TXA has been associated with survival benefit when administered immediately or within 3 hours of injury. Fibrinogen, a key factor in clot formation, can be monitored and supplemented as needed to optimize hemostasis. In conclusion, the practice of precision medicine, with the aid of TEG and ROTEM, offers the potential to enhance the safety and efficacy of PCC therapy, TXA administration, and fibrinogen supplementation. These tools are invaluable in tailoring therapy to the specific needs of each patient, potentially optimizing patient outcomes and minimizing the risk of adverse events.
Go AS, Leong TK, Sung SH, et al. Thromboembolism after treatment with 4-factor prothrombin complex concentrate or plasma for warfarin-related bleeding. J Thrombosis Thrombolysis 2022;54:470-9. DOI: https://doi.org/10.1007/s11239-022-02695-5
Margraf DJ, Brown SJ, Blue HL, et al. Comparison of 3-factor versus 4-factor prothrombin complex concentrate for emergent warfarin reversal: a systematic review and meta-analysis. BMC Emerg Med 2022;22:14. DOI: https://doi.org/10.1186/s12873-022-00568-x
Schäfer ST, Otto A-C, Acevedo A-C, et al. Point-of-care detection and differentiation of anticoagulant therapy - development of thromboelastometry-guided decision-making support algorithms. Thrombosis J 2021;19:63. DOI: https://doi.org/10.1186/s12959-021-00313-7
Topf H-G, Strasser ER, Breuer G, et al. Closing the gap – detection of clinically relevant von Willebrand disease in emergency settings through an improved algorithm based on rotational Thromboelastometry. BMC Anesthesiol 2019;19:10. DOI: https://doi.org/10.1186/s12871-018-0672-8
Hagemo JS, Christiaans SC, Stanworth SJ, et al. Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study. Critical Care 2015;19:97. DOI: https://doi.org/10.1186/s13054-015-0823-y
De Oliveira Manoel AL, Goffi A, Zampieri FG, et al. The critical care management of spontaneous intracranial hemorrhage: a contemporary review. Critical Care 2016;20:272. DOI: https://doi.org/10.1186/s13054-016-1432-0
Rossaint R, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Critical Care. 2016;20:100. DOI: https://doi.org/10.1186/s13054-016-1265-x
Spahn DR, Bouillon B, Cerny V, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Critical Care 2013;17:R76. DOI: https://doi.org/10.1186/cc12685
Moia M, Squizzato A. Reversal agents for oral anticoagulant-associated major or life-threatening bleeding. Internal Emerg Med 2019;14:1233-9. DOI: https://doi.org/10.1007/s11739-019-02177-2
Babilonia K, Trujillo T. The role of prothrombin complex concentrates in reversal of target specific anticoagulants. Thrombosis J 2014;12:8. DOI: https://doi.org/10.1186/1477-9560-12-8
Tomaselli GF, Mahaffey KW, Cuker A, et al. 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2017;70:3042-67. DOI: https://doi.org/10.1016/j.jacc.2017.09.1085
Allison TA, Lin PJ, Gass JA, et al. Evaluation of the Use of Low-Dose 4-Factor Prothrombin Complex Concentrate in the Reversal of Direct Oral Anticoagulants in Bleeding Patients. J Intensive Care Med 2020;35:903-8. DOI: https://doi.org/10.1177/0885066618800657
Roman M, Biancari F, Ahmed AB, et al. Prothrombin Complex Concentrate in Cardiac Surgery: A Systematic Review and Meta-Analysis. Ann Thorac Surg 2019;107:1275-83. DOI: https://doi.org/10.1016/j.athoracsur.2018.10.013
Sellers W, Bendas C, Toy F, et al. Utility of 4-Factor Prothrombin Complex Concentrate in Trauma and Acute-Care Surgical Patients. J Osteopathic Med 2018;118:789-97. DOI: https://doi.org/10.7556/jaoa.2018.171
Dager WE, Roberts AJ, Nishijima DK. Effect of low and moderate dose FEIBA to reverse major bleeding in patients on direct oral anticoagulants. Thrombosis Res 2019;173:71-6. DOI: https://doi.org/10.1016/j.thromres.2018.11.009
Factor VII. In: Aronson JK, editor. Meyler's Side Effects of Drugs (Sixteenth Edition). Oxford: Elsevier; 2016. p. 237-8. DOI: https://doi.org/10.1016/B978-0-444-53717-1.00725-3
Hedner U. Recombinant activated factor VII: 30 years of research and innovation. Blood Rev. 2015;29 Suppl 1:S4-8. DOI: https://doi.org/10.1016/S0268-960X(15)30002-3
Yeom RS, Wang XA, Elia E, Yoon U. Severe Congenital Factor VII Deficiency with Normal Perioperative Coagulation Profile Based on ROTEM Analysis in a Hepatectomy. Am J Case Rep 2021;22:e930245. DOI: https://doi.org/10.12659/AJCR.930245
Wu TB, Wu S, Buoni M, Orfeo T, et al. Computational Model for Hyperfibrinolytic Onset of Acute Traumatic Coagulopathy. Ann Biomed Engin 2018;46:1173-82. DOI: https://doi.org/10.1007/s10439-018-2031-9
Roberts I, Shakur-Still H, Afolabi A, et al. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet 2020;395:1927-36. DOI: https://doi.org/10.1016/S0140-6736(20)30848-5
Itagaki Y, Hayakawa M, Takahashi Y, et al. Emergency administration of fibrinogen concentrate for haemorrhage: systematic review and meta-analysis. World J Emerg Surg 2023;18:27. DOI: https://doi.org/10.1186/s13017-023-00497-5
Alvitigala BY, Gooneratne LV, Dharmasena I, et al. The use of rotational thromboelastometry parameters in understanding the coagulopathy following hump-nosed viper (Hypnale spp) bites: a preliminary study. Trop Dis Travel Med Vaccines 2023;8:28. DOI: https://doi.org/10.1186/s40794-022-00186-2
Tinchon A, Freydl E, Fitzgerald RD, et al. Real-time monitoring of intravenous thrombolysis in acute ischemic stroke using rotational thromboelastometry: a feasibility pilot study. J Neurol 2022;269:6129-38. DOI: https://doi.org/10.1007/s00415-022-11271-z
Boss K, Kribben A, Tyczynski B. Pathological findings in rotation thromboelastometry associated with thromboembolic events in COVID-19 patients. Thromb J 2021;19:10. DOI: https://doi.org/10.1186/s12959-021-00263-0
Dennhardt N, Sümpelmann R, Horke A, et al. Prevention of postoperative bleeding after complex pediatric cardiac surgery by early administration of fibrinogen, prothrombin complex and platelets: a prospective observational study. BMC Anesthesiol 2020;20:302. DOI: https://doi.org/10.1186/s12871-020-01217-1
Kumar M, Ahmad J, Maiwall R, et al. Thromboelastography‐Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial. Hepatology 2020;71:235-246. DOI: https://doi.org/10.1002/hep.30794
Da Luz LT, Nascimento B, Shankarakutty AK, et al. Effect of thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®) on diagnosis of coagulopathy, transfusion guidance and mortality in trauma: descriptive systematic review. Crit Care 2014;18:518. DOI: https://doi.org/10.1186/s13054-014-0518-9
David J-S, James A, Orion M, et al. Thromboelastometry-guided haemostatic resuscitation in severely injured patients: a propensity score-matched study. Crit Care. 2023;27:141. DOI: https://doi.org/10.1186/s13054-023-04421-w
Baulig W, Akbas S, Schütt PK, Keul W, Jovic M, Berdat P, et al. Comparison of the resonance sonorheometry based Quantra® system with rotational thromboelastometry ROTEM® sigma in cardiac surgery – a prospective observational study. BMC Anesthesiol 2021;21:260. DOI: https://doi.org/10.1186/s12871-021-01469-5
Hartmann J, Mason D, Achneck H. Thromboelastography (TEG) point-of-care diagnostic for hemostasis management. Point Care 2018;17:15-22. DOI: https://doi.org/10.1097/POC.0000000000000156
Henskens YMC, Gulpen AJW, Van Oerle R, et al. Detecting clinically relevant rivaroxaban or dabigatran levels by routine coagulation tests or thromboelastography in a cohort of patients with atrial fibrillation. Thromb J 2018;16:3. DOI: https://doi.org/10.1186/s12959-017-0160-2
Hunt H, Stanworth S, Curry N, et al. Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma-induced coagulopathy in adult trauma patients with bleeding. Cochrane Database of Systematic Reviews. 2015. DOI: https://doi.org/10.1002/14651858.CD010438.pub2
Cannon JW, Dias JD, Kumar MA, et al. Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Crit Care Explor 2021;3:e0526. DOI: https://doi.org/10.1097/CCE.0000000000000526
Bugaev N, Como JJ, Golani G, et al. Thromboelastography and rotational thromboelastometry in bleeding patients with coagulopathy: Practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg 2020;89:999-1017. DOI: https://doi.org/10.1097/TA.0000000000002944
Artang R, Anderson M, Nielsen JD. Fully automated thromboelastograph TEG 6s to measure anticoagulant effects of direct oral anticoagulants in healthy male volunteers. Res Practice Thromb Haemost 2019;3:391-6. DOI: https://doi.org/10.1002/rth2.12206
El-Menyar A, Ahmed K, Hakim S, et al. Efficacy and safety of the second in-hospital dose of tranexamic acid after receiving the prehospital dose: double-blind randomized controlled clinical trial in a level 1 trauma center. Eur J Trauma Emerg Surg 2022;48:3089-99. DOI: https://doi.org/10.1007/s00068-021-01848-0
Stabler SN, Li SS, Karpov A, Vu EN. Use of fibrinogen concentrate for trauma-related bleeding: A systematic-review and meta-analysis. J Trauma Acute Care Surg 2020;89:1212-24. DOI: https://doi.org/10.1097/TA.0000000000002920
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