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Anemia: A Public Health Problem . Aryeh Shander, MD, FCCM, FCCP Dept. of Anesthesiology, Critical Care & Hyperbaric Medicine Englewood Hospital and Medical Center, Englewood, NJ Clinical Professor of Anesthesiology, Medicine & Surgery Mount Sinai School of Medicine, New York, NY.
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Anemia: A Public Health Problem Aryeh Shander, MD, FCCM, FCCP Dept. of Anesthesiology, Critical Care & Hyperbaric Medicine Englewood Hospital and Medical Center, Englewood, NJ Clinical Professor of Anesthesiology, Medicine & Surgery Mount Sinai School of Medicine, New York, NY Recommendations from the SABM Anemia Advisory Board
WHO Definition of Anemia vs. Hb Distribution in General Population Anemia in Men: Hb <13 g/dL Anemia in Women: Hb <12 g/dL Hb Distribution in Women:13.3 g/dL 0.9 g/dL 3000 Hb Distribution in Men:15.2 g/dL0.9 g/dL 2500 2000 Frequency 1500 1000 500 0 10 10.5 11 11.5 12 12.5 13 13.5 14 14.5 15 15.5 16 16.5 17 17.5 18 Hb Level (g/dL) 1. World Health Organization. Geneva, Switzerland; 2001. 2. Dallman PR, et al. In: Iron Nutrition in Health and Disease London, UK: John Libbey& Co; 1996:65-74.
VARIOUS DEFINITIONS OF ANEMIA Men Women 16 14.2 14 14 14 13.2 13.2 13 12.3 12.2 12 12 11.7 11.6 12 10 Hb (g/dL) 8 6 4 2 0 WHO Jandl Williams Wintrobe Rapaport Goyette Beutler E, et al. Blood. 2006;107(5):1747-1750.
Anemia by the numbers (USA) • Prevalence of Anemia: Approx 1 in 77 or 1.29% or 3.5 million (NHLBI and Mayo Clinic) • 7% of children aged 1-2 had anemia in the US 1999-2000 (MMWR, NCHS, CDC) • 12% of women aged 12-49 had anemia in the US 1999-2000 (MMWR, NCHS, CDC) • 174,600 nursing home residents had anemia in the US 1999 (National Nursing Home Survey, NCHS, CDC) • 4,627 people died from anemia each year in the US 2001 (Deaths: Final Data for 2001, NCHS, CDC) • 1.6 people per 100,000 died from anemia each year in the US 2001 (Deaths: Final Data for 2001, NCHS, CDC)
Recent Data On AnemiaIn Specific Populations Prevalence & Significance Prevalence & Significance Recent Data On AnemiaIn Specific Populations
Outpatient Populations • Bager et al (2011): • Anemia in 19% of 429 IBD patients • 20% IDA; 12% ACD; 68% IDA+ACD • <5% had folate or B12 deficiency • Jones et al (2010): • Anemia in 15% of 234 pts attendingdiabetesclinics • 34% Epo deficiency; 40% abnormal hematinics; 26% unexplained • Jorgensen et al (2010): • Anemia in 3.4% of 5,286 individuals 55-74 yrs old • Anemia associated with 2.15 higher risk of non-vertebral fractures in men • Lipinski et al (2009): • Anemia in 9% of 1,799 patients referred for routine exercise testing • Significantly higher mortality (p<0.05) and cardiovascular events (p<0.001) • Zoppini et al (2010): • Anemia in 18.4% of 1,153 type 2 diabetic outpatients • Independently associated with all-cause (HR 2.11) & cardiovascular mortality (HR 2.23)
Outpatient Populations • Kim et al (2011): 7,607 Koreans aged ≥10 yrs
General Non-Surgical (Inpatient) • Nathavitharana et al (2011): • 33.3% in 1,491 non-surgical inpatient admissions • Independently associated with increased: • LOS (p <0.001) • Mortality (p <0.001) • Unplanned hospital readmission (p <0.001) • Shema-Didi et al (2010): • 27.6% in 19,271 patients with normal kidney activity admitted to hospital • Anemia at admission was associated with occurrence of acute kidney injury after controlling for potential confounders (OR 1.5)
Elderly • Resnick et al (Clin Nurs Res. 2010): • 9 case control studies - A total of 451 residents from 12 nursing homes • Average age 83.74±8.24 • 79% female • 245 (54%) were anemic • Physical performance was worse in those with anemia, and those with anemia associated with chronic kidney disease had lower self-efficacy and outcome expectations for functional activities than those without anemia
Heart Failure • Aleksova et al (2011): • 13% at baseline and 39% new-onset in 491 patients with idiopathic dilated cardiomyopathy • Anemia at baseline - an independent predictor of outcome of transplant or death (HR 1.85) • New-onset of anemia - an independent predictor of poor outcome (HR 2.85) • Hamaguchi et al (2009): • 57% in 1960 patients hospitalized with worsening HF • Increased risk of all-cause death, cardiac death, and rehospitalization after multivariable adjustment • Peterson et al (2010): • 45% at hospitalization and 35% during follow-up in 2,478 patients discharged with HF • Increased mortality rate If persistent (HR 1.65) or progressively declining Hb (HR 1.54)
Heart Failure • Saraiva et al (2011): • 43.2% in 391 patients admitted to an advanced HF care unit • Independent predictor of mortality at 1 year (p=0.035) • Tarantini et al (2011): • 31% in 2,318 patients with acute HF • In-hospital mortality was 12% and 5.3% in anemic vs. non-anemic patients (p<0.0001); an independent predictor of in-hospital mortality • von Haehling et al (2010): • 29% in 627 patients admitted with acute HF • Patients with moderate-severe anemia had increased 12-month mortality (HR 1.5, p=0.01) after adjusting for other factors
Heart Failure • Incidence of anemia in HF
Cerebrovascular Accidents • Sico et al (2011): • 6.4% in 1,306 ischemic stroke patients at admission • Independently associated with worse outcome (OR 4.17) • Tanne et al (2010): • 19% in 859 patients with acute stroke • After adjustment for baseline characteristics, anemia at admission was associated with: • Increased risk of all-cause death at 1-month (OR 1.9) and 1-year (1.72) • Increased disability (OR 2.09) • Increased nursing facility care (OR 1.83)
Critically Ill • Cardenas-Turanzas et al (2010): • Anemia prevalence was 68% and anemia incidence was 46.6% in 4,705 cancer patients admitted to ICU • Thomas et al (2010): • Anemia was present in 98% of 100 consecutive adults admitted to a general ICU
Reduced Treatment Success Decreased QoL Decreased Survival Oncology/Oncosurgery • Clinical consequences of anemia in cancer patients • Less loco-regional control after radiation therapy • Increased relapse rate
Orthopedic Procedures • Spahn – A systematic review (Anesthesiology 2010): • Prevalence of anemia • Hip - 24±9% • Knee - 44±9% • Transfusion rate • Hip - 45±25% • Knee - 44±15% • Anemic patients had higher rates of: • Infection • Poor physical recovery • HLOS • Mortality (13% vs. 6%)
No HF, No CKD, No Anemia 1 Anemia Only 1.9 CKD Only 2.05 HF Only 2.86 CKD, Anemia 3.37 HF, Anemia 3.78 HF, CKD 4.86 HF, CKD, Anemia 6.07 0 1 2 3 4 5 6 7 Relative Risk of 2-Year Mortality Anemia: A Potent Multiplier of Mortality N = 1.1 million (5% Medicare sample, 1996-1997) Herzog CA, et al. Presented at: 6th Annual Scientific Meeting of the Heart Failure Society of America; September 22-25, 2002; Boca Raton, Florida. Abstract 226.
3.5% Preoperative anemia 3.0% 2.5% 2.0% Mortality 1.5% 1.0% No anemia 0.5% 0.0% 0 30 60 90 Postoperative Day Risks of Preop Anemia in Non-Cardiac Surgeries • Beattie SW et al (Anesthesiology 2009): • Retrospective Data collection (n= 7,759) 2003 – 2006 • Preoperative anemia (39.5% for men and 39.9% for women) – 5 fold increase in odds of post op mortality • After adjustment for major confounders, anemia was still associated with increased mortality (odds ratio, 2.36; 95% confidence interval, 1.57-3.41) • Anemia is a common condition in surgical patients and is independently associated with increased mortality.
Preop Anemia & Postop Outcomes in Non-Cardiac Surgeries • Musallam KM et al (Lancet 2011) – A cohort study • 2008 - ACS NSQIP (211 Hospitals) • N= 227,425 • Preop anemia: 30% • Preop anemia independently associated with increased risk of 30-day morbidity and mortality
Preop Anemia & Postop Outcomes in Non-Cardiac Surgeries • 30-day mortality, by anemia and risk factor status Musallam KM et al. Lancet 2011
Blood Loss from Phlebotomy Blood Drawn (mL/day) Smoller BR, et al. N Engl J Med. 1986;314:1233-1235.
Diagnostic Blood Loss From Phlebotomy and Hospital-Acquired Anemia (HAA) During Acute Myocardial Infarction • N= 17 676 patients with AMI from 57 US hospitals - AMI database ( Jan 2000- Dec 2008) • Moderate to severe HAA developed in 3551 patients (20%). • The mean (SD) phlebotomy volume was higher : • HAA (173.8 [139.3] mL) vs those without HAA (83.5 [52.0 mL]; P < .001) • There was significant variation in the mean diagnostic blood loss across hospitals • For every 50 mL of blood drawn, the risk of moderate to severe HAA increased by 18% (relative risk [RR], 1.18; 95% confidence interval [CI], 1.13-1.22) • Blood loss from \phlebotomy is independently associated with the development of HAA. Salisbury, A. C. et al. Arch Intern Med 2011;171:1646-1653
Variation in mean diagnostic blood loss (DBL) across the 57 hospitals Salisbury, A. C. et al. Arch Intern Med 2011;171:1646-1653
Anemia, Comorbidities, Txn & Outcomes Shander A et al. Br J Anaesth 2011
Summary of Data • Anemia – A public health problem • Prevalence varies from population to population and region to region • The prevalence is often high (higher than expected) • An independent predictor of worse outcomes • Mortality • Morbidity • QoL • Likely to be under-screened/under-diagnosed • Responds well to treatment
Anemia Advisory Board • Why SABM got invovled? • Plan: Convene a one-day Advisory Panel of anemia and PBM experts • Sponsor: AMAG Pharmaceuticals • Proposed faculty • AryehShander, MD, FCCM, FCCP - Chair • Lawrence T. Goodnough, MD, co-Chair • Jeffrey Carson, MD • Michael Auerbach, MD • William Ershler, MD • John Glaspy, MD • Indu Lew, PharmD • Mary Ghiglione, RN, BSN, MSN, MHA • MazyarJavidroozi, MD, PhD (Researcher/Writer)
Anemia Advisory Board May 31, 2012 - Santa Monica, CA
Key Conclusions • Anemia definition: • Abide by WHO definitions • Prevalence of anemia high in hospitalized populations • Anemia is associated with worse outcome • Survival, morbidity, hospital LOS • Anemia is a modifiable risk of (for) transfusion • Hospital-acquired anemia (new or exacerbated) is often: • Overlooked, under-attended, under-appreciated • Likely to further worsen outcomes
Key Questions NATA Guidelines Goodnough LT et al. Br J Anaesth. 2011 • What is recommended to detect anemia in patients? • What diagnostic tests are best suited for evaluation of anemia? • What to do in special populations?
Key Recommendations • In general: • NATA guidelines Importance of pre-admission screening/diagnosis • Diagnostic tests: • CBC Anemia Yes/No • TSAT (cut-off 20%) ID Yes/No • Once IDA diagnosis is established Iron • Oral – Barriers: • 2-4 mg absorbed per day • Adherence – (Compliance) • IV Iron Dextran - Barriers: • Test dose – crash cart • Reimbursement • Infusion clinics • If TSAT>20% • Retic Hb concentration • % hypochromic retics • Iron • GI evaluation
Key Recommendations • Surgical patients • Elective: NATA guidelines in general • Screening • CBC • TSAT • Treatment • Iron • Cardiac/CABG: • Also follow STS guidelines
Key Recommendations • Hospitalized Patients • HAA • Screen on admission - • Iron sat at discharge; follow same algorithm • Utilization review/oversight of unnecessary/redundant tests • Small volume/peds tubes • Minimize standing orders for diagnostic testing
Key Recommendations • Elderly – high prevalence with associated adverse outcomes • Detection – annual CBC • Need for endorsement by CMS? • Evaluation - same algorithm • Iron therapy if TSAT<20%
Key Recommendations • Women • Pre-natal care (ACOG guidelines lacking?) • Intolerance to prenatal vitamins/oral iron • Opportunity for other supplemental therapies • Post-Partum • Discharge Iron Rx • TSAT<20%: IV Iron • Need for clinical trials • Dysfunctional uterine bleeding • IV Iron Rx
Key Recommendations • Oncology patients undergoing cancer treatment • Detection: CBC • Evaluation: TSAT screening for every patient • Treatment – algorithm • ESA patients • Give IV iron independent of baseline TSAT for optimal dose response • European published guidelines recommend treatment based on Sx • Early intervention when Hb<11.5 vs. Hb<10
Key Recommendations • Congestive heart failure: • Detection – CBC (Esp NYHA class II and III) • Evaluation TSAT <20% vs. >20% • Management : algorithm • Coronary syndrome: • ~30% have hgb< 11; ~20% have hgb<10 • Detection – CBC • Evaluation - TSAT • Management – algorithm
Key Recommendations • Cerebrovascular accidents Same approach • Respiratory diseases Same approach • Critically ill: • Oxidative stress models • Same approach • Exception: • Not for overtly septic patients. • For patients with uncontrollable infections – watchful waiting
Need for More Research • Impact on improved clinical outcomes • Management in geriatrics with anemia • Adverse events and role of premedication • Importance of anemia