1. Iron deficiency anemia Tsila Zuckerman

2. Anemia Definition : Decreased RBC mass and HB concentration Anemia is a result of imbalance between between RBC production and destruction Hypo-regenerative anemia is due to decreased RBC production secondary to impaired marrow function or lack of erythropoietin stimulus Hyper- regenerative anemia is due to increased peripheral RBC destruction

3. Each day 0.8% of RBC mass is exchanged by reticulocytes Normal retic count : 0.5 – 2% or 25 –125x10 9 /l Corrected retic count: %retic x patient HCT/45

4. Iron deficiency anemia The most common cause of anemia worldwide Pathogenesis : Imbalance between iron body requirement and reduced iron supply/increased lost

5. Microcytic Hypochromic Anemia Characterized by reduced RBC indices : MCV, MCH, MCHC Peripheral blood smear : small (microcytic) and pale (hypochromic) RBC Differential Diagnosis : Iron deficiency Thalassaemia Sideroblastic anemia Anemia of Chronic disease

7. Iron stores and transport Ferritin : main iron storage protein in the RES. Consists of 22 units of apoferritin and iron core. Each subunit binds  4500 atoms of iron Hemosiderin : Insoluble iron- protein complex derived from ferritin Transferin : Main iron transport protein in the blood. Normally 1/3 of iron binding sites are saturated

8. Total iron stores male 1000 female 500mg Daily iron loss 1mg

9. Iron absorption Average western diet contains 10–15 mg iron/day. 5-10% of dietary iron normally absorbed (1-1.5mg) Dietary iron is in the form of :  organic iron (heam or protein bound).  inorganic iron. Iron absorption occurs in the duodenum

10. Factors favoring absorption : Heam iron Vitamin C Acids Iron deficiency anemia Factors reducing absorption : Inorganic iron Alkalis- antacids Milk Tea Iron excess Increased iron requirement : Menstruating female,pregnancy,Infants, adolescence

12. Iron deficiency- clinical features Symptoms: Fatigue, weakness, palpitations, shortness of breath, headaches, decreased performance status,aggravation of angina pectoris Rare symptoms: Dysphagia, PICA syndrome Signs: pallor of mucous membranes, tachycardia, orthostatic hypotension, functional systolic murmur, glossitis, angular stomatitis, koilonychia

15. Laboratory workup CBC: Low HB MCV < 80fl Peripheral blood smear: microcytosis,hypochromia Body iron status: Serum iron 50-150  g/dl Transferrin 300-360  g/dl Ferritin 50-150  g/dl M,15-50  g/dl F MCV fl = HCT/RBC X 10 80-93fl

18. Cause of iron deficiency anemia Iron deficient diet (elderly, institutionalized, developing countries) Increased iron demands ( pregnancy,growth) Increased Iron loss (GIT, uterine) Malabsorption (post gastrectomy, celiac ) Stages of iron deficiency: Iron store depletion Iron deficient erythropoiesis Iron deficiency anemia

19. IDAFe def. Eryth Fe deplit  Fe stores Normal  Iron stores Iron over load 00+/-1+2-3+3-4+4+ Fe stores 410390360330- 360 330  30  300 Trasferrin  10 10  20  25100  60  250 Ferritin

20. Treatment of Iron deficiency Treatment according to severity of anemia and etiology. In adults : GIT workup mandatory. In case of iron loss  treat the cause. Oral iron: Ferrous sulfate 325mg x 1-3/d for 3-6 month Parenteral treatment : for patients with malabsorption / oral iron intolerance

22. Aplastic Anemia Definition: pancytopenia resulting from defective hematopoiesis. Pathogenesis: stem cell failure due to intrinsic damage to stem cell or an immune reaction against stem cells Epidemiology: 1000 new cases/year in USA peak incidence: 30 years, more common in Asia

23. Etiology Idiopathic 50-60% Acquired Congenital

24. Acquired AA Drugs: * Dose related mechanism chemotherapy,sulfa, chloramphenicol * Idiosyncratic mechanism chloramphenicol,indometacin,gold Radiation Chemicals:benzene,insecticides,hair dyes Viral: hepatitis A viruse

25. AA – Clinical Features Insidious/acute presentation Symptoms and signs related to Anemia  weakness, fatigue, pallor Neutropenia  infections Thrombocytopenia  purpura,epistaxis,gingival bleeding,GIT bleeding

26. Diagnosis of AA CBC : Anemia normocytic/normochromic Reticulocyte count < 1% Thrombocytopenia Leukopenia Bone marrow : hypocellular marrow

29. Severe AA : defined by presence of  2 above criteria 1. Neutrophils < 500 2. Platlets < 20,000 3. Reticulocytes < 20,000 / < 1% Super severe AA : Neutrophils < 200 Differential Diagnosis: Acute Myeloid Leukemia Myelodysplastic syndrome

30. Treatment Supportive Treatment : RBC transfusion Platelet transfusion Aggressive antibiotics Definitive treatment : Immuno suppressive treatment - Anti thymocytic globulin - Cyclosporine Allogeneic stem cell transplantation