Minimal Requirement for Concepts of Anemia

1. Minimal Requirement for Concepts of Anemia 林建廷 Dec 12, 2009

2. Erythrocyte Development EPO: 90% from kidney 10% from liver

3. Hemoglobin Fe + protoporphyrin α2β2 ↓ ↓ heme + globin ↓ Hb

4. Two main approaches for anemia that are not mutually exclusive: 1. Kinetic approach 2. Morphological approach

5. Kinetic approach of Anemia Production? Survival/ Destruction? The key test is the …..

6. Reticulocyte Production Index— an estimate of marrow production relative to normal Hct • Corrected Ret= Ret(%) * 45 Corrected Ret RPI= Maturation index

7. RPI (kinetic approach) • RPI are the most helpful: • extremely low (<0.1%) • AA/ PRCA are the first considerations • extremely high (>3%) • Blood loss/ hemorrhage • Hemolytic anemia (although 25% AIHA have normal RPI)

9. MCV>115 Vit B12, Folate Drugs that impair DNA synthesis (AZT, chemotherapy, azathioprine) MDS MCV 100 - 115 Ditto Reticulocytosis Hypothyroidism Alcoholism/ liver dz Morphological Approach-1

10. Normocytic (MCV 80-100) Anemia of chronic disease (ACD) Mixed deficiencies Renal failure BM dz (ex AA, MDS, MM…) Microcytic (MCV<80) Iron deficiency anemia Thalassemia Anemia of chronic disease (ACD, 30-40%) Sideroblastic anemia Pb intoxification Morphological Approach-2

11. Iron and IDA

12. Distribution of Iron in Adults

13. Storage iron Circulating iron  RBC iron  Tissue iron

14. Harrison’s Principles of Internal Medicine 15th Ed. 2001

15. IDA Presentation Presentation Diagnosis Ferritin: low (N=20-300) Iron/TIBC <16% (N=~33%) BM iron stain • Progressive MCV ↘ • Progressive RBC ↘ • Typically high RDW • Typically high MCV/RBC • Typically mild PLT ↑

16. Causes of IDA Increased iron requirement Inadequate iron supply Poor nutritional intake Malabsorption Gastrectomy (may also has Vit B12 deficiency) • Hypermenorrhea • GI blood loss– hemorrhoid, PUD, GI cancer, angiodysplasia • Factitious removal • Hemolysis • Hemodialysis • Hookworm infestation • Rapid growth of teenage • Pregnancy and lactation

17. Iron Supply • Oral: usually 3 months to restore iron storage • Ferrum chewable (Fe 3+) 100mg/tab • Hematonic (Fe 2+) 50mg/tab • IV • Atofen (!! Risk of allergy and anaphylaxis—0.6%)

18. Thalassemia

20. Hb Gene Harrison’s Principles of Internal Medicine 15th Ed. 2001

21. Thalassemia Presentation Presentation Diagnosis Exclude IDA Hb electrophoreis: Hb A2>3.5% or HbF>2%  β-thalassemia HbH(+)  α-thalassemia with ¾ defect (HbH dz) HbA2 and HbF: N  α-thalassemia with ¼ or 2/4 defect Gene diagnosis • Constant low MCV • Constant high RBC • Typically low RDW • Typically low MCV/RBC • Typically iron storage ↗

22. Gene Level of Thalassemia in Taiwan • α-thalassemia: Prevalence 4% • --SEAα0 deletion • -α3.7 deletion • -α4.2 deletion • HbQS or HbCS • β-thalassemia: Prevalence 2% • Codon 41/42 TCTT deletion β0 • IVS II 654 C-> T point-mutation β0 • Codon 17 A-> T β0 • Promoter 28 A-> G β+ • HbE (Codon 26 G-> A) β+ • ??% α + β-thalassemia (Severity?)

23. 優生學的理由 β –Major (終身輸血) Hb H disease (黃疸) Hydrops fetalis (死胎)

24. Thalassemia Treatment • Mild: None • Severe: • Folic acid • RBC transfusions + iron chelators • Allo-SCT

25. Comparison of Iron Chelators

26. Deferasirox (Exjade) • Common adverse effect: • Cre elevation (40%), (ref. 14% in DFO) • Proteinuria (18%) • GI (abd pain, N/V, diarrhea, 10-15%) • Hepatitis (8%) • Headache (15%), skin rash (11%) • No agranulocytosis, neutropenia or arthralgia • Pregnancy safety: • FDA category B

27. Megaloblastic Anemia

29. Megaloblastic Anemia Presentation Presentation Diagnosis ??Schilling test Low Vit B12 or folic acid Vit B12: 270~400: empirical try Vit B12< 270: definite deficiency • High high MCV • Pancytopenia • Hypersegmented PMN • Typically high RPI, hemolysis (LDH ↗), indirect hyperbilirubinemia • Tinnitus or other neurological presentation • Vegetarism (奶, 蛋, 維他命) • Gastrectomy or Pernicious anemia

30. Remember Pancytopenia • P: PNH • A: Asplatic anemia • N: Neoplasm/ Near neoplasm (including MDS) • C: Cirrhosis/ Connective tissue disease • Y: Vit B12/ Folic acid • T: Toxin/ Drug • O: Overwhelming sepsis (Hemophagocytic syndrome)/ Others

31. Vit B12/Folate Deficiency Anemia Treatment • Vit B12 deficiency: • Vit B12 1 mg im qd *5 q1wk *4  q1m*3  q6m • R/I pernicious anemia (Anti-parietal Ab, anti-IF Ab and PES) • Thyroid dz • Gastric cancer • Folate deficiency: Improved diet, folic acid

32. Usually rapid responseMost important F/U Reticulocyte, LDH Harrison’s Principles of Internal Medicine 15th Ed. 2001

33. Hemolytic Anemia

34. Is there hemolysis? • Damaged RBCs on smear • spherocytes (immune hemolysis, HS) • RBCs fragments (microangiopathic anemias) • Marrow response to hemolysis • polychromasia on smear • reticulocytosis • erythroid hyperplasia in marrow • Biochemical evidence of RBCs destruction • Indirect hyperbilirubinemia • increased LDH • decreased/absent haptoglobin

35. Extravascular vs Intravascular hemolysis Extravascular Intravascular Test Hemolysis Hemolysis LD á áá bilirubin á á haptoglobin N to absent absent hemoglobinuria absent present free Hb in plasma absent present urine hemosiderin absent present

36. An approach to hemolytic anemia Hemolytic anemia Immune Non-immune Congenital Acquired • Autoimmune • Alloimmune • Drug-induced • Defects of: • Membrane/ skeleton • (eg. Hereditary spherocytosis) • Enzymes • (eg. G6PD deficiency) • Hemoglobinopathy • PNH • Infections • sepsis • malaria • Mechanical • Prosthetic heart valve • Microangiopathic HA (TTP, HUS, DIC) • Hypersplenism

37. AIHA and DAT reactions

38. D/D of AIHA

39. Hepcidin and Anemia of Chronic Disease

41. D/D of ACD and IDA ACD may concurrently coexist with true iron deficiency (In this situation, iron/TIBC is more reliable than ferritin)

42. ACDTreatment