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Varfarin ilişkili aşırı antikoagülasyona bağlı olarak international normalized ratio değeri 4.5 - 10 arasında olan hastalarda 30 günlük mortalitenin prediktörlerinin belirlenmesi: retrospektif kohort çalışması.

Year 2023, Volume: 48 Issue: 2, 654 - 662, 02.07.2023
https://doi.org/10.17826/cumj.1247794

Abstract

Amaç: K vitamini uygulamasının international normalized ratio(INR) değeri 4.5 ila 10 arasında olan hastalara fayda sağlamadığı gösterilmiş olmasına rağmen, literatür bu hasta grubunda kanama dahil olmak üzere bazı komplikasyonların önemli ölçüde arttığını göstermektedir. Bu nedenle, INR düzeyi artmış hastalarda yüksek risk taşıyan hastaların belirlenmesi ve daha yakın takip ve izlem altına alınması önemlidir. Çalışmamızın birincil amacı, varfarin ilişkili aşırı antikoagülasyon nedeniyle INR değeri 4.5 - 10 arasında olan hastaların 30 günlük mortalite prediktörlerini belirlemektir. Çalışmamızın ikincil amacı, 30 gün içindeki mortaliteyi öngören bir regresyon modeli oluşturmak ve bu modelin performansını National Early Warning Score-2 (NEWS-2) ile karşılaştırmaktır.
Gereç ve Yöntem: Çalışmamıza, 01.01.2016 - 01.01.2022 tarihleri arasında hastaneye başvuran, 18 yaşından büyük, warfarin kullanan ve INR değeri 4.5 ila 10 arasında olan hastalar dahil edildi. Travma ile başvuran, başvuru esnasında majör kanaması olan veya veri eksiği olan hastalar çalışmamızdan dışlandı. Regresyon modeli için, backward-Wald stepwise yöntemi kullanıldı. Modelin fitliği Hosmer-Lemeshow ile test edildi. Modelin genel performansı Nagelkerke R Square ile değerlendirildi ve Reciever Operating Characteristics testi uygulandı. Eğri altında kalan alanların (AUC) karşılaştırması için DeLong testi kullanıldı.
Bulgular: İstatistiksel analizde toplam 263 hasta dahil edildi. Ortalama arteriyel basınç, SpO2, nabız ve yaş, 30 günlük mortalitenin bağımsız prediktörleri olarak bulundu. Model, hastaların %81.4'ünü doğru şekilde sınıflandırdı. Regresyon modelinin AUC değeri 0.848 0.799 - 0.898) olarak hesaplandı. Mortalite tahminindeki tanısal performansı incelendiğinde duyarlılığı %94.1, özgüllüğü %66.5 ve doğruluğu %71.9 olarak hesaplandı. 30 günlük mortalite için NEWS-2 skorunun AUC değeri 0.782(95% CI = 0.715 - 0.849) olarak hesaplandı. Modelimizin ve NEWS-2 skoru arasındaki AUC farkı istatistiksel olarak anlamlı bulundu.
Sonuç: Ortalama arteriyel basınç, SpO2, nabız ve yaş, varfarin kullanımına bağlı olarak INR değeri 4.5-10 arasında olan hastalarda 30 günlük mortalite için bağımsız prediktörler olduğu saptandı. Elde ettiğimiz regresyon modeli genel olarak iyi bir sınıflama sağladı ve NEWS-2 skorundan anlamlı şekilde daha iyi performans gösterdi.

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References

  • Crowther MA, Ageno W, Garcia D, Wang L, Witt MD, Clark NP et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150:293-300.
  • Chai-Adisaksopha C, Hillis C, Siegal DM, Movilla R, Heddle N, Iorio A et al. Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal. A systematic review and meta-analysis. Thromb Haemost. 2016;116:879-90.
  • Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018;2:3257-91.
  • Cressman AM, Macdonald EM, Yao Z, Austin PC, Gomes T, Paterson JM et al. Socioeconomic status and risk of hemorrhage during warfarin therapy for atrial fibrillation: A population-based study. Am Heart J. 2015;170:133-40.
  • Dagar S, Emektar E, Uzunosmanoglu H, Cevik Y. Assessment of factors affecting mortality in geriatric patients with warfarin overdose. Turk J Emerg Med. 2020;20:180-5.
  • Farrow GS, Delate T, McNeil K, Jones AE, Witt DM, Crowther MA et al. Vitamin K versus warfarin interruption alone in patients without bleeding and an international normalized ratio > 10. J Thromb Haemost. 2020;18:1133-40.
  • İslam MM, Ademoğlu E, Uygun C, Delipoyraz M, Satıcı MO, Aksel G et al. Comparison of the effects of different treatment protocols on mortality in patients presenting with an INR≥10 due to warfarin-associated over-anticoagulation. Afr J Emerg Med. 2023;13:8-14.
  • Smith GB, Redfern OC, Pimentel MA, Gerry S, Collins GS, Malycha J et al. The National Early Warning Score 2 (NEWS2). Clin Med (Lond). 2019;19:260.
  • Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141;2 Suppl:7S-47S.
  • Green SB. How many subjects does it take to do a regression analysis. Multivariate behavioral research. 1991;26:499–510.
  • Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007;165:710-18.
  • Khatib R, Ludwikowska M, Witt DM, Ansell J, Clark NP, Holbrook A et al. Vitamin K for reversal of excessive vitamin K antagonist anticoagulation: a systematic review and meta-analysis. Blood Adv. 2019;3:789-796.
  • Franchini S, Scarallo L, Carlucci M, Cabrini L, Tresoldi M. SIRS or qSOFA? Is that the question? Clinical and methodological observations from a meta-analysis and critical review on the prognostication of patients with suspected sepsis outside the ICU. Intern Emerg Med. 2019;14:593-602.
  • Headley J, Theriault R, Smith TL. Independent validation of APACHE II severity of illness score for predicting mortality in patients with breast cancer admitted to the intensive care unit. Cancer. 1992;70:497-503.
  • Mayow AH, Ahmad F, Afzal MS, Khokhar MU, Rafique D, Vallamchetla SK et al. A Systematic review and meta-analysis of independent predictors for acute respiratory distress syndrome in patients presenting with sepsis. Cureus. 2023;15:e37055
  • Champion HR, Sacco WJ, Copes WS, Gann DS, Gennarelli TA, Flanagan ME. A revision of the Trauma Score. J Trauma. 1989;29:623-29.
  • Champion HR, Moore L, Vickers R. Injury severity scoring and outcomes research. In Moore EE, Feliciano DV, Mattox KL. Trauma Eight Edition. McGraw-Hill. 2017;5:71-91.
  • Kobusingye OC, Lett RR. Hospital-based trauma registries in Uganda. J Trauma. 2000;48:498-502.
  • Imhoff BF, Thompson NJ, Hastings MA, Nazir N, Moncure M, Cannon CM. Rapid Emergency Medicine Score (REMS) in the trauma population: a retrospective study. BMJ Open. 2014;4:e004738.
  • Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A et al. Assessment of clinical criteria for sepsis: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [published correction appears in JAMA. 2016;315:762-4.
  • Sesso HD, Stampfer MJ, Rosner B, Hennekens CH, Gaziano JM, Manson JE et al. Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in men. Hypertension. 2000;36:801-7.
  • Guimarães PO, Lopes RD, Alexander JH, Thomas L, Hellkamp AS, Hjazi Z et al. International normalized ratio control and subsequent clinical outcomes in patients with atrial fibrillation using warfarin. J Thromb Thrombolysis. 2019;48:27-34.
  • Meng Y, Wang H, Wu C, Liu X, Qu L, Shi Y. Prediction model of hemorrhage transformation in patient with acute ischemic stroke based on multiparametric MRI radiomics and machine learning. Brain Sci. 2022;12:858.

Predictors of 30-day mortality in patients with an international normalized ratio of 4.5 - 10 due to warfarin-related overanticoagulation: a retrospective cohort study

Year 2023, Volume: 48 Issue: 2, 654 - 662, 02.07.2023
https://doi.org/10.17826/cumj.1247794

Abstract

Purpose: Although it has been shown that vitamin K administration does not benefit patients with INR levels between 4.5 to 10, there are studies in the literature showing that some complications including the risk of bleeding in these patients increase significantly. For this reason, it is crucial to select high-risk patients who present with elevated INR to apply closer follow-up and monitoring. The primary objective of our study is to define the predictors for 30-day mortality of the patients with an INR between 4.5 to 10 due to warfarin-related overanticoagulation. The secondary objective of our study is to derive a regression model which can predict mortality in 30 days and to compare the performance of this model with the National Early Warning Score-2(NEWS-2).
Materials and Methods: We included patients older than 18 years old, admitted between the dates 01.01.2016 - 01.01.2022 who are using warfarin as medication and with an INR between 4.5 – 10 in our study. We excluded patients with trauma, major bleeding on admission or patients with missing data. For the regression model, backward-wald stepwise method was utilized. We used the Hosmer-Lemeshow test for the goodness of fit. For the overall performance of the model, we evaluated the Nagelkerke R Square, and the Reciever Operating Characteristics test. DeLong test was used to compare the area under the curves (AUC).
Results: A total of 263 patients were examined in the statistical analysis. Mean arterial pressure, SpO2, pulse rate, and age were the independent predictors of 30-day mortality. The model have classified 81.4% of the patients correctly. The AUC of the regression model was 0.848 (0.799 to 0.898). The sensitivity of the model as a tool for mortality prediction was 94.1%, specificity 66.5%, and accuracy 71.9%. The AUC of the NEWS-2 score for 30-day mortality was calculated as 0.782 (95%CI = 0.715 to 0.849). The difference between the AUCs of our model and the NEWS-2 score was statistically significant.
Conclusion: Mean arterial pressure, SpO2, heart rate, and age were the independent predictors for the 30-day mortality of patients with an INR between 4.5 to 10 due to overanticoagulation because of warfarin medication. The regression model we derived showed good overall discrimination and performed significantly better than NEWS-2 score.

Project Number

Yoktur

References

  • Crowther MA, Ageno W, Garcia D, Wang L, Witt MD, Clark NP et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150:293-300.
  • Chai-Adisaksopha C, Hillis C, Siegal DM, Movilla R, Heddle N, Iorio A et al. Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal. A systematic review and meta-analysis. Thromb Haemost. 2016;116:879-90.
  • Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018;2:3257-91.
  • Cressman AM, Macdonald EM, Yao Z, Austin PC, Gomes T, Paterson JM et al. Socioeconomic status and risk of hemorrhage during warfarin therapy for atrial fibrillation: A population-based study. Am Heart J. 2015;170:133-40.
  • Dagar S, Emektar E, Uzunosmanoglu H, Cevik Y. Assessment of factors affecting mortality in geriatric patients with warfarin overdose. Turk J Emerg Med. 2020;20:180-5.
  • Farrow GS, Delate T, McNeil K, Jones AE, Witt DM, Crowther MA et al. Vitamin K versus warfarin interruption alone in patients without bleeding and an international normalized ratio > 10. J Thromb Haemost. 2020;18:1133-40.
  • İslam MM, Ademoğlu E, Uygun C, Delipoyraz M, Satıcı MO, Aksel G et al. Comparison of the effects of different treatment protocols on mortality in patients presenting with an INR≥10 due to warfarin-associated over-anticoagulation. Afr J Emerg Med. 2023;13:8-14.
  • Smith GB, Redfern OC, Pimentel MA, Gerry S, Collins GS, Malycha J et al. The National Early Warning Score 2 (NEWS2). Clin Med (Lond). 2019;19:260.
  • Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141;2 Suppl:7S-47S.
  • Green SB. How many subjects does it take to do a regression analysis. Multivariate behavioral research. 1991;26:499–510.
  • Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007;165:710-18.
  • Khatib R, Ludwikowska M, Witt DM, Ansell J, Clark NP, Holbrook A et al. Vitamin K for reversal of excessive vitamin K antagonist anticoagulation: a systematic review and meta-analysis. Blood Adv. 2019;3:789-796.
  • Franchini S, Scarallo L, Carlucci M, Cabrini L, Tresoldi M. SIRS or qSOFA? Is that the question? Clinical and methodological observations from a meta-analysis and critical review on the prognostication of patients with suspected sepsis outside the ICU. Intern Emerg Med. 2019;14:593-602.
  • Headley J, Theriault R, Smith TL. Independent validation of APACHE II severity of illness score for predicting mortality in patients with breast cancer admitted to the intensive care unit. Cancer. 1992;70:497-503.
  • Mayow AH, Ahmad F, Afzal MS, Khokhar MU, Rafique D, Vallamchetla SK et al. A Systematic review and meta-analysis of independent predictors for acute respiratory distress syndrome in patients presenting with sepsis. Cureus. 2023;15:e37055
  • Champion HR, Sacco WJ, Copes WS, Gann DS, Gennarelli TA, Flanagan ME. A revision of the Trauma Score. J Trauma. 1989;29:623-29.
  • Champion HR, Moore L, Vickers R. Injury severity scoring and outcomes research. In Moore EE, Feliciano DV, Mattox KL. Trauma Eight Edition. McGraw-Hill. 2017;5:71-91.
  • Kobusingye OC, Lett RR. Hospital-based trauma registries in Uganda. J Trauma. 2000;48:498-502.
  • Imhoff BF, Thompson NJ, Hastings MA, Nazir N, Moncure M, Cannon CM. Rapid Emergency Medicine Score (REMS) in the trauma population: a retrospective study. BMJ Open. 2014;4:e004738.
  • Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A et al. Assessment of clinical criteria for sepsis: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [published correction appears in JAMA. 2016;315:762-4.
  • Sesso HD, Stampfer MJ, Rosner B, Hennekens CH, Gaziano JM, Manson JE et al. Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in men. Hypertension. 2000;36:801-7.
  • Guimarães PO, Lopes RD, Alexander JH, Thomas L, Hellkamp AS, Hjazi Z et al. International normalized ratio control and subsequent clinical outcomes in patients with atrial fibrillation using warfarin. J Thromb Thrombolysis. 2019;48:27-34.
  • Meng Y, Wang H, Wu C, Liu X, Qu L, Shi Y. Prediction model of hemorrhage transformation in patient with acute ischemic stroke based on multiparametric MRI radiomics and machine learning. Brain Sci. 2022;12:858.
There are 23 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

Mehmet Muzaffer İslam 0000-0001-6928-2307

Project Number Yoktur
Early Pub Date July 11, 2023
Publication Date July 2, 2023
Acceptance Date June 13, 2023
Published in Issue Year 2023 Volume: 48 Issue: 2

Cite

MLA İslam, Mehmet Muzaffer. “Predictors of 30-Day Mortality in Patients With an International Normalized Ratio of 4.5 - 10 Due to Warfarin-Related Overanticoagulation: A Retrospective Cohort Study”. Cukurova Medical Journal, vol. 48, no. 2, 2023, pp. 654-62, doi:10.17826/cumj.1247794.