The role of prothrombrin complex concentrate in the management of trauma-induced coagulopathy: an integrative review

Authors

DOI:

https://doi.org/10.33448/rsd-v12i3.40283

Keywords:

Bleeding; Blood Coagulation Disorders; Prothrombin.

Abstract

Introduction: Trauma is a disease that kills almost 6 million people every year. The bleeding resulting from trauma triggers a complex coagulopathy, which requires immediate treatment to improve patient survival. Treatment is based on removing the source of bleeding, using blood products and coagulation factor concentrates, associated with permissive hypotension and controlled replacement of crystalloid fluids. Objective: To evaluate the effects of using prothrombin complex concentrates in the management of trauma-induced coagulopathy in the emergency department. Methodology: this study is an integrative literature review. The search mechanism used within the databases was: (Bleeding OR Hemorrhage OR Hemostasis OR “Blood Coagulation Disorders") AND (“Prothrombin Complex Concentrates”). Were included articles from 2017 to 2022, full texts available in English, Portuguese and Spanish. Letters, editorials and case reports, that did not correspond to the theme and duplicates were excluded. Results: After applying the inclusion and exclusion criteria, 37 articles were selected for full reading, resulting in a final sample of 15 articles to compose this integrative review, nine from MEDLINE, five from SCOPUS and one from SCIENCEDirect. Conclusion: The prothrombin complex concentrate is an important adjuvant in the management of trauma-induced coagulopathy, due to its ability to reduce the international normalized ratio and mortality without increasing the risk of thromboembolic events.

References

Academia Brasileira de Ciências – ABC. (2019). Trauma é uma doença: um apelo à ação da iap health. https://www.abc.org.br/2019/04/29/trauma-e-uma-doenca-um-apelo-a-acao-da-iap-health/#:~:text=A%20Rede%20Global%20de%20Academias,o%20trauma%20como%20uma%20doen%C3%A7a%E2%80%9D

American College of Surgions and The Committee on Trauma. (2018). Advanced Trauma Life Suport for Doctors – ATLS, Student Course Manual (10a ed.). Chicago, EUA: Library of Congress.

Arachchillage, D. R. J., Alavian, S., Griffin, J., Gurung, K., Szydlo, R., Karawitage, N., & Laffan, M. (2019). Efficacy and safety of prothrombin complex concentrate in patients treated with rivaroxaban or apixaban compared to warfarin presenting with major bleeding. British journal of haematology, 184(5), 808–816. https://doi.org/10.1111/bjh.15705

Balvers, K., Coppens, M., van Dieren, S., van Rooyen-Schreurs, I. H., Klinkspoor, H. J., Zeerleder, S. S., Baumann, H. M., Goslings, J. C., & Juffermans, N. P. (2015). Effects of a hospital-wide introduction of a massive transfusion protocol on blood product ratio and blood product waste. Journal of emergencies, trauma, and shock, 8(4), 199–204. https://doi.org/10.4103/0974-2700.166597

Baskaran, J., Lopez, R. A., & Cassagnol, M. (2022). Prothrombin Complex Concentrate. In StatPearls. StatPearls Publishing.

Batista, D. V. de A., Cassiano, C., Oberg, L. M. C. de Q., Gianvecchio, D. M., Sousa, R. M. C. de, & Nogueira, L. de S. (2021). Fatores associados ao tempo da morte de vítimas de trauma: estudo de coorte retrospectivo. Revista De Enfermagem Da UFSM, 11, e29. https://doi.org/10.5902/2179769247475

Cannon J. W. (2018). Hemorrhagic Shock. The New England journal of medicine, 378(4), 370–379. https://doi.org/10.1056/NEJMra1705649

Cannon, J. W., Khan, M. A., Raja, A. S., Cohen, M. J., Como, J. J., Cotton, B. A., Dubose, J. J., Fox, E. E., Inaba, K., Rodriguez, C. J., Holcomb, J. B., & Duchesne, J. C. (2017). Damage control resuscitation in patients with severe traumatic hemorrhage: a practice management guideline from the Eastern Association for the Surgery of Trauma. Journal of Trauma and Acute Care Surgery, 82(3), 605-617. https://doi.org/10.1097/TA.0000000000001333

Cardenas, J. C., Rahbar, E., Pommerening, M. J., Baer, L. A., Matijevic, N., Cotton, B. A., Holcomb, J. B., & Wade, C. E. (2014). Measuring thrombin generation as a tool for predicting hemostatic potential and transfusion requirements following trauma. The journal of trauma and acute care surgery, 77(6), 839–845. https://doi.org/10.1097/TA.0000000000000348

Černý, V., Maegele, M., Agostini, V., Fries, D., Leal-Noval, S. R., Nardai, G., Nardi, G., Östlund, A., & Schöchl, H. (2022). Variations and obstacles in the use of coagulation factor concentrates for major trauma bleeding across Europe: outcomes from a European expert meeting. European journal of trauma and emergency surgery : official publication of the European Trauma Society, 48(2), 763–774. https://doi.org/10.1007/s00068-020-01563-2

Chapman, M. P., Moore, E. E., Moore, H. B., Gonzalez, E., Gamboni, F., Chandler, J. G., Mitra, S., Ghasabyan, A., Chin, T. L., Sauaia, A., Banerjee, A., & Silliman, C. C. (2016). Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients. The journal of trauma and acute care surgery, 80(1), 16–25. https://doi.org/10.1097/TA.0000000000000885

Chowdary, P., Tang, A., Watson, D., Besser, M., Collins, P., Creagh, M. D., Qureshi, H., Rokicka, M., Nokes, T., Diprose, P., & Gill, R. (2018). Retrospective Review of a Prothrombin Complex Concentrate (Beriplex P/N) for the Management of Perioperative Bleeding Unrelated to Oral Anticoagulation. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 24(7), 1159–1169. https://doi.org/10.1177/1076029617753537

Costa, E. P. S. R., & Arrais, A. R. (2018). Custos da doação de sangue e dos hemocomponentes de um hemocentro público brasileiro: do doador ao receptor. ENCONTRO DA REDE DISTRITAL DE AVALIAÇÃO DE TECNOLOGIAS EM SAÚDE, 2ed,13 p. Brasília: Fiocruz Brasília. https://www.arca.fiocruz.br/handle/icict/39060

CSL Behring. (2018). Kcentra: Complete Prescribing Information. Bradley, IL. https://labeling.cslbehring.com/pi/us/kcentra/en/kcentra-prescribing-information.pdf

Curry, N., Foley, C., Wong, H., Mora, A., Curnow, E., Zarankaite, A., Hodge, R., Hopkins, V., Deary, A., Ray, J., Moss, P., Reed, M. J., Kellett, S., Davenport, R., & Stanworth, S. (2018). Early fibrinogen concentrate therapy for major haemorrhage in trauma (E-FIT 1): results from a UK multi-centre, randomised, double blind, placebo-controlled pilot trial. Critical care (London, England), 22(1), 164. https://doi.org/10.1186/s13054-018-2086-x.

Davenport, R. A., Guerreiro, M., Frith, D., Rourke, C., Platton, S., Cohen, M., Pearse, R., Thiemermann, C., & Brohi, K. (2017). Activated Protein C Drives the Hyperfibrinolysis of Acute Traumatic Coagulopathy. Anesthesiology, 126(1), 115–127. https://doi.org/10.1097/ALN.0000000000001428

Dunbar, N. M., & Chandler, W. L. (2009). Thrombin generation in trauma patients. Transfusion, 49(12), 2652–2660. https://doi.org/10.1111/j.1537-2995.2009.02335.x

Farmavisa. (2023). Beriplex p/n 500 ui 1fa c/ pó sol iv + 20ml dil + disp. De transf. C/ filtro. https://www.farmavisa.com.br/beriplex-p-n-500-ui-1fa-c-po-sol-iv-20ml-dil-disp-de-transf-c-filtro

Ganong L. H. (1987). Integrative reviews of nursing research. Research in nursing & health, 10(1), 1–11. https://doi.org/10.1002/nur.4770100103

Giordano, S., Spiezia, L., Campello, E., & Simioni, P. (2017). The current understanding of trauma-induced coagulopathy (TIC): a focused review on pathophysiology. Internal and emergency medicine, 12(7), 981–991. https://doi.org/10.1007/s11739-017-1674-0

Gonzalez, E., Moore, E. E., Moore, H. B., Chapman, M. P., Chin, T. L., Ghasabyan, A., Wohlauer, M. V., Barnett, C. C., Bensard, D. D., Biffl, W. L., Burlew, C. C., Johnson, J. L., Pieracci, F. M., Jurkovich, G. J., Banerjee, A., Silliman, C. C., & Sauaia, A. (2016). Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy: A Pragmatic Randomized Clinical Trial Comparing a Viscoelastic Assay to Conventional Coagulation Assays. Annals of surgery, 263(6), 1051–1059. https://doi.org/10.1097/SLA.0000000000001608

Gratz, J., Schlimp, C. J., Honickel, M., Hochhausen, N., Schöchl, H., & Grottke, O. (2020). Sufficient Thrombin Generation Despite 95% Hemodilution: An In Vitro Experimental Study. Journal of Clinical Medicine, 9(12), 3805. http://dx.doi.org/10.3390/jcm9123805

Grottke O., Honickel M., Braunschweig T., Reichel A., Schöchl H., & Rossaint R. (2019). Prothrombin Complex Concentrate-induced Disseminated Intravascular Coagulation Can Be Prevented by Coadministering Antithrombin in a Porcine Trauma Model. Anesthesiology, 131(3), 543–554. https://doi.org/10.1097/ALN.0000000000002797

Haas, T., Fries, D., Tanaka, K.A., Asmis, L., Curry, N.S., & Schöchl, H. (2015). Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: Is there any evidence? Br. J. Anaesth, 114(2), 217–224. https://doi.org/10.1093/bja/aeu303

Ho, V. K., Wong, J., Martinez, A., & Winearls, J. (2022). Trauma-induced coagulopathy: Mechanisms and clinical management. Annals of the Academy of Medicine, Singapore, 51(1), 40–48. https://doi.org/10.47102/annals-acadmedsg.2020381

Hofer, S., Schlimp, C. J., Casu, S., & Grouzi, E. (2022). Management of Coagulopathy in Bleeding Patients. Journal of Clinical Medicine, 11(1), 1. https://doi.org/10.3390/jcm11010001

Hoffbrand, A. V., & Moss, P. A.H. (2018). Fundamentos em hematologia de Hoffbrand (7a ed.). Porto Alegre, Brasil: Artmed.

Holcomb, J. B., Tilley, B. C., Baraniuk, S., Fox, E. E., Wade, C. E., Podbielski, J. M., & PROPPR Study Group. (2015). Transfusion of plasma, platelets, and red blood cells in a 1: 1: 1 vs a 1: 1: 2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. Jama, 313(5), 471-482. https://doi.org/10.1001/jama.2015.12

Kornblith, L. Z., Moore, H. B., & Cohen, M. J. (2019). Trauma-induced coagulopathy: The past, present, and future. Journal of thrombosis and haemostasis : JTH, 17(6), 852–862. https://doi.org/10.1111/jth.14450

Lyons W.S. (2010). Fresh frozen plasma is not independently associated with a higher risk of multiple organ failure and acute respiratory distress syndrome. The Journal of trauma, 68(3), 749. https://doi.org/10.1097/TA.0b013e3181c9c4d2

Maegele M., Zheng-TaoGu, Qiao-BingHuang, & Yang H. (2017). Updated concepts on the pathophysiology and the clinical management of trauma hemorrhage and coagulopathy. Chinese Journal of Traumatology, 20(3), 125-132. Https://doi.org/10.1016/j.cjtee.2017.03.004

Maegele M. (2019). The Diagnosis and Treatment of Acute Traumatic Bleeding and Coagulopathy. Deutsches Arzteblatt International, 116(47), 799–806. Https://doi.org/10.3238/arztebl.2019.0799

Margraf, D. J., Brown, S. J., Blue, H. L., Bezdicek, T. L., Wolfson, J., & Chapman, S. A. (2022). Comparison of 3-factor versus 4-factor prothrombin complex concentrate for emergent warfarin reversal: a systematic review and meta-analysis. BMC emergency medicine, 22(1), 14. Https://doi.org/10.1186/s12873-022-00568-x

Mendes, K.D.S., Silveira, R.C.C.P., & Galvão, C.M. (2008). Revisão integrativa: método de pesquisa para a incorporação de evidências na saúde e na enermagem. Texto Contexto Enferm., 17(4), 758-764. https://doi.org/10.1590/S0104-07072008000400018

Moher D., Liberati A., Tetzlaff J., Altman D.G., & The PRISMA Group. (2009). Preferred Reporting items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med, 6(7), e1000097. https://doi.org/10.1371/journal.pmed1000097

Moore, E. E., Moore, H. B., Kornblith, L. Z., Neal, M. D., Hoffman, M., Mutch, N. J., Schöchl, H., Hunt, B. J., & Sauaia, A. (2021). Trauma-induced coagulopathy. Nature reviews. Disease primers, 7(1), 30. https://doi.org/10.1038/s41572-021-00264-3

Nascimento Júnior, B., Scarpelini, S., & Rizoli, S. (2007). Coagulopatia no trauma. Medicina (Ribeirão Preto), 40(4), 509-517. https://doi.org/10.11606/issn.2176-7262.v40i4p509-517

National Association Of Emergency Medical Technicians. (2017). Prehospital Trauma Life Support – PHTLS (8a ed.). Burlington, Massachusetts, EUA: Jones & Bartlett Learning.

Nesek Adam, V., & Bošan-Kilibarda, I. (2022). Prothrombin complex concentrate in emergency department. Acta clinica Croatica, 61(Suppl 1), 53–58. https://doi.org/10.20471/acc.2022.61.s1.09

Osama, M., Syed, S. H., Nasir, H. M. S. A., & Zaidi, S. R. (2020). Four-Factor Prothrombin Complex Concentrate: An Indispensable Adjunct in Coagulopathy of Trauma Management - A Comparative Review of the Literature over 2 Decades. European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes, 61(2-3), 51–61. https://doi.org/10.1159/000509876

Park, M. S., Xue, A., Spears, G. M., Halling, T. M., Ferrara, M. J., Kuntz, M. M., Dhillon, S. K., Jenkins, D. H., Harmsen, W. S., Ballman, K. V., Harrison, P., & Heit, J. A. (2015). Thrombin generation and procoagulant microparticle profiles after acute trauma: A prospective cohort study. The journal of trauma and acute care surgery, 79(5), 726–731. https://doi.org/10.1097/TA.0000000000000839

Roberts, S.J., Pokrandt, P., Jewell, E., Engoren, M., Berg, M.P., & Maile, M.D. (2021). Association of four-factor prothrombin complex concentrate with subsequent plasma transfusion: A retrospective cohort study. Transfusion Med., 31(1), 69– 75. https://doi-org.ez14.periodicos.capes.gov.br/10.1111/tme.12716

Scharman, C.D., Shatzel, J.J., Kim, E., & DeLoughery, T.G. (2018). Off-label use of 4-factor prothrombin complex concentrate is common despite little known benefit: A retrospective study. Eur J Haematol, 101(3), 349–353. https://doi.org/10.1111/ejh.13105

Schoeneberg, C., Schilling, M., Hussmann, B., Schmitz, D., Lendemans, S., & Ruchholtz, S. (2017). Preventable and potentially preventable deaths in severely injured patients: a retrospective analysis including patterns of errors. European journal of trauma and emergency surgery : official publication of the European Trauma Society, 43(4), 481–489. https://doi.org/10.1007/s00068-016-0670-9

Spahn, D. R., Bouillon, B., Cerny, V., Duranteau, J., Filipescu, D., Hunt, B. J., Komadina, R., Maegele, M., Nardi, G., Riddez, L., Samama, C. M., Vincent, J. L., & Rossaint, R. (2019). The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Critical care (London, England), 23(1), 98. https://doi.org/10.1186/s13054-019-2347-3

TABELA SUS/CISAMUSEP – 2021. (2021). https://cisamusep.org.br/wp-content/uploads/2021/02/tabela_sus_referencia_set-2020.pdf

Ursi E.S. (2005). Prevenção de lesões de pele no perioperatório: revisão integrativa da literatura (Dissertação de mestrado). Universidade de São Paulo, Escola de Enfermagem de Ribeirão Preto, Brasil.

van den Brink, D. P., Wirtz, M. R., Neto, A. S., Schöchl, H., Viersen, V., Binnekade, J., & Juffermans, N. P. (2020). Effectiveness of prothrombin complex concentrate for the treatment of bleeding: A systematic review and meta-analysis. Journal of thrombosis and haemostasis, 18(10), 2457–2467. https://doi.org/10.1111/jth.14991

Voils, S. A., Lemon, S. J., Jordan, J., Riley, P., & Frye, R. (2016). Early thrombin formation capacity in trauma patients and association with venous thromboembolism. Thrombosis research, 147, 13–15. https://doi.org/10.1016/j.thromres.2016.09.024

Wirtz, M. R., Schalkers, D. V., Goslings, J. C., & Juffermans, N. P. (2020). The impact of blood product ratio and procoagulant therapy on the development of thromboembolic events in severely injured hemorrhaging trauma patients. Transfusion, 60(8), 1873–1882. https://doi.org/10.1111/trf.15917

World Health Organization (WHO). (2020). WHO Mortality Database [Internet]. Geneva: WHO. https://www.who.int/data/data-collection-tools/who-mortality-database

Zeeshan, M., Hamidi, M., Kulvatunyou, N., Jehan, F., O’Keeffe, T., Khan, M., Rashdan, L., Tang, A., Zakaria, El-Rasheid., & Joseph, B. (2019a). 3-Factor Versus 4-Factor PCC in Coagulopathy of Trauma: Four is Better Than Three. SHOCK, 52(1), 23-28. https://doi.org/10.1097/SHK.0000000000001240

Zeeshan, M., Hamidi, M., Feinstein, A. J., Gries, L., Jehan, F., Sakran, J., Northcutt, A., OʼKeeffe, T., Kulvatunyou, N., & Joseph, B. (2019b). Four-factor prothrombin complex concentrate is associated with improved survival in trauma-related hemorrhage: A nationwide propensity-matched analysis. The journal of trauma and acute care surgery, 87(2), 274–281. https://doi.org/10.1097/TA.0000000000002262

Zwinkels R. L.J., Endeman H., Hoeks S. E., de Maat M. P.M., den Hartog D., & Stolker R. J. (2020). The clinical effect of hemostatic resuscitation in traumatic hemorrhage; a before-after study. Journal of Critical Care, 56, 288-293. https://doi.org/10.1016/j.jcrc.2019.11.013

Published

17/02/2023

How to Cite

SANTOS, M. L. V. dos .; SILVA, H. B. M. da .; MOURA, E. C. R. .; ARAÚJO, F. L. S. M. de .; OLIVEIRA, C. M. B. de .; LEAL, P. da C. . The role of prothrombrin complex concentrate in the management of trauma-induced coagulopathy: an integrative review. Research, Society and Development, [S. l.], v. 12, n. 3, p. e1812340283, 2023. DOI: 10.33448/rsd-v12i3.40283. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/40283. Acesso em: 22 nov. 2024.

Issue

Section

Health Sciences