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Anemia pds patklin

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    Anemia pds patklin Anemia pds patklin Presentation Transcript

    • Agus Susanto KosasihLaboratorium Patologi KlinikRS Kanker Dharmais 1
    • 2Definition of anaemia Anaemia is defined as a reduction in the haemoglobin concentration of the blood This results in a decreased oxygen carrying capacity
    • PATHOLOGY, SYMPTOMS, AND SIGNS OF ANEMIA
    • Normal values for peripheral blood Female MaleErythrocytes (per µl) 4.8±0.6x106 5.4±0.8x106Hemoglobin (g/dl) 14 ± 2 16 ±2Hematocrit (%) 42 ±5 47 ±5Reticulocytes (%) 1 1___________________________________________Mean corpuscular volume (MCV; µm3) 82-92Mean corpuscular hemoglobin (MCH; pg) 27-32Mean corpuscular hemoglobin concentration (MCHC; %) 32-36
    • Etiologic classification of anemias (1)I. Impaired red cell production A. Disturbance of proliferation and differentiation of stem cells ( aplastic anemia, pure red cell aplasia) B. Disurbance of proliferation and maturation of erythrocytes: 1.Defective DNA synthesis (megaloblastic anemias) 2.Defective Hb synthesis: a/. Deficient heme synthesis (iron deficiency) b/. Deficient globin synthesis (thalassemia) 3. Unknown or multiple mechanisms (anemia of chronic disease, anemia of marrow replacement)
    • Etiologic classification of anemias (2)II. Increased rate of destruction (hemolytic anemias) A. Intrinsic abnormalities Hereditary 1. Red cell membrane defects (hereditary spherocytosis, hereditary eliptocytosis) 2. Red cell enzyme deficiencies a/. Glycolytic enzymes: pyruvate kinase, hexokinase b/. Enzymes of hexose monophosphate shunt: G-6PD, glutathione synthetase 3. Disorders of globin synthesis a/. Deficient globin synthesis (thalassemia) b/. Structurally abnormal globin synthesis (sickle cell anemia, unstable hemoglobins) Acquired 1. Membrane defect: paroxysmal nocturnal hemoglobinuria
    • Etiologic classification of anemias (3) B. Extrinsic abnormalities 1. Antibody mediated a/. Autoantibodies (idiopathic, drug-associated, SLE, malignancies) b/. Isohemagglutinins (transfusion reactions, erythroblastosis fetalis) 2. Mechanical trauma of RBC a/. Microangiopathic hemolytic anemias (thrombotic thrombocytopenic purpura, DIC) b/. Cardiac traumatic hemolytic anemia 3. Chemicals and microorganisms 4. Sequestration in mononuclear phagocytic system - hypersplenism
    • 8Classification of Anemia
    • Classification of Anemia
    • Morphologic classification of anemias Type MCV MCHC Common cause________________________________________________________Macrocytic anemia increased normal Vitamin B12 deficiency Folic acid deficiencyMicrocytic anemia - hypochromic decreased decreased Iron deficiency Thalassemia - normochromic decreased normal Spherocytosis or normalNormocytic anemia normal normal Aplastic anemia - normochromic Chronic renal failure Some hemolytic anemia
    • Classification of Anaemia:Microcytic Hypochromic MCV <80fl MCH <27pg Iron deficiency
    • Microcytic anaemiaFerritin >25ug/L Thalassaemia Sideroblastic anaemia (some cases) Anaemia of chronic disease (some cases) Lead poisoning
    • Classification of Anaemia:Normocytic Normochromic MCV 80-100fl MCH >26pg Often incidental finding in systemic disorders May be first manifestation of a systemic disorder Many haemolytic anaemias Anaemia of chronic disease (some cases) After acute blood loss Bone marrow failure, e.g. Post-chemotherapy, infiltration by carcinoma etc
    • Classification of Anaemia:Macrocytic MCV >100fl Megaloblastic: vitamin B12 or folate deficiency Non-megaloblastic: alcohol, liver disease, myelodysplasia, aplastic anaemia
    • Iron deficiency anaemiaAssess for Dietary Iron deficiency Malabsorption- coeliac Chronic blood loss Gastrointestinal Menorrhagia
    • Iron deficiency anaemia
    • THALASSEMIAS:Defects of Hb synthesis Hemoglobin molecule heme heme Thalassemia- : -globin chain synthesis or ( ) Thalassemia- : -globin chain synthesis or ( )
    • 18Globin chain synthesis: developmental phases
    • GEN PENYANDI SINTESIS RANTAI GLOBIN DAN 2 2 1Gen & sejenis Kromosom 16 G AGen & sejenis Kromosom 11 Hb Gower 1 ( 2 2)Hemoglobins Hb Gower 2 HbF HbA2 HbA ( 2 2) ( 2 2) ( 2 2) ( 2 2) Hb Portland ( 2 2)Masa Embrio Janin DewasaPerkembangan
    • 20 Human Hemoglobins embryonic fetal adultHb Gower 1 ( 2 2) Hb F ( 2 2) Hb A ( 2 2): 95-97%Hb Gower 2 ( 2 2) Hb A2 ( 2 2): 4%Hb Portland 1 ( 2 2) Hb F ( 2 2): <1%Hb Portland 2 ( 2 2) Hb switches: 2 major •birth: fetal to adult
    • 21Normal Hb F levels newborn 70-90% 6 months old 2-13% 1 year 1-5% 2 years <2%information on age of patient is important:interpretation of Hb levelspremature: delay in Hb switch (fetal to adult)
    • 22How is Thalassemia Classified? Thalassemia      thalasemia hemoglobinopathies
    • Genotypes to phenotypes of thalassemia Molecular defects (mutations) -globin gene -globin gene ( -thalassemia) ( -thalassemia)-globin chains /- -globin chains /- Excess of Excess of-globin chains (fetus) -globin chains-globin chains (adult)
    • 24Pathophysiology of thalassemia syndromes globin chain imbalance (excess or chains) excess chains precipitate in RBC RBC damage •ineffective erythropoiesis •peripheral hemolysis anemia
    • 25Clinical aspects: thalassemia syndromessyndrome clinical age of need for presentation BT trait asymptomatic any age none ( normal Hb) thal- moderately after age 2 or none, occ intermedia severe later some(7-10 gm/dl) thal- ( 0/ 0) severe 1-2 regular major(<7 gm/dl) ( 0/ 0)) fatal in-utero / birth
    • 26Beta-thal syndromes trait : + or 0 thalassemia-intermedia  / + +  / + 0 thalassemia-major: / 0 0
    • Identification of classical beta-thalassemia traitin an adulthallmark for classical beta-thalassaemia trait:raised Hb A2 27
    • 28 Hb subtypes in the newborninformation on age of patient is important: full-term or premature  Hb subtypes in normal newborn  F( 2 2): 70-90%  A( 2 2): 10-30% *A2( 2 2): 0% (not measurable by HPLC)
    • THALASSEMIA-βHETEROZIGOT HOMOZIGOT βo HOMOZIGOT β+ dan β+ • Asimptomatik • Anemia berat sejak usia < 1 • Anemia ringan sampai berat • Anemia ringan s/d berat tahun • Hati dan limpa normal atau • Hb 8-15 g/dL (rata-rata 12) • Perlu transfusi rutin membesar • MCV < 80 fl • Hati dan limpa membesar • Masih mempunyai HbA • HbA2 > 3.5% • MCV < 70 fl • HbF dari 10 s/d > 90% • HbF ≥ 1% • Jenis Hb hanya HbA2 and HbF • HbF > 90%
    • 30Clinical severity of -thal syndrome: related to number offunctional -globin genes functional globin genes trait mild ( +) -thal 2 (- / ) 3 severe ( 0) -thal 1(--/ ) 2 Hb H disease moderate 0 / + (--/- ) 1 more severe 0 / T (--/ T) 1 Hb Bart’s hydrops 0 / 0 (--/--) 0 fetalis
    • 31 0 or -thal 1 trait  H inclusion test positive: 1 RBC cell per 5000 or 10,000 RBC may be negative cannot be done in newborn `golf ballinclusions’
    • 32Presumptive identification of -thalassemia in newborns  anemia Hb  MCV<105 fl  MCH<27pg  Hb Bart’s >5%
    • 33Levels of Hb Bart’s ( 4) in -thalassemia in newborns syndrome genotype Hb Bart’s (%) normal / 0 trait - / 0.5-3 --/ 4-8 - /- 9-13 Hb H disease --/- 19-27% Hb Barts hydrops --/-- 97-100 fetalis Pootrakul et al 1975
    • 34BioRad Variant HPLC: -thal short program
    • FENOTIP THALASSEMIA - (CARRIER) Normal - /- - / / Normal N/anemia ringan Normal MCH : 27-31 pg < 25 pg 25-27pg HbA2 : 2.5-3.5% normal or ↓ normal or ↓ HbF : <1% ↓ atau (-) ↓ atau (-)
    • FENOTIP THALASSEMIA - (PENDERITA) Normal / --/-- - -/- 4=HbBart 4=HbHAdult FetusMCH : < 26-32 pg • Kematian janin • HbH diseaseHbA2 : 2.5-3.5% (28-32 minggu) • mild to severe anemiaHbF : <1% • Hydrops fetalis
    • HbBart’ hydrops fetalis Hb variant analysis HbBart AFFECTED HbH Normal fetus HbF 32 weeks gestational age HbA
    • Diagnosis Thalassemia Anamnesis/pedigree Pemeriksaan Fisik Pemeriksaan laboratorium
    • Anamnesis/Pedigree Pucat lama (kronik) Riwayat keluarga dengan penyakit serupa Ras Anorexia Gangguan Pertumbuhan
    • Probability Thalassemia Orang Tua Thalassemia Trait Orang Tua Thalassemia Trait Thalassemia Thalassemia Normal Trait Mayor
    • Probability Thalassemia Orang Tua Orang Tua Thalassemia Thalassemia Mayor Trait Thalassemia Thalassemia Thalassemia Thalassemia Trait Mayor Trait Mayor
    • Probability Thalassemia Orang Tua Orang TuaThalassemia Normal Trait Thalassemia Normal Trait
    • Pemeriksaan fisik► Sangat bervariasi (ringan berat)► Pucat► Gizi kurang► Pertumbuhan kurang/lambat► Facies mongoloid/ Cooley► Hepar dan limpa membesar► Fraktura patologis
    • Thalassemia Mayor Cooley’s face Hairy Skull
    • Pemeriksaan laboratorium (1)Darah perifer: - Hb rendah / normal - MCV <80fl dan MCH <27pg, - Retikulosit agak meningkat - Jumlah leukosit normal - Hitung jenis normal
    • 46Pemeriksaan Hematologi MCV : ukuran eritrosit dibandingkan dengan inti limfosit kecil (Normal) MCH : warna eritrosit atau content dari hemoglobin RDW : perbedaan ukuran eritrosit. semakin besar variasi eritrosit semakin besar RDW
    • 47 Pemeriksaan Hematologi RDW-SD:mengukur lebar kurva. Bila kurva makin lebar makan RDW SD semakin lebar  Nilai Normal :  perempuan: 36.4 – 46.3fL  Laki-laki: 35.1 – 43.9fL RDW-CV: dihitung dengan formula: RDW-CV = 1SD/MCV x 100 % 1SD merupakan variasi eritrosit sekitar mean ukuran eritrosit  Nilai Normal :  perempuan: 11.7 – 14.4 %  Laki-laki: 11.6 – 14.4 %
    • Anemia Iron Deficiency Anemia Suspected Thalassemia Messwerte <RBC-Histogram> Measurement Data Measurement Data<RBC-Histogram> Messwerte RBC + 5.97 x1012/L RBC 4.48 x1012/L 12.7g/dl HGB HGB – 8.8g/dl 41.1% HCT HCT – 29.3% MCV – 68.8fl MCV – 65.4fl MCH – 21.3pg MCH + 19.6pg MCHC – 30.9g/dl MCHC 30.0g/dl 14.7% RDW-CV RDW-CV 18.2%<PLT-Histogram> <PLT-Histogram> Measurement Data PLT 391 x109/L Measurement Data PDW 12.0fl Messwerte MPV 10.3fl PLT 235 x109/L P-LCR 27.3% PDW 11.7fl MPV 9.4fl P-LCR 21.7% (x 1000) (x 1000)
    • Anisocytosis Case 1 Case 2 RBC-Histogramm Messwerte<RBC-Histogram> Measurement Data <RBC-Histogram> Measurement Data RBC-Histogramm Messwerte RBC 4.15 x1012/L RBC 2.95 x1012/L HGB 14.0g/dl HGB 9.9g/dl HCT 40.8% HCT 28.7% MCV 98.3fl MCV 97.3fl MCH 33.7pg MCH 33.6pg MCHC 34.3g/dl MCHC 34.5g/dl + 26.4% RDW 22.7% RDW + <PLT-Histogram> Measurement Data <PLT-Histogram> PLT PL* 98 x109/L Messwerte Measurement Data PDW DW ---.-fl MPV PL ---.-fl PLT 328 x109/L P-LCR PL -.---% PDW 12.4fl MPV 10.2fl P-LCR 26.5% (x 1000) (x 1000)
    • Pemeriksaan laboratorium (2)Sedian hapus darah tepi : Khas, gambaran hemolitik kronik - Mikrositik Hipokrom - Anisositosis - Poikilositosis - Sel target - Fragmentosit - Eritrosit berinti (berat)
    • Gambaran Sediaan Hapus ThalassemiaMikrositik Hipokrom Anisositosis Poikilositosis Sel Target Fragmentosit Eritrosit berinti
    • Mikrositik Hipokrom Bukan Thalassemia Anemia def besi Elliptocytosis Stomatocytosis Spheroscytosis
    • Pemeriksaan laboratorium (3) Elektroforesis Hb Analisa Hb (HPLC) DCIP Analisis DNA
    • Elektroforesis Hb
    • Diagram migrasi fraksi Hb hasil elektroforesa pada pH alkali & asam H Bart’s+ Portland + C A F Origin H S S, D, G, Lepore A, A2, D, E, G, O A2, E, C Lepore Constant spring F, Bart’s, Portland- Origin - pH alkali (8,5) pH asam (6.0) (Pemeriksaan Laboratorium Klinik Thalassemia & Hemoglobin Varian; Riady Wirawan, Dr, SpPK FKUI, 1997)
    • Digunakan alat HPLC VariantTes-tes Hb yang dapat dilakukan di alat Variant : Beta Thal Short Sickle Cell Short Alpha Thal Short Globin Chains HbA1c
    • A S F C A2
    • 300 points with 15 zones Curve
    • Normal Hb Type
    • Beta thal heterozygote
    • Hb E heterozygoye E A2
    • Hb Constant Spring homozygote
    • Hb Bart’s(Baby’s blood) Hb Bart Hb F Hb A Hb Bart’s
    • Alpha thalassemia with Hb H Hb Hb A H Alk. H A A2Hb H Anh. Hb A2 Car. N
    • Badan Inklusi HbHHbH adalah hemoglobin yang tidak stabil akanmengalami denaturasi oksidatif dan presipitasijika eritrosit terpapar dengan zat warna newmethylene blue atau brilliant cresyl blue danmembentuk gambaran seperti “bola golf” Badan inklusi HbH dijumpai pada eritrosit penderita :- HbH- Thalassemia a-1 trait, (1/100–1/10.000 eritrosit),
    • HbH disease HbH inclusion bodies
    • 67Limitations in new born adult with thalassemia normal newbornBlood counts Hb: N or High Hb (14-20 g/dl) MCV<80 fl, MCH<27pg MCV fl>105 fl, MCH>27pgBlood films Hypochromia Effects of relative Thalassemia picture hyposplenismHb subtypes Hb A2:4% -thal trait Hb F: 90-100% Hb F(95-100%): -thal major Hb A: 5-20% Hb A2: not measurableH-inclusion test -thalassemia: + cannot be used
    • Thalassemia merupakan penyakit yang dapatmenurunkan kualitas hidupMemerlukan biaya yang cukup besar untuk terapithalassemia (terutama pasien thalassemia yangmembutuhkan transfusi sepanjang hidupnyaInsiden thalassemia dapat diminimalkan melaluipemeriksaan skrining yang optimal (Total Solution)Meningkatkan kesadaran masyarakat mengenaipenyakit thalassemia dan akibatnya
    • terima kasih 70