anemia guidelines and the use of erythropoietin in turkey
DESCRIPTION
Anemia Guidelines and The Use of Erythropoietin in Turkey. Kenan ATEŞ, MD Department of Nephrology Ankara University Faculty of Medicine. Anemia in chronic renal failure. Erythropoietin deficiency. GFRTRANSCRIPT
Anemia Guidelines and The Use of Anemia Guidelines and The Use of
Erythropoietin in TurkeyErythropoietin in Turkey
Kenan ATEŞ, MD
Department of NephrologyAnkara University Faculty of Medicine
Anemia in chronic renal failure
GFR <40 ml/minGFR <40 ml/min
ANEMİAANEMİA
Normocytic normochromic Normocytic normochromic
Erythropoietin deficiencyErythropoietin deficiency
Iron deficiencyIron deficiency
Folate/Vitamin BFolate/Vitamin B1212 deficiency deficiency
InflammationInflammation
Aluminium overloadAluminium overload
Blood lossBlood loss
HemolysisHemolysis
Erythropoesis inhibitionErythropoesis inhibition
Anemia is importantAnemia is important
Decreased tissue oxygenDecreased tissue oxygendelivery and utilizationdelivery and utilization
Increased cardiac outputIncreased cardiac output
Ventricular hypertrophyVentricular hypertrophy
Cardiac enlargementCardiac enlargement
Angina pectorisAngina pectoris
Congestive heart failureCongestive heart failure
Decreased cognition andDecreased cognition andmental acuitymental acuity
Altered menstrual cyclesAltered menstrual cycles
Decreased sexual functionDecreased sexual function
Impaired immune responsivenessImpaired immune responsiveness
Growth retardationGrowth retardation
Decreased intellectual performanceDecreased intellectual performance
Reduced quality of lifeReduced quality of life
Decreased survivalDecreased survival
Poor patient rehabilitationPoor patient rehabilitation
Treatment of anemia
Adequate dialysisAdequate dialysis
Adequate nutritionAdequate nutrition
Treatment of secondaryTreatment of secondaryhyperparathyroidismhyperparathyroidism
Prevention of inflammationPrevention of inflammation
Iron supplementationIron supplementation
TargetTargetHb/Hct LevelHb/Hct Level
ERYTHROPOIETINERYTHROPOIETIN
Not all dialysis patients will require treatment with EPONot all dialysis patients will require treatment with EPO
HDHD
PDPD
20%20%
40%40%
Adequate dialysisAdequate dialysis
Adequate nutritionAdequate nutrition
Iron supplementationIron supplementation
Other measuresOther measures
C O S T
EPO therapy is a very expensive treatmentEPO therapy is a very expensive treatment
One month costOne month cost
HEMODIALYSISHEMODIALYSIS 900 $900 $
EPO (6000 U/wk)EPO (6000 U/wk) 500 $500 $
ANEMIA GUIDELINES
Anemia Guidelines
The aim of guidelines is to provide an evidence-basedThe aim of guidelines is to provide an evidence-basedstandard of care for management of anemia in patientsstandard of care for management of anemia in patientswith chronic renal failurewith chronic renal failure
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
19961996
19991999
20032003 TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
When to initiate the work-up of anemia
Hb <11 g/dl (Hct <33%)Hb <11 g/dl (Hct <33%)Pre-menopausal femalesPre-menopausal femalesPre-pubertal patientsPre-pubertal patients
Post-menopausal femalesPost-menopausal femalesAdult malesAdult males
Hb <12 g/dl (Hct <37%)Hb <12 g/dl (Hct <37%)
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Evaluation of anemia
Hemoglobin and/or hematocritHemoglobin and/or hematocrit
Red blood cell indicesRed blood cell indices
Reticulocyte countReticulocyte count
Occult blood in stoolOccult blood in stool
Serum ironSerum iron
TIBCTIBC
Transferrin saturationTransferrin saturation
Serum ferritinSerum ferritin
Percen. of hypochromic red cellsPercen. of hypochromic red cells
Iron parametersIron parameters
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
CRPCRP
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Evaluation of anemia
Serum vitamin BSerum vitamin B1212 and folic acid and folic acid
Differential white blood countDifferential white blood count
Tests for hemolysisTests for hemolysis
Serum protein electroforesisSerum protein electroforesis
Bone marrow examinationBone marrow examination
Serum aluminiumSerum aluminium
A fuller work-up should also include the following, as indicatedA fuller work-up should also include the following, as indicated
Hemoglobin electroforesisHemoglobin electroforesis TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
EUROPEAN BESTEUROPEAN BEST PRACTICE GUIDELINESPRACTICE GUIDELINES
No cause for anemia is detected by the work-upNo cause for anemia is detected by the work-up
Erythropoietin deficiency
Anemia is most likely due to EPO deficiencyAnemia is most likely due to EPO deficiency
IfIf
A normocytic, normochromic anemia is presentA normocytic, normochromic anemia is present
Impairment of renal function is presentImpairment of renal function is present
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Indications for starting treatment with Erythropoietin
EPO treatment should be consideredEPO treatment should be considered when the Hb concentration is consistently less thanwhen the Hb concentration is consistently less than 11 g/dl on repeating testing (Hct <33%) 11 g/dl on repeating testing (Hct <33%) when other causes of anemia have been excludedwhen other causes of anemia have been excluded
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
Indications for starting treatment with Erythropoietin
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Hb <10 g/dlHb <10 g/dlHtc <30%Htc <30%
EPO TREATMENTEPO TREATMENT
Higher Hb and/or Hct levelsHigher Hb and/or Hct levels
ASYMPTOMATICASYMPTOMATICPATIENTSPATIENTS
SYMPTOMATICSYMPTOMATICPATIENTSPATIENTS
Heart failure, anginaHeart failure, angina
Serum creatinine Serum creatinine 2 mg/dl2 mg/dl
Check HbCheck Hb
Work-upWork-up
NormalNormal Fe deficiencyFe deficiency
Treat with EPOTreat with EPOif indicatedif indicated
Anemia not correctedAnemia not corrected
<12 g/dl in males and post-menopausal females<12 g/dl in males and post-menopausal females<11 g/dl in pre-menopausal females and pre-pubertal patients<11 g/dl in pre-menopausal females and pre-pubertal patients
Treat with ironTreat with iron
Anemia correctedAnemia corrected
HematologyHematologywork-upwork-up
NoNo
Target hematocrit/hemoglobin for erythropoietin therapy
HemoglobinHemoglobin
HematocritHematocrit
11-12 g/dl11-12 g/dl
33-36%33-36%
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Variations in the target Hb may be requiredVariations in the target Hb may be requiredin patients with co-morbidityin patients with co-morbidity
Assesment of iron status
Serum ironSerum iron
Total iron binding capacityTotal iron binding capacity
Transferrin saturationTransferrin saturation
Serum ferritinSerum ferritin
Percentage of hypochromic red cellsPercentage of hypochromic red cells
Iron stores in bone marrowIron stores in bone marrow
RBC ferritin concentrationRBC ferritin concentration
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
BEST PRACTICE GUIDELINESBEST PRACTICE GUIDELINES
Target iron level
Transferrin saturationTransferrin saturation
Serum ferritinSerum ferritin
>20%>20%
>100 ng/ml>100 ng/ml
30-40%30-40%
200-500 ng/ml200-500 ng/ml
The patients should have sufficient iron to achieve andmaintain an Hb (Hct) of 11-12 g/dl (33-36%)
Hypochromic red cellsHypochromic red cells <10%<10% <2.5% (<5%)<2.5% (<5%)
OPTIMALOPTIMAL
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINESNKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
Monitoring iron status
Every monthEvery month
Every 3 monthsEvery 3 months Every 3-6 monthsEvery 3-6 months
Patients treated with EpoPatients treated with Epo Patients not treated with EpoPatients not treated with Epo
Hb/Hct stableHb/Hct stable
Ferritin Ferritin 100 ng/ml100 ng/mlTSAT TSAT 20%20%
Hb <11 g/dlHb <11 g/dlHct <33%Hct <33%
Hb 11-12 g/dlHb 11-12 g/dlHct 33-36%Hct 33-36%
Every 3 monthsEvery 3 months
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
BEST PRACTICE GUIDELINESBEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
ReceivingReceivingIV ironIV iron
Not receivingNot receivingIV ironIV iron
Administration of supplemental iron
TSAT <20%TSAT <20%Ferritin <100 ng/mlFerritin <100 ng/ml
100-125 mg IV iron100-125 mg IV ironat every HD seansat every HD seans
for 8-10 dosesfor 8-10 doses
25-125 mg IV iron25-125 mg IV ironper weekper week
100-125 mg IV iron at every HD seans100-125 mg IV iron at every HD seansfor 8-10 dosesfor 8-10 doses
TSAT <20%TSAT <20%Ferritin <100 ng/mlFerritin <100 ng/ml
TSAT >20%TSAT >20%Ferritin >100 ng/mlFerritin >100 ng/ml
IV iron therapyIV iron therapyshould be withheldshould be withheld
for 3 monthsfor 3 months
TSAT >50%TSAT >50%Ferritin >800 ng/mlFerritin >800 ng/ml
Oral iron therapy
It should be given as 200 mg of elemental iron per day,It should be given as 200 mg of elemental iron per day,in two to three divided doses in the adult patient, andin two to three divided doses in the adult patient, and2-3 mg/kg/day in the pediatric patient2-3 mg/kg/day in the pediatric patient
When oral iron is usedWhen oral iron is used
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Route of administration of erythropoietin
EPO should be administered SC in PD patientsEPO should be administered SC in PD patients
The most effective route of EPO is SC in HD patientsThe most effective route of EPO is SC in HD patients
INTRAVENOUSINTRAVENOUS
SUBCUTANEOUSSUBCUTANEOUS
INTRAPERITONEALINTRAPERITONEAL
INTRADERMALINTRADERMAL
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Initial erythropoietin administration
SCSC 80-120 units/kg/week, in two to three doses per week80-120 units/kg/week, in two to three doses per week
IVIV 120-180 units/kg/week, in three doses per week120-180 units/kg/week, in three doses per week
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
Initial erythropoietin administration
SCSC The starting dose should be in the lower rangeThe starting dose should be in the lower range
IVIV The starting dose should be in the upper rangeThe starting dose should be in the upper range
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
The starting dose of EPO should be 50-150 units/kg/weekThe starting dose of EPO should be 50-150 units/kg/week
Initial erythropoietin administration
SCSC The starting dose should be 75 units/kg/weekThe starting dose should be 75 units/kg/week
IVIV The starting dose should be 150 units/kg/weekThe starting dose should be 150 units/kg/week
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Monitoring of Hb/Hct during erythropoietin therapy
Every 1-2 weeksEvery 1-2 weeks
Every 2-4 weeksEvery 2-4 weeks
Target Hb/Hct is achievedTarget Hb/Hct is achieved
Target Hb/Hct is not achievedTarget Hb/Hct is not achieved
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
BEST PRACTICE GUIDELINESBEST PRACTICE GUIDELINES Every 1-2 weeksEvery 1-2 weeks
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES Every 2 weeksEvery 2 weeks
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
BEST PRACTICE GUIDELINESBEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Every 4-6 weeksEvery 4-6 weeks
Every 4 weeksEvery 4 weeks
Titration of erythropoietin dosage
Dose should be increased byDose should be increased by50%50%
Dose should be decreased byDose should be decreased by25-50%25-50%
After initation of EPOAfter initation of EPOAfter a dose increaseAfter a dose increase
If the increase in Hb (Hct) isIf the increase in Hb (Hct) is<0.7 g/dl (<2%) over a 2-4 <0.7 g/dl (<2%) over a 2-4 week periodweek period
If the increase in Hb/Hct isIf the increase in Hb/Hct is>2.5 g/dl (>8%) per month>2.5 g/dl (>8%) per month
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
BEST PRACTICE GUIDELINESBEST PRACTICE GUIDELINES
If the Hb (Hct) exceedsIf the Hb (Hct) exceedsthe target levelsthe target levels
Titration of erythropoietin dosage
Dose should be increased byDose should be increased by12.5-25 units/kg/week12.5-25 units/kg/week
Dose should be decreased byDose should be decreased by50%50%
After initation of EPOAfter initation of EPOAfter a dose increaseAfter a dose increase
If the increase in Hb (Hct) isIf the increase in Hb (Hct) is<1.0 g/dl (<3%) over a 4-6 <1.0 g/dl (<3%) over a 4-6 week periodweek period
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
If the increase in Hb/Hct isIf the increase in Hb/Hct is>1.5 g/dl (>5%) per month>1.5 g/dl (>5%) per month
Inadequate response to erythropoietin
Failure to achieve target Hb/Hct in the presence of adequateiron stores at dose of 450 units/kg/wk IV or 300 units/kg/wkSC within 4-6 months or failure to maintain target Hb/Hct subsequently at that dose
DEFINITIONDEFINITION
Failure to attain the target Hb concentration while receivingmore than 300 units/kg/wk (~20.000 units/wk) of EPO SC ora continued need for such dosage to maintain the target
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
Inadequate response to erythropoietin
DEFINITIONDEFINITION
TSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
Despite the EPO therapy at dose of 300 units/kg/week,no increase in Hb more than 2 g/dl within 12 weeks
Causes of inadequate response to erythropoietin
Iron deficiencyIron deficiency
Infection/inflamationInfection/inflamation
Chronic blood lossChronic blood loss
Osteitis fibrosaOsteitis fibrosa
Aluminium overloadAluminium overload
Folate/Vitamin BFolate/Vitamin B1212 deficiency deficiency
HemoglobinopathiesHemoglobinopathiesMalnutritionMalnutrition
HemolysisHemolysis Multiple myelomaMultiple myeloma
NKF-DOQI GUIDELINESNKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINESEUROPEAN BEST PRACTICE GUIDELINES
EPO RESISTANCEEPO RESISTANCE
Non-complianceNon-compliance
Iron storesIron stores
AdequateAdequate
CRPCRP
ReticulocyteReticulocyteLDHLDHBilirubinBilirubinBlood smearBlood smear
Occult bloodOccult bloodin stoolin stool
Vitamin BVitamin B1212/Folate/FolateBlood smearBlood smear
PTHPTHBone marrowBone marrowexaminationexamination
Serum aluminiumSerum aluminium
Hb electrof.Hb electrof.
InadequateInadequate
InfectionInfectionInflammationInflammationMalignancyMalignancy
Blood lossBlood loss
HemolysisHemolysis
VitaminVitamindeficiencydeficiency
AluminiumAluminiumoverloadoverload
Bone marrowBone marrowfibrosisfibrosis
HemoglobinopathiesHemoglobinopathiesTSN ANEMIA GUIDELINESTSN ANEMIA GUIDELINES
LEGAL ARRANGEMENTS
Ministry of Finance2003 Fiscal Year
Budget Application Directions
Official Gazette: Date 01.02.2003, Number 25011 Official Gazette: Date 01.02.2003, Number 25011
Use of erythropoietin in patients with chronic renal failureUse of erythropoietin in patients with chronic renal failure
The target Hct level for EPO therapy is 30-35%The target Hct level for EPO therapy is 30-35%
If the target Hct is achieved, EPO dose should be decreasedIf the target Hct is achieved, EPO dose should be decreased
If the Hct level exceeds 40%, EPO therapy should beIf the Hct level exceeds 40%, EPO therapy should beinterrupted until Hct is decreased to target levelinterrupted until Hct is decreased to target level
EPO should be administered subcutaneouslyEPO should be administered subcutaneously
If failure to achieve the target Hct within 3 months, EPOIf failure to achieve the target Hct within 3 months, EPOtherapy should be interrupted and causes of resistancetherapy should be interrupted and causes of resistanceshould be examinedshould be examined
Social Insurance Institution (SSK)2002 Year Drug Application Directions
EPO therapy should be used when the Hb (Hct) is less thanEPO therapy should be used when the Hb (Hct) is less than8 g/dl (24%) 8 g/dl (24%)
If the following conditions is determined during the initialIf the following conditions is determined during the initialevaluation, EPO therapy should not be usedevaluation, EPO therapy should not be used
Iron deficiencyIron deficiency
Blood lossBlood loss
HemolysisHemolysis
Chronic infectionChronic infection
Aluminium overloadAluminium overload
HyperparathyroidismHyperparathyroidism
Uncontrolled hypertensionUncontrolled hypertension
Vascular access thrombosisVascular access thrombosis
Ischemic vascular diseaseIschemic vascular disease
Item 30 Principles of erythropoietin usage
Social Insurance Institution (SSK)2002 Year Drug Application Directions
EPO Resistance:EPO Resistance: Despite the EPO therapy at dose of Despite the EPO therapy at dose of150 units/kg/week, no increase in Hb/Hct within 3 months150 units/kg/week, no increase in Hb/Hct within 3 months
The target Hb (Hct) level is 10-11 g/dl (30-33%)The target Hb (Hct) level is 10-11 g/dl (30-33%)
If the Hb (Hct) level exceeds the 11 g/dl (33%), EPO therapyIf the Hb (Hct) level exceeds the 11 g/dl (33%), EPO therapyshould be interruptedshould be interrupted
If no increase in Hb/Hct level within two months, EPOIf no increase in Hb/Hct level within two months, EPOtherapy should be interruptedtherapy should be interrupted
EPO should be administered subcutaneouslyEPO should be administered subcutaneously
CURRENT ASPECTS OF ANEMIA THERAPY AND USE OF
ERYTHROPOIETIN IN TURKEY
Use of erythropoietin in dialysis patients in Turkey
0
20
40
60
80
100
1996 1997 1998 1999 2000 2001 2002
HD
PD%
TSN RegistryTSN Registry
Use of erythropoietin in hemodialysis patients in Turkey
52,9 56,6
71,1 75
0
20
40
60
80
100
Universityhospital
SSK hospital Ministry ofHealth
hospital
Privateenterprise
%
Ministry of Health DataMinistry of Health Data
Mean hemoglobin level in dialysis patients in Turkey
7
8
9
10
11
12
Mea
n H
b (
g/d
l)
HD PD
TSN Registry-2002TSN Registry-2002
Percent of patients with hemoglobin 11 g/dl in Turkey
0
20
40
60
80
100
2001 2002
HDPD
%
TSN RegistryTSN Registry
The success rate with erythropoietin in dialysis patients in Turkey
0
20
40
60
80
100
Hb >11 g/dl withEPO
EPO resistance
HDPD
%
TSN Registry-2002TSN Registry-2002
Use of iron therapy in dialysis patients in Turkey
0
20
40
60
80
100
Oral Parenteral
HDPD
%
TSN Registry-2002TSN Registry-2002
Serum ferritin level in dialysis patients in Turkey
0
10
20
30
40
50
60
70
<100 100-399 400-800 >800
HD
PD%
TSN Registry-2002TSN Registry-2002
Data of United Kingdom Renal Registry
0
20
40
60
80
100
Use of EPO Hb >11 g/dl
HD PD
7
8
9
10
11
12
13
Mean Hb
%
CONCLUSION
Today, anemia treatment and use of erythropoietin is guidedToday, anemia treatment and use of erythropoietin is guidedby social security organisations in Turkey by social security organisations in Turkey
Anemia is present in the majority of the patients with CRF, andAnemia is present in the majority of the patients with CRF, andwhen untreated, it is associated with poor clinical outcomeswhen untreated, it is associated with poor clinical outcomes
Directions of erythropoietin usage suggested by theseDirections of erythropoietin usage suggested by theseorganisations are cost-based but not evidence-basedorganisations are cost-based but not evidence-based
Principles of anemia treatment in Turkey should be rearrangedPrinciples of anemia treatment in Turkey should be rearrangedaccording to TSN Anemia Guidelinesaccording to TSN Anemia Guidelines