896 Short communication
Pulmonary embolism risk stratification: the intermediate-risk group Luis Paivaa, Se´rgio Barrab and Rui Provideˆnciac Despite all the advances on acute pulmonary embolism risk stratification, a grey area still justifies ongoing debate. Although growing scientific evidence has clarified the extremes of pulmonary embolism risk continuum and has given support to every day’s clinical practice decisions, on who may be sent home or needs promptly aggressive measures, the intermediate-risk pulmonary embolism patients are still a challenging group. Moreover, recent studies reported most interesting findings, exposing weaknesses of traditional markers of pulmonary embolism prognosis (e.g. right-ventricular dysfunction), and shed some light on how we can potentially overcome the difficulties of risk assessment in these cases. Our intention is to briefly discuss the recent developments in pulmonary embolism risk stratification, aiming at clarifying their
Risk stratification is the cornerstone of pulmonary embolism management, crucial for reliable identification of patients at risk of hemorrhagic or recurrent thromboembolic complications. It should allow proper signaling of those high-risk cases that could benefit from aggressive therapeutic interventions and those suitable for outpatient management (partial or complete home treatment), which would favorably impact in healthcare costs [1]. Pulmonary embolism displays a wide variety of clinical presentations, and one of the major concerns is that some patients initially considered being at low risk based on physical, imaging findings and overall comorbidity may experience progressive clinical deterioration, which can lead to dismal clinical errors, and is the reason why pulmonary embolism-related clinical research needs to provide improved risk algorithms with a high-standard performance. Presently, the most used pulmonary embolism risk scores are the clinical prediction rule proposed by the European Society of Cardiology (ESC) [2], Pulmonary Embolism Severity Index (PESI) [3] and its simplified version, and the recent Dutch Hestia study [4]. The proposition that truly low-risk patients with acute pulmonary embolism can be safely treated as outpatients has been addressed previously [5], namely in the metaanalysis by Zondag et al. [6]. The authors reported that incidences of recurrent venous thromboembolism, major bleeding and mortality, after correction for comorbidities, were statistically comparable between groups, and concluded that home treatment of selected low-risk patients with pulmonary embolism is as safe as inpatient treatment, as long as easy and fast access to healthcare is possible. Nevertheless, these findings should be 0957-5235 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins
usefulness in current pulmonary embolism management. Blood Coagul Fibrinolysis 24:896–898 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Blood Coagulation and Fibrinolysis 2013, 24:896–898 Keywords: pulmonary embolism, stratification, management a
Coimbra’s Hospital and University Centre, Coimbra, Portugal, bPapworth Hospital, Cambridge, England, UK and cClinique Pasteur, Toulouse, France Correspondence to Luis Paiva, MD, Quinta dos Vales, 3041–801, S. Martinho do Bispo, Portugal Tel: +351 239 800 093; fax: +351 239 445 737; e-mail: [email protected] Received 28 May 2013 Revised 19 July 2013 Accepted 21 July 2013
interpreted carefully, as most studies did not consider rarer complications of pulmonary embolism, such as postthrombotic syndrome, chronic pulmonary thromboembolism, complex arrhythmias, and side effects of anticoagulation therapy that might mitigate the overall benefit of the outpatient strategy. It is reasonably accepted that symptomatic individuals and those with clinical or imaging evidence of rightventricular dysfunction should be excluded from outpatient management. Moreover, some authors claim that high levels of traditional prognostic biomarkers such as troponin [7] and brain natriuretic peptide (BNP) [8] identify a more risky cohort that must be monitored closely and, possibly, treated more aggressively. Lastly, it is known that the overall comorbidity burden strongly correlates with increased risk of adverse cardiovascular events. However, currently used validated pulmonary embolism risk algorithms classify a significant percentage of patients into prognostic categories that are not clearly defined, as they do not clarify whether patients may be sent home or should be treated more aggressively (the ESC intermediate-risk class). Although hemodynamically stable, these patients may present some risk features, such as signs of right-ventricular dysfunction, pulmonary hypertension, elevated biomarkers, or other organ dysfunction markers. These are often the cases that undergo brisk clinical deterioration, with circulatory failure and ultimately cardiac arrest. Unfortunately, it also comprises patients with chronic conditions (e.g. known heart failure, chronic pulmonary hypertension, and chronic lung disease), without a significant acute decompensation of the long-lasting illness and, more DOI:10.1097/MBC.0b013e32836551d1
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pulmonary embolism risk stratification Paiva et al. 897
evidence that some selected cases among a larger intermediate-risk group of pulmonary embolism patients may be safely treated as outpatients. Furthermore, a recent work by Moores et al. [10] reported similar findings, demonstrating that, in a cohort of intermediate-risk patients with acute pulmonary embolism, a 48-h re-calculation of PESI allowed the identification of a truly low-risk group that would be eligible for early discharge. This deferred PESI approach seems to identify those intermediate-risk patients that respond to medical treatment and have a favorable clinical course. Conversely, Hestia stratifies pulmonary embolism risk using only clinical variables obtained at admission.
importantly, patients displaying an apparently good overall clinical picture. A finer risk stratification of the intermediate-risk group is needed in order to support clinical practice and physicians caring for patients with acute pulmonary embolism. A recent study by Zondag et al. [9] reported that by using the Hestia criteria (comprising 11 variables based on signs/symptoms and personal history) in a pulmonary embolism population, 35% of the patients treated at home (low-risk group) would still present asymptomatic right-ventricular dysfunction, demonstrated by an increase in right ventricle (RV)/left ventricle (LV) ratio at the computed tomographic pulmonary angiography (CTPA). These patients would have been, otherwise, excluded from outpatient management if traditional excluding features (i.e. right-ventricular dysfunction) were to be applied, since the current guidelines consider pulmonary embolism outpatient treatment only in cases without laboratory, hemodynamic, or imaging evidence of circulatory disturbance. These authors have given
In the other spectrum of pulmonary embolism wide clinical presentation are the hemodynamically unstable patients or those who suffer extensive clinical deterioration, therefore considered as being high-risk cases that would potentially benefit from aggressive therapy strategies, such as thrombolysis. Although the lytic strategies are often associated with dismal bleeding complications
Fig. 1
Pulmonary embolism Risk assessment [ESC rule]
High risk
Consider: • Fibrinolysis • Embolectomy
Not high-risk [High troponin and/or RV dysfunction] Finer
Risk assessment [Hestia, PESI]
Low risk
Inpatient treatment
Symptomatic
Intermediate risk
Hospital admission PESI re-assessment
Difficult access to hospital care
[24–48 h]
Low risk
Poor treatment compliance
Not low risk
Consider: tenecteplase + heparin
If low bleeding risk
High comorbidity burden
Outpatient treatment
Early discharge
Inpatient treatment
Anticoagulation + close monitoring
Proposed decision management algorithm according to pulmonary embolism risk-stratification schemes and treatment modalities. ESC, European Society of Cardiology; PESI, pulmonary embolism severity index.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
898 Blood Coagulation and Fibrinolysis 2013, Vol 24 No 8
(e.g. intracranial hemorrhage), they are seen as last-resort measures in patients with unfavorable early prognosis. Recently, preliminary data from the largest trial ever of thrombolysis for intermediate-risk patients – Pulmonary Embolism Thrombolysis Study (PEITHO) [11] – revealed that the addition of tenecteplase to standard treatment in intermediate-risk patients, with evidence of right-ventricular dysfunction and myocardial injury, significantly reduced death or hemodynamic collapse. Yet, the advantages of the thrombolysis equaled the risks of major bleeding. Although the potential benefit of thrombolysis in this clinical setting may have been finally properly documented, there is much to advance concerning the selection of those pulmonary embolism intermediate-risk cases that would frankly benefit from more aggressive therapies and that are not in jeopardy of major bleeding events. For lysis therapy to play a future role in pulmonary embolism management, we need to learn much more about how to predict bleeding complications in this pulmonary embolism setting, possibly through the implementation of comprehensive bleeding risk algorithms, as those used for atrial fibrillation [e.g. Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/ Alcohol Concomitantly (HAS-BLED) score] [12] or acute coronary syndromes management [Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) score] [13]. Lastly, a decision tree is illustrated in Fig. 1 that aims at clarifying pulmonary embolism management according to the risk-stratification schemes. This model conceptualizes ESC rule as a fast-track decision score, using objective and easily accessible prognostic markers, followed by a finer risk assessment with HESTIA or PESI scores.
References 1
2
3
4
5
6
7
8
9
10
11
12
13
Acknowledgements Conflicts of interest
The authors have no conflicts of interest.
Aujesky D, Roy PM, Verschuren F, Righini M, Osterwalder J, Egloff M, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, noninferiority trial. Lancet 2011; 378:41–48. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie` N, Pruszczyk P, et al. Guidelines on the diagnosis an management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008; 29:2276–2315. Jime´nez D, Aujesky D, Moores L, Go´mez V, Lobo JL, Uresandi F, 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. Zondag W, Mos IC, Creemers-Schild D, Hoogerbrugge AD, Dekkers OM, Dolsma J, et al. Hestia Study Investigators. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost 2011; 9:1500–1507. Erkens PMG, Gandara E, Wells PS, Shen AYH, Bose G, Le Gal G, et al. Does the Pulmonary Embolism Severity Index accurately identify low risk patients eligible for outpatient treatment. Thromb Res 2012; 129:710–714. Zondag W, Kooiman J, Klok F, Dekkers O, Huisman M. Outpatient versus inpatient treatment in patients with pulmonary embolism: a meta-analysis. Eur Respir J 2013; 42:134–144. Vuilleumier N, Le Gal G, Verschuren F, Perrier A, Bournameaux H, Turck N, et al. Cardiac biomarkers for risk stratification in nonmassive pulmonary embolism: a multicenter prospective study. J Thromb Haemost 2009; 7:391–398. Verschuren F, Bonnet M, Benoit MO, Gruson D, Zech F, Couturaud F, et al. The prognostic value of pro-B-type natriuretic peptide in acute pulmonary embolism. Thromb Res 2013; 131:e235–e239. Zondag W, Vingerhoets L, Durian M, Dolsma A, Faber L, Hiddinga B, et al. The Hestia Study Investigators. Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function. J Thromb Haemost 2013; 11:686–692. Moores L, Zamarro C, Go´mez V, Aujesky D, Garcı´a L, Nieto R, et al. on behalf of the IRYCIS Pulmonary Embolism Study Group. Changes in PESI score predict mortality in intermediate-risk patients with acute pulmonary embolism. Eur Respir J 2013; 41:354–359. Steering Committee. Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Am Heart J 2012; 163:33–38. Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/ Alcohol Concomitantly) score. J Am Coll Cardiol 2011; 57:173–180. Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) bleeding score. Circulation 2009; 119:1873–1882.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pulmonary embolism risk stratification: the intermediate-risk group Luis Paivaa, Se´rgio Barrab and Rui Provideˆnciac Despite all the advances on acute pulmonary embolism risk stratification, a grey area still justifies ongoing debate. Although growing scientific evidence has clarified the extremes of pulmonary embolism risk continuum and has given support to every day’s clinical practice decisions, on who may be sent home or needs promptly aggressive measures, the intermediate-risk pulmonary embolism patients are still a challenging group. Moreover, recent studies reported most interesting findings, exposing weaknesses of traditional markers of pulmonary embolism prognosis (e.g. right-ventricular dysfunction), and shed some light on how we can potentially overcome the difficulties of risk assessment in these cases. Our intention is to briefly discuss the recent developments in pulmonary embolism risk stratification, aiming at clarifying their
Risk stratification is the cornerstone of pulmonary embolism management, crucial for reliable identification of patients at risk of hemorrhagic or recurrent thromboembolic complications. It should allow proper signaling of those high-risk cases that could benefit from aggressive therapeutic interventions and those suitable for outpatient management (partial or complete home treatment), which would favorably impact in healthcare costs [1]. Pulmonary embolism displays a wide variety of clinical presentations, and one of the major concerns is that some patients initially considered being at low risk based on physical, imaging findings and overall comorbidity may experience progressive clinical deterioration, which can lead to dismal clinical errors, and is the reason why pulmonary embolism-related clinical research needs to provide improved risk algorithms with a high-standard performance. Presently, the most used pulmonary embolism risk scores are the clinical prediction rule proposed by the European Society of Cardiology (ESC) [2], Pulmonary Embolism Severity Index (PESI) [3] and its simplified version, and the recent Dutch Hestia study [4]. The proposition that truly low-risk patients with acute pulmonary embolism can be safely treated as outpatients has been addressed previously [5], namely in the metaanalysis by Zondag et al. [6]. The authors reported that incidences of recurrent venous thromboembolism, major bleeding and mortality, after correction for comorbidities, were statistically comparable between groups, and concluded that home treatment of selected low-risk patients with pulmonary embolism is as safe as inpatient treatment, as long as easy and fast access to healthcare is possible. Nevertheless, these findings should be 0957-5235 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins
usefulness in current pulmonary embolism management. Blood Coagul Fibrinolysis 24:896–898 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Blood Coagulation and Fibrinolysis 2013, 24:896–898 Keywords: pulmonary embolism, stratification, management a
Coimbra’s Hospital and University Centre, Coimbra, Portugal, bPapworth Hospital, Cambridge, England, UK and cClinique Pasteur, Toulouse, France Correspondence to Luis Paiva, MD, Quinta dos Vales, 3041–801, S. Martinho do Bispo, Portugal Tel: +351 239 800 093; fax: +351 239 445 737; e-mail: [email protected] Received 28 May 2013 Revised 19 July 2013 Accepted 21 July 2013
interpreted carefully, as most studies did not consider rarer complications of pulmonary embolism, such as postthrombotic syndrome, chronic pulmonary thromboembolism, complex arrhythmias, and side effects of anticoagulation therapy that might mitigate the overall benefit of the outpatient strategy. It is reasonably accepted that symptomatic individuals and those with clinical or imaging evidence of rightventricular dysfunction should be excluded from outpatient management. Moreover, some authors claim that high levels of traditional prognostic biomarkers such as troponin [7] and brain natriuretic peptide (BNP) [8] identify a more risky cohort that must be monitored closely and, possibly, treated more aggressively. Lastly, it is known that the overall comorbidity burden strongly correlates with increased risk of adverse cardiovascular events. However, currently used validated pulmonary embolism risk algorithms classify a significant percentage of patients into prognostic categories that are not clearly defined, as they do not clarify whether patients may be sent home or should be treated more aggressively (the ESC intermediate-risk class). Although hemodynamically stable, these patients may present some risk features, such as signs of right-ventricular dysfunction, pulmonary hypertension, elevated biomarkers, or other organ dysfunction markers. These are often the cases that undergo brisk clinical deterioration, with circulatory failure and ultimately cardiac arrest. Unfortunately, it also comprises patients with chronic conditions (e.g. known heart failure, chronic pulmonary hypertension, and chronic lung disease), without a significant acute decompensation of the long-lasting illness and, more DOI:10.1097/MBC.0b013e32836551d1
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pulmonary embolism risk stratification Paiva et al. 897
evidence that some selected cases among a larger intermediate-risk group of pulmonary embolism patients may be safely treated as outpatients. Furthermore, a recent work by Moores et al. [10] reported similar findings, demonstrating that, in a cohort of intermediate-risk patients with acute pulmonary embolism, a 48-h re-calculation of PESI allowed the identification of a truly low-risk group that would be eligible for early discharge. This deferred PESI approach seems to identify those intermediate-risk patients that respond to medical treatment and have a favorable clinical course. Conversely, Hestia stratifies pulmonary embolism risk using only clinical variables obtained at admission.
importantly, patients displaying an apparently good overall clinical picture. A finer risk stratification of the intermediate-risk group is needed in order to support clinical practice and physicians caring for patients with acute pulmonary embolism. A recent study by Zondag et al. [9] reported that by using the Hestia criteria (comprising 11 variables based on signs/symptoms and personal history) in a pulmonary embolism population, 35% of the patients treated at home (low-risk group) would still present asymptomatic right-ventricular dysfunction, demonstrated by an increase in right ventricle (RV)/left ventricle (LV) ratio at the computed tomographic pulmonary angiography (CTPA). These patients would have been, otherwise, excluded from outpatient management if traditional excluding features (i.e. right-ventricular dysfunction) were to be applied, since the current guidelines consider pulmonary embolism outpatient treatment only in cases without laboratory, hemodynamic, or imaging evidence of circulatory disturbance. These authors have given
In the other spectrum of pulmonary embolism wide clinical presentation are the hemodynamically unstable patients or those who suffer extensive clinical deterioration, therefore considered as being high-risk cases that would potentially benefit from aggressive therapy strategies, such as thrombolysis. Although the lytic strategies are often associated with dismal bleeding complications
Fig. 1
Pulmonary embolism Risk assessment [ESC rule]
High risk
Consider: • Fibrinolysis • Embolectomy
Not high-risk [High troponin and/or RV dysfunction] Finer
Risk assessment [Hestia, PESI]
Low risk
Inpatient treatment
Symptomatic
Intermediate risk
Hospital admission PESI re-assessment
Difficult access to hospital care
[24–48 h]
Low risk
Poor treatment compliance
Not low risk
Consider: tenecteplase + heparin
If low bleeding risk
High comorbidity burden
Outpatient treatment
Early discharge
Inpatient treatment
Anticoagulation + close monitoring
Proposed decision management algorithm according to pulmonary embolism risk-stratification schemes and treatment modalities. ESC, European Society of Cardiology; PESI, pulmonary embolism severity index.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
898 Blood Coagulation and Fibrinolysis 2013, Vol 24 No 8
(e.g. intracranial hemorrhage), they are seen as last-resort measures in patients with unfavorable early prognosis. Recently, preliminary data from the largest trial ever of thrombolysis for intermediate-risk patients – Pulmonary Embolism Thrombolysis Study (PEITHO) [11] – revealed that the addition of tenecteplase to standard treatment in intermediate-risk patients, with evidence of right-ventricular dysfunction and myocardial injury, significantly reduced death or hemodynamic collapse. Yet, the advantages of the thrombolysis equaled the risks of major bleeding. Although the potential benefit of thrombolysis in this clinical setting may have been finally properly documented, there is much to advance concerning the selection of those pulmonary embolism intermediate-risk cases that would frankly benefit from more aggressive therapies and that are not in jeopardy of major bleeding events. For lysis therapy to play a future role in pulmonary embolism management, we need to learn much more about how to predict bleeding complications in this pulmonary embolism setting, possibly through the implementation of comprehensive bleeding risk algorithms, as those used for atrial fibrillation [e.g. Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/ Alcohol Concomitantly (HAS-BLED) score] [12] or acute coronary syndromes management [Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) score] [13]. Lastly, a decision tree is illustrated in Fig. 1 that aims at clarifying pulmonary embolism management according to the risk-stratification schemes. This model conceptualizes ESC rule as a fast-track decision score, using objective and easily accessible prognostic markers, followed by a finer risk assessment with HESTIA or PESI scores.
References 1
2
3
4
5
6
7
8
9
10
11
12
13
Acknowledgements Conflicts of interest
The authors have no conflicts of interest.
Aujesky D, Roy PM, Verschuren F, Righini M, Osterwalder J, Egloff M, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, noninferiority trial. Lancet 2011; 378:41–48. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie` N, Pruszczyk P, et al. Guidelines on the diagnosis an management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008; 29:2276–2315. Jime´nez D, Aujesky D, Moores L, Go´mez V, Lobo JL, Uresandi F, 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. Zondag W, Mos IC, Creemers-Schild D, Hoogerbrugge AD, Dekkers OM, Dolsma J, et al. Hestia Study Investigators. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost 2011; 9:1500–1507. Erkens PMG, Gandara E, Wells PS, Shen AYH, Bose G, Le Gal G, et al. Does the Pulmonary Embolism Severity Index accurately identify low risk patients eligible for outpatient treatment. Thromb Res 2012; 129:710–714. Zondag W, Kooiman J, Klok F, Dekkers O, Huisman M. Outpatient versus inpatient treatment in patients with pulmonary embolism: a meta-analysis. Eur Respir J 2013; 42:134–144. Vuilleumier N, Le Gal G, Verschuren F, Perrier A, Bournameaux H, Turck N, et al. Cardiac biomarkers for risk stratification in nonmassive pulmonary embolism: a multicenter prospective study. J Thromb Haemost 2009; 7:391–398. Verschuren F, Bonnet M, Benoit MO, Gruson D, Zech F, Couturaud F, et al. The prognostic value of pro-B-type natriuretic peptide in acute pulmonary embolism. Thromb Res 2013; 131:e235–e239. Zondag W, Vingerhoets L, Durian M, Dolsma A, Faber L, Hiddinga B, et al. The Hestia Study Investigators. Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function. J Thromb Haemost 2013; 11:686–692. Moores L, Zamarro C, Go´mez V, Aujesky D, Garcı´a L, Nieto R, et al. on behalf of the IRYCIS Pulmonary Embolism Study Group. Changes in PESI score predict mortality in intermediate-risk patients with acute pulmonary embolism. Eur Respir J 2013; 41:354–359. Steering Committee. Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Am Heart J 2012; 163:33–38. Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/ Alcohol Concomitantly) score. J Am Coll Cardiol 2011; 57:173–180. Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) bleeding score. Circulation 2009; 119:1873–1882.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
