PERDARAHAN AKUT PERDARAHAN KRONIS

H E M O L I T I K

ANEMIA

dr. FX Hendriyono,SpPK

27 Maret 2008

Acute blood loss

Bleeding

Post hemorrhagic anaemia (normocytic

anaemia)

Thrombocytopenia

Plasma volume RBC mass

Thrombocytosis Leukocytosis Neutrophilia

Haemodilution after 24

hourErythropoiesis

activity

BM hiperplasia

Reticulocytosis polychromatophilia RBC macrocytosis

Phase I (day 1-3)

Hypovolumic stage

Phase II (day 3-5)

Regeneration stage

Anemia of Chronic Disease

Anemia in :- Chronic inflammation, malignancy, post extensive trauma / surgery- Take place > 2 month

Mechanism :1. Phagocytic cells release apolactoferrin binds Fe2. RBC life span 3. Marrow failure (EPO )

Lab :Iron normalStores

Anemia of Chronic Disease

Fe storesRES

Endotoksin

Antigen Tantangan fagosit

Protein fase akutAbsorbsi besi Interleukin-1 Leukositosis Feritin serum Demam

Sintesis feritin

Besi Perubahan membran

Besi serum Ambilan Aktivitas fagosit eritrosit dan metabolisme Penglepasan

Eritropoesis Umur eritrositDefisiensi Fe

Soluble factor (s)

Hambatan eritropoesis

Eritropoetin Sel T

Mekanisme defisiensi besi pada ACD

ACD Anemia Kombinasi defisiensi besi

Hb Jarang < 9 g/dL Bervariasi Bervariasi

MCV & MCHC Normal / Selalu rendah Selalu rendah rendah ringan

Besi serum Rendah Rendah Rendah

DIBT (TIBC) Normal / Selalu tinggi Bervariasi, rendah ringan sering batas

atas normal

Feritin > 25ug/L, < 12ug/L Sering < 12 ug/Lsering > 50 ug/L

Besi SUTUL Normal atau tinggi Kosong Kosong

Sideroblas (%) Kurang Sangat kurang Sangat kurang

Respon besi Tidak ada Baik Sebagian

Perbandingan hasil laboratorium antara ACD dan anemia defisiensi besi

Anemia of Chronic Disease

Haemolytic anaemia

Haemolytic anaemia

Rate of RBC destruction

RBC production

Reticulocyte counts

Reticulocytosis in haemolytic anaemia

EXTRAVASCULAR HAEMOGLOBIN DEGRADATION

Macrophage

Haemoglobin Heme + globinplasma protein and amino acid pool

Biliverdin + CO + Fe transferrin + Fe Bone marrow

lungs

Bilirubin

plasma albumin

Bilirubin-Albumin (unconjugated)

liver

Bilirubin diglucuronide (conjugated)

bile duct to duodenum

Urobilinogen Blood

stool Urobilinogen (urine)

kidney

Urobilinogen + stercobilinogen

INTRAVASCULAR HAEMOGLOBIN DEGRADATIONFree Hb in blood

Haptoglobin (102 mg/dL)

Hgb-haptoglobin liver (catabolism same as extravascular)

Hb

in excess of haptoglobin

Methaemoglobin

globin amino acid pool

Heme (Fe+

++)

haemopexinhaemopexin-heme

albuminmethemalbumin

albumin

heme

RE cells in liver

dimers

kidney

Urine haemoglobin

Urine haemosiderin

tubular reabsorption

CAUSED OF HAEMOLYTIC ANAEMIAS

Intrinsic Causes(Congenital)

1. Haemoglobinopathies

(S, C, D)

2. Thalassaemia

3. Unstable haemoglobins

4. Enzyme deficiencies (that is, G-6-PD)

5. Hereditary spherocytosis

6. Hereditary haemolytic ovalocytosis

Extrinsic Causes(Acquired)

1. Autoimmune

2. Drug associated, that is, methyldopa, penicillin

a. Warm antibodies

b. Cold antibodies

3. Snake venoms

4. Parasitism (malaria)

5. Microangiopathic haemolytic anaemic

6. Hypersplenism

7. Isoimmune

LABORATORY OF HAEMOLYTIC ANAEMIAS

BLOOD FILM

Microspherocyte : 1. Autoimmuno haemolytic anaemia=AIHA

2. Hereditary spherocytosis

3. Haemoglobinopathies : HbC

4. Hipersplenisme

MCV N

MCH N

MCHC

AIHASpherocyte

A : normal

B : spherocytosis

Osmotic fragility test

A

B

A : congenital non-spherocytic anaemias

B : spherocytosis

Osmotic fragility test

LABORATORY

• RBC abnormalities

Sel target : HbC

Fragmented RBC : schistocytes

burr cells

helmet cells (MAHA)

• Plasmodium

HbC Helmet cells Burr cellsP. falciparum

LABORATORY

BONE MARROW

Erythroid hyperplasia : rubrisit predominant

Iron stores : negative / or

G-6PD deficiency

• X-linked disorders, heterozygote females only

rarely have significant haemolysis

• Haemolysis cause by infection, acidosis, drugs & toxins

• Red blood cells membrane oxidation

• Precipitation of haemoglobin Heinz bodies

• PB smear bite cells

• In acute haemolytic episode G-6PD activity

maybe normal

G-6PD Deficiency

NADPH : nicotinamide adenine dinucleotide phosphate GSSH : glutathione oxidized form G-6PD : glucose-6 phosphate dehydrogenase

• RBC in PNH are abnormally sensitive to

lysis to complement

• Diagnosis can be made by :

1. Abnormal lysis of RBC by acidic serum (Ham’s tests)

2. Hypotonic medium solution (Sugar water test)

Paroxymal nocturnal haemoglobinuria (PNH)

ANTIGLOBULIN TESTS (COOMB’S TEST)

Direct antihuman globulin tests (DAT)

Indirect antihuman globulin tests (IDAT)

LABORATORY DIAGNOSIS OF NORMOCYTIC ANAEMIA

OTHER HAEMOLYTIC ANAEMIAS

Parasites

Hypersplenism

Microangiopathic

haemolysis

Hereditary

spherocytosis

Paroxysmal noctural

haemoglobinuria

Enzyme deficiencies

Drug or toxin

Haemoglobinopathies

AUTO IMMUNO HAEMOLYTIC ANAEMIA

Erythroblastosis

foetalis

Transfusion

reaction

Collagen

vascular

disease

OTHER

Renal disease

Infection

Malnutrition

Aplastic

anaemia

Radiation

MYELOPHTHISIC

Tumor

Myelofibrosis

Infection

Leukaemia

BLOOD LOSS ANAEMIA

REPLACEMENT OF NORMAL

MARROW ELEMENTS

DECREASED CELLULARITY

HYPERCELLULAR ERYTHROID HYPERPLASIA

HYPERCELLULAR ERYTHROID HYPERPLASIA

POSITIVE

POSITIVE

NEGATIVE NEGATIVE

NEGATIVE

INCREASED

REDUCED

NORMOCYTIC ANAEMIA

INTERPRETATIONLABORATORY TEST

PERIPHERAL SMEAR

RETICULOCYTE COUNT

BLOOD IN STOOL OR OTHER SOURCE OF BLEEDING IDENTIFIED

ANTIHUMAN GLOBULIN (COOMBS’TEST)

BONE MARROW AND BONE MARROW BIOPSY

DIAGNOSIS

INDICATION FOR BONE MARROW BIOPSY

1. Suspected aplastic anaemia

2. Suspected myelofibrosis3. Suspected aleukaemic

leukaemia4. Suspected metastatic

tumor

5. Suspected miliary granulomatus infection

6. Suspected malignant lymphoma

Tumor metastasisAplastic anaemia (biopsy)

Aplastic anaemiaAcute leukaemia

NORMOCYTIC NORMOCHROMIC ANAEMIA & RETICULOCYTOPENIA

• Reduced proliferative erythroid cells1. Renal disease2. Infections, inflammation, malignancy3. Protein malnutrition4. Aplastic anaemia5. Marrow replacement (myelophtisic)

a. Tumorb. Leukaemiac. Fibrosisd. Infection (chronic granuloma)

6. Toxin, poison, radiation, drugs7. Endocrine disorders (thyroid disease)

LABORATORY

BLOOD FILM1. Anaemia myelophthisic

invasion with tumor cell or

increased in fibrotic tissues (myelofibrosis)

infection with TBC

• Moderate to marked anisocytosis &

poikilocytosis tear drop cellsNRBC Leukoerythroblastic

• WBC count normal or elevated picture

Shift to the left, including blast cells

• BM biopsy

Tear drop cells Metastasis Bronchial carcinoma cells in

bone marrow

2. Acute or chronic infection

• PMN increased

• Shift to the left

• Classic changes of infection : toxic granulation, Dohle bodies, vacuolisation & pyknotic nucleus

Dohle bodies Toxic granule

Shift to the left

Bacteria & Vacuole

Pyknotic

3. Aplastic anaemia

Clinical features :

• Bleeding, bruising, infection, lethargy, shortness of breath, no adenopathy and hepatosplenomegaly

Diagnostic Criteria :

1. Severe aplastic anaemia

Hypocellular marrow and two of the following three criteria :

• Absolute reticulocyte count < 40,0000 / L

• Absolute neutrophil count < 500 / L

• Platelet count < 20,000 / L

2. Very severe aplastic anaemia

• Absolute neutrophil count < 200 / L

BONE MARROW

BM aspiration

• Leukaemia, myelophthisic anaemia, aplastic anaemia

granuloma, infection

• BM biopsy

NORMOCYTIC NORMOCHROMIC ANAEMIA & RETICULOCYTOSIS