Anemia I , blok hematologi , fk umsu 2013

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AnemiaAnemiadr Shahrul Rahman, Sp.PD FINASIM

Departemen Ilmu Penyakit DalamFakultas Kedokteran

Universitas Muhammadiyah Sumatera Utara

RBC-The important playersRBC-The important players HemoglobinHemoglobin

• reversibly binds and transports 0reversibly binds and transports 022 from from lungs to tissueslungs to tissues

• 4 globin chains & iron4 globin chains & iron

RBC-The important players (2)RBC-The important players (2) IronIron

• key element in the production of key element in the production of hemoglobinhemoglobin

• absorption is poorabsorption is poor TransferrinTransferrin

• iron transporteriron transporter FerritinFerritin

• iron binder, measure of iron stores, *also iron binder, measure of iron stores, *also acute phase reactant*acute phase reactant*

Sites of Sites of absorption absorption of iron and of iron and vitamin B12vitamin B12

IF secretion

DefinitionsDefinitions Anemia-values of hemoglobin, Anemia-values of hemoglobin,

hematocrit or RBC counts which are hematocrit or RBC counts which are more than 2 standard deviations more than 2 standard deviations below the meanbelow the mean• HGB<13.5 g/dL (men)HGB<13.5 g/dL (men) <12 (women)<12 (women)• HCT<41% (men)HCT<41% (men) <36 (women)<36 (women)

Anemia is a laboratory diagnosisAnemia is a laboratory diagnosis

MenMen WomenWomenHemoglobin Hemoglobin (g/dL)(g/dL) 14-17.414-17.4 12.3-15.312.3-15.3Hematocrit Hematocrit (%)(%) 42-50%42-50% 36-44%36-44%RBC Count RBC Count (10(1066/mm/mm33)) 4.5-5.94.5-5.9 4.1-5.14.1-5.1ReticulocytesReticulocytes 1.6 ± 0.5%1.6 ± 0.5% 1.4 1.4 ±± 0.5% 0.5%WBC WBC (cells/mm(cells/mm33)) ~4,000-11,000~4,000-11,000MCV MCV (fL)(fL) 80-96 80-96 MCH MCH (pg/RBC)(pg/RBC) 30.4 30.4 ±± 2.8 2.8MCHC MCHC (g/dL of RBC)(g/dL of RBC) 34.4 34.4 ±± 1.1 1.1RDW RDW (%)(%) 11.7-14.5%11.7-14.5%

Erythrocytes - less informative index Erythrocytes - less informative index of anemia than the level of of anemia than the level of hemoglobin therefore, in the hemoglobin therefore, in the general practice the basic criterion general practice the basic criterion of severity is precisely Hb: of severity is precisely Hb:

Light degree of anemia - Hb 11-9 Light degree of anemia - Hb 11-9 g/dl, g/dl,

The average degree of severity - The average degree of severity - Hb 9-7 g/dl, Hb 9-7 g/dl,

Severe anemia - Hb below 7 g/dlSevere anemia - Hb below 7 g/dl

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Anemia adalah suatu keadaan dimana Anemia adalah suatu keadaan dimana kadar hemoglobin lebih rendah dari kadar hemoglobin lebih rendah dari kadar hemoglobin terendah pada umur kadar hemoglobin terendah pada umur dan jenis kelaminnya.dan jenis kelaminnya.

Pada wanita hamil nilainya lebih rendah Pada wanita hamil nilainya lebih rendah dari wanita tidak hamil.dari wanita tidak hamil.

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Hemoglobin normal:Hemoglobin normal:WHO Group of Experts on Nutritional Anaemias, menentukan Hb WHO Group of Experts on Nutritional Anaemias, menentukan Hb

normal berdasarkan umur dan jenis kelamin:normal berdasarkan umur dan jenis kelamin:

KelompokKelompok Kadar Hb Kadar Hb

• Anak-anak 6 bln-6 thnAnak-anak 6 bln-6 thn 11 g/dl11 g/dl• Anak-anak 6-14 thnAnak-anak 6-14 thn 12 g/dl12 g/dl• Dewasa laki-lakiDewasa laki-laki 13 g/dl13 g/dl• Dewasa wanita tidak hamilDewasa wanita tidak hamil 12 g/dl12 g/dl• Dewasa wanita hamilDewasa wanita hamil 11 g/dl11 g/dl

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Tanda-tanda anemia:Tanda-tanda anemia: A. Tanda-tanda umum :A. Tanda-tanda umum :

Pucat.Pucat. Takikardia.Takikardia. Tekanan nadi yang lebar.Tekanan nadi yang lebar. Tanda hiperdinamik di precordial.Tanda hiperdinamik di precordial. Desah sistolik didaerah pulmoner.Desah sistolik didaerah pulmoner.

B. Tanda-tanda khas utk etiologi tertentu:B. Tanda-tanda khas utk etiologi tertentu:• 1. Koagulopati, trombositopenia dan pansitopenia: 1. Koagulopati, trombositopenia dan pansitopenia:

ptekie, perdarahan retina, mudah lembam.ptekie, perdarahan retina, mudah lembam.• 2. Anemia karena penyakit kronis : deformitas 2. Anemia karena penyakit kronis : deformitas

sendi yang berat.sendi yang berat.

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Gejala anemia:Gejala anemia: A. Anemia akut:A. Anemia akut:

• 1. Serebral1. Serebral: oyong kalau berdiri, vertigo, tinnitus, : oyong kalau berdiri, vertigo, tinnitus, sinkope, “bintik didepan mata”.sinkope, “bintik didepan mata”.

• 2. Sirkulasi2. Sirkulasi: palpitasi, sesak nafas kalau bekerja, lelah, : palpitasi, sesak nafas kalau bekerja, lelah, angina, klaudikasio.angina, klaudikasio.

• 3. Demam3. Demam : tanda infeksi, bisa juga ok proses penyakit : tanda infeksi, bisa juga ok proses penyakit darah.darah.

• 4. Lain-lain4. Lain-lain : hiperse : hipersennsitif thd dingin, anorexia, gangguan sitif thd dingin, anorexia, gangguan pencernaan, haid tidak teratur, impotensi, libido hilang.pencernaan, haid tidak teratur, impotensi, libido hilang.

B. Anemia kronik:B. Anemia kronik:• Tubuh dapat menyesuaikan dengan anemia yang terjadi Tubuh dapat menyesuaikan dengan anemia yang terjadi

lambatlambat• Gejalanya ringan, kadang-kadang hanya rasa lelah.Gejalanya ringan, kadang-kadang hanya rasa lelah.

Presentation/historyPresentation/history Mild anemia:Mild anemia:

• few or no symptoms; may be discovered few or no symptoms; may be discovered accidentally on lab testaccidentally on lab test

May complain of:May complain of:• Fatigue, decr. exercise tolerance, SOB, Fatigue, decr. exercise tolerance, SOB,

palpitations, CP, lightheadedness on arisingpalpitations, CP, lightheadedness on arising• Sore tongue (glossitis), cracking mouth corners Sore tongue (glossitis), cracking mouth corners

(angular cheilitis), peripheral paresthesias (angular cheilitis), peripheral paresthesias (numb toes, etc.)(numb toes, etc.)

Hx:Hx:• EtOH use, FH anemia, pica, vegetarian diet, EtOH use, FH anemia, pica, vegetarian diet,

melena/hematochezia, malabsorption melena/hematochezia, malabsorption syndromes, Crohn’s diseasesyndromes, Crohn’s disease

Evaluation of the Patient Evaluation of the Patient HISTORYHISTORY

• Is the patient bleeding?Is the patient bleeding? Actively? In past?Actively? In past?

• Is there evidence for increased RBC Is there evidence for increased RBC destruction?destruction?

• Is the bone marrow suppressed?Is the bone marrow suppressed?• Is the patient nutritionally deficient? Pica?Is the patient nutritionally deficient? Pica?• PMH including medication review, toxin PMH including medication review, toxin

exposureexposure

Evaluation of the Patient (2)Evaluation of the Patient (2)REVIW OF SYMPTOMSREVIW OF SYMPTOMS Decreased oxygen delivery to tissuesDecreased oxygen delivery to tissues

• Exertional dyspneaExertional dyspnea• Dyspnea at restDyspnea at rest• FatigueFatigue• Signs and symptoms of hyperdynamic stateSigns and symptoms of hyperdynamic state

Bounding pulsesBounding pulses PalpitationsPalpitations

• Life threatening: heart failure, angina, myocardial Life threatening: heart failure, angina, myocardial infarctioninfarction

HypovolemiaHypovolemia• Fatiguablitiy, postural dizziness, lethargy, hypotension, Fatiguablitiy, postural dizziness, lethargy, hypotension,

shock and deathshock and death

Evaluation of the Patient (3)Evaluation of the Patient (3)PHYSICAL EXAMPHYSICAL EXAM

••Stable or Unstable?Stable or Unstable?-ABCs-ABCs-Vitals-Vitals••PallorPallor••JaundiceJaundice-hemolysis-hemolysis••LymphadenopathyLymphadenopathy••HepatosplenomegallyHepatosplenomegally••Bony PainBony Pain••PetechiaePetechiae••Rectal-? Occult bloodRectal-? Occult blood

Anemia: Special PopulationsAnemia: Special Populations Higher Hb/HCT:Higher Hb/HCT:

• Patients living at high altitudesPatients living at high altitudes• Smokers and patients living in air pollution Smokers and patients living in air pollution

areasareas• Endurance athletes have increased HCTEndurance athletes have increased HCT

Lower Hb/HCT:Lower Hb/HCT:• African-Americans have 0.5 to 1 g/dl lower Hb African-Americans have 0.5 to 1 g/dl lower Hb

than do Caucasiansthan do Caucasians• Elderly (slowed erythropoiesis)Elderly (slowed erythropoiesis)• Pregnant women (hemodilution)Pregnant women (hemodilution)

Differential diagnosisDifferential diagnosis

Consider:Consider:• AnemiaAnemia• HypothyroidismHypothyroidism• DepressionDepression• Cardiac (congestive heart failure, aortic Cardiac (congestive heart failure, aortic

stenosis)stenosis)• Pulmonary causes of SOB/DOEPulmonary causes of SOB/DOE• Chronic fatigue syndrome, othersChronic fatigue syndrome, others

Physical examinationPhysical examination Pallor (may be jaundiced– think hemolytic)Pallor (may be jaundiced– think hemolytic) Tachycardia, bounding pulsesTachycardia, bounding pulses Systolic flow murmurSystolic flow murmur GlossitisGlossitis Angular cheilosisAngular cheilosis Decreased vibratory sense/ joint position Decreased vibratory sense/ joint position

sense (B12 deficiency, w/ or w/o hematologic sense (B12 deficiency, w/ or w/o hematologic changes)changes)

Ataxia, positive Romberg sign (severe Ataxia, positive Romberg sign (severe B12/folate deficiency)B12/folate deficiency)

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Pemeriksaan awal anemiaPemeriksaan awal anemia::

A. Kuantitatif:A. Kuantitatif:• HbHb• HtHt• Hitung eritrositHitung eritrosit• MCHMCH• MCVMCV• MCHCMCHC• Hitung retikulositHitung retikulosit• Hitung lekositHitung lekosit• Hitung trombositHitung trombosit• LED.LED.

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Pemeriksaan awal anemia:Pemeriksaan awal anemia:

Kualitatif:Kualitatif:• Gambaran morfologi darah tepi dg pengecatan Gambaran morfologi darah tepi dg pengecatan

Wright: hipokromik, polikromasia, normokromik.Wright: hipokromik, polikromasia, normokromik.• Besar sel : mikrositer, makrositer, anisositosis.Besar sel : mikrositer, makrositer, anisositosis.• Bentuk sel : poikilositosis, sferositosis, sel oval dan Bentuk sel : poikilositosis, sferositosis, sel oval dan

tear drops, fragmented cells, ghost cells, dll.tear drops, fragmented cells, ghost cells, dll.• Badan-badan intraseluler: eritrosit berinti, badan Badan-badan intraseluler: eritrosit berinti, badan

Howell-Jolly, siderosit, badan Papenheimer, badan Howell-Jolly, siderosit, badan Papenheimer, badan Heinz dan malaria.Heinz dan malaria.

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Pemeriksaan lanjutan:Pemeriksaan lanjutan: BilirubinBilirubin Besi serum (SI)Besi serum (SI) TIBCTIBC TransferrinTransferrin BMPBMP Hemoglobin elektroforesisHemoglobin elektroforesis Coomb’s testCoomb’s test G6PDG6PD Vit B12Vit B12 Asam folatAsam folat

AnemiaAnemia

DefinitionDefinition

TypesTypes

C/PC/P

A-Dyshaemopoietic anaemia: (Decreased

maturation due to deficiency of maturation

factors essential for erythropoiesis).

Mineral deficiency: iron, zinc, selenium, cupper

Vitamin deficiency: B12, folic acid ; Vit C&

pyridoxine

Hormonal deficiency: anaemia of renal

diseases, pituitary, thyroid or suprarenal

deficiency.

Protein deficiency : high class

AETIOLOGICAL CLASSIFICATIONI- Decrease red cell production.

AnemiaAnemia

TypesTypes

B- Hypoproliferative anaemias (BM failure ):B- Hypoproliferative anaemias (BM failure ):

Aplastic anaemia.Aplastic anaemia.

Myelophthisic anaemia (BM replacement Myelophthisic anaemia (BM replacement

anaemia).anaemia).

Anaemia of chronic diseases.Anaemia of chronic diseases.

AETIOLOGICAL CLASSIFICATIONAETIOLOGICAL CLASSIFICATIONI- Decrease red cell production.I- Decrease red cell production.

AnemiaAnemia

TypesTypes

II- Haemolytic anaemia:II- Haemolytic anaemia:

Short life-span of RBCsShort life-span of RBCs

III- Acute post haemorrhagic anaemia:III- Acute post haemorrhagic anaemia:

Loss of RBCsLoss of RBCs

IV- Mixed anaemia.IV- Mixed anaemia.

eg. Megalobastosis associated with haemolysis eg. Megalobastosis associated with haemolysis

V: Dilutconal anaemia:V: Dilutconal anaemia: (raised plasma volume) (raised plasma volume)

PregnancyPregnancy

Oliguric RFOliguric RF

Volume-overloadVolume-overload

AETIOLOGICAL CLASSIFICATIONAETIOLOGICAL CLASSIFICATION

AnemiaAnemia

TypesTypes

MORPHOLOGICAL CLASSIFICATION

A. Microcytic-hypochromic anaemias:

Thalassaemia.

Iron deficiency anaemia.

Anaemia of chronic disease.

Sideroblastic anaemia: Hereditary

Chronic lead poisoning.

AnemiaAnemia

TypesTypes

MORPHOLOGICAL CLASSIFICATION

B-Normocytic-normochromic anaemias:

Acute post –haemorrhagic anaemia.

Hemolytic anaemia.

Aplastic anaemia.

Myelophthisic anaemia.

Anaemia of chronic diseases .

AnemiaAnemia

TypesTypes

MORPHOLOGICAL CLASSIFICATION

C- Macrocytic- normochromic anaemias:

Megaloblastic anaemia.

Marked reticulocytosis.

Myelodysplastic syndromes.

Myxoedema.

Acquired sideroblastic anaemia.

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Klasifikasi klinis:Klasifikasi klinis:

1. Anemia ok kehilangan darah banyak.1. Anemia ok kehilangan darah banyak.

2. Anemia ok berkurangnya produksi 2. Anemia ok berkurangnya produksi eritrosit.eritrosit.

3. Anemia ok meningkatnya destruksi 3. Anemia ok meningkatnya destruksi eritrosit.eritrosit.

4. Anemia ok berkurangnya produksi dan 4. Anemia ok berkurangnya produksi dan meningkatnya destruksi eritrosit.meningkatnya destruksi eritrosit.

Differential DiagnosisDifferential Diagnosis Classification by Pathophysiology Classification by Pathophysiology

• Blood LossBlood Loss• Decreased ProductionDecreased Production• Increased Destruction Increased Destruction

Classification by MorphologyClassification by Morphology• NormocyticNormocytic• MicrocyticMicrocytic• MacrocyticMacrocytic

LabsLabs For all: CBC, reticulocyte count, ± For all: CBC, reticulocyte count, ±

peripheral smearperipheral smear For some:For some:

• B12, folate, hemoglobin electrophoresisB12, folate, hemoglobin electrophoresis• Bone marrow aspirate to assess possible Bone marrow aspirate to assess possible

defective hematopoiesis defective hematopoiesis • Other labs to assess other differential Other labs to assess other differential

diagnoses (e.g. thyroid function tests, diagnoses (e.g. thyroid function tests, etc.)etc.)

Macrocytic AnemiaMacrocytic Anemia MCV > 100MCV > 100 Megaloblastic:AbnormaMegaloblastic:Abnorma

lities in nucleic acid lities in nucleic acid metabolismmetabolism• B12, FolateB12, Folate

Non-Non-megaloblastic:Abnormamegaloblastic:Abnormal RBC maturationl RBC maturation• MyelodysplasiaMyelodysplasia

ETOH, liver dz, ETOH, liver dz, hypothryroidism, hypothryroidism, chemotherapy/drugschemotherapy/drugs

Microcytic AnemiaMicrocytic Anemia MCV <80MCV <80 Reduced iron Reduced iron

availabilityavailability Reduced heme Reduced heme

synthesissynthesis Reduced globin Reduced globin

productionproduction

Microcytic AnemiaMicrocytic AnemiaREDUCED IRON AVAILABILTYREDUCED IRON AVAILABILTY

Iron DeficiencyIron Deficiency• Deficient Diet/AbsorptionDeficient Diet/Absorption• Increased RequirementsIncreased Requirements• Blood LossBlood Loss• Iron SequestrationIron Sequestration

Anemia of Chronic DiseaseAnemia of Chronic Disease• Low serum iron, low TIBC, normal serum Low serum iron, low TIBC, normal serum

ferritinferritin• MANY!! MANY!!

Chronic infection, inflammation, cancer, liver diseaseChronic infection, inflammation, cancer, liver disease

Microcytic AnemiaMicrocytic AnemiaREDUCED HEME SYNTHESISREDUCED HEME SYNTHESIS

Lead poisoningLead poisoning Acquired or Acquired or

congenital congenital sideroblastic sideroblastic anemiaanemia

Characteristic Characteristic smear finding: smear finding: Basophylic Basophylic stipplingstippling

Microcytic AnemiaMicrocytic AnemiaREDUCED GLOBIN PRODUCTIONREDUCED GLOBIN PRODUCTION

ThalassemiasThalassemias Smear Smear

CharacteristicsCharacteristics• HypochromiaHypochromia• MicrocytosisMicrocytosis• Target CellsTarget Cells• Tear DropsTear Drops

Ineffective erythropoiesisIneffective erythropoiesis All with normal/low reticulocyte All with normal/low reticulocyte

countcount

• Microcytic: think FeMicrocytic: think Fe++++ deficiency deficiency • Macrocytic: think B12/folate deficiencyMacrocytic: think B12/folate deficiency• Normocytic: think anemia of chronic Normocytic: think anemia of chronic

disease, marrow problems, or other disease, marrow problems, or other problemsproblems

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PembagianPembagian anemia:anemia: Anemia defisiensi besi.Anemia defisiensi besi. Anemia aplastik.Anemia aplastik. Anemia hemolitik.Anemia hemolitik. Anemia karena penyakit kronik.Anemia karena penyakit kronik. Anemia megaloblastik.Anemia megaloblastik. Anemia karena kanker.Anemia karena kanker.

Decreased ProductionDecreased ProductionNUTRITIONAL DEFICIENCYNUTRITIONAL DEFICIENCY

IronIron B12B12 FolateFolate

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Anemia defisiensi Anemia defisiensi besibesi

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Anemia defisiensi besi.Anemia defisiensi besi. Tingkatannya:Tingkatannya:

• 1.deplesi besi: cadangan besi berkurang atau 1.deplesi besi: cadangan besi berkurang atau tidak ada sama sekali, belum anemia.tidak ada sama sekali, belum anemia.

• 2.defisiensi besi: cadangan besi berkurang 2.defisiensi besi: cadangan besi berkurang atau tidak ada + rendahnya besi serum dan atau tidak ada + rendahnya besi serum dan jenuh transferin, belum anemia.jenuh transferin, belum anemia.

• 3.anemia defisiensi besi: cadangan besi 3.anemia defisiensi besi: cadangan besi berkurang atau tidak ada + rendahnya besi berkurang atau tidak ada + rendahnya besi serum dan jenuh transferin + Hb rendah dan serum dan jenuh transferin + Hb rendah dan Ht rendah. Sudah anemia.Ht rendah. Sudah anemia.

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Penyebab anemia defisiensi besi.Penyebab anemia defisiensi besi. Perdarahan: Perdarahan:

• sal.urogenital, sal.urogenital, • sal.pencernaan, sal.pencernaan, • sal.pernafasan.sal.pernafasan.

Kebutuhan meningkat: Kebutuhan meningkat: • prematur, prematur, • hamil, hamil, • haid,haid,• masa pertumbuhan.masa pertumbuhan.

Malabsorpsi.Malabsorpsi. Makanan kurang bergizi.Makanan kurang bergizi.

FeFe++++ deficiency anemia deficiency anemia Most commonly due to chronic Most commonly due to chronic

bleeding and erythropoiesis limited by bleeding and erythropoiesis limited by iron stores that have been depletediron stores that have been depleted

May be dietary (pica, lack of meat/ May be dietary (pica, lack of meat/ vegetables, other)vegetables, other)

Iron balance is very close in Iron balance is very close in menstruating women, so Femenstruating women, so Fe++++ deficiency is not uncommon with no deficiency is not uncommon with no other source of bleedingother source of bleeding

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Gambaran klinis:Gambaran klinis:

Keluhan: Keluhan: • pucat,pucat,• lemah, lemah, • nyeri menelan,nyeri menelan,• pika, pika, • nyeri epigastrik.nyeri epigastrik.

Tanda-tanda: Tanda-tanda: • anemia, anemia, • glositis, glositis, • atrofi papil lidah,atrofi papil lidah,• koilonikia, koilonikia, • keluhan penyakit dasarnya.keluhan penyakit dasarnya.

Physical Manifestation : “Spoon Physical Manifestation : “Spoon Nails” in Iron Deficiency Nails” in Iron Deficiency

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PemeriksaanPemeriksaan

Anamnesis dan pemeriksaan fisik.Anamnesis dan pemeriksaan fisik. Laboratorium:Laboratorium:

• Anemia mikrositer-hipokromik.Anemia mikrositer-hipokromik.• SI menurun, TIBC meningkatSI menurun, TIBC meningkat• SI/TIBC < 16 %SI/TIBC < 16 %• Hemosiderin sstl (-)Hemosiderin sstl (-)• Kadar feritin < 12 Kadar feritin < 12 g/lg/l

LabsLabs Iron and ferritin will be lowIron and ferritin will be low TIBC (total iron binding capacity) will be TIBC (total iron binding capacity) will be

high, since iron stores are not saturating high, since iron stores are not saturating their binding sites on transferrintheir binding sites on transferrin

Reduced RBC counts (definition of anemia)Reduced RBC counts (definition of anemia) Microcytosis & hypochromia are hallmarks, Microcytosis & hypochromia are hallmarks,

but early Febut early Fe++++ may be normocytic (± may be normocytic (± hypochromic)hypochromic)

Usually, MCH and MCHC will both be low Usually, MCH and MCHC will both be low (whereas in macrocytic anemia, the MCH (whereas in macrocytic anemia, the MCH may be normal while the MCHC is low, may be normal while the MCHC is low, because of the larger cell size)because of the larger cell size)

LabsLabs Most practitioners would agree that if Most practitioners would agree that if

a patient has microcytic hypochromic a patient has microcytic hypochromic anemia with a low reticulocyte count, anemia with a low reticulocyte count, it would be reasonable to use a trial it would be reasonable to use a trial of FeSOof FeSO44 to diagnose to diagnose

5-10 days after initiating therapy, a 5-10 days after initiating therapy, a robust rise in reticulocytes confirms robust rise in reticulocytes confirms the diagnosisthe diagnosis

LABORATORY TEST

INTERPRETATIONHypochromic &

microcytic anaemia

Absent Increased

Ringed sideroblasts

NormalAbnormalNormal

Peripheral smear

Iron(Bone

marrow)

Haemoglobin electrophoresi

s

Diagnosis Iron

deficiency

anaemia

Thalassaemia

haemoglobino-pathies

LABORATORY DIAGNOSIS OF HYPOCHROMIC MICROCYTIC ANAEMIA

Sideroblastic anaemia

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Pengobatan:Pengobatan:

11. Atasi penyakit dasarnya.. Atasi penyakit dasarnya. 2. Preparat besi oral/parenteral dan lanjutkan 3 2. Preparat besi oral/parenteral dan lanjutkan 3

bulan setelah Hb normal.bulan setelah Hb normal.

TreatmentTreatment Iron, oral in most cases, parenteral in Iron, oral in most cases, parenteral in

cases of malabsorptioncases of malabsorption All forms of iron are constipating; the All forms of iron are constipating; the

amount of constipation directly relates to amount of constipation directly relates to the amount of elemental iron deliveredthe amount of elemental iron delivered• If intolerant of FeSOIf intolerant of FeSO44 (cheapest), reduce the (cheapest), reduce the

dose, rather than switching formdose, rather than switching form• Start 325 mg QD, increase slowly to TIDStart 325 mg QD, increase slowly to TID

Follow up the cause of the iron Follow up the cause of the iron deficiency!deficiency!

Treatment of Iron Deficiency AnemiaTreatment of Iron Deficiency Anemia Diet: meat, liver, yeast, fishDiet: meat, liver, yeast, fish Oral preparations: recovery rate Hb Oral preparations: recovery rate Hb

does not differ from parenteral does not differ from parenteral introduction, side effects are less, introduction, side effects are less, excessive introduction does not lead excessive introduction does not lead to hemosiderosis. to hemosiderosis.

- Dosage : 1 hour prior to the meal- Dosage : 1 hour prior to the meal in the evening time (absorption in the evening time (absorption

increase in the second-half of a day) increase in the second-half of a day)

During first 3 days - half dose of the selected During first 3 days - half dose of the selected preparation. preparation.

Possibilities : dark colour of stool and transitory Possibilities : dark colour of stool and transitory dyspeptic disorders (nausea, diarrhea or watery dyspeptic disorders (nausea, diarrhea or watery stool) stool)

Check analysis of the blood: in 7-10 days – Check analysis of the blood: in 7-10 days – reticulocyte reaction; 4 weeks - increase Hb and reticulocyte reaction; 4 weeks - increase Hb and HtHt

During the normalization of the indices of the During the normalization of the indices of the blood – reduce the dose of preparationblood – reduce the dose of preparation

Parenteral Introduction of IronParenteral Introduction of Iron in exceptional casesin exceptional cases in severe iron deficiency anemiain severe iron deficiency anemia rendering to special aidrendering to special aid intolerance of oral preparations (after repeated intolerance of oral preparations (after repeated

replacement and reduction in the dose)replacement and reduction in the dose) diseases of gastro-intestinal tractdiseases of gastro-intestinal tract syndrome of the disrupted intestinal absorbtionsyndrome of the disrupted intestinal absorbtion after the extensive resection of the small after the extensive resection of the small

intestineintestine continuous blood losscontinuous blood loss not compensated by oral method not compensated by oral method

Complications of Parenteral IntroductionComplications of Parenteral Introduction

Local reactions (pains, phlebitis)Local reactions (pains, phlebitis) General reactions (anaphylaxis, fever, General reactions (anaphylaxis, fever,

head and articulate pains, vomiting, head and articulate pains, vomiting, rash, bronchospasm). rash, bronchospasm).

Preparations: Preparations: Venofer - for the intravenous Venofer - for the intravenous

introduction,introduction,Maltofer, Ferrum-Lek - intramuscularMaltofer, Ferrum-Lek - intramuscular

Overdose of IronOverdose of Iron

In the first 6-8 hours - epigastral pains, In the first 6-8 hours - epigastral pains, nausea, vomiting (including with the blood), nausea, vomiting (including with the blood), diarrhea, pallor, sleepiness, acrocyanosis)diarrhea, pallor, sleepiness, acrocyanosis)

For 12-24 hours - metabolic acidosis, For 12-24 hours - metabolic acidosis, leukocytosis, there can be spasms, coma, leukocytosis, there can be spasms, coma, after 2-4 days - necroses of the liver and after 2-4 days - necroses of the liver and kidneys.kidneys.

Treatment: emetic means, stomach Treatment: emetic means, stomach lavage, the method of milk with the egg lavage, the method of milk with the egg white, Deferoksamin, Desferal, symptomatic white, Deferoksamin, Desferal, symptomatic therapy. therapy.

Iron Overload SyndromeIron Overload Syndrome ! ! Human does not have special mechanism of the Human does not have special mechanism of the

excretion of iron! Its excessive introduction leads to excretion of iron! Its excessive introduction leads to hemosiderosis. Clinical manifestations: Gradual hemosiderosis. Clinical manifestations: Gradual increase of the dimensions of the liver, spleen, increase of the dimensions of the liver, spleen, cardiopathy, suprarenal insufficiency, diabetes cardiopathy, suprarenal insufficiency, diabetes mellitus, eunuchoidism.mellitus, eunuchoidism.

Laboratory signs: Laboratory signs:

Increase in serum iron (more than 30 mmol/liter), Increase in serum iron (more than 30 mmol/liter), percentage of saturation transferrin by iron it is more percentage of saturation transferrin by iron it is more than 45%, ferritin of serum it is more than 1000 than 45%, ferritin of serum it is more than 1000 ng/ml; Test with desferalom; + the specific signs of ng/ml; Test with desferalom; + the specific signs of the defect of internal organs (ECG, level biochemical the defect of internal organs (ECG, level biochemical index of functions of the liver, the level of hormones index of functions of the liver, the level of hormones and others) and others)

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Anemia megaloblastikAnemia megaloblastik Akibat gangguan sistesis DNA dan Akibat gangguan sistesis DNA dan

ditandai dgn sel megaloblastikditandai dgn sel megaloblastik Pada sel yang perubahannya cepat Pada sel yang perubahannya cepat

(sel hemopoetik, epitel (sel hemopoetik, epitel gastrointestinal)gastrointestinal)

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Klasifikasi anemia megaloblastikKlasifikasi anemia megaloblastikDefisiensi kobalaminDefisiensi kobalamin

Defisiensi asam folatDefisiensi asam folat

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Defisiensi kobalaminDefisiensi kobalaminanemia pernisiosa, anemia pernisiosa, paska gastrektomipaska gastrektomiorganisme intestinsalorganisme intestinsalabnormalitas ileumabnormalitas ileumnitrous oxidenitrous oxide

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History ofHistory ofthe Management of Anemiathe Management of Anemia

• Risks of transfusion Risks of transfusion infection infection

• Transfusion guidelinesTransfusion guidelines– Moderate/severe anemiaModerate/severe anemia– Hb Hb 8 g/dL8 g/dL

• Hb 10 g/dL• Hb 8 g/dL

• Continued transfusion risks• Epoetin alfa• QOL assessment tools• Relationship of anemia to

fatigue

• Before 1980

• 1980s

• 1990s and beyond

Abels (1992) Glaspy 1997) Demetri 1998 Cleland (1999)

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Defisiensi asam folatDefisiensi asam folatasupan tidak memadaiasupan tidak memadaikebutuhan meningkatkebutuhan meningkatmalabsorbsimalabsorbsiobat-obatan ;obat-obatan ;-penghambat sintesa DNA langsung-penghambat sintesa DNA langsung

(analog purine, analog pirimidin)(analog purine, analog pirimidin)-antagonis asam folat-antagonis asam folat-antikonvulsan-antikonvulsan

Macrocytic anemia with ineffective Macrocytic anemia with ineffective erythropoiesiserythropoiesis

Low/normal reticulocyte count, Low/normal reticulocyte count, macrocytosismacrocytosis

Most common is folate/B12 deficiencyMost common is folate/B12 deficiency• Dietary: folate far more common, B12 may Dietary: folate far more common, B12 may

occur in strict vegansoccur in strict vegans• Pernicious anemia: lack of B12 protection in Pernicious anemia: lack of B12 protection in

stomach and gutstomach and gut• Poor uptake in terminal ileum (e.g. in Crohn’s Poor uptake in terminal ileum (e.g. in Crohn’s

disease)disease)• B12 and folate are essential for cell maturation B12 and folate are essential for cell maturation

and DNA synthesis, erythrocytes end up large, and DNA synthesis, erythrocytes end up large, usually normochromic, since iron is not lackingusually normochromic, since iron is not lacking

Other: drugs, toxins, myelodysplasia Other: drugs, toxins, myelodysplasia

Folate deficiencyFolate deficiency Folate intake is usually dietary, and Folate intake is usually dietary, and

may be deficient with low fresh fruit may be deficient with low fresh fruit & vegetable intake& vegetable intake

Folate supplementation of bread Folate supplementation of bread prevents neural tube defects in prevents neural tube defects in pregnancypregnancy

PE may include neurological effects if PE may include neurological effects if severe deficiencysevere deficiency

B12 deficiencyB12 deficiency Less common, usually caused by absorption Less common, usually caused by absorption

problems, rather than dietary deficiencyproblems, rather than dietary deficiency B12 needs Intrinsic Factor for protection from B12 needs Intrinsic Factor for protection from

degradation in gutdegradation in gut• Produced by parietal cells of stomach, protects Produced by parietal cells of stomach, protects

through gut for uptake at terminal ileumthrough gut for uptake at terminal ileum• Pernicious anemia from immune attack of IF Pernicious anemia from immune attack of IF

productionproduction• EtOH-related gastritis can affect IF production, and EtOH-related gastritis can affect IF production, and

liver disease may also contribute to macrocytosisliver disease may also contribute to macrocytosis

Neurological effectsNeurological effects Deficiency results in damage to Deficiency results in damage to

dorsal columns (sensory) and lateral dorsal columns (sensory) and lateral columns (motor) of spinal cordcolumns (motor) of spinal cord

Decreased vibration sense and Decreased vibration sense and position sense of joints detectable, position sense of joints detectable, and may affect gait, etc.and may affect gait, etc.

May have positive Romberg’s testMay have positive Romberg’s test Severe effects may include ataxia Severe effects may include ataxia

and dementiaand dementia

LabsLabs Folate and B12 levelsFolate and B12 levels Schilling test may be useful to establish Schilling test may be useful to establish

etiology of B12 deficiencyetiology of B12 deficiency• Assesses radioactive B12 absorption with and Assesses radioactive B12 absorption with and

without exogenous IFwithout exogenous IF Other tests if pernicious anemia is Other tests if pernicious anemia is

suspectedsuspected• Anti- parietal cell antibodies, anti-IF antibodiesAnti- parietal cell antibodies, anti-IF antibodies• Secondary causes of poor absorption should be Secondary causes of poor absorption should be

sought (gastritis, ileal problems, ETOH, etc.)sought (gastritis, ileal problems, ETOH, etc.)

LABORATORY DIAGNOSIS OF MACROCYTIC ANAEMIALABORATORY

TESTINTERPRETATIO

NMacrocytic anaemia

Megaloblastic changes

No megaloblastic

changes

Low LowHigh

Possible liver disease

(evaluate liver function

tests)

Probable haemolytic

anaemia (continue workup)

Responds to folic

acid

Responds to vit

B12

Peripheral smear

Bone marrow

examination

Reticulocyte count

Therapeutic response

Diagnosis

Vit B12 deficiency (determine if dietary

or abnormal

absorption

Folic acid

deficiency

Treatment– supplementationTreatment– supplementation Do NOT correct folate levels unless B12 is OKDo NOT correct folate levels unless B12 is OK

• Correction of folate deficiency will correct Correction of folate deficiency will correct hematologic abnormalities without correcting hematologic abnormalities without correcting neurological abnormalitiesneurological abnormalities

• Check B12 and correct firstCheck B12 and correct first B12 usually 1000 mg I.M. q monthB12 usually 1000 mg I.M. q month

• B12 stores take a long time to deplete; missed B12 stores take a long time to deplete; missed doses are not usually a problemdoses are not usually a problem

• Oral supplementation is gaining support; usually Oral supplementation is gaining support; usually effective in pernicious anemia (1-2 mg PO QD)effective in pernicious anemia (1-2 mg PO QD)

Reticulocyte count should respond in 1 wkReticulocyte count should respond in 1 wk

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DiagnosisDiagnosis

Klinis Klinis Pemeriksaan penunjangPemeriksaan penunjang-darah perifer-darah perifer-MCV>100 fl, -MCV>100 fl, -MCV>110 fl -MCV>110 fl sangkaan kuat sangkaan kuat-defisiensi kadar kobalamin < 200 pg/ml (300-900 -defisiensi kadar kobalamin < 200 pg/ml (300-900 pg/ml)pg/ml)-defisiensi kadar asam folat <4 ng/ml (6-20 ng/ml)-defisiensi kadar asam folat <4 ng/ml (6-20 ng/ml)

Tes schilling Tes schilling penentuan patogenesis penentuan patogenesis

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DeficiencyDeficiency Folic acidFolic acid Serum Serum vit. Bvit. B1212

SerumSerum RBCRBC

Folic acidFolic acid

Vit BVit B1212

Folic acid & BFolic acid & B1212

N /N /

NN

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PenatalaksanaanPenatalaksanaan

Atasi penyebabAtasi penyebabDefisiensi Kobalamin :Defisiensi Kobalamin :Kobalamin 1000 ug IM tiap minggu sd 8 minggu, Kobalamin 1000 ug IM tiap minggu sd 8 minggu, lanjutkan kobalamin 1000 ug IM tiap bulanlanjutkan kobalamin 1000 ug IM tiap bulanVit B12 2 mg perhariVit B12 2 mg perhari

Evaluasi retikositosis pada hari ke 4-5 puncaknya Evaluasi retikositosis pada hari ke 4-5 puncaknya pada hari ke 7.pada hari ke 7.

Defisiensi asam folatDefisiensi asam folatasam folat 1 mg per hari per-oral (maksimal 5 mg asam folat 1 mg per hari per-oral (maksimal 5 mg perhari), pemberian selama 1 sd 2 bulan atau perhari), pemberian selama 1 sd 2 bulan atau sampai keadaan terkoreksi.sampai keadaan terkoreksi.

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THERAPEUTIC TRIALS• Usual diet

0,2 mg folic acid oral

1 weekreticulocyte response

+ - + 1-2 g

vit B12

reticulocyte response

Thank YouThank You