Effect of Prothrombin Complex Concentrates on Time to Surgery in Patients with Hip Fracture Anticoagulated with Vitamin K Antagonists A Retrospective Cohort Study
Main Article Content
Keywords
Vitamin K antagonists, Acute hip fracture, Emergency surgery, Prothrombin complex concentrate
Abstract
Objectives: To determine the time to surgery (TTS) among patients with acute hip fracture who are anticoagulated with vitamin K antagonists (VKAs) who receive prothrombic complex concentrate (PCC) compared to those who do not receive PCC.
Method: We conducted a retrospective cohort study of consecutive patients with an acute hip fracture presenting to the emergency department (ED) of the Jewish General Hospital, a 637-bed tertiary care hospital center in Montreal, Quebec, between January 1st, 2015 and March 1st, 2020. Eligible patients were identified via the ED electronic database. Inclusion criteria were: (1) > 18 years of age; (2) acute hip fracture and admission for surgical repair; (3) VKA use and international normalized ratio (INR) > 1.5 at admission. Follow-up was limited to index hospitalization. The primary outcome of TTS, reported in hours, was defined as the time from hospital admission to the time of surgery. Mann-Whitney U test was used to assess any difference in median TTS between the two groups.
Results: A total of 53 patients were included in our cohort of which 43.4% (23/53) received PCC with a median time to first dose of 25.5 hours (IQR 19.4-51.6). 84.9 % (45/53) received vitamin K with a median time to the first dose of 16 h (IQR 7.5-26.7). The median TTS in the PCC and no PCC groups was 51.8 h (IQR 26.8–71.4) vs. 63.5 h (IQR 49.4-73.2) respectively (p=0.71).
Conclusion: This study did not identify shorter TTS between patients who received PCC and those who did not. Median TTS in both groups surpassed the recommended 48h benchmark, and PCC and vitamin K administration timing was suboptimal. These findings demonstrate a significant care gap among this vulnerable population and represent a call for future initiatives to ensure a more streamlined and multidisciplinary approach to anticoagulation management starting at the onset of presentation criteria were: (1) > 18 years of age; (2) acute hip fracture and admission for surgical repair; (3) VKA use and international normalized ratio (INR) ˃ 1.5 at admission. Follow-up was limited to index hospitalization. The primary outcome of TTS, reported in hours, was defined as time from hospital admission to time of surgery. Mann-Whitney U test was used to assess any difference in median TTS between the two groups.
Résumé
Objectifs: Déterminer le délai avant l’intervention chirurgicale (DAIC) parmi les patients présentant une fracture aigüe de la hanche qui suivent une anticoagulothérapie par des antagonistes de la vitamine K (AVK) et qui reçoivent un concentré de complexe prothrombique (CCP) par rapport à ceux qui ne reçoivent pas le CCP.
Méthodologie: Nous avons mené une étude de cohorte rétrospective de patients consécutifs présentant une fracture aigüe de la hanche à leur arrivée à l’urgence de l’Hôpital général juif, un centre hospitalier de 637 lits de soins tertiaires situé à Montréal (Québec), entre le 1er janvier 2015 et le 1er mars 2020. Les patients admissibles ont été repérés par l’intermédiaire de la base de données électronique du service des urgences. Les critères d’inclusion sont : 1) personne âgée de plus de 18 ans; 2) fracture aiguë de la hanche et hospitalisation en vue d’une réparation chirurgicale; 3) prise d’AVK et rapport international normalisé (RIN) supérieur à 1,5 lors de l’admission à l’hôpital. Le suivi se limite à l’admission initiale. Le critère d’évaluation principal du DAIC, indiqué en heures, est défini comme étant le délai entre l’admission à l’hôpital et le moment de l’intervention chirurgicale. Le test U de Mann-Whitney est utilisé pour évaluer toute différence dans les DAIC médians entre les deux groupes.
Résultats: Au total, 53 patients font partie de la cohorte dont 43,4 % (23/53) ont reçu le CCP, le délai médian avant la première dose étant de 25,5 heures (écart interquartile [EI] de 19,4 à 51,6), et 84,9 % (45/53) ont reçu de la vitamine K, le délai médian avant la première dose étant de 16 heures (EI de 7,5 à 26,7). Le DAIC médian est de 51,8 heures (EI de 26,8 à 71,4) pour le groupe recevant le CCP et de 63,5 heures (EI de 49,4 à 73,2) pour celui ne recevant pas le CCP (p = 0,71).
Conclusion: Cette étude révèle une tendance vers des DAIC plus courts chez les patients recevant le CCP que chez ceux qui ne le reçoivent pas. Le DAIC médian dans les deux groupes est supérieur au délai de référence recommandé de 48 heures, et le moment où le CCP et la vitamine K sont administrés est sous-optimal. Ces constatations montrent une lacune importante en matière de soins chez cette population vulnérable et représentent un appel à des initiatives visant à assurer une approche simplifiée et multidisciplinaire de la prise en charge de l’anticoagulothérapie qui commence dès l’arrivée du patient à l’hôpital.
References
2. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporosis Int. 2006;17(12):1726-33.
3. Hopkins RB, Burke N, Von Keyserlingk C, Leslie WD, Morin SN, Adachi JD, et al. The current economic burden of illness of osteoporosis in Canada. Osteoporos Int. 2016;27(10):3023-32.
4. Papadimitropoulos E, Coyte PC, Josse RG, Greenwood CE. Current and projected rates of hip fracture in Canada. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 1997;157 10:1357-63.
5. Moja L, Piatti A, Pecoraro V, Ricci C, Virgili G, Salanti G, et al. Timing matters in hip fracture surgery: patients operated within 48 hours have better outcomes. A meta-analysis and meta-regression of over 190,000 patients. PLoS One. 2012;7(10):e46175.
6. Pincus D, Ravi B, Wasserstein D, Huang A, Paterson JM, Nathens AB, et al. Association Between Wait Time and 30-Day Mortality in Adults Undergoing Hip Fracture Surgery. JAMA. 2017;318(20):1994-2003.
7. Borges FK, Bhandari M, Guerra-Farfan E, Patel A, Sigamani A, Umer M, et al. Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial. The Lancet. 2020;395(10225):698-708.
8. Sobolev B, Guy P, Sheehan KJ, Kuramoto L, Sutherland JM, Levy AR, et al. Mortality effects of timing alternatives for hip fracture surgery. Can Med Assoc J. 2018;190(31):E923-E32.
9. Tran T, Delluc A, de Wit C, Petrcich W, Le Gal G, Carrier M. The impact of oral anticoagulation on time to surgery in patients hospitalized with hip fracture. Thromb Res. 2015;136(5):962-5.
10. Caruso G, Andreotti M, Marko T, Tonon F, Corradi N, Rizzato D, et al. The impact of warfarin on operative delay and 1-year mortality in elderly patients with hip fracture: a retrospective observational study. J Orthop Surg Res. 2019;14(1):169.
11. Cafaro T, Simard C, Tagalakis V, Koolian M. Delayed time to emergency hip surgery in patients taking oral anticoagulants. Thrombosis Res. 2019;184:110-4.
12. You D, Xu Y, Ponich B, Ronksley P, Skeith L, Korley R, et al. Effect of oral anticoagulant use on surgical delay and mortality in hip fracture. Bone Joint J. 2021;103-B(2):222-33.
13. Horlocker TT, Vandermeuelen E, Kopp SL, Gogarten W, Leffert LR, Benzon HT. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med. 2018;43(3):263-309.
14. Xu Y, You D, Krzyzaniak H, Ponich B, Ronksley P, Skeith L, et al. Effect of oral anticoagulants on hemostatic and thromboembolic complications in hip fracture: A systematic review and meta-analysis. J Thromb Haemostas. 2020;18(10):2566-81.
15. Ahmed I, Khan MA, Nayak V, Mohsen A. An evidence-based warfarin management protocol reduces surgical delay in hip fracture patients. J Orthop Traumatol. 2014;15(1):21-7.
16. Moores TS, Chatterton BD, Walker MJ, Roberts PJ. Standardised warfarin reversal expedites time to theatre for fractured neck of femur surgery and improves mortality rates: a matched cohort study. Adv Orthop. 2018;2018:4791214.
17. Buecking B, Eschbach D, Bliemel C, Oberkircher L, Struewer J, Ruchholtz S, et al. Effectiveness of vitamin K in anticoagulation reversal for hip fracture surgery--a prospective observational study. Thromb Res. 2014;133(1):42-7.
18. Mattisson L, Lapidus LJ, Enocson A. Is fast reversal and early surgery (within 24 h) in patients on warfarin medication with trochanteric hip fractures safe? A case-control study. BMC Musculoskelet Disord. 2018;19(1):203.
19. Jay-Caillierez L, Friggeri A, Viste A, Lefevre M, Decullier E, Bernard L, et al. Safety and efficacy of a strategy of vitamin K antagonist reversal with prothrombin complex concentrates compared to vitamin K in patients with hip fracture. Can J Surg. 2021;64(3):E330-E8.
20. Sheehan KJ, for The Canadian Collaborative Study on Hip F, Filliter C, Sobolev B, Levy AR, Guy P, et al. Time to surgery after hip fracture across Canada by timing of admission. Osteoporosis International : With other metabolic bone diseases. 2018;29(3):653-63.
21. Pincus D, Wasserstein D, Ravi B, Byrne JP, Huang A, Paterson JM, et al. Reporting and evaluating wait times for urgent hip fracture surgery in Ontario, Canada. CMAJ. 2018;190(23):E702-e9.
22. Tran T, Delluc A, de Wit C, Petrcich W, Le Gal G, Carrier M. The impact of oral anticoagulation on time to surgery in patients hospitalized with hip fracture. Thromb Res. 2015;136(5):962-5.
23. Flemons K, Marcil G, Kachra R, et al. Barriers to Implementing Internist Recommendations for perioperative anticoagulation management by surgical teams: a qualitative study. Can J Gen Intern Med. 2022;17(1):14-28.
24. Grymonprez M, Simoens C, Steurbaut S, De Backer TL, Lahousse L. Worldwide trends in oral anticoagulant use in patients with atrial fibrillation from 2010 to 2018: a systematic review and meta-analysis. EP Europace. 2021;24(6):887-98.
25. Burnett AE, Barnes GD. A call to action for anticoagulation stewardship. Research and Practice in Thromb Haemos. 2022;6(5):e12757.
26. Geller AI, Shehab N, Lovegrove MC, Rose KO, Weidle NJ, Goring SK, et al. Emergency visits for oral anticoagulant bleeding. J Gen Intern Med. 2020;35(1):371-3.
27. Piazza G, Nguyen TN, Cios D, Labreche M, Hohlfelder B, Fanikos J, et al. Anticoagulation-associated adverse drug events. Am J Med. 2011;124(12):1136-42.
28. Zhang X-L, Zhang X-W, Wang T-Y, Wang H-W, Chen Z, Xu B, et al. Off-Label Under- and overdosing of direct oral anticoagulants in patients with atrial fibrillation: a meta-analysis. Circulation: Cardiovasc Qual Outcomes. 2021;14(12):e007971.
29. Li A, Li MK, Crowther M, Vazquez SR. Drug-drug interactions with direct oral anticoagulants associated with adverse events in the real world: A systematic review. Thromb Res. 2020;194:240-5.
30. Moesker MJ, de Groot JF, Damen NL, Huisman MV, de Bruijne MC, Wagner C. How reliable is perioperative anticoagulant management? Determining guideline compliance and practice variation by a retrospective patient record review. BMJ Open. 2019;9(7):e029879.
31. Henriksen JN, Nielsen LP, Hellebek A, Poulsen BK. Medication errors involving anticoagulants: Data from the Danish patient safety database. Pharmacol Res Perspect. 2017;5(3):e00307.
32. Douketis JD, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, et al. Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST. 2012;141(2):e326S-e50S.
33. Koolian M, Wiseman D, Mantzanis H, Kampouris N, Kerzner RS, Kahn SR. Anticoagulation stewardship: Descriptive analysis of a novel approach to appropriate anticoagulant prescription. Res Pract Thromb Haemo. 2022;6(6).
34. Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13):1206-14.
35. Pengo V, Denas G, Zoppellaro G, Jose SP, Hoxha A, Ruffatti A, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132(13):1365-71.
36. Abbattista M, Capecchi M, Martinelli I. Treatment of unusual thrombotic manifestations. Blood. 2020;135(5):326-34.
37. Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemo. 2016;14(6):1308-13.
38. Ribic C, Crowther M. Thrombosis and anticoagulation in the setting of renal or liver disease. Hematology. 2016;2016(1):188-95.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Articles are published under a Creative Commons Attribution - Non Commercial 4.0 International License. Authors and users are free to copy and redistribute the material in any medium or format, with proper attribution, for non-commercial purposes. Authors retain copyright to their article.