ANEMIA

PERDARAHAN AKUT PERDARAHAN KRONIS HEMOLITIK

dr. FX Hendriyono,SpPK
27 Maret 2008

Acute blood loss

Bleeding Post hemorrhagic anaemia (normocytic anaemia) Plasma volume RBC mass Thrombocytopenia

Phase I (day 1-3) Hypovolumic stage

Thrombocytosis Leukocytosis Neutrophilia

Haemodilution after 24 hour

Erythropoiesis activity Phase II (day 3-5) Regeneration stage Reticulocytosis polychromatophilia RBC macrocytosis BM hiperplasia

Anemia of Chronic Disease Anemia in : - Chronic inflammation, malignancy, post extensive trauma / surgery - Take place > 2 month Mechanism : 1. Phagocytic cells release apolactoferrin binds Fe 2. RBC life span 3. Marrow failure (EPO ) Lab : Iron normal Stores

Anemia of Chronic Disease

Fe stores RES

Mekanisme defisiensi besi pada ACD

Endotoksin
Antigen Tantangan fagosit

Absorbsi besi Feritin serum

Interleukin-1

Protein fase akut Leukositosis Demam

Sintesis feritin Besi Besi serum Ambilan Penglepasan Eritropoesis Defisiensi Fe Soluble factor (s) Umur eritrosit Aktivitas fagosit Perubahan membran eritrosit dan metabolisme

Hambatan eritropoesis

Eritropoetin

Sel T

Perbandingan hasil laboratorium antara ACD dan anemia defisiensi besi

ACD Anemia defisiensi besi Kombinasi

Hb MCV & MCHC

Jarang < 9 g/dL Normal / rendah ringan Rendah Normal / rendah ringan

Bervariasi Selalu rendah

Bervariasi Selalu rendah

Besi serum DIBT (TIBC)

Rendah Selalu tinggi

Rendah Bervariasi, sering batas atas normal Sering < 12 ug/L

Feritin

> 25ug/L, sering > 50 ug/L Normal atau tinggi Kurang Tidak ada

< 12ug/L

Besi SUTUL Sideroblas (%) Respon besi

Kosong Sangat kurang Baik

Kosong Sangat kurang Sebagian

Anemia of Chronic Disease

Haemolytic anaemia

Haemolytic anaemia
Rate of RBC destruction

RBC production

Reticulocyte counts

Reticulocytosis in haemolytic anaemia

EXTRAVASCULAR HAEMOGLOBIN DEGRADATION

Haemoglobin Macrophage Heme + globin plasma protein and amino acid pool lungs

Biliverdin + CO + Fe

transferrin + Fe

Bone marrow

Bilirubin plasma albumin Bilirubin-Albumin (unconjugated) liver Bilirubin diglucuronide (conjugated) bile duct to duodenum Urobilinogen stool Urobilinogen + stercobilinogen Blood kidney Urobilinogen (urine)

INTRAVASCULAR HAEMOGLOBIN DEGRADATION

Free Hb in blood
Haptoglobin (102 mg/dL) Hgb-haptoglobin liver (catabolism same as extravascular)

Hb
ab dimers kidney in excess of haptoglobin Methaemoglobin tubular reabsorption Heme (Fe+++) Urine haemoglobin Urine haemosiderin haemopexin haemopexin-heme albumin methemalbumin albumin heme RE cells in liver

globin

amino acid pool

CAUSED OF HAEMOLYTIC ANAEMIAS

Intrinsic Causes (Congenital) Haemoglobinopathies (S, C, D) Thalassaemia Unstable haemoglobins Enzyme deficiencies (that is, G-6-PD) Hereditary spherocytosis Hereditary haemolytic ovalocytosis Extrinsic Causes (Acquired) Autoimmune Drug associated, that is, methyldopa, penicillin a. Warm antibodies b. Cold antibodies Snake venoms Parasitism (malaria) Microangiopathic haemolytic anaemic Hypersplenism Isoimmune

1.

1. 2.

2. 3. 4.

3. 4. 5.

5. 6.

6. 7.

LABORATORY OF HAEMOLYTIC ANAEMIAS

BLOOD FILM
Microspherocyte : 1. Autoimmuno haemolytic anaemia=AIHA 2. Hereditary spherocytosis 3. Haemoglobinopathies : HbC 4. Hipersplenisme MCV MCH N N

MCHC

Spherocyte

AIHA

Osmotic fragility test

A : normal B : spherocytosis

Osmotic fragility test

A : congenital non-spherocytic anaemias B : spherocytosis

LABORATORY
RBC abnormalities

Sel target

: HbC
burr cells helmet cells (MAHA)

Fragmented RBC : schistocytes

Plasmodium

P. falciparum

HbC

Helmet cells

Burr cells

LABORATORY
BONE MARROW
Erythroid hyperplasia Iron stores : rubrisit predominant : 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 PB smear maybe normal bite cells Heinz bodies

In acute haemolytic episode G-6PD activity

G-6PD Deficiency

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

Paroxymal nocturnal haemoglobinuria (PNH)

RBC in PNH are abnormally sensitive to lysis to complement Diagnosis can be made by :

1. Abnormal lysis of RBC by acidic serum (Hams tests)

2. Hypotonic medium solution (Sugar water test)

ANTIGLOBULIN TESTS (COOMBS TEST)

Indirect antihuman globulin tests (IDAT)

Direct antihuman globulin tests (DAT)

LABORATORY DIAGNOSIS OF NORMOCYTIC ANAEMIA

LABORATORY TEST
PERIPHERAL SMEAR RETICULOCYTE COUNT BLOOD IN STOOL OR OTHER SOURCE OF BLEEDING IDENTIFIED ANTIHUMAN GLOBULIN (COOMBSTEST) BONE MARROW AND BONE MARROW BIOPSY INCREASED

INTERPRETATION
NORMOCYTIC ANAEMIA REDUCED

POSITIVE

NEGATIVE

POSITIVE

NEGATIVE

NEGATIVE

HYPERCELLULAR ERYTHROID HYPERPLASIA

HYPERCELLULAR ERYTHROID HYPERPLASIA

DECREASED CELLULARITY

REPLACEMENT OF NORMAL MARROW ELEMENTS

DIAGNOSIS

BLOOD LOSS ANAEMIA

AUTO IMMUNO HAEMOLYTIC ANAEMIA Erythroblastosis foetalis Transfusion

OTHER HAEMOLYTIC ANAEMIAS Parasites Hypersplenism Microangiopathic haemolysis Hereditary spherocytosis Paroxysmal noctural haemoglobinuria Enzyme deficiencies Drug or toxin

OTHER

MYELOPHTHISIC Tumor Myelofibrosis Infection Leukaemia

Renal disease
Infection Malnutrition Aplastic anaemia Radiation

reaction
Collagen vascular disease

Haemoglobinopathies

INDICATION FOR BONE MARROW BIOPSY

1. 2.

3.
4.

Suspected aplastic anaemia Suspected myelofibrosis Suspected aleukaemic leukaemia Suspected metastatic tumor

5.

6.

Suspected miliary granulomatus infection Suspected malignant lymphoma

Acute leukaemia

Aplastic anaemia

Aplastic anaemia (biopsy)

Tumor metastasis

NORMOCYTIC NORMOCHROMIC ANAEMIA & RETICULOCYTOPENIA

Reduced proliferative erythroid cells
1.
2. 3. 4. 5.

6. 7.

Renal disease Infections, inflammation, malignancy Protein malnutrition Aplastic anaemia Marrow replacement (myelophtisic) a. Tumor b. Leukaemia c. Fibrosis d. Infection (chronic granuloma) Toxin, poison, radiation, drugs Endocrine disorders (thyroid disease)

LABORATORY
BLOOD FILM
1. Anaemia myelophthisic invasion with tumor cell or increased in fibrotic tissues (myelofibrosis) infection with TBC Moderate to marked anisocytosis & poikilocytosis tear drop cellsNRBC WBC count normal or elevated Shift to the left, including blast cells BM biopsy Leukoerythroblastic picture

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 / mL Absolute neutrophil count < 500 / mL Platelet count < 20,000 / mL Absolute neutrophil count < 200 / mL

2. Very severe aplastic anaemia

NORMOCYTIC NORMOCHROMIC ANAEMIA & RETICULOCYTOSIS

BONE MARROW
BM aspiration

Leukaemia, myelophthisic anaemia, aplastic anaemia

granuloma, infection BM biopsy