Anemia Guidelines and The Use of Erythropoietin in Turkey

1
Anemia Guidelines and The Use of Erythropoietin
in Turkey

• Kenan ATES, MD
• Department of Nephrology
• Ankara University Faculty of Medicine

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Anemia in chronic renal failure
Erythropoietin deficiency
GFR lt40 ml/min
Erythropoesis inhibition
Hemolysis
ANEMIA
Blood loss
Iron deficiency
Normocytic normochromic
Folate/Vitamin B12 deficiency
Inflammation
Aluminium overload
3
Anemia is important
Decreased tissue oxygen delivery and utilization
Decreased cognition and mental acuity
Increased cardiac output
Altered menstrual cycles
Ventricular hypertrophy
Decreased sexual function
Cardiac enlargement
Impaired immune responsiveness
Angina pectoris
Growth retardation
Congestive heart failure
Decreased intellectual performance
Reduced quality of life
Poor patient rehabilitation
Decreased survival
4
Treatment of anemia
Iron supplementation
Adequate dialysis
Adequate nutrition
Target Hb/Hct Level
Treatment of secondary hyperparathyroidism
Prevention of inflammation
ERYTHROPOIETIN
5
Not all dialysis patients will require treatment
with EPO
Adequate dialysis
HD
20
Adequate nutrition
Iron supplementation
PD
40
Other measures
6
C O S T
EPO therapy is a very expensive treatment
One month cost
HEMODIALYSIS
900
EPO (6000 U/wk)
500
7
ANEMIA GUIDELINES
8
Anemia Guidelines
The aim of guidelines is to provide an
evidence-based standard of care for management of
anemia in patients with chronic renal failure
NKF-DOQI GUIDELINES
1996
EUROPEAN BEST PRACTICE GUIDELINES
1999
TSN ANEMIA GUIDELINES
2003
9
When to initiate the work-up of anemia
Pre-menopausal females Pre-pubertal patients
Hb lt11 g/dl (Hct lt33)
Post-menopausal females Adult males
Hb lt12 g/dl (Hct lt37)
NKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINES
10
Evaluation of anemia
Hemoglobin and/or hematocrit
Red blood cell indices
Serum iron
Reticulocyte count
TIBC
Iron parameters
Serum ferritin
Transferrin saturation
Occult blood in stool
Percen. of hypochromic red cells
CRP
NKF-DOQI GUIDELINES
TSN ANEMIA GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
11
Evaluation of anemia
A fuller work-up should also include the
following, as indicated
Serum vitamin B12 and folic acid
Differential white blood count
Tests for hemolysis
Serum protein electroforesis
Hemoglobin electroforesis
TSN ANEMIA GUIDELINES
Bone marrow examination
EUROPEAN BEST PRACTICE GUIDELINES
Serum aluminium
12
Erythropoietin deficiency
Anemia is most likely due to EPO deficiency
If
Impairment of renal function is present
A normocytic, normochromic anemia is present
No cause for anemia is detected by the work-up
NKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINES
13
Indications for starting treatment with
Erythropoietin

• EPO treatment should be considered
• when the Hb concentration is consistently less
  than
• 11 g/dl on repeating testing (Hct lt33)
• when other causes of anemia have been excluded

NKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
14
Indications for starting treatment with
Erythropoietin
TSN ANEMIA GUIDELINES
SYMPTOMATIC PATIENTS Heart failure, angina
ASYMPTOMATIC PATIENTS
Hb lt10 g/dl Htc lt30
Higher Hb and/or Hct levels
EPO TREATMENT
15
Serum creatinine ?2 mg/dl
Check Hb
lt12 g/dl in males and post-menopausal females lt11
g/dl in pre-menopausal females and pre-pubertal
patients
Work-up
No
Hematology work-up
Normal
Fe deficiency
Treat with iron
Treat with EPO if indicated
Anemia corrected
Anemia not corrected
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Target hematocrit/hemoglobin for erythropoietin
therapy
Hemoglobin
11-12 g/dl
Hematocrit
33-36
Variations in the target Hb may be required in
patients with co-morbidity
NKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINES
17
Assesment of iron status
Serum iron
Total iron binding capacity
Transferrin saturation
Percentage of hypochromic red cells
Serum ferritin
Iron stores in bone marrow
NKF-DOQI GUIDELINES
RBC ferritin concentration
BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINES
18
Target iron level
The patients should have sufficient iron to
achieve and maintain an Hb (Hct) of 11-12 g/dl
(33-36)
OPTIMAL
Serum ferritin
gt100 ng/ml
200-500 ng/ml
Transferrin saturation
gt20
30-40
Hypochromic red cells
lt10
lt2.5 (lt5)
TSN ANEMIA GUIDELINES
NKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
19
Monitoring iron status
Patients treated with Epo
Patients not treated with Epo
Hb/Hct stable
Hb lt11 g/dl Hct lt33
Hb 11-12 g/dl Hct 33-36
Ferritin ?100 ng/ml TSAT ?20
Every 3 months
Every 3-6 months
Receiving IV iron
Not receiving IV iron
NKF-DOQI GUIDELINES
BEST PRACTICE GUIDELINES
Every month
Every 3 months
TSN ANEMIA GUIDELINES
20
Administration of supplemental iron
TSAT lt20 Ferritin lt100 ng/ml
100-125 mg IV iron at every HD seans for 8-10
doses
TSAT lt20 Ferritin lt100 ng/ml
TSAT gt20 Ferritin gt100 ng/ml
TSAT gt50 Ferritin gt800 ng/ml
100-125 mg IV iron at every HD seans for 8-10
doses
25-125 mg IV iron per week
IV iron therapy should be withheld for 3 months
21
Oral iron therapy
When oral iron is used
It should be given as 200 mg of elemental iron
per day, in two to three divided doses in the
adult patient, and 2-3 mg/kg/day in the pediatric
patient
NKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINES
22
Route of administration of erythropoietin
INTRAVENOUS
INTRAPERITONEAL
SUBCUTANEOUS
INTRADERMAL
EPO should be administered SC in PD patients
The most effective route of EPO is SC in HD
patients
NKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
TSN ANEMIA GUIDELINES
23
Initial erythropoietin administration
SC
80-120 units/kg/week, in two to three doses per
week
IV
120-180 units/kg/week, in three doses per week
NKF-DOQI GUIDELINES
24
Initial erythropoietin administration
The starting dose of EPO should be 50-150
units/kg/week
SC
The starting dose should be in the lower range
IV
The starting dose should be in the upper range
EUROPEAN BEST PRACTICE GUIDELINES
25
Initial erythropoietin administration
SC
The starting dose should be 75 units/kg/week
IV
The starting dose should be 150 units/kg/week
TSN ANEMIA GUIDELINES
26
Monitoring of Hb/Hct during erythropoietin therapy
Target Hb/Hct is not achieved
Every 1-2 weeks
NKF-DOQI GUIDELINES
BEST PRACTICE GUIDELINES
Every 1-2 weeks
TSN ANEMIA GUIDELINES
Every 2 weeks
Target Hb/Hct is achieved
NKF-DOQI GUIDELINES
Every 2-4 weeks
BEST PRACTICE GUIDELINES
Every 4-6 weeks
TSN ANEMIA GUIDELINES
Every 4 weeks
27
Titration of erythropoietin dosage
After initation of EPO After a dose increase
If the increase in Hb (Hct) is lt0.7 g/dl (lt2)
over a 2-4 week period
If the increase in Hb/Hct is gt2.5 g/dl (gt8) per
month
If the Hb (Hct) exceeds the target levels
Dose should be increased by 50
Dose should be decreased by 25-50
NKF-DOQI GUIDELINES
BEST PRACTICE GUIDELINES
28
Titration of erythropoietin dosage
After initation of EPO After a dose increase
If the increase in Hb (Hct) is lt1.0 g/dl (lt3)
over a 4-6 week period
If the increase in Hb/Hct is gt1.5 g/dl (gt5) per
month
Dose should be decreased by 50
Dose should be increased by 12.5-25 units/kg/week
TSN ANEMIA GUIDELINES
29
Inadequate response to erythropoietin
DEFINITION
NKF-DOQI GUIDELINES
Failure to achieve target Hb/Hct in the presence
of adequate iron stores at dose of 450
units/kg/wk IV or 300 units/kg/wk SC within 4-6
months or failure to maintain target Hb/Hct
subsequently at that dose
EUROPEAN BEST PRACTICE GUIDELINES
Failure to attain the target Hb concentration
while receiving more than 300 units/kg/wk
(20.000 units/wk) of EPO SC or a continued need
for such dosage to maintain the target
30
Inadequate response to erythropoietin
DEFINITION
TSN 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
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Causes of inadequate response to erythropoietin
Iron deficiency
Osteitis fibrosa
Infection/inflamation
Aluminium overload
Chronic blood loss
Folate/Vitamin B12 deficiency
Hemoglobinopathies
Malnutrition
Hemolysis
Multiple myeloma
NKF-DOQI GUIDELINES
EUROPEAN BEST PRACTICE GUIDELINES
32
Infection Inflammation Malignancy
EPO RESISTANCE
CRP
Non-compliance
Occult blood in stool
Blood loss
Iron stores
Reticulocyte LDH Bilirubin Blood smear
Hemolysis
Adequate
Inadequate
Vitamin B12/Folate Blood smear
Vitamin deficiency
PTH Bone marrow examination
Bone marrow fibrosis
Aluminium overload
Serum aluminium
TSN ANEMIA GUIDELINES
Hb electrof.
Hemoglobinopathies
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LEGAL ARRANGEMENTS
34
Ministry of Finance2003 Fiscal YearBudget
Application Directions
Official Gazette Date 01.02.2003, Number 25011
Use of erythropoietin in patients with chronic
renal failure
The target Hct level for EPO therapy is 30-35
If the target Hct is achieved, EPO dose should be
decreased
If the Hct level exceeds 40, EPO therapy should
be interrupted until Hct is decreased to target
level
If failure to achieve the target Hct within 3
months, EPO therapy should be interrupted and
causes of resistance should be examined
EPO should be administered subcutaneously
35
Social Insurance Institution (SSK)2002 Year Drug
Application Directions
Item 30
Principles of erythropoietin usage
EPO therapy should be used when the Hb (Hct) is
less than 8 g/dl (24)
If the following conditions is determined during
the initial evaluation, EPO therapy should not be
used
Iron deficiency
Chronic infection
Ischemic vascular disease
Blood loss
Aluminium overload
Uncontrolled hypertension
Hemolysis
Hyperparathyroidism
Vascular access thrombosis
36
Social Insurance Institution (SSK)2002 Year Drug
Application Directions
The target Hb (Hct) level is 10-11 g/dl (30-33)
If the Hb (Hct) level exceeds the 11 g/dl (33),
EPO therapy should be interrupted
EPO Resistance Despite the EPO therapy at dose
of 150 units/kg/week, no increase in Hb/Hct
within 3 months
If no increase in Hb/Hct level within two months,
EPO therapy should be interrupted
EPO should be administered subcutaneously
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CURRENT ASPECTS OF ANEMIA THERAPY AND USE OF
ERYTHROPOIETIN IN TURKEY
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Use of erythropoietin in dialysis patients in
Turkey

TSN Registry
39
Use of erythropoietin in hemodialysis patients in
Turkey

Ministry of Health Data
40
Mean hemoglobin level in dialysis patients in
Turkey
TSN Registry-2002
41
Percent of patients with hemoglobin ?11
g/dl in Turkey

TSN Registry
42
The success rate with erythropoietin in
dialysis patients in Turkey

TSN Registry-2002
43
Use of iron therapy in dialysis patients in Turkey

TSN Registry-2002
44
Serum ferritin level in dialysis patients in
Turkey

TSN Registry-2002
45
Data of United Kingdom Renal Registry

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CONCLUSION
Anemia is present in the majority of the patients
with CRF, and when untreated, it is associated
with poor clinical outcomes
Today, anemia treatment and use of erythropoietin
is guided by social security organisations in
Turkey
Directions of erythropoietin usage suggested by
these organisations are cost-based but not
evidence-based
Principles of anemia treatment in Turkey should
be rearranged according to TSN Anemia Guidelines