alternate of blood transfusion
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ALTERNATIF OF BLOOD ALTERNATIF OF BLOOD TRANSFUSIONTRANSFUSION
OPTIONS FOR ANAEMIA MANAGEMENT
No treatment(60%)
Iron alone(7%)
Epoetin(18%)
Transfusion(15%)
European Cancer Anaemia Survey (ECAS), Ludwig et al. Ann Oncol 2002; 13 (Suppl 5): 169 [A623PD]
Management Anemia :
Blood Transfusion (erytrocyte) : No Transfusion : HB >10g/dl
Indication Hb <7g/dlHb 7-10 g/dl UnclearHb <8g/dl for age >65th,
Kardiovascular Disease and Pulmonary Disease
Drawbacks of Transfusion
Emergency treatment for acute, severe anaemia.
Usually not given until symptomatic severe anaemia (Hb 8–9 g/dl).
Effects are immediate, but transient and unsustainable.1
Associated with serious side effects.2, 3
(iron overload, immunosuppression, haemolysis, infections).1. Österborg. Med Oncol 1998; 15 (Suppl 1): S47–9
2. Williamson et al. BMJ 1999; 319: 16–193. Jensen et al. Blood 2003; 101: 91–6
Drawbacks of Transfusion
Transfused red blood cells are functionally defective with shorter survival time.
Blood supply becoming less available owing to decreasing donor pool1 and requirement for more stringent processing.2
Inconvenient for both the patient and healthcare professional.
1. Brittenham et al. Hematology (Am Soc Hematol Educ Program) 2001: 422–32 2. Goodnough. Curr Opin Hematol 2001; 8: 405–10
Transfusion - Transmitted Infections
Indonesian Red Cross (Position on Screening):– All blood supply screened
– Major blood-borne diseases screened (HIV, HCV, HBV, Syphylis ).
Historical data in Indonesia: Incidence of HIV and hepatitis C from blood donor have been documented (Syaifullah Noer, 1994).
Up to 60% haemodialysis patients infected Hepatitis C (Haemodialysis center Indonesian multi center study-2005, PIT Pernefri july ’05).
Several Private Hospitals re-screen blood supply to avoid blood-borne diseases (additional cost to patients).
Adverse Events Associated with Blood Transfusions
Incorrect blood/component transfused
Acute transfusion reaction
Delayed transfusion
reaction
Graft vs host disease
Acute lung injury
Post-transfusion purpura
Transfusion-transmitted infections
52%
15%
14%
2%8%
6%
3%
Williamson et al. BMJ 1999; 319: 16–19
ALTERNATIF OF BLOOD TRANSFUSION:
Intravenous iron: when to use it?Intravenous iron: when to use it?
Eritropoetin: when to use it?Eritropoetin: when to use it?
Erythropoietin: Properties
Glycoprotein 34 Kda, regulating erythropoiesis.
Produced in kidney and liver; trace amounts in brain.
Produced primarily by renal peritubular fibroblasts and transported via bloodstream to bone marrow.
Production is upregulated under anaemic or hypoxic conditions.
Binds to specific receptor on erythroid progenitor cells.
Stimulates proliferation, differentiation, and survival of erythroid progenitors.
Fisher. Exp Biol Med 2003; 228: 1–14
Lacombe (1998, 1999) Krantz (1991) Bernaudin (2000)
Decrease in oxygen delivery to the kidneysDecrease in oxygen delivery to the kidneys
Peritubular interstitial cells detect low oxygen levels in the blood
Proerythroblasts in red bone marrow mature more quickly into reticulocytes
More reticulocytes enter circulating blood
Larger number of RBCs in circulation
Increased oxygen delivery to tissues
Increased oxygen delivery to tissues
Return to homeostasis when response brings oxygen delivery to kidneys back to normal
Return to homeostasis when response brings oxygen delivery to kidneys back to normal
EPO
Peritubular interstitial cells secrete EPO into the blood
Mulcahy L. Semin Oncol. 2001;28(2 suppl 8):19-23.
The Physiologic Role of EPO
Initial Categorization of Anemia
Reticulocyte Production Index
> 2% ≤ 2%
Hemolytic Hypoproliferative Ineffective
Smear N Macrocytic/microcytic
No fragments Fragments
LDH N LDH
Bilirubin N - Bilirubin N -
Cellularity Cellularity
Normal morphology Megaloblastoid/reduced hemoglobinization
Anemia of Chronic Disease
Second most common form of anemia, after iron deficiency anemia.
Develops after 1 or 2 months of sustained disease.
Severity proportional to severity of underlying disease.
Huguley CM Jr. In: Hurst J W, ed. Medicine for the Practicing Physician. Woburn, Mass: Butterworth; 1983.
Anemia of Chronic Disease: Etiology
Chronic infections
Noninfectious inflammatory diseases
Renal disease
Neoplastic disorders
Huguley CM Jr. In: Hurst J W, ed. Medicine for the Practicing Physician. Woburn, Mass: Butterworth; 1983.
Anemia of Chronic Disease: Mechanisms
Huguley CM Jr. In: Hurst J W, ed. Medicine for the practicing physician. Woburn, Mass: Butterworth; 1983.
Exact cause of anemia of chronic disease is not fully understood.
However, at least 3 elements are involved– Impaired reutilization of iron– Shortened life span of erythrocytes – Reduced production of EPO
Anemia of Chronic Disease: Laboratory Values
Laboratory Variable ResultHematocrit Low normal to below normal
Hb Low
Reticulocyte count Low to normal
Serum ferritin level Normal to elevated
Serum iron Low
Total iron binding capacity Normal to reduced
Bone marrow iron stores Elevated
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Prevalence of Anemia of Cancer
Chemotherapy-related anemiaAnemia of cancer,
no cancer treatment
Groopman JE, et al. J Natl Cancer Inst. 1999;91:1616-1634. Health Care Industries Association Inc., 1998.
38%
Cancer-Related Anemia, Total Population = 870,000
62%
79%
21%
Hematologic malignancies (n = 2956) Solid tumors (n = 11,071)
36%* anemic at enrollment
66% became anemic during 6-month study
36% received treatment for anemia
Initiated when median Hb = 9.6 g/dL
53%* anemic at enrollment
72% became anemic during 6-month study
47% received treatment for anemia
Initiated when median Hb = 8.8 g/dL
*Anemia defined as Hb <12 g/dL.
Ludwig H, et al. ASCO 2002. Abstract 884.
Prevalence of Anemia in Various Cancer Populations
Activatedimmune system
Anemia
Shortenedsurvival
Anemia-inducing substance
RBCs
ReducedEPO
production
Impairediron
utilization
SuppressedBFU-ECFU-E
TNFErythrophagocytosis
Dyserythropoiesis
IFN-IL-1TNF1-antitrypsin
IFN-IL-1TNF
IL-1 , TNF
Macrophages
Tumor cells
Nowrousian M et al. In: Smyth JF, et al, eds. rhErythropoietin in cancer supportive treatment. New York, NY: Marcel Dekker Inc; 1996:13-34.
Etiology of Cancer-Related Anemia Is Multifactorial
Erythropoietic agents produce a smooth and sustained Hb increase
Österborg. Med Oncol 1998;15(Suppl 1):S47–9Ludwig et al. N Engl J Med 1990;322:1693–9
Erythropoietic agents
Transfusions
0 30 60 90 120 150 180 210
Hb
(g
/dL
)
Days of treatment
8
12
14
10
4
6
transfusion given
Advantages of Epoetin over Transfusion
Epoetin
– can be used for treatment of mild-to-moderate anaemia1, 2
– produces smooth and sustained increase in Hb3
– improves Quality of Life by maintaining higher Hb targets
– is well tolerated
– is more convenient than transfusions
– induces red blood cells that function normally1
1. Ludwig et al. Hematol J 2002; 3: 121–302. Rizzo et al. J Clin Oncol 2002; 20: 4083–1073. Ludwig et al. N Engl J Med 1990; 322: 1693–9
History of Anemia Rx in Oncology
1907-1991– Red cell transfusion only
available therapy
– Focus on severe anemia (Hb < 8 g/dL)
1991-1997– rhuEPO to decrease
transfusion risk
– Focus on prevention/ treatment of severe anemia
1998-2003– ESAs to improve quality
of life
– Focus on mild/moderate anemia (Hb 10-12 g/dL)
2004-2008– Flexible dosing
– Iron
Evidence-based guidelines recommend Hb levels be maintained between Evidence-based guidelines recommend Hb levels be maintained between 11 and 12-13 g/dL during erythropoietic therapy11 and 12-13 g/dL during erythropoietic therapy
Recommendation ASCO/ASH[1] NCCN[2] EORTC[3]
Initiate ESA therapy
Hb ≤ 10 g/dL (clinical decision if Hb
> 10 to ≤ 12 g/dL)
Hb ≤ 11 g/dL Hb 9-11 g/dL(clinical decision if
Hb ≤ 11.9 g/dL)
Goal of treatment Maintain Hb at or near 12 g/dL
Maintain between10-12 g/dL
Target Hb should be 11-13 g/dL
1. Rizzo JD, et al. J Clin Oncol. 2008;26:132-149. 2. NCCN Clinical Practice Guidelines in Oncology. Available at: http://www.nccn.org. Accessed May 27, 2008. 3. Bokemeyer C, et al. Eur J Cancer. 2004;40:2201-2216.
Summary of International Evidence-Based Guidelines
Options for Erythropoietic Therapy
FDA-approved doses Epoetin alfa[1]
– 150 U/kg SQ TIW
– 40,000 U SQ weekly
Darbepoetin alfa[2]
– 2.25 µg/kg SQ weekly
– 500 µg SQ every 3 weeks
Epoetin beta [3]
- 30.000 U SQ weekly
Other commonly used doses Darbepoetin alfa
– 200 µg every 2 weeks
– 300 µg every 3 weeks
1. Epoetin alfa [package insert]. Thousand Oaks, Calif; Amgen Inc: 2008. 2. Darbepoetin alfa [package insert]. Thousand Oaks, Calif; Amgen Inc: 2008
3. Bokemeyer et al. Eur J Cancer 2006, doi:10.1016/j.ejca.2006.10.014
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Iron Supplement forIron Deficiency Anemia
Intravenous iron: when to use it?Intravenous iron: when to use it?
1316
13-16
13-1612-14
Iron values in the development of iron deficiency anaemia
TREATMENT
Therapeutic Trial•Should be via oral route
* Expect - peak reticulocytosis at 1 to 2 week - significant increase in Hb concentration at 3-4 weeks - one-half of Hb deficit corrected at 4-5 weeks - Hb level normal at 2 to 4 months
•Unless there is continued bleeding, absence of these changes indicates that iron deficiency is not cause of anemia. Iron treatment should be stopped and another mechanism sought
Oral Iron Therapy* Dietary sources may not be sufficient for treatment
* Safest, cheapest are oral ferrous salt* Nonenteric coated forms are preferred* Avoid multiple hematinics* Do not give with meals or antacids or inhibitor acid productions* Continue for 12 months after Hb level is normal to replenish iron stores* Daily total 150-200 mg elemental iron in 3 to 4 doses, each 1 h before meals
TREATMENT
Intravenous iron: when to use it?Intravenous iron: when to use it?
Parental Iron Therapy Routine use rarely justifed* Indications are: - malabsorpsi - intolerance to oral iron preparations (colitis, enteritis) - needs in excess of amount that can be given orally - patient uncooperative or unavailable for follow-up
* Continue therapy for 12 months after Hb level is normal, in order to replenish iron stores.* Therapy may be needed indefinitely if bleeding continues.
TREATMENT
Stepwise approach to use of iv iron in pregnancy
Max single dose 200mg / Cumulative 1600mg
Hb >10
Hb 9-10
Hb<9
Oral Fe
Iron sucrose 100 -200mg iv1-2 weekly
IronSucrose200mg 2 weekly
Reports by Breymann over 2000 women treated
IV Iron Therapy and AEs
FDA Medwatch reports (2001-2003) show iron dextran was associated with a 3.4-fold increase in odds of life-threatening AEs[1]
4 separate reports confirm 2- to 8-fold increase in reactions with high molecular-weight dextran compared with low molecular-weight dextran[2-
5]Lif
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AE
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Mill
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1. Chertow GM, et al. Nephrol Dial Transplant. 2006;21:378-382. 2. Fletes R, et al. Am J Kidney Dis. 2001;37:743-749. 3. McCarthy JT, et al. Am J Nephrol. 2000;20:455-462. 4. Mamula P, et al. J Pediatr Gastroenterol Nutr. 2002;34:286-290. 5. Coyne DW, et al. Kidney Int. 2003;63:217-224.
High molecular- weight dextranLow molecular- weight dextran
Ferric gluconateIron sucrose
0
2
4
6
8
10
12
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Update on adverse drug events associated with parenteral iron
Chertow GM et al Nephrology Dialysis Transplantation. 2006 21(2):378-382
Iron sucrose 0.6 per millionSodium ferric gluconate 0.9.per millionLMW iron dextran 3.3 per millionHMW iron dextran 11.3 per million
Treatment Correction
To increased Hb 1 gr/dL Need Fe endogen ± 2,5 mg/bw initial Fe:
– Fe = ( Fe serum x 0,2 x BW) mg, or– Fe = (Hb x 2,5 x BW) mg
Iron Dextran max. 1,5 mg/kgBW/day– Jectofer ® 75 mg/2mL amp.– Injektion 75 mg/deep im
Iron Sucrose– Cosmofer, Venofer ® 100 mg/amp– Cara infusi 100 mg in 100cc NS 1jam
Iron sucrose 125 mg/d iv infusions– Dose (mg) = (15 - patient's hemoglobin in g/dL) ×
(body weight in kg) × 3
Management Options for Anaemia : Summary
Red blood cell transfusion has many disadvantages
Eritropoetin treatment produces smooth and sustained Hb increases and is an alternative treatment option to transfusion
Pada anemia def fe pemberian Iron Supplement harus adequat untuk optimalisasi sebaiknya menggunakan Parenteral Iron therapy
No treatment is not an appropriate option