Human prothrombin complex, use in patients with intracranial hemorrhage: rapid reversal of the effect of warfarin
DOI:
https://doi.org/10.35954/SM2026.45.2.8.e502Keywords:
factor Xa inhibitors, intracranial hemorrhages, anticoagulation reversal, warfarinAbstract
Introduction: Intracerebral hemorrhage is one of the most severe complications associated with oral anticoagulant therapy and requires rapid reversal of anticoagulation. Warfarin is one of the most widely used oral anticoagulants in medicine.
Objective: Determine the role of human prothrombin complex concentrate in this regard, with a view to implementing its use in patients admitted to the emergency department with intracranial hemorrhagic injuries.
Clinical cases: Three clinical cases assisted by the authors are presented, along with the available scientific evidence supporting the use of human prothrombin complex concentrate to reverse the effect of warfarin.
NOTE: This article was approved by the Editorial Committee.
Received for review: January 2025.
Accepted for publication: September 2025.
Publication date: July 2026.
Correspondence: Maciel Hospital. 174 25 de Mayo St. ZIP Code 11000. Tel.: (+598) 29153000. Montevideo, Uruguay.
Contact email:: rialmariana@gmail.com
Downloads
References
Otero AM (coord.). Consenso uruguayo sobre anticoagulación oral. Montevideo: Aventis, 2003. 62 p.
Farreras Rozman. Vol II. Sección 14. Capítulo 219. pp.232, 234.
Yasaka M, Minematsu K, Naritomi H, Sakata T, Yamaguchi T. Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin. Thromb Haemost. 2003; 89(2):278-83. PMID:12574807.
Gorter JW. Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups. Neurology 1999 Oct 12; 53(6):1319-27. PMID:10522891. https://doi.org/10.1212/wnl.53.6.1319
Smith EE, Rosand J, Knudsen KA, Hylek EM, Greenberg SM. Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke. Neurology 2002 Jul 23; 59(2):193-7. PMID:12136056. https://doi.org/10.1212/wnl.59.2.193
Rosand J, Hylek EM, O'Donnell HC, Greenberg SM. Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology 2000 Oct 10; 55(7):947-51. PMID:11061249. https://doi.org/10.1212/wnl.55.7.947
Roob G, Schmidt R, Kapeller P, Lechner A, Hartung HP, Fazekas F. MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology 1999 Mar 23; 52(5):991-4. PMID:10102418. https://doi.org/10.1212/wnl.52.5.991
Wintzen AR, de Jonge H, Loeliger EA, Bots GT. The risk of hemorrhage during oral anticoagulant treatment; a population study. Ann Neurol. 1984; 16(5):553-8. PMID:6508238. https://doi.org/10.1002/ana.410160505
Hart RG, Benavente O, Pearce LA. Increased risk of intracranial hemorrhage when aspirin is combined with warfarin: A meta-analysis and hypothesis. Cerebrovasc Dis. 1999; 9(4):215-7. PMID:10393408. https://doi.org/10.1159/000015958
Mina AA, Bair HA, Howells GA, Bendick PJ. Complications of preinjury warfarin use in the trauma patient. J Trauma. 2003 May; 54(5):842-7. PMID:12777897. https://doi.org/10.1097/01.TA.0000063271.05829.15
Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. Stroke 1995; 26(8):1471-7. PMID:7631356. https://doi.org/10.1161/01.str.26.8.1471
Berwaerts J, Webster J. Analysis of risk factors involved in oral-anticoagulant-related intracranial haemorrhages. QJM. 2000; 93(8):513-21. PMID:10924533. https://doi.org/10.1093/qjmed/93.8.513
Rådberg JA, Olsson JE, Rådberg CT. Prognostic parameters in spontaneous intracerebral hematomas with special reference to anticoagulant treatment. Stroke 1991 May; 22(5):571-6. PMID:2028484. https://doi.org/10.1161/01.str.22.5.571
Berwaerts J, Dijkhuizen RS, Robb OJ, Webster J. Prediction of functional outcome and in-hospital mortality after admission with oral anticoagulant-related intracerebral hemorrhage. Stroke. 2000; 31(11):2558-62. PMID:11062275. https://doi.org/10.1161/01.str.31.11.2558
Phan TG, Koh M, Wijdicks EF. Safety of discontinuation of anticoagulation in patients with intracranial hemorrhage at high thromboembolic risk. Arch Neurol. 2000 Dec;57(12):1710-3. PMID:11115236. https://doi.org/10.1001/archneur.57.12.1710
Wijdicks EF, Schievink WI, Brown RD, Mullany CJ. The dilemma of discontinuation of anticoagulation therapy for patients with intracranial hemorrhage and mechanical heart valves. Neurosurgery. 1998 Apr; 42(4):769-73. PMID:9574641. https://doi.org/10.1097/00006123-199804000-00053
Tindall GT. The Practice of Neurosurgery. Versión 4.18.4. Baltimore: MD: Williams & Wilkins, Electronic Media, 1998.
Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D'Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berrettini M, Musolesi S. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet 1996 Aug 17; 348(9025):423-8. PMID:8709780. https://doi.org/10.1016/s0140-6736(96)01109-9
Sjöblom L, Hårdemark HG, Lindgren A, Norrving B, Fahlén M, Samuelsson M, Stigendal L, Stockelberg D, Taghavi A, Wallrup L, Wallvik J. Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study. Stroke 2001 Nov; 32(11):2567-74. PMID:11692018. https://doi.org/10.1161/hs1101.098523
Butler AC, Tait RC. Restarting anticoagulation in prosthetic heart valve patients after intracranial haemorrhage: a 2-year follow-up. Br J Haematol. 1998; 103(4):1064-6. PMID:9886320. https://doi.org/10.1046/j.1365-2141.1998.01078.x
Crawley F, Bevan D, Wren D. Management of intracranial bleeding associated with anticoagulation: balancing the risk of further bleeding against thromboembolism from prosthetic heart valves. J Neurol Neurosurg Psychiatry. 2000; 69(3):396-8. PMID:10945818; PMCID:1737111. https://doi.org/10.1136/jnnp.69.3.396
Fredriksson K, Norrving B, Strömblad LG. Emergency reversal of anticoagulation after intracerebral hemorrhage. Stroke. 1992; 23(7):972-7. PMID:1615547. https://doi.org/10.1161/01.str.23.7.972
Eckman MH, Rosand J, Knudsen KA, Singer DE, Greenberg SM. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke. 2003; 34(7):1710-6. Epub 2003 Jun 12. PMID:12805495. https://doi.org/10.1161/01.STR.0000078311.18928.16
Cartmill M, Dolan G, Byrne JL, Byrne PO. Prothrombin complex concentrate for oral anticoagulant reversal in neurosurgical emergencies. Br J Neurosurg. 2000; 14(5): 458-61. PMID:11198768. https://doi.org/10.1080/02688690050175265
Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med. 2004 Apr 26; 164(8):880-4. PMID:15111374. https://doi.org/10.1001/archinte.164.8.880
Goldstein JN, Thomas SH, Frontiero V, Joseph A, Engel C, Snider R, Smith EE, Greenberg SM, Rosand J. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke 2006 Jan; 37(1):151-5. Epub 2005 Nov 23. PMID:16306465. https://doi.org/10.1161/01.STR.0000195047.21562.23
Samama CM. Prothrombin complex concentrates: a brief review. Eur J Anaesthesiol. 2008; 25(10):784-9. Epub 2008 Jun 9. PMID:18538049. https://doi.org/10.1017/S0265021508004675
Makris M, Greaves M, Phillips WS, Kitchen S, Rosendaal FR, Preston EF. Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost. 1997 Mar; 77(3):477-80. PMID:9065997.
Pigretti Santiago G., Mirofsky Matías, García Darío E., Issac Cristian, Valdez Pascual, Persi Gabriel G. et al. Recomendaciones en el abordaje del hematoma intracerebral espontáneo durante la internación. Medicina (B. Aires) [Internet]. 2022 nov [citado24 de octubre de 2024]; 82(Suppl 4):1-56. Disponible en: https://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0025-76802022000800001&lng=es
Zuluaga-Gómez M, Zuluaga-Arbeláez N, Berrouet-Mejía MC, Estrada-Atehortúa AF. Reversión de anticoagulantes orales directos: una perspectiva desde Urgencias. MedUNAB [Internet]. 26 de noviembre de 2020 [citado 22 de octubre de 2024]; 23(3):483-90. Disponible en: https://revistas.unab.edu.co/index.php/medunab/article/view/3841
Gutiérrez Sougarret B. Reversión de la anticoagulación en cirugía de urgencia. Rev mexican Anestesiol 2017; 40(Supl. 2):S411-S415. Disponible en: https://www.medigraphic.com/pdfs/rma/cma-2017/cmas172f.pdf
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 : Mariana Rial, Maria Samantha Pinazzo Correa, Gastón Hayek.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Until 2024 we use the Creative Commons Attribution/NonCommercial Attribution 4.0 International License https://creativecommons.org/licenses/by-nc/4.0/deed.es. Which states that: you are free to share, copy and redistribute the material in any medium or format, as well as to adapt, remix, transform and build upon the material. Under the following terms:
Attribution: you must give proper credit , provide a link to the license, and indicate if changes have been made . You may do so in any reasonable manner, but not in such a way as to suggest that you or your use is endorsed by the licensor.
NonCommercial: you may not use the material for commercial purposes.
As of 2025 authors retain their copyright and assign to the journal the right of first publication of their work, which shall simultaneously be subject to the license https://creativecommons.org/licenses/by-nc-sa/4.0/deed.es that permits sharing, copying and redistribution of the material in any medium or format provided that initial publication in this journal is indicated. Adapt, remix, transform and build upon the material. If you remix, transform, or build from the material, you must distribute your contribution under the same license as the original and may not make use of the material for commercial purposes.
Under the following terms:
1. Attribution: you must give proper credit, provide a link to the license, and indicate whether changes have been made. You may do so in any reasonable manner, but not in such a way as to suggest that you or your use is endorsed by the licensor.
2. NonCommercial: you may not use the material for commercial purposes.
3. ShareAlike: if you remix, transform or build upon the material, you must distribute your contribution under the same license as the original.
PlumX Metrics
