Download PDF
Thromb Haemost 2016; 115(06): 1191-1199
DOI: 10.1160/TH15-11-0869
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

High mortality in patients presenting with acute pulmonary embolism and elevated INR not on anticoagulant therapy

Christopher C. Y. Wong
1   Department of Cardiology, Concord Hospital, University of Sydney, Concord, New South Wales, Australia
,
Austin C. C. Ng
1   Department of Cardiology, Concord Hospital, University of Sydney, Concord, New South Wales, Australia
2   Vascular Biology Group, ANZAC Research Institute, Concord, New South Wales, Australia
,
Jerrett K. Lau
1   Department of Cardiology, Concord Hospital, University of Sydney, Concord, New South Wales, Australia
2   Vascular Biology Group, ANZAC Research Institute, Concord, New South Wales, Australia
,
Vincent Chow
1   Department of Cardiology, Concord Hospital, University of Sydney, Concord, New South Wales, Australia
2   Vascular Biology Group, ANZAC Research Institute, Concord, New South Wales, Australia
,
Vivien Chen
2   Vascular Biology Group, ANZAC Research Institute, Concord, New South Wales, Australia
3   Department of Haematology, Concord Hospital, University of Sydney, Concord, New South Wales, Australia
,
Arnold C. T. Ng
4   Department of Cardiology, Princess Alexandra Hospital, University of Queensland, St. Lucia, Queensland, Australia
,
Andy S. C. Yong
1   Department of Cardiology, Concord Hospital, University of Sydney, Concord, New South Wales, Australia
2   Vascular Biology Group, ANZAC Research Institute, Concord, New South Wales, Australia
,
Andrew P. Sindone
1   Department of Cardiology, Concord Hospital, University of Sydney, Concord, New South Wales, Australia
,
Thomas H. Marwick
5   Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia
,
Leonard Kritharides
1   Department of Cardiology, Concord Hospital, University of Sydney, Concord, New South Wales, Australia
2   Vascular Biology Group, ANZAC Research Institute, Concord, New South Wales, Australia
› Author Affiliations Financial support: LK is supported by NHMRC of Australia Program grant 1037903.
Further Information

Publication History

Received: 12 November 2015

Accepted after minor revision: 07 January 2016

Publication Date:
27 November 2017 (online)

    Permissions and Reprints

Summary

The prognostic significance of patients presenting with pulmonary embolism (PE) and elevated International Normalised Ratio (INR) not on anticoagulant therapy has not been described. We investigated whether these patients had higher mortality compared to patients with normal INR. A retrospective study of patients admitted to a tertiary hospital with acute PE from 2000 to 2012 was undertaken, with study outcomes tracked using a state-wide death registry. Patients were excluded if they were taking anticoagulants or had inadequate documentation of their INR and medication status. Of the 1,039 patients identified, 94 (9 %) had an elevated INR (> 1.2) in the absence of anticoagulant use. These patients had higher mortality at six months follow-up (26 % vs 6 %, p< 0.001) compared to controls (INR ≤ 1.2). An INR > 1.2 at diagnosis was an independent predictor of death at six months post-PE (hazard ratio [HR] 2.9, 95 % confidence interval [CI] 1.8–4.7, p< 0.001). The addition of INR to a multivariable model that included the simplified pulmonary embolism severity index (sPESI), chest pain, and serum sodium led to a significant net reclassification improvement estimated at 8.1 %. The final model’s C statistic increased significantly by 0.04 (95 % CI 0.01–0.08, p=0.03) to 0.83 compared to sPESI alone (0.79). In summary, patients presenting with acute PE and elevated INR while not on anticoagulant therapy appear to be at high risk of death. Future validation studies in independent cohorts will clarify if this novel finding can be usefully incorporated into clinical decision making in patients with acute PE.

Keywords

International Normalised Ratio - anticoagulant - mortality - prognosis - pulmonary embolism

 

  • References

  • 1 White R. The epidemiology of venous thromboembolism. Circulation 2003; 107: I4-I8.
    PubMedGoogle Scholar
  • 2 Goldhaber S, Visani L, Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353: 1386-1389.
    CrossrefPubMedGoogle Scholar
  • 3 Laporte S, Mismetti P, Decousus H. et al. Clinical Predictors for Fatal Pulmonary Embolism in 15520 Patients With Venous Thromboembolism: Findings From the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation 2008; 117: 1711-1716.
    CrossrefPubMedGoogle Scholar
  • 4 Spencer F, Goldberg R, Lessard D. et al. Factors Associated With Adverse Outcomes in Outpatients Presenting With Pulmonary Embolism: The Worcester Venous Thromboembolism Study. Circ Cardiovasc Qual Outcomes 2010; 3: 390-394.
    CrossrefPubMedGoogle Scholar
  • 5 Heit J, Silverstein M, Mohr D. et al. Predictors of Survival After Deep Vein Thrombosis and Pulmonary Embolism. Arch Intern Med 1999; 159: 445-453.
    CrossrefPubMedGoogle Scholar
  • 6 Ng AC, Chung T, Yong AS. et al. Long-term cardiovascular and noncardiovascular mortality of 1023 patients with confirmed acute pulmonary embolism. Circ Cardiovasc Qual Outcomes 2011; 4: 122-128.
    CrossrefPubMedGoogle Scholar
  • 7 Riley R, Rowe D, Fisher L. Clinical Utilization of the International Normalized Ratio (INR). J Clin Lab Anal 2000; 14: 101-114.
    CrossrefPubMedGoogle Scholar
  • 8 Hirsh J, Poller L. The International Normalized Ratio: A Guide to Understanding and Correcting Its Problems. Arch Intern Med 1994; 154: 282-288.
    CrossrefPubMedGoogle Scholar
  • 9 Wiesner R, Edwards E, Freeman R. et al. Model for End-Stage Liver Disease (MELD) and Allocation of Donor Livers. Gastroenterology 2003; 124: 91-96.
    CrossrefPubMedGoogle Scholar
  • 10 Moutzouris JP, Ng AC, Chow V. et al. Acute pulmonary embolism during warfarin therapy and long-term risk of recurrent fatal pulmonary embolism. Thromb Haemost 2013; 110: 523-533.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Ng A, Chow V, Yong A. et al. Fluctuation of Serum Sodium and Its Impact on Short and Long-Term Mortality following Acute Pulmonary Embolism. PLoS One. 8. e61966.
    PubMedGoogle Scholar
  • 12 Moutzouris J, Chow V, Yong A. et al. Acute Pulmonary Embolism in Individuals Aged 80 and Older. J Am Geriatr Soc 2014; 62: 2004-2006.
    CrossrefPubMedGoogle Scholar
  • 13 Torbicki A, Perrier A, Konstantinides S. et al. Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2008; 29: 2276-2315.
    CrossrefPubMedGoogle Scholar
  • 14 Jimenez D, Aujesky D, Moores L. et al. Simplification of the Pulmonary Embolism Severity Index for Prognostication in Patients With Acute Symptomatic Pulmonary Embolism. Arch Intern Med 2010; 170: 1383-1389.
    CrossrefPubMedGoogle Scholar
  • 15 Australian Bureau of Statistics. 2007 Available at http://www.abs.gov.au Accessed March, 2009.
    PubMed
  • 16 National Center for Health Statistics. Instructions for Classifying the Underlying Cause-of-Death, ICD-10. 2008: 1-259 Available at http://www.cdc.gov/ nchs/about/major/dvs/im.htm Accessed June 10, 2009.
    PubMedGoogle Scholar
  • 17 Peltan I, Vande V, Maier R. et al. An International Normalized Ratio-Based Definition of Acute Traumatic Coagulopathy Is Associated With Mortality, Venous Thromboembolism, and Multiple Organ Failure After Injury. Crit Care Med 2015; 43: 1429-1438.
    CrossrefPubMedGoogle Scholar
  • 18 Peugh J, Enders C. Missing data in educational research: A review of reporting practices and suggestions for improvement. Rev Educational Res 2004; 74: 525-556.
    PubMedGoogle Scholar
  • 19 Harrell Jr FE, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996; 15: 361-387.
    CrossrefPubMedGoogle Scholar
  • 20 Newson RB. Comparing the predictive powers of survival models using Harrell’s C or Somers’ D. Stata J 2010; 10: 339-358.
    PubMedGoogle Scholar
  • 21 Hosmer Jr DW, Lemeshow S. Applied Logistic Regression. New York, NY: John Wiley & Sons Inc; 1989
    Google Scholar
  • 22 Pencina MJ, D’Agostino Sr RB, D’Agostino Jr RB. et al. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27: 157-172 discussion 207-212.
    CrossrefPubMedGoogle Scholar
  • 23 Scherz N, Labarere J, Mean M. et al. Prognostic Importance of Hyponatremia in Patients with Acute Pulmonary Embolism. Am J Respir Crit Care Med 2010; 182: 1178-1183.
    CrossrefPubMedGoogle Scholar
  • 24 Dabbagh O, Oza A, Prakash S. et al. Coagulopathy Does Not Protect Against Venous Thromboembolism in Hospitalized Patients With Chronic Liver Disease. Chest 2010; 137: 1145-1149.
    CrossrefPubMedGoogle Scholar
  • 25 Moller S, Bernadi M. Interactions of the heart and the liver. Eur Heart J 2013; 34: 2804-2811.
    CrossrefPubMedGoogle Scholar
  • 26 Lee A. Cancer and thromboembolic disease: pathogenic mechanisms. Cancer Treat Rev 2002; 28: 137-140.
    CrossrefPubMedGoogle Scholar
  • 27 Sato Y, Honda Y, Hayashida N. et al. Vitamin K Deficiency and Osteopenia in Elderly Women With Alzheimer’s Disease. Arch Phys Med Rehabil 2005; 86: 576-581.
    CrossrefPubMedGoogle Scholar
  • 28 Galli M, Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome. Blood 1999; 93: 2149-2157.
    PubMedGoogle Scholar
  • 29 Leitner J, Jilma B, Spiel A. et al. Massive pulmonary embolism leading to cardiac arrest isassociated with consumptive coagulopathy presenting as disseminated intravascular coagulation. J Thromb Haemost 2010; 8: 1477-1482.
    CrossrefPubMedGoogle Scholar
  • 30 Stahl R, Javid J, Lackner H. Unrecognized Pulmonary Embolism Presenting as Disseminated Intravascular Coagulation. Am J Med 1984; 76: 772-778.
    CrossrefPubMedGoogle Scholar
  • 31 Pesola G, Carlon G. Pulmonary embolus-induced disseminated intravascular coagulation. Crit Care Med 1987; 15: 983-984.
    CrossrefPubMedGoogle Scholar