HEMATOLOGY

Anemia

Dairion Gatot, Savita Handayani

Divisi Hematologi-Onkologi MedikDepartemen Ilmu Penyakit Dalam FK-USU/RS H.Adam Malik, Medan 2011

Normal Blood Cells:

RBC disorders (Anemias) :

““Anemia is decreased red Anemia is decreased red cell mass affecting tissue cell mass affecting tissue

oxygenation”oxygenation”

Practical - Low Hb* or Low Hematocrit*Practical - Low Hb* or Low Hematocrit*

C.B.C Haemoglobin PCV Haematocrit, effective RBC volume - better RBC count MCHC Hb/PCV, Hb synthesis within RBC MCH Average Hb in RBC MCV PCV/RBC

Mikrositik hipokrom

Normositik normokrom Makrositik

MCV < 80 fL 80 – 100 fL > 100 fL

MCH ≤ 27 pg > 27 pg > 27 pg

MCHC < 30 g/dL 30 g/dL 30 g/dL

Penggolongan menurut Penggolongan menurut Morfologi Morfologi volumetrikvolumetrik

MCV= (Ht/Eritosit)x10 fLMCH=(Hb/Eritrosit)x10 pgMCHC=(Hb/Ht)x100 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 only Iron Deficiency

Iron Metabolism Limited absorption* and no proper excretory

mech*. Recycling of iron – dead cells to new cells 1mg/day 3-6G body 1mg/day 10% of the 10 to 20 mg of dietary iron. Iron is absorbed in Jejunum. Stored as Ferritin & Hemosiderin.

IDA - Etiology

Blood loss Bleeding – Parasites, Gynecologic, ulcers…

Increased need Pregnancy, children

Poor diet / poor absorption Malnutrition (greens & meat),

malabsorption, intestinal surgery, gastric atrophy.

IDA - Pathogenesis:

Decreased Iron stores 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, which leads to reduced 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.

Angular cheilitis

Angular cheilitis & Glossitis

Koilonychia in Iron def.Koilonychia in Iron def.

Koilonychia in Iron def.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 ellptocytes

- 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

LeucocytesLeukopenia (3000 to 4400/l)is found in a small number of patients. 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 chemotherapy

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 µg/liter- Level 0f 10 to 20 µg/liter are presumptive, but not diagnostic- May be elevated wit 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 deficincy and lead poisoning

Anemia Defisiensi BesiAnemia Defisiensi Besi

Serum feritin <20 ng/mL, atau Indeks saturasi transferin (IST)< 15%

(syarat: TIBC within normal limit)

Normal limit: SI 50 -150 g/dL TIBC 250-410 g/dL Serum feritin 20-200 ng/mL,

excess >400 ng/mL

%100*TIBC

SI IST

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 Deficiency Occurs in Stages

Iron depletion: storage iron decreased or absent

Iron deficiency: storage iron decreased or absent

with low serum iron concentration and transferrin saturation

Iron deficiency: storage iron decreased or absent with low serum iron concentration and transferrin saturation and low hemoglobin level and reduced hematocrit

Iron values in the development of iron deficiency anaemia

1316

13-16

13-1612-14

C.B.C

Haemoglobin - 15±2.5, 14 ±2.5 - g/dl PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%)

Haematocrit, effective RBC volume - better RBC count - 5.5 ±1, 4.8 ± 1 x1012/l MCHC - Hb/PCV - 30-36 - g/dl

Hb synthesis within RBC MCH - Hb/RBC - 29.5 ± 2.5 pg/l

Average Hb in RBC MCV - PCV/RBC 85 ± 8 - fl

Rasio retikulosit = ‰

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

Pria :

Wanita :

RetikulositRetikulosit

Hitung RetikulositHitung Eritrosit

x 1000

Rasio retikulositx42Ht

Rasio Retikulosit (‰)HtHb

Rasio retikulositx39Ht

Pria Wanita

17 514.2 – 12.5

3.9 – 11.716 48

4.4 – 13.2

4.1 – 12.415 45

4.7 – 14.1

4.4 – 13.114 42

5.0 – 15.0

4.7 – 14.013 39

5.4 – 16.1

5.0 – 15.012 36

5.8 – 17.3

5.4 – 16.211 33

6.3 – 18.8

5.8 – 17.510 30

6.8 – 20.5

6.4 – 19.1

18 544.0 – 11.8

3.6 – 11.0

Microcytic Anemia (IDA)

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

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

Koreksi defisiensi besi serumKoreksi defisiensi besi serum

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

Kebutuhan initial Fe: Fe = ( Kadar Fe serum x 0,2 x BB) mg, atau Fe = (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

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* Iron dextran: - only product available in United States - 50 mg elemental iron/ml - Approximately 70 % readily available for Hb synthesis - May be given IM or IV - Be aware of danger anaphylaxis or other systemic side effects

TREATMENTParental Iron Therapy* Continue therapy for 12 months after Hb level 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)

Differential diagnosis of Anemia Microcytic Hipochrome

LABORATORY TEST

INTERPRETATION

Hypochromic & microcytic anaemia

Absent Increased

Ringed sideroblasts

NormalAbnormalNormal

Peripheral smear

Iron

(Bone marrow)

Haemoglobin electrophoresi

s

Diagnosis Iron

deficiency

anaemia

Thalassaemia

haemoglobino-pathies

DIAGNOSIS OF HYPOCHROMIC MICROCYTIC ANAEMIA

Sideroblastic anaemia

SI/TIBC, PERRITIN

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