Tabuk University

1. Tabuk University Hematology – 1, MLT 205 Sideroblastic anemia, Anemia of chronic disease & Lead Poisoning Faculty of Applied Medical Sciences Department Of Medical Lab. Technology 2nd Year – Level 4 – AY 1433-1434 Mr. Waggas Ela’as, M.Sc, MLT

2. Objectives: • Identify, classify and know the pathogenesis of Sideroblastic anemia. • Identify ring sideroblasts, and their presence in the bone marrow. • List the lab findings of Sideroblastic anemia • Identify, classify and know the pathogenesis of anemia of chronic diseases. • List the lab findings of anemia of chronic diseases. • Express the lead poisoning and its route . • Identify Basophilic stippling found in Sideroblastic anemia & lead poisoning.

3. Sideroblastic anemias are group of disorders commonly linked in defect in Haem synthesis.In Sideroblastic anemia erythrocytes are prevented from absorbing iron, consequently lesshemoglobin is produced. Due to less absorption of iron by the red cells, iron is accumulated in the body, and the metabolism mechanisms of the body are turned to produce more iron, which in turn never gets absorbed in the red blood cells and iron further gets concentrated in the bones and other body organs.

4. Characterized by • Increase in total body iron • Presence of ringed sideroblasts in bone marrow (iron incorporated in erythroblasts is not used to form Haem, so it is deposited in mitochondria that make a ring around the nucleus) • Hypochromic anemia.

5. Classification (according to causes) • Hereditary form (Disturbances of enzymes regulating heme synthesis) • Acquired form (more common) • primary – MDS(Myelodysplastic syndrome) • Secondary : (Nutritional deficiencies (copper, vitamin B6),Lead poisoning, Zinc overdose, Alcohol, Drugs (eg, antituberculous agents, antibiotics), Idiopathic)

6. Clinically • moderate to severe anemias with Hb levels between 4 to 10g/dl. • usual symptoms of anemia including fatigue, decreased tolerance to physical activity, and dizziness.

7. Iron overload Capacity of serum transferrin to bind iron is exceeded EFFECTS OF IRON OVERLOAD Non-transferrin-bound iron (NTBI) circulates in the plasma Excess iron promotes tissue damage Excess iron promotes the generation of free hydroxyl radicals, propagators of oxygen-related tissue damage Liver damage or cancer Cardiac failure Diabetes mellitus Growth failure

8. Laboratory findings – Peripheral Blood • Moderate to severe anemia : Low Hb. • Decreased MCV and MCH in hereditary type but MCV is increased in acquired type. Target cells • Basophilic stippling. • Increased ferritin levels. • Normal TIBC. • Serum Iron: High. • High transferrin saturation.

9. Basophilic stippling • Aggregation of ribosomal RNA in the cytoplasm of erythrocytes. These aggregates stain, and hence are visible, with routine hematology stains.

10. Bone marrow • Sideroblastic anaemia is diagnosed when 15% or more of marrow erythroblasts are ring sideroblasts but they can be found at lower numbers in a variety of hematological conditions. • Ringed sideroblasts are stained by special stain: (Perl,s Prussian Blue stain ).

11. Lead poisoning • Lead is a heavy metal that has long been used in the manufacturing of paintالدهانات , plumbing pipes اللحام, leaded gasoline, batteries and many other products. When products containing lead deteriorate, tiny lead particles can contaminate homes and the environment.

12. Lead poisoning * Lead inhibits both haem and globin synthesis at a number of points. (interferes with the activity of the enzyme delta-aminolevulinic acid dehydratase) * In addition it interferes with the breakdown of RNA and causing accumulation of denatured RNA in red cells, basophilic stippling on the ordinary staining. *The anaemia may be hypochromic or predominantly haemolytic, and the bone marrow may show ring sideroblasts. * Free erythrocyte protoporphyrin is raised.

13. Basophilic stippling of erythrocytes in lead poisoning

14. Anemia of chronic disease =Anemia of chronic disorders (ACD)

15. Anemia of chronic disease(ACD) * ACD is a common type of anemia that occurs in patients with infectious, inflammatory, or neoplastic diseases that persist for more than 1 or 2 months. * Probably it is the second most common form of anemia. (what is the 1st most common form?) * ACD is the most common cause of anemia in hospitalized patients.

16. Causes of ACD • Chronic infections : tuberculosis, lung abscess, sub acute endocarditis • Non infectious inflammatory diseases : rheumatoid arthritis, systemic lupus erythematosus. • Neoplastic Disorders : Hodgkin`s disease, lung and breast carcinoma.

17. Pathogenesis 1. Shortened red cell life span(from 120 to 60-90 days) 2. Relative bone marrow(erythropoiesis) failure: - Cytokines released from inflammatory cells (TNF-, IL-1, IFN-) affects erythropoiesis by inhibiting the growth of erythroid progenitors. 3. ABNORMAL IRON METABOLISM • activation of the reticuloendothelial system with increased iron retention and storage within it. • impaired release of iron from macrophages to circulating plasma transferrin.

18. laboratory findings • The anemia is usually mild or moderate ( Hb 7-11g/dl) • The anemia is most often normochromic and normocytic (MCHC and MCV are normal) (but in one third of the cases it presents as hypochromicmicrocytic) • Iron metabolism 1. Serum Iron - decreased(it is necessary for the diagnosis of ACD) 2. TIBC - reduced 3. Transferrin saturation(TS) – normal/ decreased 4. Serum Ferritin-increased / normal

19. Normocytic normochromic red cells

20. Microcytic hypochromic red cells

21. The bone marrow in ACD • The bone marrow structure and cellularity on biopsy and aspiration, are generally normal, except for alterations occasioned by underlying disease. So the bone marrow examination is rarely done for diagnosis of ACD.

22. Anemia of chronic disease (ACD) -differential diagnosis • Unlike other hypochromicanaemias, BOTHserum iron & TIBC are low in ACD.

23. DIFFERENTIAL DIAGNOSIS OF HYPOCHROMIC MICROCYTIC ANEMIAS The causes of hypochromic microcytic anemia include iron deficiency, thalassemias and other genetic disorders of hemoglobin, the anemia of chronic disorders, sideroblastic anemia, and lead poisoning. These causes may be differentiated by special tests, including measurement of serum iron, total iron-binding capacity, and serum ferritin.