PK Anemia dr. Bastiana, SpPK

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Gangguan Eritrosit:

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Gangguan Eritrosit

Anemia

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ANEMIA

Definisi Anemia:

 Sindroma klinis yang disebabkan penurunan massa eritrosit total dalam tubuh.

 Keadaan dimana massa eritrosit dan atau massa hemoglobin tidak dapat memenuhi fungsinya untuk menyediakan oksigen bagi jaringan tubuh

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ANEMIA

Penurunan Hb dan Hct :

< batas bawah 95% interval referens dari kelompok usia, jenis kelamin

dan lokasi geografis (ketinggian)

Hb12-14 g/dl ; (Hct 36-41%),

Hb7g/dl  symptom (+)

Akut: hipovolumia (pucat,

ggn penglihatan, syncope, tachycardia) ;

Kronis: tissue hypoxia (fatique, dyspnea, Headache, angina)

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ANEMIA

→ symptoms / syndrome

 Hb ↓

 PCV ↓ Hypoxia → Otak , Otot

 RBC ↓

Kompensasi :

- heart rate ↑→ tachycardia → flow rate ↑ → cardiomegaly → heart failure → †

- blood flow priority (pallor)

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Klasifikasi Anemia

Berdasarkan patofisiologi:

I. Kegagalan produksi sel darah merah:

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Lanjutan…..anemia berdasarkan patofisiologi

E. Gangguan karena mekanisme lain:  Anemia karena penyakit kronis,

 anemia sideroblastik

 Anemia karena infiltrasi sumsum tulang

II. Peningkatan destruksi sel darah merah:  Anemia Hemolitik

III. Kehilangan darah (Blood Loss)

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Anemia

Anemia berdasarkan morfologi

Anemia sec. morfologi eritrosit, dilihat dari:

- ukuran dan warna di bawah mikroskop atau - indeks eritrosit (MCV, MCH, dan MCHC)

Kriteria Ukuran (size): Normositik, Mikrositik, Makrositik

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Cara Mengetahui Ukuran eritrosit:

* membandingkan dengan inti sel limfosit kecil (di bawah mikroskop) :

→ ukuran sama = normositik lebih kecil = mikrositik lebih besar = makrositik

* Menghitung MCV (Mean Cell Volume) MCV= PCV/Ery X 10 (fL)

(1 fL=10-12L= 1μm3)

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Perhatikan Warna sel eritrosit

:

- Bandingkan diameter central pallor(CP)

dengan diameter sel eritrosit tersebut .

- Normal, bentuk sel eritrosit adalah seperti cakram bikonkaf (biconcave disk) →

pada hapusan darah tepi terlihat bulat, Ø 7-8 μ dengan area central pallor di bagian tengah

CP≤ 1/3 Ø Eri = normokromik

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Eritrosit dengan

central palor (CP)

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Warna, dapat diketahui juga dari MCH (Mean Cell Hb) MCH= Hb/RBC x 10 (pg)

Dewasa: MCH=27-32 pg, Anak-anak: MCH=23-31 pg (1pg=10-12g=1μμg)

MCH normal → normokromik

MCH < normal → hipokromik

MCHC (Mean Cell Hb Concentration) : MCHC=Hb/PCV x 100 (g/dL)

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Klasifikasi Anemia secara morfologi

1. Anemia Hipokromik-Mikrositik.

2. Anemia Normokromik-_Normositik

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1

Contoh: - Anemia defisiensi Fe

- _Thalasemia - _{Anemia akibat}

Penyakit Kronik

- _Anemia

sideroblastik

2

Contoh:

- Anemia pasca

perdarahan akut

- Anemia aplastik - Anemia hemolitik - Anemia akibat

penyakit kronik

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 makrosit-oval

(Anemia megaloblastik ditandai oleh makrosit oval ini)

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Pendekatan diagnostik Anemia:

Anamnesis:

onset /bleeding tendency / routine

medicinal / occupation / hobby / travel history / family / diet / GI symptoms / menstruation cycle / history of previous

pregnancy-delivery / alcohol consumption , etc

Pemeriksaan fisik :

conjunctiva & lips (pallor) / mouth

(cheilosis) / tongue (glossitis) / gum / nails (koilonychia) , hair (signa de bandera,

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 _{Pemeriksaan Laboratorium}

- CBC (complete blood count )→ to confirm anemia (Hb, PCV, RBC) & the type of anemia (MCV; MCH; MCHC), RDW

- Reticulocyte count → reflects marrow’s responses .

- PBS : to look for the RBCs’ shape and any abnormalities of

RBCs besides the other blood cell lines

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- Radiological examinations ( Chest X-ray, USG , MRI )

- Cardiological examinations (EKG,Treadmill, Echocardiography)

Notes ! :

- First confirm Anemia ( Hb , PCV , RBC ) - Classify the anemia (MCV, MCH, MCHC)

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Anemia Hipokromik-Mikrositik

Setiap kondisi yang menimbulkan gangguan sintesis Hb  gambaran hipokromik

mikrositik

Anemia Defisiensi Besi penyebab tersering dari anemia Hipokromik-Mikrositik

_{Perhatikan penyebab lain (DD=diff diagnosis)}

sebelum mendiagnosis Anemia def. besi, spt: - anemia akibat penyakit kronis

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ANEMIA DEFISIENSI BESI

 Definisi:

Anemia yang timbul akibat kosongnya cadangan besi tubuh besi utk eritropoeisis  pembentukan Hb

 Anemia def. Fe, ditandai dgn: - anemia hipokromik mikrositik - besi serum

- TIBC (Total Iron Binding Capacity) - Saturasi transferin

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Faktor Penyebab (Etiologi)

I.

Keseimbangan negatif Fe (Negative Iron

balance):

-

Asupan Fe ↓

(inadequate diet , impaired absorption)

- Fe loss ↑

(GI bleeding, excessive menstrual flow, bleeding diathesis)

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II. Inadequate presentation to erythroid precursors:

- atransferrinemia - Anti TrfR Ab

III. Abnormal Fe balance :

- Aceruloplasminemia

- Autosomal dominant hemochromatosis ( mutations in ferroportin )

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Patogenesis desifisiensi Fe

3 pathogenetic factors:

- Impaired Hb synthesis (consequence of reduced Fe supply)

Transferin saturation< 16% inadequate Fe-supply to marrow → Hb contents of RBC ↓ → hypochromic & microcytosis

- Generalized defect in cellular proliferation - Fe-deficient → oxidative damage to the red

cell’s membrane → RBC deformability ↓ → RBC

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Status besi tubuh:

 Serum Iron = SI

 _{Total Iron Binding Capacity (TIBC)}

 % Transferrin Saturation = SI/TIBCx100%

 Simpanan besi (Iron storage):

- Hemosiderin →produk degradasi feritin yang tidak larut dalam air → mayoritas tdd aggregat kristal

ferric oxyhydroxide, FeOOH (di Hepar danSutul→ dideteksi dengan biopsi/aspirasi dan pengecatan besi (prosedur invasif)

- Ferritin → kompleks garam Fe3+dan apoferitin yang larut dalam air, dengan jumlah yang sangat kecil di serum.

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 Kandungan besi tubuh = 35-50 mg/kgBB:

±80% - Fe fungsional, sebagai heme-Iron

(65% Hb, myoglobin, enzim heme : cytochrom-C,A,A3,B, catalase , peroxidase)

- Non-heme-Fe (sebagian kecil)

20% - simpanan besi / Iron storage (ferritin, hemosiderin)

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Iron Cycle in the body :

_{Fe-diet → as heme-Fe (Hb, myoglobin,}

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Enhancers (zat yang menstimulasi penyerapan (absorbsi) :

Ascorbate, Cytrate, organic acids / other amino acids , by reducing Fe3+ to Fe2+.

Inhibitors (zat yang menghambat absorbsi) :

Carbonate, Phytate, Tannins, Phosphate, Oxalat chelate Non-heme-Fe →

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Bahan makanan yang menghambat absorbsi besi non heme (Non-heme Iron) :

- Phytate (dari legumes, sayuran)

- Tannin & Polyphenol (dari teh, kopi, wine, coklat )

- Phosphate/phosphoprotein dari kuning telur

- Minerals (Ca, Zn, Cd)

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Siklus Fe dalam tubuh

:

Diet’s Iron → duodenum / proximal jejunum .

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The development of IDA

• _{Stage-1 (prelatent Fe-deficient):} - progressive loss of storage-Fe

- body’s Fe reserve is still sufficient to

maintain both the transport and functional compartment , so RBC development is

still normal .

- peripheral blood picture is normal , no symptoms of anemia , but ferritin is ↓ .

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* Stage-2 (latent Fe-deficient)

- Exhaustion of storage-Fe , RBC

production is still normal , Ferritin ↓↓

- Circulating-Fe (SI) begin ↓ , Receptor ↑ .

* Stage-3 (Fe-Deficiency Anemia)

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Symptoms Morphology SI - TIBC Ferritin

I D A Anemia Hypo –

Micro TIBC ↑SI↓ - ↓↓

A.C D Anemia Hypo –

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Pendekatan Diagnostik Anemia Defisiensi Fe

1. Anamnesis – pola menstruasi, kehamilan /

persalinan, tendensi perdarahan, penyakit kronis, diet, pekerjaan, riwayat bepergian

2. Pemeriksaan fisik – sistematik dari seluruh

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3. Laboratorium- Hema (DL, LED, Hapusan darah tepi, Retikulosit)

- Serum (SI,TIBC,Ferritin, Bilirubin) - BMA (Bone Marrow Aspiration) - Pemeriksaan Urine dan tinja

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S I

TIBC

Normal _N

(1/3 mol.Trsf)

N

I D A _{↓ ↑}

An.of Chronic

Disease ↓ N / ↓

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Pemeriksaan Lab. Anemia def. Fe

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% Saturasi Transferrin = SI/TIBC X 100%

Erythropoeisis impaired when % Tf.Sat < 15%

3. Ferritin Serum :

Serum Ferritin level ~ Fe-storage

Ferritin <15 ug/L → Definitive Fe-Deficient N/↑ Ferritin in IDA , if :

- impaired liver function ( damaged hepatocyte),

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4. Transferrin Serum :

measured by immunodiffusion methode Normal value : 2-4 g/L

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Anemia of Chronic In

fection

 Gejala klinis miripdengan anemia def.Fe

 Gambaran lab. hematologi = Anemia def. Fe (An.Hypo-Micro, MCV , MCH , SI ) , tapi ↓ ↓ ↓

TIBC N/ and Ferritin N/ )↓ ↑

 Pathogenesis :

Fe storage // Transferrin→

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1. Impairment of Fe release from macrophage in competing with

lactoferrin, phagocyte’s product , even

storage-Fe is still enough .

2. Inadequate EPO Respons towards anemia (effects of cytokine production by macrophage) .

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Diagnosis Anemia akibat penyakit kronis:

 lab hematologi:

- Anemia hipokromik mikrositik - SI ↓ , TIBC ↓/N , Ferritin N/↑

( jika Ferritin ↓, An. Def.Fe ) - Inflamasi / infeksi (+) :

CRP and LED ↑

Problem: IDA with inflammation → ferritin ↑ (falsely diagnosed as ACD) ; it can be

differentiated by sTfR exam (serum

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Anemia Sideroblastik

Defek pada sintesis Heme → akumulasi Fe di mitochondria → degenerasi Fe → granula Fe di sekitar inti normoblast, membentuk

struktur spt cincin {paling jelas terlihat

dengan pengecatan Perl (Perls’ stain) } → Ringed Sideroblast (karakteristik anemia Sideroblastik)

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 Classification of Sideroblastic

Anemia

1. Hereditary : X-linked, defect in heme-synthesis enzyme pathway

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2. Acquired :

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Primary :

Stem cell clonal mutations(MDS =

MyeloDysplastic Syndromes , RA-RS) Normochromic-macrocytic anemia . Marrow : erythroid hyperplasia with

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Secondary;

Abnormal metabolism of Vit.B6 (alcoholism, malabsorption) , impairment of heme

synthesis ( Pb intoxication) , Rhematoid Arthritis , or An.megaloblastik .

Usually related to myeloproliferative

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Macrocytic Anemia

- Non-Megaloblastic Macrocytic Anemia :

 Reticulocytosis

 Liver disease / Alcoholism

 Myelodysplastic Syndrome

 Erythroleukemia (FAB-M6)

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macrocyte = erythrocyte with MCV > normal . macrocyte/microcyte depend on the balance

between nuclei & cytoplasmic maturation .

(nuclear dividing stopped when intracellular Hb production reach a proper level ) .

If nuclear maturation delayed ( in DNA

synthesis’s defect ) or cytoplasmic maturation ↑ ( increase of EPO’s activities ) → critical level of Hb achieved earlier → Macrocyte

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Megaloblast = bigger than normal normoblast .

Megaloblastic changes = increased size of hemopoietic precursor cells in bone marrow ( not only in normoblast !)

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_{Etiology of DNA synthesis defect :}

deficiency of vit.B12 and folic acid →

maturation dysharmony between nuclei & cytoplasm (delayed nuclei maturation) → increased cels (megaloblastic changes) → marrow’s ineffective erythropoiesis →

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

_{Deficiency of Folic acid:}

- Inadequate diet

(intake < / demand ↑ in pregnancy

lactation , child’s growth / malabsorption in tropical sprue / bowel resection / small intestine inflammation )

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

_{Deficiency of Folic acid:}

- Inadequate diet

(intake < / demand ↑ in pregnancy

lactation , child’s growth / malabsorption in tropical sprue / bowel resection / small intestine inflammation )

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

_{Deficiency of Vit.B12:}

- Inadequate diet :

Intake < in vegetarians , demand ↑ , impaired absorption caused by

decreased Intrinsic Factor

( gastrectomy , pernicious anemia )

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VITAMIN B12 ASAM FOLAT

-Food from animal products -Heat stabile

-Storage : enough for 3 yrs -Relatively low needs (only 1% of folate requirements)

-Limited sources (vegetable ,

fruits)

-Heat labile

-Storage enough only for 3 mths

-Higher folate needs

CAUSE OF DEFICIENCY CAUSE OF DEFICIENCY

-Vegetarian (seldom)

-Impaired Intrinsic Factor (pernicious anemia)

-Gastrectomy

-Atropic Gastritis

-Anticonvulsant, alcoholism

-Nutrition (alcoholism, goat’s milk diet)

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Pathogenesis of Megaloblastic Anemia

:

_{Megaloblastic changes}

 atrophy of tongue papilla & mucosal GI → glossitis , gastritis, nausea , constipation.

_{B12 defic → demyelinisation of spinal cord &}

peripheral nerve → loss of foot’s balance / sensory (Neuropatia)

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B12 Metabolism

 Vit.B12 → purine & pyrimidin synthesis → synthesis DNA & RNA → mitosis and

maturation

 Vit.B12 made from microbiological source because plants do not produce B12 ( meat ,

liver, eggs and milk are rich of Vit B12 ).

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Vit.B12 absorption

 B12 diet → in gaster bind by IF (Intrinsic Factor) produced by parietal cells → IF-B12 complex → ileum : B12 absorbed , IF freed into the lumen

 impaired IF : gastrectomy/gastritis/ Auto-Ab-antiIF or Auto-Ab-antiparietal) → no absorption of B12 →

impaired DNA synthesis → (Pernicious Anemia with Achlorhydria)

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Hematological pictures of Megaloblastic Anemia

_{Bone Marrow :}

- megaloblastosis

- ineffective erythropoiesis

Peripheral blood : - Oval macrocytosis

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Megaloblastic Anemia

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Diagnosis of Megaloblastic Anemia

Screening :

- CBC , Neutrophil’s lobe count

- Serum Indirect Bilirubin , LDH (lactate dehydrogenase)

Spesific tests :

- Bone Marrow Aspiration: megaloblastosis & megaloblastic changes, erythropoietic activitiy ↑ ( ineffective erythropoiesis)

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Anemia Hemolitik

 _{Anemia hemolitik: anemia yang disebabkan}

oleh proses hemolitik.

 Hemolisis: pemecahan eritrosit sebelum

waktunya (sebelum masa hidup rerata eritrosit, yaitu 120 hari).

(Proses pemecahan eri karena sdh waktunya

senescence=penuaan)

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HEMOLYTIC ANEMIA

_{Normal red cell’s survival = 110-120 days →}

destructed by macrophage in marrow and spleen .

When the survival are shortened → EPO

production is stimulated (compensated) → no Hb changes → anemia (–) .

_{If the destruction is acute or chronic with}

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Definition of Hemolytic Anemia

:

_{anemia caused by shortened red cell’s}

survival as a result of excessive

uncompensated destruction of red cells .

Hemolytic process = every process of red cells destruction with still / without

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Compensation ability of bone marrow :

Ability to ↑ red cells production ( 6-8 x normal ) :

- survival shorten ½ → production ↑ 2x - survival shorten ¼ → production ↑ 4x - survival shorten 1/6 → production ↑ 6x - survival shorten 1/8 → production ↑ 8x

↑ of production 6-8 x is maksimum .

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Diagnostic approach in Hemolytic

Anemia

:

1. Confirm anemia (Hb/PCV/RBC)

an acute case usually acquired , and chronic case is mostly hereditary .

2. To find the signs of hemolytic process . 3. Extra or Intravascular ?

4. Hereditary or acquired ?

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The signs of Hemolytic process :

1. Increased of red cells destruction

- Unconjug.bilirubin serum ↑ → jaundice - Urobilinogenuria

- Hb-uria → sign of intravascular hemolysis

- Abdom.pain → splenomegaly, spleen infarction - Leg’s Ulcer → intrinsic defect of erythrocyte - Haptoglobin serum ↓↓/neg → intravascular hemolisys .

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2.Destruksi eritrosit :

Microspherocyte, Fragmentocyte, Poikilocyte

_{Erythrocyte Osmotic Fragility ↑} Positive Autohemolysis test

Shortened of red cells’ survival

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 Hemolisis ekstravaskular lebih sering dijumpai dibandingkan hemolisis intravaskular

 Hemolisis terjadi di sel makrofag dari sistem

retikuloendothelial (RES) terutama pada Lien, hepar dan sutul karena sel ini mengandung enzim heme oksigenase

 Lisis terjadi karena kerusakan membran eritrosit (misal Akibat reaksi Ag-Ab; presipitasi hb di

sitoplasma, menurunnya fleksibilitas eri,dll)

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Klasifikasi Anemia Hemolitik

Dibagi atas 2 golongan besar, yaitu:

1. Anemia hemolitik karena faktor di dalam

eritrosit sendiri (gangguan intra korpuskuler) 2. Anemia hemolitik karena faktor di luar

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lanjutan….Klasifikasi anemia hemolitik :

1. Gangguan intra korpuskular (Hereditary Hemolytic Anemia )

- Membrane abnormality (hereditary

spherocytosis , hereditary ovalocytosis ) - defect of globin chain (Thalassemia, Hb- pathia)

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2. Gangguan ekstrakorpuskular (Acquired Hemolytic Anemia):

- physical / chemical substances

- infections (bacteria, parasites, viruses, fungi)

- mechanical trauma (prostetic heart valves) - Immune mechanism (Alloimmune /

Autoimmune / Drug-Induced HA)

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- Hereditary Spherocytosis :

 autosomal dominant

 Spherocytosis, decreased membrane surface area relative to cell volume → osmotic fragility test (OFT)↑ among the family member .

 The primary lesion is caused by membrane protein defects (↓of spectrin) → cytoskeleton instability .

 60% - chronic anemia , jaundice, splenomegaly, 20% without hemolysis / splenomegaly .

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Thalassemia :

 Defect of 1 or more globin-chain synthesis (the amount = quantitatively) :

- deficiency of α globin-chain → α-thalassemia - deficiency of β globin-chain → β-thalassemia - deficiency of δβ globin-chain → δβ-thalassemia

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α-Thalassemia

_{α-Thalassemia = is caused by the impairment}

of α-globin chain production/synthesis .

_{α-globin chain synthesis is directed by 2}

pairs of α-gene (4 locus α-gen) → depending of the number of defected locus → 3 types of α-Thalassemia (α-thal trait , HbH Disease,

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Clinical consequences in α-Thalassemia

Deficiency of α-globin chain → excess of β, γ chain since fetal life to form β4-tetramers

(HbH) or γ4-tetramers (HbBart) .

Defect of 1-2 α-Gen = α-trait (clinically good)

Defect of 3 α-Gen = HbH disease ( Hb 10-11 g/dl) → excess of β-chain → to form

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Defect of 4 α-gene (HbBarts’hydrops fetalis) → clinically severe , stillborn baby with

hydrops fetalis ( severe hypoxia ) .

HbBarts = γ4-tetramers (excess of γ-chains that unable to form HbF ) .

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- β-Thalassemia

_{Clinically consequences in β-Thalassemia :}

- No problems during fetal life because HbF synthesis is normally produced

(normal α and γ chains)

- When HbA is dominantly needed , the clinically

problems exist as incapability to synthesize

HbA (α2β2) → excess of α-chain →

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- severe anemia → repeated transfusion is

oftenly needed → Fe↑↑ → hemochromatosis

- chronic ineffective erythropoiesis →

medullary hypertrophy in childhood → facial malformation:

* Frontal bossing

* Maxillary hypertrophy

* Hypertelorism (mongoloid’s eye)

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- β-chain deletion forms :

β0-Thalassemia : no β-chain

production.

β+Thalassemia : β-chain production

<<

in heterozygous case : medium severe

in homozygous : severe (Cooley’s

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Laboratory Diagnosis in Thalassemia

1. CBC, Peripheral Blood Smear

2. Hb-Electrophoresis : in Celulose-Acetat (pH 8.4) for thalassemia and Hb-pathia

screening

Using hemolysate → formed bands of

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3. HbA2 mesurement to diagnose β-Thalassemia trait using anion-exchange resin column chromatography

in both HbELP and chromatography , HbC, HbE and HbO can interrupt the conclusion because of the

same band location with HbA2 .

4. HbF determination :

- Alkali Denaturation Test

- Acid-elution (Kleihauer) test

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5. HbH Inclusion detection :

- Supravital staining using Brilliant Cresyl Blue (BCB) or NewMethylene Blue (NMB)

- HbH inclusion seen as dispersed green granules in red cells

(compare with reticulocyte as a filament) - in HbH disease : HbH inclusion +++

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- Oxidant → produce H2O2 → oxidizing

Hb’s free sulfhydryl → to form Sulf-Hb → aggregates that precipitated as Heinz

Bodies → destructed in spleen .

- Oxidant / Sulf-Hb are controlled by Reduced Glutathione (GSH)

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- X-linked, ± 300 variants .

normal G-6PD genes : - type B (GdB) - type A (GdA)

- Abnormal enzyme types : 1. GdA– (type A–)

2. Gd-Mediterranean (GdMed) 3. Gd-Canton : many in Asia

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- Substances causing lysis in G-6PD deficiency :

1. Antimalaria 6. Fava beans

2. Sulfonamides 7. Naphtalene 3. Vit.K, Vit.C 8. Uremia

4. Lung Infection 9. Antibiotics (virus,bacteria) (Penicilline ,

5. Antipyreticum streptomycine

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The highest G-6PD activity is in reticulocyte .

G-6PD screening test :

Test’s principle :

G-6PD

G-6P + NADP 6-PG + NADPH UV

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Acquired Hemolytic Anemia

:

- Secondary Hemolytic Anemia caused by

infection / systemic disorders :

Malignancy – Autoimmune-reacted hemolysis , microangiopathy or

hypersplenisme , appearing Anemia of

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_{Disseminated Intravascular Coagulation}

(DIC):

Systemic intravascular coagulation → fibrin deposit intravascularly / endothelial damage (microangiopathyi) caused by sepsis → red cells destruction .

Chronic Liver Disease : hemolysis caused by hypersplenism .

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Acquired Hemolytic Anemia (extracorpusc.)

Red cell membrane-bound Ab hemolysis .

The speed & hemolysis location depend on IgG or IgM, and the ability to activate

complement .

Optimal temperature to bind Ab : 370C – Warm-IgG-Type

<300C – Cold-IgG-Type

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Cell+IgG → destructed by spleen

Cell+IgM → enhance the activation of complement’s cascade → intravascular hemolysis

Immune destruction often cause minimally membrane damage → shape change into spherocyte .

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Immune Hemolytic Anemia classification :

1. Alloimmune : Transfusion Rx , Hemolytic Disease of the Newborn (HDN)

2. Autoimmune : Warm/Cold AIHA, Paroxysmal Cold Hb-uria (PCH)

LOGO Hemolytic Disease of the Newborn (HDN) –

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Antiglobulin Tests (Coombs) :

_{Direct Coombs Test (Direct Antiglobulin Test/}

DAT) = Ab detection test (IgG and or C3d /complement-bound red cells) .

Indirect Coombs Test = test for serum free Ab .

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Drug-Induced hemolytic anemia :

 Penicilline type : drug as hapten binds red cell

membrane → antigenic → stimulate Ab production against Drug in drug-red cell complex

Phenacetin/Quinidin type : Drug (hapten) adsorbed protein → stimulated-Ab binds drug-protein complex → activate complement → red cell lysis.

 Aldomet type : drug change red cell membrane’s

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Aplastic (Hypoplastic?) Anemia

Severe & fatal Anemia because of ↓ red cells/leucocytes/platelet production

(pancytopenia) caused by Stem Cells

impairment (radiation, chemicals, drugs, or genetic matters)

Marrow aplasia / hypoplasia-causing substances - radiation , benzene, cytostatics (6-MP,

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Symptoms & Lab.appearance of Aplastic Anemia

 fatigue, palpitation, infections, bleeding tendency

 Lab : - pancytopenia

- normochromic normocytic

- ‘dry-tap’ marrow , hypocellularity

 Prognosis :

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Treatment for Aplastic Anemia :

1. Avoid every toxic material

2. Avoid infections / bleeding tendency

3. Use Washed-Erythrocyte if transfusion is needed or Plat.Concentrate (PC) for any profuse bleeding ( give corticosteroid if bleeding is minimal)

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POLISITEMIA

(ERITROSITOSIS)

 Peningkatan patologis massa eritrosit

 massa eritrosit normal : (sea level) - o : 26 - 32 ml / kg BB

- o : 23 - 29 ml / kg BB

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•

_{Klasifikasi :}

I. Primer (Otonomik)

A. Polisitemia Vera

B. Eritrositosis Murni (Eritremia)

II. Sekunder

A. Fisiologis (

Oksigenasi Jaringan

)

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ERYTHROCYTOSIS - DIAGNOSTIC TESTS

•

_{Complete Blood Count}

• _{Bone Marrow examination} • _{Arterial Blood Gas analysis}

• _{Leukocyte Alkaline Phosphatase} • P_5O

• _{IVP or renal ultrasound}

• _{Liver ultrasound or CT scan} • _{Erythropoietin level}

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POLISITEMIA VERA

• Proliferasi klonal neoplastik sel

progenitor hematopoitik pluripoten

• _{Kriteria diagnosis P.V. :}

Kategori A

1.Massa eritrosit:

Lk > 36 ml / kgBB (PCV > 54%)

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Kategori B

1. Trombositosis (> 400.000 /

m

l)

2. Lekositosis (> 12.000 /

m

l)

3. Skor LAP

_­

4. B12 serum > 900 pg/ml

•

_{Diagnosis PV bila :}

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PRIMARY “PURE” ERYTHROCYTOSIS

( ERYTHREMIA )

•

peningkatan massa eritrosit murni

•

_{tidak ada penyebab eritrositosis sekunder}

•

_{kadar eritropoitin normal atau rendah}

•

_{mungkin akibat mutasi gene reseptor}

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II. ERITROSITOSIS SEKUNDER

•

_{Merupakan respons terhadap keadaan lain}

yang bersifat :

- fisiologis : akibat oksigenasi jaringan yang

¯

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III.ERITROSITOSIS RELATIF

•

_{Sindroma Gaisbock}

•

_{Stress erythrocytosis}

•

Pseudo erythrocytosis

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1. Nyonya Ana, usia 40 tahun, MRS (Masuk Rumah Sakit) dengan keluhan pusing, dan badan terasa lemah. Pemeriksaan

fisik: KU lemah, Tensi: 100/60 mmHg, Nadi:90 x/menit, RR: 20 x/ menit, suhu:37˚C. Kepala/Leher: anemia (+), tidak dijumpai

ikterus, dyspnea dan sianosis, Thorak/Cor dan Abdomen :dalam batas normal (dbn). Extremitas: dbn. Hasil laboratorium: Hb 8 g/dl, RBC 3,20 x 1012/L, Hematokrit 24 %, MCV 75 fl, MCH 25

pg, MCHC 33 g/dl. Jika anda adalah dokter jaga di RS tersebut, dari data yang ada, kemungkinan diagnosis pasien tersebut adalah:

A. Anemia normokromik-normositik

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2. Dari kasus ny. Ana, 40 tahun tersebut, diagnosis diferensial untuk penyebab anemianya adalah:

A. Anemia defisiensi folat, anemia defisiensi Vitamin B12, B. Anemia karena perdarahan akut, anemia aplastik

C. Anemia defisiensi besi, thalasemia, anemia sideroblastik D. Anemia hemolitik, anemia pada penyakit mielofibrosis

E. Anemia pada penyakit liver, anemia pada penyakit hipotiroid

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3. Dari soal kasus Ny. Ana, 40 tahun tersebut, langkah pemeriksaan laboratorium selanjutnya yang perlu

dilakukan untuk konfirmasi diagnosis adalah:

A. pemeriksaan bilirubin, haptoglobin, hitung retikulosit

B. Serum Iron, TIBC dan Feritin

C. Pemeriksaan B12 dan asam folat dalam darah D. Pemeriksaan T3, T4 dan TSH

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A 35-year-old man complains of chronic physical fatigue, which began 3-4 weeks ago. He said he felt tired all of the time even through his occupation as a software developer was mentally but not physically demanding. He breathed comfortably at rest but,

when he exerted himself, he experienced difficulty in breathing and had hard time catching his breath. He also complained of „more than usual” mental fatigue, confessing an increasing inability to concentrate and focus his attention on tasks at hands. Colleagues noticed his pallor and his inattentiveness at brainstorming sessions and suggested he reschedule his annual physical examination for an earlier date. He complained of vague abdominal pain and sense of abdominal fullness. His appetite was depressed, and he thought perhaps his physical and mental symptoms were caused by poor diet. However, attempts to increase eating resulted in nausea. His stools, he said, were sometimes loose and tarry. Eventually,

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Laboratory findings revealed the

following:

_{Laboratory test}

_Patient

_Normal

RBC (red blood cell count) 3.5 T/L 4.5-6.0 T/

L

HCT (hematocrit ratio) 28% 40-52%

Hb (hemoglobin) 8.0g/dL 13-17g/dL

MCV (mean corpuscular volume)

70fL 78-95fL

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Case history questions:

1. What general medical condition is suggested by the person’s symptoms?

2. What fundamental change in function of blood related to the red blood cells could

simultaneously affect the function of several systems (cardiovascular, respiratory,

gastrointestinal, and others)?

3. What specific diagnosis is supported by the laboratory findings?

4. How could the stool be related to the laboratory

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Answers:

1. Anemia

2. A reduction in oxygen-carrying capacity of

the blood and thus a reduction in the delivery of oxygen to various body tissues

3. An iron defficiency anemia

4. Most cases of iron-defficiency anemia result from internal blood loss. Dark, tarry loose stools suggest bleeding from the gastrointestinal tract and warrant

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