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Anemia

Dr. dr. Shahrul Rahman, Sp.PD, FINA

Departemen Ilmu Penyakit Dalam


Fakultas Kedokteran
Universitas Muhammadiyah Sumatera Utara
1
RBC-The important players
Hemoglobin
reversibly binds and transports 02 from
lungs to tissues
4 globin chains & iron
RBC-The important players (2)
Iron
key element in the production of
hemoglobin
absorption is poor
Transferrin
iron transporter
Ferritin
iron binder, measure of iron stores, *also
acute phase reactant*
IF secretion

Sites of
absorption
of iron and
vitamin B12
Definitions
Anemia-values of hemoglobin,
hematocrit or RBC counts which are
more than 2 standard deviations
below the mean
HGB<13.5 g/dL (men) <12 (women)
HCT<41% (men) <36 (women)
Anemia is a laboratory diagnosis
Men Women
Hemoglobin (g/dL) 14-17.4 12.3-15.3
Hematocrit (%) 42-50% 36-44%
RBC Count (106/mm3) 4.5-5.9 4.1-5.1
Reticulocytes 1.6 0.5% 1.4 0.5%
WBC (cells/mm3) ~4,000-11,000
MCV (fL) 80-96
MCH (pg/RBC) 30.4 2.8
MCHC (g/dL of RBC) 34.4 1.1
RDW (%) 11.7-14.5%
Erythrocytes - less informative index
of anemia than the level of
hemoglobin therefore, in the
general practice the basic criterion
of severity is precisely Hb:
Light degree of anemia - Hb 11-9

g/dl,
The average degree of severity - Hb

9-7 g/dl,
Severe anemia - Hb below 7 g/dl
Anemia adalah suatu keadaan dimana
kadar hemoglobin lebih rendah dari
kadar hemoglobin terendah pada umur
dan jenis kelaminnya.
Pada wanita hamil nilainya lebih rendah
dari wanita tidak hamil.

9
Hemoglobin normal:
WHO Group of Experts on Nutritional Anaemias, menentukan Hb
normal berdasarkan umur dan jenis kelamin:

Kelompok Kadar Hb

Anak-anak 6 bln-6 thn 11 g/dl


Anak-anak 6-14 thn 12 g/dl
Dewasa laki-laki 13 g/dl
Dewasa wanita tidak hamil 12 g/dl
Dewasa wanita hamil 11 g/dl

10
Tanda-tanda anemia:
A. Tanda-tanda umum :
Pucat.
Takikardia.
Tekanan nadi yang lebar.
Tanda hiperdinamik di precordial.
Desah sistolik didaerah pulmoner.

B. Tanda-tanda khas utk etiologi tertentu:


1. Koagulopati, trombositopenia dan pansitopenia:
ptekie, perdarahan retina, mudah lembam.
2. Anemia karena penyakit kronis : deformitas
sendi yang berat.

11
Gejala anemia:
A. Anemia akut:
1. Serebral: oyong kalau berdiri, vertigo, tinnitus,
sinkope, bintik didepan mata.
2. Sirkulasi: palpitasi, sesak nafas kalau bekerja, lelah,
angina, klaudikasio.
3. Demam : tanda infeksi, bisa juga ok proses penyakit
darah.
4. Lain-lain : hipersesitif thd dingin, anorexia, gangguan
pencernaan, haid tidak teratur, impotensi, libido hilang.
B. Anemia kronik:
Tubuh dapat menyesuaikan dengan anemia yang terjadi
lambat
Gejalanya ringan, kadang-kadang hanya rasa lelah.

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Presentation/history
Mild anemia:
few or no symptoms; may be discovered
accidentally on lab test
May complain of:
Fatigue, decr. exercise tolerance, SOB,
palpitations, CP, lightheadedness on arising
Sore tongue (glossitis), cracking mouth corners
(angular cheilitis), peripheral paresthesias
(numb toes, etc.)
Hx:
EtOH use, FH anemia, pica, vegetarian diet,
melena/hematochezia, malabsorption
syndromes, Crohns disease
Evaluation of the Patient
HISTORY
Is the patient bleeding?
Actively? In past?
Is there evidence for increased RBC
destruction?
Is the bone marrow suppressed?
Is the patient nutritionally deficient? Pica?
PMH including medication review, toxin
exposure
Evaluation of the Patient (2)
REVIW OF SYMPTOMS
Decreased oxygen delivery to tissues

Exertional dyspnea
Dyspnea at rest
Fatigue
Signs and symptoms of hyperdynamic state
Bounding pulses
Palpitations
Life threatening: heart failure, angina, myocardial
infarction
Hypovolemia
Fatiguablitiy, postural dizziness, lethargy, hypotension,
shock and death
Evaluation of the Patient (3)
PHYSICAL EXAM
Stable or Unstable?
-ABCs
-Vitals
Pallor
Jaundice
-hemolysis
Lymphadenopathy
Hepatosplenomegally
Bony Pain
Petechiae
Rectal-? Occult blood
Anemia: Special Populations
Higher Hb/HCT:
Patients living at high altitudes
Smokers and patients living in air pollution
areas
Endurance athletes have increased HCT
Lower Hb/HCT:
African-Americans have 0.5 to 1 g/dl lower Hb
than do Caucasians
Elderly (slowed erythropoiesis)
Pregnant women (hemodilution)
Differential diagnosis
Consider:
Anemia
Hypothyroidism
Depression
Cardiac (congestive heart failure, aortic
stenosis)
Pulmonary causes of SOB/DOE
Chronic fatigue syndrome, others
Physical examination
Pallor (may be jaundiced think hemolytic)
Tachycardia, bounding pulses
Systolic flow murmur
Glossitis
Angular cheilosis
Decreased vibratory sense/ joint position
sense (B12 deficiency, w/ or w/o hematologic
changes)
Ataxia, positive Romberg sign (severe
B12/folate deficiency)
Pemeriksaan awal anemia:
A. Kuantitatif:
Hb
Ht
Hitung eritrosit
MCH
MCV
MCHC
Hitung retikulosit
Hitung lekosit
Hitung trombosit
LED.

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Pemeriksaan awal anemia:
Kualitatif:
Gambaran morfologi darah tepi dg pengecatan
Wright: hipokromik, polikromasia, normokromik.
Besar sel : mikrositer, makrositer, anisositosis.
Bentuk sel : poikilositosis, sferositosis, sel oval dan
tear drops, fragmented cells, ghost cells, dll.
Badan-badan intraseluler: eritrosit berinti, badan
Howell-Jolly, siderosit, badan Papenheimer, badan
Heinz dan malaria.

21
Pemeriksaan lanjutan:
Bilirubin
Besi serum (SI)
TIBC
Transferrin
BMP
Hemoglobin elektroforesis
Coombs test
G6PD
Vit B12
Asam folat

22
Anemia AETIOLOGICAL CLASSIFICATION
I- Decrease red cell production.

Definition A-Dyshaemopoietic anaemia: (Decreased


maturation due to deficiency of maturation
factors essential for erythropoiesis).
Mineral deficiency: iron, zinc, selenium, cupper
Types
Vitamin deficiency: B12, folic acid ; Vit C&
pyridoxine
Hormonal deficiency: anaemia of renal
C/P
diseases, pituitary, thyroid or suprarenal
deficiency.
Protein deficiency : high class
Anemia AETIOLOGICAL CLASSIFICATION
I- Decrease red cell production.

B- Hypoproliferative anaemias (BM failure ):


Aplastic anaemia.
Myelophthisic anaemia (BM replacement
Types anaemia).
Anaemia of chronic diseases.
Anemia AETIOLOGICAL CLASSIFICATION

II- Haemolytic anaemia:


Short life-span of RBCs
III- Acute post haemorrhagic anaemia:
Loss of RBCs
Types IV- Mixed anaemia.
eg. Megalobastosis associated with haemolysis
V: Dilutconal anaemia: (raised plasma volume)
Pregnancy
Oliguric RF
Volume-overload
Anemia MORPHOLOGICAL CLASSIFICATION

A. Microcytic-hypochromic anaemias:
Thalassaemia.
Iron deficiency anaemia.

Types Anaemia of chronic disease.


Sideroblastic anaemia:
Hereditary
Chronic lead poisoning.
Anemia MORPHOLOGICAL CLASSIFICATION

B-Normocytic-normochromic anaemias:
Acute post haemorrhagic anaemia.
Hemolytic anaemia.

Types Aplastic anaemia.


Myelophthisic anaemia.
Anaemia of chronic diseases .
Anemia MORPHOLOGICAL CLASSIFICATION

C- Macrocytic- normochromic anaemias:


Megaloblastic anaemia.
Marked reticulocytosis.
Myelodysplastic syndromes.
Types
Myxoedema.
Acquired sideroblastic anaemia.
Klasifikasi klinis:

1. Anemia ok kehilangan darah banyak.

2. Anemia ok berkurangnya produksi


eritrosit.

3. Anemia ok meningkatnya destruksi


eritrosit.

4. Anemia ok berkurangnya produksi dan


meningkatnya destruksi eritrosit.
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Differential Diagnosis
Classification by Pathophysiology
Blood Loss
Decreased Production
Increased Destruction
Classification by Morphology
Normocytic
Microcytic
Macrocytic
Labs
For all: CBC, reticulocyte count,
peripheral smear
For some:

B12, folate, hemoglobin electrophoresis


Bone marrow aspirate to assess possible
defective hematopoiesis
Other labs to assess other differential
diagnoses (e.g. thyroid function tests,
etc.)
Macrocytic Anemia
MCV > 100
Megaloblastic:Abnormal
ities in nucleic acid
metabolism
B12, Folate
Non-
megaloblastic:Abnorma
l RBC maturation
Myelodysplasia
ETOH, liver dz,
hypothryroidism,
chemotherapy/drugs
Microcytic Anemia
MCV <80
Reduced iron
availability
Reduced heme
synthesis
Reduced globin
production
Microcytic Anemia
REDUCED IRON AVAILABILTY
Iron Deficiency
Deficient Diet/Absorption
Increased Requirements
Blood Loss
Iron Sequestration
Anemia of Chronic Disease
Low serum iron, low TIBC, normal serum
ferritin
MANY!!
Chronic infection, inflammation, cancer, liver disease
Microcytic Anemia
REDUCED HEME SYNTHESIS
Lead poisoning
Acquired or
congenital
sideroblastic
anemia
Characteristic
smear finding:
Basophylic stippling
Microcytic Anemia
REDUCED GLOBIN PRODUCTION
Thalassemias
Smear
Characteristics
Hypochromia
Microcytosis
Target Cells
Tear Drops
Ineffective erythropoiesis
All with normal/low reticulocyte
count

Microcytic: think Fe++ deficiency


Macrocytic: think B12/folate deficiency
Normocytic: think anemia of chronic
disease, marrow problems, or other
problems
Pembagian anemia:
Anemia defisiensi besi.
Anemia aplastik.
Anemia hemolitik.
Anemia karena penyakit kronik.
Anemia megaloblastik.
Anemia karena kanker.

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Decreased Production
NUTRITIONAL DEFICIENCY
Iron
B12

Folate
Anemia defisiensi
besi

40
Anemia defisiensi besi.
Tingkatannya:
1.deplesi besi: cadangan besi berkurang atau
tidak ada sama sekali, belum anemia.
2.defisiensi besi: cadangan besi berkurang
atau tidak ada + rendahnya besi serum dan
jenuh transferin, belum anemia.
3.anemia defisiensi besi: cadangan besi
berkurang atau tidak ada + rendahnya besi
serum dan jenuh transferin + Hb rendah dan
Ht rendah. Sudah anemia.

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Penyebab anemia defisiensi besi.
Perdarahan:
sal.urogenital,
sal.pencernaan,
sal.pernafasan.
Kebutuhan meningkat:
prematur,
hamil,
haid,
masa pertumbuhan.
Malabsorpsi.
Makanan kurang bergizi.

42
Fe deficiency anemia
++

Most commonly due to chronic


bleeding and erythropoiesis limited by
iron stores that have been depleted
May be dietary (pica, lack of meat/

vegetables, other)
Iron balance is very close in

menstruating women, so Fe++


deficiency is not uncommon with no
other source of bleeding
Gambaran klinis:

Keluhan:
pucat,
lemah,
nyeri menelan,
pika,
nyeri epigastrik.
Tanda-tanda:
anemia,
glositis,
atrofi papil lidah,
koilonikia,
keluhan penyakit dasarnya.

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Physical Manifestation : Spoon
Nails in Iron Deficiency
Pemeriksaan

Anamnesis dan pemeriksaan fisik.


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

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Labs
Iron and ferritin will be low
TIBC (total iron binding capacity) will be
high, since iron stores are not saturating
their binding sites on transferrin
Reduced RBC counts (definition of anemia)
Microcytosis & hypochromia are hallmarks,
but early Fe++ may be normocytic (
hypochromic)
Usually, MCH and MCHC will both be low
(whereas in macrocytic anemia, the MCH
may be normal while the MCHC is low,
because of the larger cell size)
Labs
Most practitioners would agree that if
a patient has microcytic hypochromic
anemia with a low reticulocyte count,
it would be reasonable to use a trial
of FeSO4 to diagnose
5-10 days after initiating therapy, a

robust rise in reticulocytes confirms


the diagnosis
LABORATORY DIAGNOSIS OF HYPOCHROMIC
MICROCYTIC ANAEMIA
LABORATORY INTERPRETATIO
TEST N
Peripheral Hypochromic &
smear microcytic anaemia

Iron Absent Increased


(Bone
marrow)
Ringed
sideroblasts

Haemoglobin Normal Abnormal Normal


electrophoresi
s
Iron Thalassaemi Sideroblast
Diagnosis deficienc a ic anaemia
y haemoglobi
anaemia no-pathies
Pengobatan:

1. Atasi penyakit dasarnya.


2. Preparat besi oral/parenteral dan lanjutkan 3
bulan setelah Hb normal.

50
Treatment
Iron, oral in most cases, parenteral in
cases of malabsorption
All forms of iron are constipating; the

amount of constipation directly relates to


the amount of elemental iron delivered
If intolerant of FeSO4 (cheapest), reduce the
dose, rather than switching form
Start 325 mg QD, increase slowly to TID
Follow up the cause of the iron
deficiency!
Treatment of Iron Deficiency Anemia
Diet: meat, liver, yeast, fish
Oral preparations: recovery rate Hb

does not differ from parenteral


introduction, side effects are less,
excessive introduction does not lead
to hemosiderosis.
- Dosage : 1 hour prior to the meal
in the evening time (absorption
increase in the second-half of a day)
During first 3 days - half dose of the selected
preparation.

Possibilities : dark colour of stool and transitory


dyspeptic disorders (nausea, diarrhea or watery
stool)

Check analysis of the blood: in 7-10 days


reticulocyte reaction; 4 weeks - increase Hb and
Ht

During the normalization of the indices of the blood


reduce the dose of preparation
Parenteral Introduction of Iron
in exceptional cases
in severe iron deficiency anemia
rendering to special aid
intolerance of oral preparations (after repeated
replacement and reduction in the dose)
diseases of gastro-intestinal tract
syndrome of the disrupted intestinal absorbtion
after the extensive resection of the small
intestine
continuous blood loss
not compensated by oral method
Complications of Parenteral Introduction

Local reactions (pains, phlebitis)


General reactions (anaphylaxis, fever,

head and articulate pains, vomiting,


rash, bronchospasm).
Preparations:
Venofer - for the intravenous
introduction,
Maltofer, Ferrum-Lek - intramuscular
Overdose of Iron

In the first 6-8 hours - epigastral pains,


nausea, vomiting (including with the blood),
diarrhea, pallor, sleepiness, acrocyanosis)

For 12-24 hours - metabolic acidosis,


leukocytosis, there can be spasms, coma,
after 2-4 days - necroses of the liver and
kidneys.

Treatment: emetic means, stomach


lavage, the method of milk with the egg
white, Deferoksamin, Desferal, symptomatic
therapy.
Iron Overload Syndrome
! Human does not have special mechanism of the
excretion of iron! Its excessive introduction leads to
hemosiderosis. Clinical manifestations: Gradual
increase of the dimensions of the liver, spleen,
cardiopathy, suprarenal insufficiency, diabetes
mellitus, eunuchoidism.

Laboratory signs:

Increase in serum iron (more than 30 mmol/liter),


percentage of saturation transferrin by iron it is
more than 45%, ferritin of serum it is more than
1000 ng/ml; Test with desferalom; + the specific
signs of the defect of internal organs (ECG, level
biochemical index of functions of the liver, the level
of hormones and others)
Anemia megaloblastik
Akibat gangguan sistesis DNA dan
ditandai dgn sel megaloblastik
Pada sel yang perubahannya cepat

(sel hemopoetik, epitel


gastrointestinal)

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Klasifikasi anemia megaloblastik
Defisiensi kobalamin

Defisiensi asam folat

59
Defisiensi kobalamin
anemia pernisiosa,
paska gastrektomi
organisme intestinsal
abnormalitas ileum
nitrous oxide

60
History of
the Management of Anemia
Before 1980 Hb 10 g/dL
Hb 8 g/dL
Risks of transfusion
1980s infection
Transfusion guidelines
Moderate/severe anemia
Hb 8 g/dL

1990s and beyond Continued transfusion risks


Epoetin alfa
QOL assessment tools
Relationship of anemia to
fatigue
Abels (1992) Glaspy 1997) Demetri 1998 Cleland (1999)
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Defisiensi asam folat
asupan tidak memadai
kebutuhan meningkat
malabsorbsi
obat-obatan ;
-penghambat sintesa DNA langsung
(analog purine, analog pirimidin)
-antagonis asam folat
-antikonvulsan

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Macrocytic anemia with ineffective
erythropoiesis
Low/normal reticulocyte count,
macrocytosis
Most common is folate/B12 deficiency
Dietary: folate far more common, B12 may occur
in strict vegans
Pernicious anemia: lack of B12 protection in
stomach and gut
Poor uptake in terminal ileum (e.g. in Crohns
disease)
B12 and folate are essential for cell maturation
and DNA synthesis, erythrocytes end up large,
usually normochromic, since iron is not lacking
Other: drugs, toxins, myelodysplasia
Folate deficiency
Folate intake is usually dietary, and
may be deficient with low fresh fruit
& vegetable intake
Folate supplementation of bread

prevents neural tube defects in


pregnancy
PE may include neurological effects if

severe deficiency
B12 deficiency
Less common, usually caused by absorption
problems, rather than dietary deficiency
B12 needs Intrinsic Factor for protection from
degradation in gut
Produced by parietal cells of stomach, protects
through gut for uptake at terminal ileum
Pernicious anemia from immune attack of IF
production
EtOH-related gastritis can affect IF production, and
liver disease may also contribute to macrocytosis
Neurological effects
Deficiency results in damage to
dorsal columns (sensory) and lateral
columns (motor) of spinal cord
Decreased vibration sense and

position sense of joints detectable,


and may affect gait, etc.
May have positive Rombergs test

Severe effects may include ataxia

and dementia
Labs
Folate and B12 levels
Schilling test may be useful to establish

etiology of B12 deficiency


Assesses radioactive B12 absorption with and
without exogenous IF
Other tests if pernicious anemia is
suspected
Anti- parietal cell antibodies, anti-IF antibodies
Secondary causes of poor absorption should be
sought (gastritis, ileal problems, ETOH, etc.)
LABORATORY DIAGNOSIS OF MACROCYTIC
LABORATORY ANAEMIA
INTERPRETATIO
TEST N
Peripheral Macrocytic
smear anaemia

Bone Megaloblasti No
marrow c changes megaloblastic
examination changes

Reticulocyt Low Hig Low


e count h

Therapeuti Respond Responds Probable Possible liver


c response s to vit to folic haemolytic disease
B12 acid anaemia (evaluate
(continue liver function
Diagnosi Vit B12 Folic workup) tests)
s deficiency acid
(determine deficienc
if dietary y
or
abnormal
Treatment supplementation
Do NOT correct folate levels unless B12 is OK
Correction of folate deficiency will correct
hematologic abnormalities without correcting
neurological abnormalities
Check B12 and correct first
B12 usually 1000 mg I.M. q month
B12 stores take a long time to deplete; missed
doses are not usually a problem
Oral supplementation is gaining support; usually
effective in pernicious anemia (1-2 mg PO QD)
Reticulocyte count should respond in 1 wk
Diagnosis

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

Tes schilling penentuan patogenesis

70
Deficiency Folic acid Serum
vit. B12
Serum RBC

Folic acid N

Vit B12 N/

Folic acid & B12


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Penatalaksanaan

Atasi penyebab
Defisiensi Kobalamin :
Kobalamin 1000 ug IM tiap minggu sd 8 minggu,
lanjutkan kobalamin 1000 ug IM tiap bulan
Vit B12 2 mg perhari

Evaluasi retikositosis pada hari ke 4-5 puncaknya


pada hari ke 7.

Defisiensi asam folat


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

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THERAPEUTIC TRIALS
Usual diet

0,2 mg folic acid


oral
1 week
reticulocyte response

+ -
+ 1-2 g vit
B12
73
Thank You