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New concepts in diagnosis and management of iron deficiency Dr Jane KEIDAN With thanks to Vifor Pharma UK Ltd Rachael de Nobrega · Medical Advisor Claire.

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Presentation on theme: "New concepts in diagnosis and management of iron deficiency Dr Jane KEIDAN With thanks to Vifor Pharma UK Ltd Rachael de Nobrega · Medical Advisor Claire."— Presentation transcript:

1 New concepts in diagnosis and management of iron deficiency Dr Jane KEIDAN With thanks to Vifor Pharma UK Ltd Rachael de Nobrega · Medical Advisor Claire Atterbury Mr Toby Richards

2 Outline Iron metabolism Treatment options Clinical use of intravenous iron-current and developing areas

3 Total body iron: grams Mostly within the cardiovascular system, liver and muscles 1 : Red blood cells1.8 g RES macrophages0.6 g Liver1.0 g Bone marrow0.3 g Muscles (myoglobin)0.3 g Other tissues0.1 g Bound to transport protein Transferrin g Each ml of blood contains approximately 0.5 mg of iron 1. Hentze MW et al. Cell. 2004;117:285-97

4 Iron content of a balanced diet A balanced diet contains 5-6 mg of iron/1,000 kcal Recommended amount of iron –Adult man: 5-10 mg / day –Adult woman: 7-20 mg / day

5 Iron in diet Richest sources of heme iron -lean meat, seafood. Dietary sources of nonheme iron - nuts, beans, vegetables, and fortified grain products. Heme iron has higher bioavailability than nonheme iron- bioavailability % from mixed diets that include substantial amounts of meat/fish and 5% to 12% from vegetarian diets Vitamin C enhances the bioavailability of nonheme iron Meat, poultry, and fish enhance nonheme iron absorption, whereas phytate (present in grains and beans) and certain polyphenols in some non-animal foods (such as cereals and legumes) inhibit absorption

6 Prevalence of iron deficiency anaemia CountriesIndustrialised (%)Developing (%) Children (0-4 years) Children (5-14 years) Pregnant women Women in reproductive age Men (15-59 years) Seniors World Health Organisation Iron Deficiency: Assessment, Prevention and Control.

7 Symptoms of iron deficiency with or without anaemia Shortness of breath Fatigue Reduced physical performance and endurance Decreased concentration span Reduced vitality Increased susceptibility for infections Pale skin colour, hair loss and brittle nails

8 Non-haematological benefits of iron 1 Physical performance Thermoregulation Cognitive function Restless legs syndrome Immune function 1. Agarwal R. Am J Neph 2007;27:

9

10 Iron status without inflammation 1 1 Adapted from Crichton RR et al. Iron Therapy With a Special Emphasis on Intravenous Administration (4 th edition). UNI-MED Verlag AG, Bremen, Germany, 2008 Stage 1Stage 2 NormalIron deficiencyIron deficiency anaemia Storage iron Transport iron Erythron iron Ferritin (µg/l)100±60< 25< 10 Transferrin saturation (%)35±15< 30< 10 Haemoglobin (g/dl)Normal (12-13) Low (< 12-13)

11 Iron status with inflammation 1 1 Adapted from Crichton RR et al. Iron Therapy With a Special Emphasis on Intravenous Administration (4 th edition). UNI-MED Verlag AG, Bremen, Germany, 2008 Inflammation NormalIron depletionAbsolute iron deficiency Functional iron deficiency Storage iron Transport iron Erythron iron Ferritin (µg/l)100±60< 25< 10>100 Transferrin saturation (%)35±15< 30< 10<20 Haemoglobin (g/dl)Normal Low

12 HEPCIDIN and FERROPORTIN Hepcidin is a hormone produced by the liver Discovered in 2000 Pivotal in iron metabolism, principle regulator Inhibits iron transport across cell membranes via ferroportin In gut prevents iron absorption by blocking iron release from enterocytes In macrophages prevents stored iron release to marrow Hepcidin production inhibited by iron deficiency-increased absorption and release of iron from stores Hepcidin production stimulated by inflammation- poor absorption and iron trapped in stores

13

14 Absolute & functional iron deficiency Functional iron deficiency  Inadequate iron supply to meet demand despite normal or abundant iron stores –Normal or high ferritin levels –TSAT <20% –High hepcidin Absolute iron deficiency  Depleted body iron stores –Low serum ferritin (<100ng/ml) or –TSAT <20% –Low hepcidin Wish JB. Clin J Am Soc Nephrol 2006;1:S4-8 ESA, erythropoiesis stimulating agent; TSAT, transferrin saturation

15 Iron replacement strategies Dietary iron Oral iron Parenteral iron Blood transfusion

16 Oral iron therapy Advantages : cheap : easy to administer Disadvantages :poorly absorbed(max 5-10 mg/day) :GI side-effects common :compliance often poor :absorption limited if ferritin elevated :absorption reduced in inflammation

17 Limitations of oral iron therapies 1,2 1.Macdougall IC. Curr Med Res Opin 2010;26:473–83; 2.Crichton RR et al. Iron Therapy With a Special Emphasis on Intravenous Administration (4 th edition). UNI-MED Verlag AG, Bremen, Germany, 2008

18 Parenteral iron in UK 60 years HMW Iron dextran (Imferon from Fisons) Iron sucrose (Venofer) 1998 LMW Iron dextran (Cosmofer) 2001 Ferric carboxymaltose (Ferinject) 2008 Iron isomaltoside 1000 (Monofer) 2010 Ferumoxytol (Rienso) 2012

19 Use of intravenous iron Indicated for treatment of iron deficiency when oral iron preparations are ineffective or cannot be used. Comparative clinical trials show a faster and more prolonged response with IV iron than with oral iron. IV iron is more effective, better tolerated and improves QoL to a greater extent than oral iron. Concerns regarding allergic reactions. 1. British National Formulary (BNF) 2. Gasche C et al. Inflamm Bowel Dis 2007;13:1545–53

20 Blood Transfusion BCSH Guidelines for Clinical Use of Red Cell Transfusions (2001) INDICATED where Hb level < 7g/dl NOT INDICATED where Hb level > 10g/dl UNCLEAR where Hb level is 7-10g/dl – Symptomatic – Inability to compensate

21 Blood transfusion Cost £122/unit plus admin costs Supply limitations Risks unique to transfusion

22 Risks associated with transfusion CategoryRisk per components issued Total risk of death1 in 125,000 Total risk of major morbidity1 in 19,157 Risk of death from error1 in 454,545 Risk of major morbidity from error1 in 196,078 Risk of death from TACO1 in 227,273 Risk of major morbidity from TACO1 in 81,3000 Risk of major morbidity from ATR1 in 36,764 CategoryRisk of infected donation entering blood supply HBV1 in 1.3 million HCV1 in 28.6 million HIV1 in 7.1 million Copyright SHOT July 2014

23 SHOT Cumulative data: 17 years n=13141 Adverse events due to mistakes Transfusion reactions which may not be preventable Possibly or probably preventable by improved practice and monitoring Copyright SHOT July 2014

24 Summary of treatment options Oral ironIV ironBlood transfusion Cost 1 High iron contentEssential in cases of cardiovascular instability 1 Non-invasive100% bioavailableReplaces RBCs Simple administration 1 Compliance Convenient 2 Fast acting 5 Well tolerated 2 Malabsorption in inflammatory conditions 3 Potential adverse reactions Potential transfusion reactions 6,7 Intolerance 3 Invasive Potential poor compliance 3 Day case / inpatient Slower to increase haemoglobin vs IV iron 4 CostCost 8 Interactions with many common oral drugs 4 Limited supply 7 Can delay investigative procedures, i.e. colonoscopies Increased risk of morbidity and mortality in patients with cardiac disease 7 Can only absorb 10-20mg a dayMay worsen outcomes in acute bleeds and surgical cases 9 Complex administration 7 Advantage Disadvantages 1. Goddard AF et al. Gut 2011;60:1309e Gasche C et al Inflamm Bowel Dis 2007;13(12): Macdougall IC. Curr Med Res Opin 2010;26(2): Crichton R et al. Iron Therapy With Special Emphasis on Intravenous Administration. UNI-MED Verlag AG Kulnigg S et al. Am J Gastroenterol 2007;102: Marik PE & Corwin HL. Crit Care Med 2008;36(11): Knowles S Transfus Altern Transfus Med 2007;9(S2)2-9 8 Vifor Pharma UK Data on File 9. Restellini S et al. Aliment Pharmacol Ther 2013;37:

25 Clinical use of intravenous iron Chronic kidney disease (dialysis and non-dialysis) Antenatal and postpartum Gastroenterology – Inflammatory (Crohn’s & colitis), acute/chronic blood loss Pre- and post-operatively Oncology Chronic Heart Failure ITU, care of the elderly, palliative care (not covered further)

26 NEPHROLOGY

27 Renal medicine Erythropoeitin (ESA) licensed in 1989 Intravenous iron improves Hb responses and reduces ESA requirements-overcomes iron“supply” issue Approved by NICE

28 NICE Guidelines for Anaemia Management in CKD Recommendation: ‘In non-dialysis patient with anaemia of CKD in whom there is evidence of absolute or functional iron deficiency, this should be corrected before deciding whether ESA therapy is necessary.’ NICE 2011 Anaemia management in people with chronic kidney disease (CG114)

29 Table 3.1 Test for functional iron deficiency with ferritin and TSAT or ferritin and %HRC FerritinTsat%MCV%HRC Functional iron deficiency>100µg/l<20Normal range>6 Absolute iron deficiency<100µg/l<20Low>6 TSAT = transferrin saturation; MCV = mean corpuscular volume; HRC = hypochromic red cells NICE Guideline 114 Management of anaemia should be considered in people with anaemia of chronic kidney disease (CKD) when the haemoglobin level is less than or equal to 11.0g/dl. Patients receiving ESA maintenance therapy should be given iron supplements to keep ferritin between µg/l & TSAT >20% or %HRC <6%. In practice it is likely this will require intravenous iron. NICE 2011 Anaemia management in people with chronic kidney disease (CG114)

30 OBSTETRICS & GYNAECOLOGY

31 Risk factors for iron deficiency in pregnant women 1 Ethnicity Educational level/social class Diet Multiparity Obesity Anaemia during pregnancy Total blood loss at delivery > 0.5L Not exclusively breastfeeding 1. Bodnar LM et al. Am J Epidemiol. 2002;156: ©

32 Adverse effects of iron deficiency in pregnancy, at delivery and post partum- maternal Unpleasant symptoms – Lethargy, dyspnoea, fatigue, insomnia, light headedness, dizziness and disorientation Increased susceptibility to infection Decrease in thermoregulation Ante partum haemorrhage ++ Post partum haemorrhage ++ Delayed wound healing Reduced quality and quantity of lactation or even halted Excessive fatigue and failure to cope

33 And for the fetus/baby………. Poor uterine growth Decreased liquor Asymmetrical growth patterns Small for dates Premature delivery Low birth weight Failure to thrive (poor lactation) And if it continues - poor concentration and reduced scholarly achievements (Source SMA)

34 Antenatal iron deficiency anaemia Very common Estimated requirements of ~800 mgs extra iron over the course of one pregnancy Detection poor Detection late

35 Iron deficiency anaemia becomes more prevalent as pregnancy progresses Scholl TO. Am J Clin Nutr. 2005;81:1218S-1222S Percentage of women Anaemia*Iron deficiency anaemia** * Hb <11 g/dL in trimester 1, Hb <10.5 g/dL in trimester 2, Hb <11 g/dL in trimester 3 ** Anaemia with serum ferritin <12 ng/mL First trimester Second trimester Third trimester

36 Iron therapy in pregnancy Oral iron works well if started early but can be poorly tolerated Intravenous irons are contraindicated in the first trimester – use must be confined to 2 nd and 3 rd trimesters if benefits outweigh the risks.

37 Venofer ® IV Iron Sucrose Syner-Med (PP) Ltd

38 Post partum iron deficiency Lethargy, dyspnoea, fatigue, insomnia, light headedness, dizziness and disorientation Increased susceptibility to infection Post partum haemorrhage ++ Delayed wound healing Reduced quality and quantity of lactation or even halted Excessive fatigue and failure to cope

39 44 women with haemoglobin (Hb) of <9 g/dl and ferritin of <15 microgram/l at 24–48 hours post delivery. Oral ferrous sulphate 200 mg twice daily for 6 weeks or 200mg iron sucrose x 2 Women treated with intravenous iron had significantly higher Hb levels on days 5 and 14 (P < 0.01) than those treated with oral iron Conclusion: Intravenous iron sucrose increases the Hb level more rapidly than oral ferrous sulphate in women with postpartum IDA Bhandal N, Russell R. BJOG 2006;113:

40 Oral iron vs IV iron in the postpartum Bhandal N, Russell R. BJOG 2006;113:

41 The King’s Lynn experience Midwife-led service for prevention/management of anaemia in pregnancy and reduction of transfusion exposure

42 Background We began to promote the use of intravenous iron in place of blood transfusion having noted that some women who received blood in pregnancy or post partum were iron deficient. OTHER DRIVERS FOR CHANGE Anaemia contributes to adverse outcomes for both mother and baby. Transfusion avoidance is a national UK priority

43 Data from King’s Lynn

44 Units used vs number of women transfused

45 How did we achieve this? Regular interdepartmental meetings Midwife education days Creating “champions” Designing clear algorithms to empower the midwives to appropriately diagnose and manage anaemia in pregnancy to reduce transfusion rates and rationalise use of intravenous iron. Providing easy access to haematology advice Dietary information emphasised to expectant mothers

46 It starts at booking……… A careful history – General health – Dietary history – Family history – Bleeding history – Obstetric and otherwise – Any previous history of anaemia? Beliefs and wishes and fears concerning blood transfusion Drug history Allergies esp iron

47 Hb less than 11 g/dl at booking (or less than 10.5 if above 12 weeks gestation) = ANAEMIA MCV below 81flMCV above 99MCV Flow Chart 1a – Anaemia at Booking See Flow Chart 1bSee Flow Chart 1cSee Flow Chart 1d

48 Hb less than 11 g/dl at booking (or less than 10.5 if above 12 weeks gestation) = ANAEMIA AND MCV less than 81fl Dietary advice and Oral Iron Check Ferritin (if not previously done) Ferritin below 30Ferritin above 30 Unable to tolerate oral iron or failure to show rise in Hb after 2 weeks oral iron Consider intravenous iron in second trimester Re-check Hb in 4 weeks after IV Iron No response Seek Haematology Advice Check Haemoglobinopathy Screen No action Thalassemia Trait Normal Low Flow Chart 1b – Anaemia at Booking and MCV less than 81 Re-check Hb in 2 weeks Normal Check Ferritin

49 Danger of overuse of intravenous iron REMEMBER many women can be easily (and cheaply) treated with oral iron if their anaemia is detected and managed early in pregnancy.

50 Iron Therapy Timeline in O&G

51 Dietary advice and Oral Iron Check B 12 /Folate Ferritin below 30 Normal Ferritin Unable to tolerate oral iron or failure to show rise in Hb after 2 weeks oral iron Consider intravenous iron in second trimester Low B 12 Re-check Hb in 4 weeks after IV Iron No response Seek Haematology advice Reschedule FBC in 2 weeks Hb less than 11 (or less than 10.5 if above 12 weeks gestation) seek Haematology advice Check Haemoglobinopathy Screen Normal If low see flow chart 1d Thalassemia Trait Check Ferritin Normal Below 30 Check B 12 /Folate Check Hb in 2 weeks Check Ferritin (if not previously done) Normal Low Folate Follow flow chart 1d Flow Chart 1c – Anaemia at Booking and MCV 81 – 99 Hb less than 11g/dl at booking (or less than 10.5 if above 12 weeks gestation) and MCV 81 – 99 = ANAEMIA AND MCV 81-99fl

52 Hb less than 11 g/dl at booking (or less than 10.5 if above 12 weeks gestation) and MCV above 99 = ANAEMIA AND MCV above 99fl Check B 12 /Folate Low B 12 Take sample for intrinsic factor antibodies. Take sample before giving B 12 (but do not wait for result) If antibodies positive = Pernicious Anaemia Refer to GP Re-check Hb in 4 weeks No response Seek Haematology Advice Low Folate Dietary advice and oral folic acid (5mg daily) Hydroxycobalamin 1mg x 6 doses im If antibodies negative B INDETERMINATE Hydroxycobalamin 1mg one dose im if still Request GP re- check B 12 3 months post partum B INDETERMINATE Repeat in 4-8 weeks B 12 <211 = DEFICIENT High risk if: Vegan Diet, Ileal Disease, Malabsorption, Bariatric Surgery or Family History PA; Normal Reschedule FBC in 2 weeks Hb less than 11, seek Haematology advice B 12 normal Flow Chart 1d – Anaemia at Booking and MCV above 99

53 Another chance at 28 weeks Review blood results and ACT ON THEM

54 Hb less than 10.5 g/dl at 28 weeks = ANAEMIA MCV <81 [exclude thalassemia - check booking bloods] Dietary advice and Oral Iron MCV above 99 Check B 12 /Folate MCV Check Ferritin Low Ferritin (below 30) Normal Ferritin Unable to tolerate oral iron or >34 /40 gestation or Hb <7 Follow IV Iron protocol (Confirm iron deficiency – check Ferritin) Low B 12 Take sample for intrinsic factor antibodies. Take sample before giving B 12 but do not wait for result If antibodies positive = Pernicious Anaemia Refer to GP Re-check Hb in 2 weeks No response Seek Haematology advice Low Folate Dietary advice and oral folic acid (5mg daily) B 12 <211 = DEFICIENT High risk if: Vegan Diet, Ileal Disease, Malabsorption, Bariatric Surgery or Family History PA; Hydroxycobalamin 1mg x 6 doses im If antibodies negative B INDETERMINATE Hydroxycobalami n 1mg one dose im if still Request GP re- check B 12 3 months post partum B INDETERMINATE Repeat in 2-4 weeksRecheck Hb in 2 weeks Continue Oral Iron Rise in Hb No rise in Hb B 12 normal Seek Haematology advice if Hb<10.5 Flow Chart 2: Anaemia in Pregnancy at 28 weeks

55 Iron Therapy Timeline in O&G

56 Conclusions Collaboration between laboratory and midwifery staff has improved care of pregnant women by early identification and appropriate treatment of anaemia, reducing pregnancy-related transfusion rates. For laboratory staff, the project delivers on the UK national priority of transfusion avoidance, and has promoted dialogue across the clinical –laboratory interface. For the midwives, the project has empowered them to independently diagnose and manage anaemia in pregnancy For the mothers and babies, reduction in antenatal and postnatal anaemia is known to improve outcomes. PLUS If applied nationally, this approach would save blood AND increase the blood donor pool

57 GASTROENTEROLOGY

58 British Society of Gastroenterology Guidelines for the management of iron deficiency anaemia 2011 Definition of anaemia Iron deficiency*Treatment Acknowledge WHO cut-offs: Men Hb <13g/dl Women Hb <12g/dl Suggest cut-off for diagnosis of anaemia should be the lower limit of the normal range as defined by laboratory doing thr test. Low ferritin (cut-off varies between µg/l in absence of inflammation). Low TSAT. Low iron. Raised TIBC. Raised red cell zinc protoporphyrin. Raised serum transferrin receptor. Reticulocyte Hb content or % hypochromic red cells for diagnosis & monitoring of functional ID. All patients should have iron supplementation to correct anaemia & replenish body stores. Trial of oral or parenteral iron can help distinguish true iron deficiency. For those intolerant or not responding to oral iron parenteral iron preparations can be used. Blood transfusions only for patient with symptomatic anaemia despite iron therapy or those at risk of cardiovascular instability. Iron treatment should follow transfusion to replenish stores. * Values unspecified in guidelines

59

60 Guidelines on the Diagnosis and Management of Iron Deficiency and Anaemia in IBD (Gasche et al, 2007)

61 Treatment of Anaemia in IBD: Iron Supplementation The preferred route of iron supplementation in IBD is intravenous, even though many patients will respond to oral iron. Intravenous iron is more effective, better tolerated, and improves the quality of life to a greater extent than oral iron supplements (Grade A). Statement 4a

62 PATIENT BLOOD MANAGEMENT

63 Three pillars of Patient Blood Management

64 In patients undergoing total hip or knee arthroplasty and hip fracture surgery, preoperative anaemia was highly prevalent, ranging from 24 +/- 9% to 44 +/- 9%, respectively. Postoperative anaemia was even more prevalent (51% and 87 +/- 10%, respectively). Perioperative anaemia was associated with a blood transfusion rate of 45 +/- 25% and 44 +/- 15%, postoperative infections, poorer physical functioning and recovery, and increased length of hospital stay and mortality. Treatment of preoperative anemia with iron, with or without erythropoietin, and perioperative cell salvage decreased the need for blood transfusion and may contribute to improved patient outcomes. High-impact prospective studies are necessary to confirm these findings and establish firm clinical guidelines. Spahn DR. Anaesthesiology 2010;113:482-95

65 31 of 75 women with iron deficiency treated with IV iron preoperatively. IV iron sucrose (760± 290 mg) increased preoperative Hb (Δ Hb: 2.2 ± 1.2 g/dL;P<0.001) and reduced postoperative transfusion rates compared with the control group (32% vs 0%, respectively; P <0.001). Fewer women from the IV iron group were anemic on postoperative day 21 (23% vs 68%; P <0.01). No life-threatening adverse events occurred with iron sucrose. Because of the rapid increase in Hb levels, IV iron sucrose administration seems to be an effective approach for treating preoperative anemia and reducing transfusion rates in this female population. Diez-Lobo AI et al. TATM. 2007;9:

66 US Veterans Database (NSQIP)(n=227,425) Anaemia(n=69,229; 30.4%) 30day mortality 30day composite morbidities (9 defined areas) Multivariate regression (9 defined subgroups) (56 cofactors)

67 Effect of Anaemia on Outcome

68 941,406 patients 173 Hospitals ,291 transfused

69 Management of Anaemia

70

71 Restrictive Hb 70-90g/l Liberal Hb g/l

72 Outcome - BT

73 Outcome - Mortality

74 Cost of anaemia on outcome Increased length of hospital stay (median 9 v 6 days, p=0.001) Increased post operative complications (25-35%)

75 Conclusions Avoid anaemia Avoid transfusion THINK IRON EARLY

76 Lost to Follow up / Discontinued (n=15) Analyse (n=235) Lost to Follow up / Discontinued (n=15) Analyse (n=235) Assess for Eligibility : Patients undergoing elective major surgery Anaemia (Hb: <12 g/dl) days before operation Informed consent Randomisation 1:1 (n=500 planned) Exclusion: Iron therapy or blood transfusion in 90 days B12 or Folate deficiency Unstable cardiac disease Renal dialysis or creatinine > 180 ALT or AST > 3 x upper limit of normal Ferric Carboxymaltose (n= 250) Dose by weight (1000mg max) Placebo (n=250) N/Saline infusion 100

77 ONCOLOGY

78 Venofer ® IV Iron Sucrose Syner-Med (PP) Ltd Shander A et al. Transfusion 2010;50:

79

80 Dangsuwan P, Manchana T. Gynecol Oncol. 2010;116:522-5

81 ‘ The original question raised in this study of which patients need iron in addition to ESAs might rather read which patients need ESAs in addition to iron.’ Steinmetz HT et al. Support Care Cancer. 2010;19:261-9

82 CONGESTIVE HEART FAILURE

83 Prevalence of anaemia in CHF 11. Anand I et al. Circulation 2005;112:1121– Sharma R et al. Eur Heart J 2004;25:1021– Anand I et al. Circulation 2004;110:149– Komajda M et al. Eur Heart J 2006;27:1440– O’Meara et al Circulation 2006;113:986− , Cleland JG et al. Eur Heart J 2003;24:442− Komajda M et al. Eur Heart J 2003;24:464− Adams KF et al. Am Heart J 2005;149:209− Maggioni AP et al. J Card Fail 2005;11:91−98 5. Horwich TB et al. J Am Coll Cardiol 2002;39:1780− Silverberg DS et al. J Am Coll Cardiol 2000;35:1737– McClellan W et al. Curr Med Res Opin 2004;20:1501– van Tellingen A et al. Neth J Med 2001;59:270− Ezekowitz JA et al. Circulation 2003;107: Cohn JN et al. N Engl J Med 2001;345:1667–1675

84 Anaemia in HF adversely affects outcome Meta-analysis, 34 studies, n=153,180 HF patients; anemics – 37% 1 Mortality: anemics – 46.8% vs non-anemics – 29.5%; OR=1.96 (1.74−2.21) 1 Anemia independent risk of mortality; adjusted HR – 1.46 (1.26−1.69) 1 1. Groenveld HF et al. J Am Coll Cardiol 2008;52:818−827; 2. O’Meara E et al. Circulation 2006;113:986− Per 1000 pt-years CVNon-CV Reduced LVEF Preserved LVEF CVNon-CV 300 Hospital admission Per 1000 pt-years CVNon-CV Reduced LVEF Preserved LVEF CVNon-CV Mortality Anemics Non-anemics CHARM program 2

85 Kaplan-Meier analysis of all-cause mortality according to anemia status 1 Persistence of anaemia in ambulatory HF patients is related to poor outcome 1. Tang WH et al. J Am Coll Cardiol 2008;51:569– % Log-rank p< Chi square= 227 Total baseline population (n=6159) Survival (%) Years Without anemia (n=5101) With anemia (n=1058) Log-rank p< Chi square= month follow-up (n=1393) Survival (%) Years Resolved anemia (n=143) No anemia (n=860) Incident anemia (n=210) Persistent anemia (n=180)

86 Anker SD et al. Eur J Heart Failure 2009;11:

87

88

89 Cardiorenal anaemia syndrome: a vicious circle of destruction CHF AnaemiaCRF

90 Anaemia and cardiovascular disease Anaemia Tissue hypoxia Peripheral vasodilation  Blood pressure  Sympathetic activity  Renal blood flow  Renin angiotensin aldosterone ADH Fluid retention  Plasma volume  Ventricular diameter LVH and eventual cell death CHF

91 CONCLUSIONS

92 New concepts in diagnosis and management of iron deficiency Role of hepcidin True versus functional iron deficiency Importance of anaemia on clinical outcomes Risks of transfusion Role of intravenous iron

93 THANK YOU


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