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Anemia pds patklin
- 1. Agus Susanto Kosasih LaboratoriumPatologi Klinik RS Kanker Dharmais 1
- 2. 2 Definition of anaemia Anaemia is defined as a reduction in the haemoglobin concentration of the blood This results in a decreased oxygen carrying capacity
- 3. PATHOLOGY, SYMPTOMS, ANDSIGNS OF ANEMIA
- 4. Normal values forperipheral blood Female Male Erythrocytes (per µl) 4.8±0.6x106 5.4±0.8x106 Hemoglobin (g/dl) 14 ± 2 16 ±2 Hematocrit (%) 42 ±5 47 ±5 Reticulocytes (%) 1 1 ___________________________________________ Mean corpuscular volume (MCV; µm3) 82-92 Mean corpuscular hemoglobin (MCH; pg) 27-32 Mean corpuscular hemoglobin concentration (MCHC; %) 32-36
- 5. Etiologic classification ofanemias (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)
- 6. Etiologic classification ofanemias (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
- 7. Etiologic classification ofanemias (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
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- 10. Morphologic classification ofanemias Type MCV MCHC Common cause ________________________________________________________ Macrocytic anemia increased normal Vitamin B12 deficiency Folic acid deficiency Microcytic anemia - hypochromic decreased decreased Iron deficiency Thalassemia - normochromic decreased normal Spherocytosis or normal Normocytic anemia normal normal Aplastic anemia - normochromic Chronic renal failure Some hemolytic anemia
- 11. Classification of Anaemia: MicrocyticHypochromic MCV <80fl MCH <27pg Iron deficiency
- 12. Microcytic anaemia Ferritin >25ug/L Thalassaemia Sideroblastic anaemia (some cases) Anaemia of chronic disease (some cases) Lead poisoning
- 13. Classification of Anaemia: NormocyticNormochromic 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
- 14. Classification of Anaemia: Macrocytic MCV >100fl Megaloblastic: vitamin B12 or folate deficiency Non-megaloblastic: alcohol, liver disease, myelodysplasia, aplastic anaemia
- 15. Iron deficiency anaemia Assessfor Dietary Iron deficiency Malabsorption- coeliac Chronic blood loss Gastrointestinal Menorrhagia
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- 17. THALASSEMIAS: Defects of Hbsynthesis Hemoglobin molecule heme heme Thalassemia- : -globin chain synthesis or ( ) Thalassemia- : -globin chain synthesis or ( )
- 18. 18 Globin chain synthesis:developmental phases
- 19. GEN PENYANDI SINTESISRANTAI GLOBIN DAN 2 2 1 Gen & sejenis Kromosom 16 G A Gen & 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 Dewasa Perkembangan
- 20. 20 Human Hemoglobins embryonic fetal adult Hb 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
- 21. 21 Normal Hb Flevels 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)
- 22. 22 How is ThalassemiaClassified? Thalassemia thalasemia hemoglobinopathies
- 23. Genotypes to phenotypesof 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)
- 24. 24 Pathophysiology of thalassemiasyndromes globin chain imbalance (excess or chains) excess chains precipitate in RBC RBC damage •ineffective erythropoiesis •peripheral hemolysis anemia
- 25. 25 Clinical aspects: thalassemiasyndromes syndrome 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
- 26. 26 Beta-thal syndromes trait : + or 0 thalassemia-intermedia / + + / + 0 thalassemia-major: / 0 0
- 27. Identification of classicalbeta-thalassemia trait in an adult hallmark for classical beta-thalassaemia trait: raised Hb A2 27
- 28. 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)
- 29. THALASSEMIA-β HETEROZIGOT 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%
- 30. 30 Clinical severity of-thal syndrome: related to number of functional -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. 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 ball inclusions’
- 32. 32 Presumptive identification of-thalassemia in newborns anemia Hb MCV<105 fl MCH<27pg Hb Bart’s >5%
- 33. 33 Levels of HbBart’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
- 34. 34 BioRad Variant HPLC:-thal short program
- 35. 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 (-)
- 36. FENOTIP THALASSEMIA - (PENDERITA) Normal / --/-- - -/- 4=HbBart 4=HbH Adult Fetus MCH : < 26-32 pg • Kematian janin • HbH disease HbA2 : 2.5-3.5% (28-32 minggu) • mild to severe anemia HbF : <1% • Hydrops fetalis
- 37. HbBart’ hydrops fetalis Hb variant analysis HbBart AFFECTED HbH Normal fetus HbF 32 weeks gestational age HbA
- 38. Diagnosis Thalassemia Anamnesis/pedigree Pemeriksaan Fisik Pemeriksaan laboratorium
- 39. Anamnesis/Pedigree Pucat lama (kronik) Riwayat keluarga dengan penyakit serupa Ras Anorexia Gangguan Pertumbuhan
- 40. Probability Thalassemia Orang Tua Thalassemia Trait Orang Tua Thalassemia Trait Thalassemia Thalassemia Normal Trait Mayor
- 41. Probability Thalassemia Orang Tua Orang Tua Thalassemia Thalassemia Mayor Trait Thalassemia Thalassemia Thalassemia Thalassemia Trait Mayor Trait Mayor
- 42. Probability Thalassemia OrangTua Orang Tua Thalassemia Normal Trait Thalassemia Normal Trait
- 43. Pemeriksaan fisik ► Sangat bervariasi (ringan berat) ► Pucat ► Gizi kurang ► Pertumbuhan kurang/lambat ► Facies mongoloid/ Cooley ► Hepar dan limpa membesar ► Fraktura patologis
- 44. Thalassemia Mayor Cooley’s face Hairy Skull
- 45. Pemeriksaan laboratorium (1) Darahperifer: - Hb rendah / normal - MCV <80fl dan MCH <27pg, - Retikulosit agak meningkat - Jumlah leukosit normal - Hitung jenis normal
- 46. 46 Pemeriksaan 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. 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 %
- 48. 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)
- 49. 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)
- 50. Pemeriksaan laboratorium (2) Sedianhapus darah tepi : Khas, gambaran hemolitik kronik - Mikrositik Hipokrom - Anisositosis - Poikilositosis - Sel target - Fragmentosit - Eritrosit berinti (berat)
- 51. Gambaran Sediaan HapusThalassemia Mikrositik Hipokrom Anisositosis Poikilositosis Sel Target Fragmentosit Eritrosit berinti
- 52. Mikrositik Hipokrom BukanThalassemia Anemia def besi Elliptocytosis Stomatocytosis Spheroscytosis
- 53. Pemeriksaan laboratorium (3) Elektroforesis Hb Analisa Hb (HPLC) DCIP Analisis DNA
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- 55. Diagram migrasi fraksiHb 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)
- 56. Digunakan alat HPLCVariant Tes-tes Hb yang dapat dilakukan di alat Variant : Beta Thal Short Sickle Cell Short Alpha Thal Short Globin Chains HbA1c
- 57. A S F C A2
- 58. 300 points with15 zones Curve
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- 61. Hb E heterozygoye E A2
- 62. Hb Constant Springhomozygote
- 63. Hb Bart’s (Baby’s blood) Hb Bart Hb F Hb A Hb Bart’s
- 64. Alpha thalassemia withHb H Hb Hb A H Alk. H A A2 Hb H Anh. Hb A2 Car. N
- 65. Badan Inklusi HbH HbHadalah hemoglobin yang tidak stabil akan mengalami denaturasi oksidatif dan presipitasi jika eritrosit terpapar dengan zat warna new methylene blue atau brilliant cresyl blue dan membentuk gambaran seperti “bola golf” Badan inklusi HbH dijumpai pada eritrosit penderita : - HbH - Thalassemia a-1 trait, (1/100–1/10.000 eritrosit),
- 66. HbH disease HbH inclusion bodies
- 67. 67 Limitations in newborn adult with thalassemia normal newborn Blood counts Hb: N or High Hb (14-20 g/dl) MCV<80 fl, MCH<27pg MCV fl>105 fl, MCH>27pg Blood films Hypochromia Effects of relative Thalassemia picture hyposplenism Hb subtypes Hb A2:4% -thal trait Hb F: 90-100% Hb F(95-100%): -thal major Hb A: 5-20% Hb A2: not measurable H-inclusion test -thalassemia: + cannot be used
- 68. Thalassemia merupakan penyakityang dapat menurunkan kualitas hidup Memerlukan biaya yang cukup besar untuk terapi thalassemia (terutama pasien thalassemia yang membutuhkan transfusi sepanjang hidupnya Insiden thalassemia dapat diminimalkan melalui pemeriksaan skrining yang optimal (Total Solution) Meningkatkan kesadaran masyarakat mengenai penyakit thalassemia dan akibatnya
- 70. terima kasih 70