Approach to RBC disorders, anemia microcytic

This is a PowerPoint presentation about RBC DISORDERS.

1. Approach to RBC disorders By: Biruk Mulat , M.D Assistant prof. of Internal Medicine Lecture for C1 Medical students Yekatit 20/2015

2. Outline Introduction Erythropoiesis Anemia Clinical approach to anemic patients IDA Megaloblastic anemia Hemolytic anemia

3. Introduction

4. Erythropoiesis

5. RBCs Biconcave disc A diameter of 7 to 8 μm Average volume of ~90 fL S urface area of ~140 μm A life span of ~120 days

6. Anemia Anemia has been defined as a reduction in one or more of the major RBC measurements obtained as a part of the CBC: hemoglobin concentration, HCT, or RBC count WHO criteria for anemia in adult males is hemoglobin <13 and in adult females is hemoglobin <12 g/dL

7. Cont’d Normal values might not apply in certain settings Causes of lower values Intense physical activity Pregnancy   Older age Causes of Higher values Smoking Medications/Drugs Hemoconcentration High altitude

8. RBC Indices The RBC indices describe RBC size, hemoglobin content, and uniformity of the RBC population . MCV, MCH, MCHC, RDW The MCV and RDW are generally the most useful

9. Clinical features T he cardinal signs and symptoms of anemia result from impaired oxygen delivery Symptoms of anemia also reflect the rate with which RBC mass declines, which determines the extent of compensatory changes Patients with anemia usually seek medical attention because of decreased work or exercise tolerance , shortness of breath , palpitations , or other signs of cardiorespiratory adjustments to anemia

10. Clinical features Headache, vertigo, tinnitus, faintness, scotomata , lack of mental concentration, drowsiness, restlessness, and muscular weakness are common symptoms of severe anemia Pallor-best detected in the mucous membranes of the mouth and pharynx, the conjunctivae, the lips, and the nail beds Other physical findings depending on the cause

11. Approach to anemic patients To identify the cause of anemia, information from the medical history and physical examination must be integrated with some key laboratory tests Is anemia associated with other hematologic abnormalities? Is there an appropriate reticulocyte response to anemia? If anemia is associated with reticulocytosis , is there any evidence for hemolysis? If anemia is associated with a lower than appropriate reticulocyte response, what are the RBC indices ?

12. Approach… There are two general approaches one can use to help identify the cause of anemia. ●A  kinetic approach , addressing the mechanism(s) responsible for the fall in hemoglobin concentration ●A  morphologic approach  categorizing anemias via alterations in RBC size (i.e., MCV) and the reticulocyte response

13. Approach… Absolute reticulocyte count (ARC) - the actual number of reticulocytes in 1L of whole blood. ARC= Reported retic .%XRBC count/100 Reference range- 25-75000 Corrected reticulocyte count - reticulocyte index CRC=Reported retic .% X patient’s Hct /normal Hct (45%) Reticulocyte production index (RPI) RPI=CRC/shift factor (maturation time)

14. Approach…

15. Iron deficiency anemia (IDA)

16. Introduction Iron is a critical element in the function of all cells

17. IDA Iron deficiency is one of the most prevalent forms of malnutrition Globally , 50% of anemia is attributable to iron deficiency and accounts for approximately nearly a million deaths annually worldwide

18. IDA-Causes

19. IDA-Clinical features The usual presenting symptoms in adults with iron deficiency are primarily due to anemia Pica, Restless leg syndrome A cardinal rule is that the appearance of iron deficiency in an adult male or post-menopausal female means GI blood loss until proven otherwise

20. Clinical features Pallor Dry or rough skin Blue sclerae Atrophic glossitis with loss of tongue papillae, which may be accompanied by tongue pain or dry mouth Cheilosis (also called angular cheilitis ) Koilonychia (spoon nails) Esophageal web, which may be accompanied by dysphagia ( eg , Plummer-Vinson or Patterson-Kelly syndrome; rare) Alopecia (rare) in especially severe cases Chlorosis (pale, faintly green complexion; extremely rare)

21. Diagnosis CBC ● Low RBC count ● Low Hgb and Hct ●Low absolute retic . count ●Low MCV and low MCH ● Increased Platelet count Peripheral morphology ● Anisocytosis ●Microcytic hypochromic RBCs Iron studies ● Low Transferrin saturation ● Low Serum Iron ● Low Serum Ferritin level The gold standard for documenting iron deficiency is an iron stain (Prussian blue stain) of a bone marrow aspirate smear

22. Treatment Regardless of the presence of symptoms, all patients with iron deficiency anemia and most with iron deficiency without anemia should be treated

23. Treatment

24. Treatment response Pica- often disappears almost as soon as oral or IV iron therapy is begun The patient will note an improved feeling of well-being within the first few days of treatment RLS- within 72hours Reticulocytosis - within 4 to 7 days

25. Response… The hemoglobin concentration will rise slowly, usually beginning after approximately 1 to 2 weeks of treatment, and will rise approximately 2 g/dL over the ensuing three weeks. The hemoglobin deficit should be halved by approximately one month, and the hemoglobin level should return to normal by 6 to 8 weeks

26. Megaloblastic anemia

27. Megaloblastic anemia Megaloblastic anemia is a term that refers to anemia in which the process of nucleic acid metabolism is impaired, resulting in nuclear-cytoplasmic dyssynchrony , reduced number of cell divisions in the bone marrow, and nuclear abnormalities in both myeloid and erythroid precursors

28. MBA- Causes

29. Cont’d Both vitamin B12 and folate deficiencies cause megaloblastic anemia The classic findings associated with vitamin B12 and folate deficiency include severe macrocytic anemia, yellow skin (caused by combined anemia and jaundice), and variable neurologic abnormalities more prominent in vitamin B12 deficiency (mental sluggishness, shuffling gait )

30. Vitamin B12 deficiency Cobalamin is synthesized solely by microorganisms T he only source for humans is food of animal origin, for example, meat, fish, and dairy products

31. Folate deficiency The duodenum and proximal jejunum is the principal site of folate absorption The highest concentrations of folate are found in liver, yeast, spinach, other greens, and nuts

32. Clinical findings Unexplained anemia, macrocytosis (MCV > 100fL ), pancytopenia, or hypersegmented neutrophils Unexplained neurologic or psychiatric symptoms Associated conditions, such as bariatric surgery, malnutrition, or strict vegan diet without appropriate supplementation

33. Diagnosis CBC and P/M ●Anemia ●Macrocytic or macroovalocytosis ● Mild leukopenia and/or thrombocytopenia ●Low reticulocyte count ● Hypersegmented neutrophils ● Low serum B12 ● Low RBC folate ● Elevated homocysteine and/or MMA

34. Diagnosis…

35. Treatment All individuals with documented vitamin B12 and/or  folate deficiency should be treated Urgency of correction Symptomatic anemia or neurologic or neuropsychiatric findings Pregnancy Neonates and infants Vit . B12- Cyanocobalamin , Hydroxocobalamin Folic acid

36. Treatment response A hematologic response to vitamin B12 and/or folic acid should occur within a predictable timeframe, provided that the bone marrow is functioning normally and there are no other causes of anemia

37. Response… Laboratory changes ● Hemolysis markers – Day 1 to 2 ● Reticulocytosis – Day 3 to 4 ●Anemia – Week 1 to 2 (initial improvement) and week 4 to 8 (normalization) ● Hypersegmented neutrophils – Day 10 to 14 ●Leukopenia and/or thrombocytopenia – Week 2 to 4

38. Hemolytic anemia

39. Hemolysis Causes of hemolysis can be categorized in various ways, including whether the abnormality is intrinsic or extrinsic to the RBC ( Intracorpuscular vs Extracorpuscular defects) whether the condition is Inherited or Acquired whether the hemolysis is Acute or Chronic whether the mechanism involves immune destruction due to antibodies ( Immune vs non-immune mechanism) and whether the hemolysis occurs in the vasculature or in the reticuloendothelial macrophages in the liver and spleen ( Intravascular vs Extravascular hemolysis )

40. Cont’d… Intravascular hemolysis refers to hemolysis that occurs primarily within the vasculature. This occurs when there is a considerable amount of structural damage to the RBC membrane ( e.g , mechanical shearing, complement MAC) or when the RES becomes overwhelmed Extravascular hemolysis refers to hemolysis that occurs primarily via macrophages of the reticuloendothelial system in the liver, spleen, bone marrow, and lymph nodes

41. Cont’d

42. Clinical features Helpful clues from the history and physical examination include the following, if present: ●Rapid onset of symptoms of anemia in the absence of bleeding ●Jaundice ● Dark urine is consistent with intravascular hemolysis ●Recent blood transfusion suggests possible acute hemolytic transfusion reaction ●Initiation of a new medication with potential for causing hemolysis suggests possible drug-induced etiology ●History of hemolytic anemia or unexplained anemia in family members suggests an inherited disorder; this is more likely if multiple first degree family members are affected. ●History of pigmented gallstones or presence of gallstones implies chronic hemolysis that overwhelms the reticuloendothelial system. ●Splenomegaly suggests expansion of the reticuloendothelial capacity

43. Clinical features

44. Thank you!