HAEMATOLOGY

Anemia Defisiensi
Savita handayani
Hematologi-Onkologi Medik
Departemen Ilmu Penyakit Dalam

Normal Blood Cells:

Steps in Erythropoesis
Early

Proerythroblast
(Pronormoblast)

Intermediate Late

Polychromatophilic
Normoblast

Basophilic
Normoblast

Reticulocyte

Orthochromatophilic
Normoblast

Erythrocyte

RBC disorders (Anemias) :

Anemia is decreased red

cell mass affecting tissue
oxygenation

Practical - Low Hb* or Low Hematocrit*

Penggolongan menurut Morfologi

volumetrik
Mikrositik
hipokrom
MCV
< 80 fL
MCH
27 pg
MCHC < 30 g/dL

Normositik
normokrom Makrositik
80 100 fL
> 27 pg
30 g/dL

MCV= (Ht/Eritosit)x10 fL
MCH=(Hb/Eritrosit)x10 pg
MCHC=(Hb/Ht)x100 g/dL

> 100 fL
> 27 pg
30 g/dL

Mechanism of Anemia :

Decreased Production:

Nutrient Deficiency.
Iron, B12/Folate

Hemopoietic cell damage:

Aplastic, Hypoplastic Neoplasms,
radiation, drugs

Iron Deficiency Anemia:

Most abundant metal but most common

deficiency..!
Common in developing world,
Parasitic Worm infestation + Malnutrition
Chronic blood loss GI & genitourinary
tract

Iron Metabolism

Recycling of iron dead cells to new cells

10% of the 10 to 20 mg of dietary iron.
Iron is absorbed in Jejunum.
Stored as Ferritin & Hemosiderin.

Iron Mathematics

Minimum daily iron requirement 12-15mg/day.

Absorbed 1-2.5 mg/day.

The normal iron content is 3-4 gr. It exists in the

following forms:
Hemoglobin = 2.5 grams
Iron containing proteins (myoglobin,
cytochromes and catalase) = 400 mg

Iron bound to transferrin = 3-7 mg

Storage iron (ferritin or hemosiderin).

IDA - Etiology

Blood loss

Increased need

Bleeding Parasites, Gynecologic, ulcers

Pregnancy, children

Poor diet / poor absorption

Malnutrition (greens & meat), malabsorption,

intestinal surgery, gastric atrophy.

IDA Pathogenesis: Steps of IDA

Decreased Iron stores.

Storage iron in adult men 10 mg/kg, mostly in liver,
spleen, and bone marrow. Adult women have less
storage iron.

Decreased Hb Synthesis
Delayed maturation of erythroblasts
(cytoplasmic)
Decreased cytoplasm, more division
(microcytes)
Decreased Hb content (hypochromia)
Anemia.

PATHOGENESIS
Lack of iron interferes with heme synthesis
hemoglobin synthesis and defective erythropoiesis
There is decreased activity of iron-containing proteins
such as the cytochromes and succinic dehydrogenase
Neurologic dysfunction may occur, with impaired
intellectual performance, paresthesias
Gastric acid secretion is reduced, often irreversibly
Atrophy of oral and gastrointestinal mucosa may
occur

Clinical Features:

General features of Anemia

Pallor, Weakness, Lethargy,

Breathlessness on exertion
Palpitations heart failure pedal edema

Special features in IDA:

Angular cheilitis, atrophic glossitis,

Oesophageal atrophy/web dysphagia,
Koilonychia, brittle nails, gastric atrophy.
Pica

Angular cheilitis

Koilonychia in Iron deficiency

Koilonychia in Iron def.

LABORATORY CHANGES
Red Blood Cells
- Earlist change is anisocytosis and increased red cell
distribution width (RDW)
- Mild ovalocytosis, target cells
- Elongated hypochromic elliptocytes
- Progressive hypochromia (low MCH),microcytosis
(low MCV), MCHC variable
- Reticulocytes normal or reduced
- The erythrocyte count, hemoglobin level and
hematocrit are all proportionately reduced

LABORATORY CHANGES
Leucocytes
Leukopenia (3000 to 4400/l) in some. Differential
count is normal
Platelets
- Thrombocytopenia develops in 28 percent of
children and may occur in adult
- Thrombocytosis found in
- 35 % of children
- 50 to 70 % of adults-usually secondary to
chronic active blood loss

LABORATORY CHANGES
Marrow
- Marrow cellularity and M/E ratio variable
- Decreased to absent sideroblast
- Decreased to absent hemosiderin by Prussian blue
staining
- Erythroblasts may be small, with narrow rim of
ragged cytoplasm and poor hemoglobin formation

LABORATORY CHANGES
Serum Iron Concentration
- Usually low but may be normal
- May be reduced with concomitant acute or chronic
inflammation malignancy, acute myocardial
infarction in the absence or iron deficiency.
- May be elevated 3 to 7 days after therapy

Total Iron Binding Capacity (TIBC)

- Usually increased in iron deficiency
- Saturation (Iron/TIBC) is often 15 % or less but this
is not specific for iron deficiency

LABORATORY CHANGES
Serum Ferritin
- Level of less than 10 g/liter
- Level of 10 to 20 g/liter are presumptive, but not
diagnostic
- May be elevated with concomitant inflammatory
disease
Free Erythrocyte Protoporphyrin (FEP)
- Concentration is usually increased
- Very sensitive for diagnosis of iron deficiency and
suitable for large scale screening of children, detecting
both iron deficiency and lead poisoning

Anemia Defisiensi Besi

Serum feritin <20 ng/mL, atau

Indeks saturasi transferin (IST)< 15%
(syarat: TIBC within normal limit)

SI
IST
* 100%
TIBC
Normal limit:
SI
TIBC
Serum feritin

50 -150 g/dL
250-410 g/dL
20-200 ng/mL,
excess >400 ng/mL

DIAGNOSIS

Evaluation of clinical information from a

review of the history & physical
examination
Evaluation of the basic blood
examination & specialized laboratory
examination
Micrositer, Hipochrom
Decreased SI and Elevated TIBC
SI/TIBC <16%
Bone marrow Hemosiderin (-)
Ferritin <12 ug/l

Iron values in the development of iron deficiency anaemia

13-16

1316

12-14
13-16

Retikulosit

Rasio retikulosit = Hitung Retikulosit x 1000

Indeks/koreksi retikulosit (Normal: 5-15 .);

Hitung Eritrosit

Pria

: Ht x Rasio retikulosit

Wanita

42
Ht
x
39

Rasio retikulosit

Hb

Ht

18
17
16
15
14
13
12
11
10

54
51
48
45
42
39
36
33
30

Rasio Retikulosit ()
Pria
Wanita
4.0 11.8
3.6 11.0
4.2 12.5
3.9 11.7
4.4 13.2
4.1 12.4
4.7 14.1
4.4 13.1
5.0 15.0
4.7 14.0
5.4 16.1
5.0 15.0
5.8 17.3
5.4 16.2
6.3 18.8
5.8 17.5
6.8 20.5
6.4 19.1

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

TREATMENT
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 is normal to replenish iron stores
* Daily total 150-200 mg elemental iron in 3 to 4 doses, each 1 h ac

Koreksi defisiensi besi serum

Untuk menaikkan Hb sebesar 1 gr/dL dibutuhkan Fe endogen 2,5

mg/kgBB

Kebutuhan initial Fe:

Fe = (D Kadar Fe serum x 0,2 x BB) mg, atau
Fe = (D Hb x 2,5 x BB) mg

Iron Dextran max. 1,5 mg/kgBB/day

Jectofer 75 mg/2mL amp.
Cara 75 mg/deep im

Iron Sucrose
Venofer 100 mg/amp
Cara infusi 100 mg in 100cc NS 1jam

TREATMENT
Parenteral Iron Therapy
* Routine use rarely justified
* Indications are:
- malabsorption
- intolerance to oral iron preparations (colitis, enteritis)
- needs in excess of amount that can be given orally
- patient uncooperative or unavailable for follow-up
* Iron dextran:
- 50 mg elemental iron/ml
- Approximately 70 % readily available for Hb synthesis
- May be given IM or IV
- Be aware of anaphylaxis or other systemic side effects

TREATMENT
Parenteral Iron Therapy
* Continue therapy for 12 months after Hb is normal, in order to
replenish iron stores.
* Therapy may be needed indefinitely if bleeding continues

Failure to respond to therapy

* Wrong oral preparation
* Bleeding not controlled
* Therapy not long enough to show response
* Patient not taking medication
* Concomitant deficiencies (Vit. B12, folate, thyroid)
* Concomitant illness (infection, malignancy, hepatic
disease, renal disease, inflammation)

Hypochromic Microcytic RBC

Megaloblastic anemia:

Vitamin B12/Folic acid deficiency

Multi System disease All organs with
increased cell division.
Macrocytic anemia, pancytopenia.
Pernicious anaemia

autoimmune, Gastric atrophy, VitB12 def.

Megaloblastic anemia - Etiology

Malnutrition, vegetarian
Intrinsic factor Ab - Pernicious anemia
Gastrectomy, Ileal resection
Inflammatory bowel disease
Malabsorption syndromes - Sprue
Blind loop syndrome

Megaloblastic anemia - Pathogenesis:

Decreased Vit B12 / Folate

Decreased DNA Synthesis
Delayed maturation of erythroblasts
Increased cell size (macrocytes)
Normal Hb content (Normochromia)
Decreased RBC number
Decreased WBC number (pancytopenia)
Anemia & Pancytopenia.

Diagnosis

Hb level, leukocyte, platelet, reticulocytes count, ESR

Red cells indices (MCV, MCH, MCHC) MCV >100 fl
Examination of peripheral blood film
Hypersegmented Neutrophil (Five Lobes)
BM examination

-B12 defisiensi
-Folate defisiensi

< 200 pg/ml (300-900 pg/ml)

< 4 ng/ml (6-20 ng/ml)

Deficiency

Folic acid

Serum
vit. B12

Serum

RBC

Folic acid

Vit B12

N /

Folic acid & B12

THERAPEUTIC TRIALS

Usual diet
0,2 mg folic acid oral
1 week
reticulocyte response

+ 1-2 g vit B12

reticulocyte response

Management
B12 Defisiensi :
B12 1000 ug IM weekly until 8 weeks,
and B12 1000 ug IM monthly

Folat Defisiensi :
1 mg oral daily ( 5 mg daily maximal dose), treatmane
for 1 until 2 month or defisiensi corected.
Reticulosit Evaluation on day 4 and 5, than peak level
reticulosit on day 7.

Macrocytic Anemia (Meg.):

Macroovalocytes & Macropoly

Megaloblastic Anemia :