Correction of the effect of vitamin K antagonists and antiplatelet agents in hemorrhagic stroke

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BACKGROUND

Hemorrhagic stroke (HS) is associated with high risk of mortality or disability. To date, up to 25% of HSs are associated with anticoagulants and antiplatelet agents. Early hemostatic therapy and correction of effect of antithrombotic drugs in patients with HS significantly reduce the risk of adverse outcomes. The latest international guidelines on this issue were presented almost 10 years ago.

MATERIAL AND METHODS

In accordance with the PRISMA recommendations, we reviewed the PubMed, eLibrary and UpToDate databases and identified 137 articles. Of these, 52 were enrolled as the most relevant.

RESULTS AND DISCUSSION

Regarding correction of the effect of indirect anticoagulants, various researchers discuss the possibility of either individual dosing or injection of a fixed dose of 4- or 3-factor prothrombin complex (1000—2000 IU regardless of body weight and international normalized ratio). To correct the effect of antiplatelet agents, platelet transfusion and desmopressin are proposed. There is currently no evidence of safety and effectiveness of both methods in patients with HS.

CONCLUSION

The optimal drug for correction of the effect of indirect anticoagulants is 4- or 3-factor prothrombin complex. In the last case, it is necessary to administer factor VIIa or fresh frozen plasma, as well as parenteral form of phytomenadione (vitamin K₁) in all cases. The issue of correction of the effects of antiplatelet agents remains open. Regular analysis of available data with updating the guidelines for correction of the effect of anticoagulants and antiplatelet agents in HS is necessary.

Keywords:

hemorrhagic stroke

anticoagulants

antiplatelet agents

hemostatic therapy

antithrombotic drugs

Authors:

Baranich A.I.

Burdenko Neurosurgical Center;
Plekhanov Russian University of Economics

RSCI AuthorID: 1006875
Scopus AuthorID: 57202735861
ORCID: 0000-0002-1167-0742

Sychev A.A.

Burdenko Neurosurgical Center

SPIN RSCI: 1171-7690
Scopus AuthorID: 36997601100
ORCID: 0000-0002-0038-1005

Savin I.A.

Burdenko Neurosurgical Center

SPIN RSCI: 1342-7065
Scopus AuthorID: 35974373500
ORCID: 0000-0003-3874-4147

Kudrina V.G.

Plekhanov Russian University of Economics;
Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0002-4329-1165

Kozlov A.V.

Burdenko Neurosurgical Center;
Andijan State Medical Institute

ORCID: 0000-0002-3181-6470

Received:

18.07.2024

Accepted:

20.09.2024

List of references:

Hostettler IC, Seiffge DJ, Werring DJ. Intracerebral hemorrhage: an update on diagnosis and treatment. Expert Review of Neurotherapeutics. 2019;19(7):679-694. https://doi.org/10.1080/14737175.2019.1623671
Concha M, Cohen AT. Recommendations for Research Assessing Outcomes for Patients With Anticoagulant-Related Intracerebral Bleeds. Stroke. 2021;52(4):1520-1526. https://doi.org/10.1161/STROKEAHA.120.031730
Maragkos GA, Nelton EB, Richter S, Stippler M. Low Risk of Traumatic Intracranial Hematoma Expansion with Factor Xa Inhibitors without Andexanet Reversal. World Neurosurgery. 2020;142:e95-e100. https://doi.org/10.1016/j.wneu.2020.06.069
Kuramatsu JB, Sembill JA, Huttner HB. Reversal of oral anticoagulation in patients with acute intracerebral hemorrhage. Critical Care. 2019;23(1):206. https://doi.org/10.1186/s13054-019-2492-8
Tanaka K, Toyoda K. Clinical Strategies Against Early Hematoma Expansion Following Intracerebral Hemorrhage. Frontiers in Neurosciences. 2021;15:677744. https://doi.org/10.3389/fnins.2021.677744
Clinical recommendations «Hemorrhagic stroke» (approved by the Russian Ministry of Health). Association of Neurosurgeons of Russia, All-Russian Society of Neurologists, Association of Anesthesiologists and Reanimatologists of Russia, Association of Rehabilitologists of Russia. Revision 2022. (In Russ.). https://ruans.org/Text/Guidelines/hemorrhagic-stroke-2022.pdf
Sheth KN, Solomon N, Alhanti B, Messe SR, Xian Y, Bhatt DL, Hemphill JC, Frontera JA, Chang RC, Danelich IM, Huang J, Schwamm L, Smith EE, Goldstein JN, Mac Grory B, Fonarow GC, Saver JL. Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage. JAMA Neurology. 2024;81(4):363-372. https://doi.org/10.1001/jamaneurol.2024.0221
Frontera JA, Lewin JJ 3rd, Rabinstein AA, Aisiku IP, Alexandrov AW, Cook AM, del Zoppo GJ, Kumar MA, Peerschke EI, Stiefel MF, Teitelbaum JS, Wartenberg KE, Zerfoss CL. Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocritical Care. 2016;24(1):6-46. https://doi.org/10.1007/s12028-015-0222-x
Parry-Jones AR, Moullaali TJ, Ziai WC. Treatment of intracerebral hemorrhage: From specific interventions to bundles of care. International Journal of Stroke. 2020;15(9):945-953. https://doi.org/10.1177/1747493020964663
Lexidrug (Lexicomp) www.lexi.com
Ostroumova OD, Listratov AI, Ostroumova TM, Kochetkov AI, Sychev DA. Drug-induced non-traumatic intracranial hemorrhage associated with the use of anticoagulants and antiplatelet agents. Nevrologiya, neiropsikhiatriya, psikhosomatika. 2022;14(6):80-88. (In Russ.). https://doi.org/10.14412/2074-2711-2022-6-80-88
Christensen H, Cordonnier C, Kõrv J, Lal A, Ovesen C, Purrucker JC, Toni D, Steiner T. European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage. European Stroke Journal. 2019;4(4):294-306. https://doi.org/10.1177/2396987319849763
Chaudhary R, Singh A, Chaudhary R, Bashline M, Houghton DE, Rabinstein A, Adamski J, Arndt R, Ou NN, Rudis MI, Brown CS, Wieruszewski ED, Wanek M, Brinkman NJ, Linderbaum JA, Sorenson MA, Atkinson JL, Thompson KM, Aiyer AN, McBane RD 2nd. Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage: A Systematic Review and Meta-analysis. JAMA Network. 2022;5(11):e2240145. https://doi.org/10.1001/jamanetworkopen.2022.40145
Reyes R, Viswanathan M, Aiyagari V. An update on neurocritical care for intracerebral hemorrhage. Expert Review of Neurotherapeutics. 2019;19(6):557-578. https://doi.org/10.1080/14737175.2019.1618709
Marcolini E, Stretz C, DeWitt KM. Intracranial Hemorrhage and Intracranial Hypertension. Emergency Medicine Clinics of North America. 2019;37(3):529-544. https://doi.org/10.1016/j.emc.2019.04.001
Reversal of anticoagulation in intracranial hemorrhage. https://www.uptodate.com/contents/reversal-of-anticoagulation-in-intracranial-hemorrhage?search=warfarin&topicRef=1334&source=see_link
Abdoellakhan RA, Khorsand N, Ter Avest E, Lameijer H, Faber LM, Ypma PF, Nieuwenhuizen L, Veeger NJGM, Meijer K. Fixed Versus Variable Dosing of Prothrombin Complex Concentrate for Bleeding Complications of Vitamin K Antagonists-The PROPER3 Randomized Clinical Trial. Annals of Emergency Medicine. 2022;79(1):20-30. https://doi.org/10.1016/j.annemergmed.2021.06.016
Galstyan GM. Label and off-label applications of prothrombin complex concentrates. New perspectives of old drugs. Russian journal of hematology and transfusiology. 2018;63(1):78-91. (In Russ.). https://doi.org/10.25837/HAT.2018.30..1..008
Sweidan AJ, Singh NK, Conovaloff JL, Bower M, Groysman LI, Shafie M, Yu W. Coagulopathy reversal in intracerebral haemorrhage. Stroke and Vascular Neurology. 2020;5(1):29-33. https://doi.org/10.1136/svn-2019-000274
Faulkner H, Chakankar S, Mammi M, Lo JYT, Doucette J, Al-Otaibi N, Abboud J, Le A, Mekary RA, Bunevicius A. Safety and efficacy of prothrombin complex concentrate (PCC) for anticoagulation reversal in patients undergoing urgent neurosurgical procedures: a systematic review and metaanalysis. Neurosurgical Review. 2021;44(4):1921-1931. https://doi.org/10.1007/s10143-020-01406-z
Makhoul T, Kelly G, Kersten B, Nadler M, Zammit CG, Jones CMC, Scott R, Acquisto NM. Incidence of thromboembolic events following administration of four-factor prothrombin complex concentrate (4F-PCC) for oral anticoagulation reversal. Thrombosis Research. 2020;194:158-164. https://doi.org/10.1016/j.thromres.2020.06.028
Management of warfarin-associated bleeding or supratherapeutic INR. https://www.uptodate.com/contents/management-of-warfarin-associated-bleeding-or-supratherapeutic-inr?sectionName=VITAMIN%20K%20DOSE%2C%20ROUTE%2C%20FORMULATION&search=warfarin&topicRef=1325&anchor=H21790898&source=see_link#H21790898
Koyama H, Yagi K, Hara K, Matsubara S, Tao Y, Uno M. Combination Therapy Using Prothrombin Complex Concentrate and Vitamin K in Anticoagulated Patients with Traumatic Intracranial Hemorrhage Prevents Progressive Hemorrhagic Injury: A Historically Controlled Study. Neurologia Medico-Chirurgica. 2021;61(1):47-54. https://doi.org/10.2176/nmc.oa.2020-0252
Houskamp EJ, Liu Y, Silva Pinheiro do Nascimento J, Jahromi BS, Lindholm PF, Kwaan HC, Naidech AM. P2Y12 inhibitor use predicts hematoma expansion in patients with intracerebral hemorrhage. Annals of Clinical and Translational Neurology. 2024;11(6):1535-1540. https://doi.org/10.1002/acn3.52070
Scotti P, Séguin C, Lo BWY, de Guise E, Troquet JM, Marcoux J. Antithrombotic agents and traumatic brain injury in the elderly population: hemorrhage patterns and outcomes. Journal of Neurosurgery. 2019;133(2):486-495. https://doi.org/10.3171/2019.4.JNS19252
Suehiro E, Fujiyama Y, Kiyohira M, Haji K, Ishihara H, Nomura S, Suzuki M; Japan Neurotrauma Data Bank Committee. Risk of Deterioration of Geriatric Traumatic Brain Injury in Patients Treated with Antithrombotic Drugs. World Neurosurgery. 2019;127:e1221-e1227. https://doi.org/10.1016/j.wneu.2019.04.108
Senzel L, Ahmed T, Spitzer ED. Laboratory Monitoring of Platelet P2Y12 Receptor Inhibitors and Reversal of Antiplatelet Agents. American Journal of Clinical Pathology. 2019;152(1):1-6. https://doi.org/10.1093/ajcp/aqy151
Khan H, Kanny O, Syed MH, Qadura M. Aspirin Resistance in Vascular Disease: A Review Highlighting the Critical Need for Improved Point-of-Care Testing and Personalized Therapy. International Journal of Molecular Sciences. 2022;23(19):11317. https://doi.org/10.3390/ijms231911317
Berenson AM, Hawken TN, Fort DG, Money SR, Ramee SR, Sternbergh WC 3rd, Bazan HA. Clopidogrel resistance is common in patients undergoing vascular and coronary interventions. Vascular. 2023;31(1):58-63. https://doi.org/10.1177/17085381211059394
Platelet biology and mechanism of anti-platelet drugs. https://www.uptodate.com/contents/platelet-biology-and-mechanism-of-anti-platelet-drugs?search=antiplatelets&source=search_result&selectedTitle=2%7E150&usage_type=default&display_rank=2#H2541929462
Laguta PS, Panchenko EP. Niche of prasugrel among other platelet P2Y12-receptor inhibitors. Atherothrombosis. 2017;(2):43-52. (In Russ.).
Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database and Systematic Reviews. 2023;10(10):CD005951. https://doi.org/10.1002/14651858.CD005951.pub5
Borchert RJ, Simonato D, R Hickman C, Fuschi M, Thibault L, Henkes H, Fiorella D, Tan BY, Yeo LL, D Makalanda HL, Wong K, Bhogal P. P2Y12 inhibitors for the neurointerventionalist. Interventional Neuroradiology. 2022;28(1):92-103. https://doi.org/10.1177/15910199211015042
Pokhabov DS, Shestakov EA, Fedyk OV, Zhiburt EB. Hemoglobin concentration and transfusion of ABO‐incompatible platelets. Tromboz, Gemostaz i Reologiya. 2024;(1):30-36. (In Russ.). https://doi.org/10.25555/THR.2024.1.1084
Kuznetsov SI, Kudinova EV, Zhiburt EB. Donor platelets collection in a pandemic of COVID-19 infection. Manager Zdravoochranenia. 2020;9:43-46. (In Russ.). https://doi.org/10.37690/1811-0185-2020-9-43-46
Magid-Bernstein J, Beaman CB, Carvalho-Poyraz F, Boehme A, Hod EA, Francis RO, Elkind MSV, Agarwal S, Park S, Claassen J, Connolly ES, Roh D. Impacts of ABO-incompatible platelet transfusions on platelet recovery and outcomes after intracerebral hemorrhage. Blood. 2021;137(19):2699-2703. https://doi.org/10.1182/blood.2020008381
Desborough MJR, Al-Shahi Salman R, Stanworth SJ, Havard D, Brennan PM, Dineen RA, Coats TJ, Hepburn T, Bath PM, Sprigg N. Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH): protocol for a phase II double-blind randomised controlled feasibility trial. BMJ Open. 2020;10(11):e037555. https://doi.org/10.1136/bmjopen-2020-037555
Barletta JF, Abdul-Rahman D, Hall ST, Mangram AJ, Dzandu JK, Frontera JA, Zach V. The Role of Desmopressin on Hematoma Expansion in Patients with Mild Traumatic Brain Injury Prescribed Pre-injury Antiplatelet Medications. Neurocritical Care. 2020;33(2):405-413. https://doi.org/10.1007/s12028-019-00899-x
Kapapa T, Röhrer S, Struve S, Petscher M, König R, Wirtz CR, Woischneck D. Desmopressin acetate in intracranial haemorrhage. Neurology Research International. 2014;2014:298767. https://doi.org/10.1155/2014/298767
Schmidt KJ, Sager B, Zachariah J, Raad BF, James EG, Fletcher JJ. Cohort analysis of desmopressin effect on hematoma expansion in patients with spontaneous intracerebral hemorrhage and documented pre-ictus antiplatelet use. Journal of Clinical Neuroscience. 2019;66:33-37. https://doi.org/10.1016/j.jocn.2019.05.032

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