2. Back to Basics - Hematology

3. Objectives LMCC objectives – Anemia fatigue – Jaundice – Lymphadenopathy – Elevated hemoglobin – Splenomegaly – Neck mass – Venous thrombosis

4. PRINCIPLES - Anemia Anemia is not a disease Investigation should be logical – Start with CBC and Blood film Leads to other tests – non specific – specific Guides therapy

5. Further Principles Symptoms are more related to rate of fall in hemoglobin not level. Non specific symptoms More specific symptoms Drug History – including EtOH Physical examination

6. Anemia and Fatigue What’s the link? Hemoglobin in RBCs – Iron-containing oxygen transport protein – Function to transport oxygen to every tissue in the body

7. Starts With CBC High yield parameters – Hgb – MCV: approach – Reticulocyte count Morphology – Blood film (smear) Confirmatory tests

9. Peripheral blood film MorphologyLab testsDiagnosis Hypochromic, microcyticLow Fe, high TIBC, low ferritin Iron deficiency Hypochromic, microcyticHigh Hb A2 or high Hb FBeta- thalassemia MacrocyticLow B12 or low folateB12 or folate deficiency Macrocytic, other cell lines abnormal Normal B12,folate, low WBC, low plt Myelodysplasia (other possibilities) Normocytic, normochromic Low Fe, low TIBC, abnormal liver, abnormal kidney, high ESR, normal or high ferritin Anemia of chronic inflammation

10. Peripheral blood film MorphologyLab testsDiagnosis Nucleated RBC, Teardrops Other cell lines, marrow aspirate and biopsy Myelofibrosis, Marrow infiltration SchistocytesCoombs test, PTT, INR, fibrinogen Microangiopathic hemolytic anemie, ie. DIC SpherocytesCoombs test, Osmotic fragility Immune hemolysis, Hereditary spherocytosis Sickle cellsSickle prep.Sickle cell syndromes Target cellsAbnormal Hb electrophoresis HbC, D, thalassemia

11. Test results  Hgb 77 g/L  MCV 66  f/L  RBC 3.2 x10 12 /L  WBC 5.6 x10 6 /L  Plat 525 x10 9 /L  Retic count ‘normal’ This is a 55 year old woman who has fatigue. Her only other symptom is a craving for chewing ice cubes. Apart from being pale her examination is normal.

12. Microcytic, hypochromic

13. STAGES OF IRON DEPLETION Loss of body stores Fall in serum iron Anemia develops Microcytosis Hypochromasia

14. ASSESSMENT OF IRON STATUS Identify high risk groups Children Menstruation Pregnancy - Lactation Frequent Blood Donors Chronic GI loss Malabsorption Diet

15. IRON BALANCE ;Ingest 10-20 mg. per day ;Absorb 1-3 mg per day ;Lose 1 + mg per day – menstrual loss 30-50 ml ;Total iron content in body 3 – 4 grams ; most in RBC (~2.5 g) ;Stores 1 gram – ferritin, hemosiderin ;Easy to achieve negative balance

16. INVESTIGATION OF CAUSE ;Investigate when cause not Clear ;Symptoms of cause often unreliable ;Upper GI cause higher Yield ;If upper GI lesion found then a colonic lesion unlikely ;TESTS - Radiologic, Endoscopic Biopsy, Angiographic.

17. THERAPY Replace iron Treat underlying cause if possible

18. Anemia of Chronic disease Usually mild to moderate anemia normocytic normochromic low retic count Low serum Fe and low TIBC sat % 15-20 Ferritin normal or high A responsible disease is present Usually a systemic disorder

19. SIDE TRACK ….Very High Iron Mulitple regulators of iron metabolism Think of – reactive/inflammatory processes Infection, inflammation, malignancy, alcoholic liver disease, nonalcoholic steatohepatitis, metabolic syndrome – hemochromatosis

20. Hemochromatosis Fe overload Genetic predisposition to increased Fe absorption – hepcidin Common Screen with Fe saturation (ferritin) – >=60% males – >=50 women – >=45% - lower cutoff advocated by some guidelines Confirm with Genetic testing: HFE gene 3 genes tested C282Y ( H63D, S65C) Treatment - phlebotomy

21. BACK TO ANEMIA….

22. Test results  Hgb 85 g/L  MCV 110  fL  RBC 3.9 x10 12 /L  WBC 2.4 x10 6 /L  Plat 89 x10 9 /L  Retic count A 65 year old woman is referred to you because of memory loss. Her family physician had received tests which included bilirubin of 28  mol/L and an LDH of 1560 U/L. He was puzzled by these results.

23. Oval Macrocytes Hypersegmented neutrophils

24. Megaloblastic Anemias Vitamin B12 Folic Acid

25. Reasons for measuring B12 Investigation of macrocytic anemia Investigation of any anemia Investigation of fatigue Routine Geriatric Screen Investigation of neurologic symptoms

26. Symptom Complex Classic presentation uncommon Often a screen in older patients Memory loss prominent Neuropathy Non specific symptoms of anemia

27. Causes Pernicious anemia 10 % of all cobalamin deficiencies Antibodies against intrinsic factor – malabsorption

28. Causes of Low Serum B12 Malabsorption of free cobalamin Pernicious anemia Post gastrectomy state Small bowel diseases

29. Causes of Low Serum B12 Malabsorption of food cobalamin Atrophic gastritis Postgastrectomy state Chronic nonspecific gastritis H2 receptor blocking agents, PPI

30. Tests CBC - RBC indices – Most are macrocytic Blood film – Macro-ovalocytes - hypersegmented polys Retic count Serum B12 Biochemical abnormalities – LDH bilirubin  elevated seconday to ineffective erythropoiesis an premature RBC destruction in the bone marrow

31. Folic acid deficieny Dietary source is vegetables Absorption no specific carrier Deficiency mainly dietary. Alcoholism a risk Anemia macrocytic No neurologic symptoms Measure Serum folate (food supplementation)

32. Therapy Replace B12 - folic acid

33. Therapy Vitamin B12 IM Oral Folic acid – pregnancy – treatment

34. Jaundice: Hemolytic anemias History of jaundice and anemia – Biochemical and clinical definition Elevated bilirubin: unconjugated hyperbilirubinemia in hemolysis (ddx: decreased hepatic uptake or conjugation  CHF, Gilbert’s syndrome, neonatal jaundice) May have splenomegaly May have a family history anemia with reticulocytosis specific morphologic changes LDH : elevated Specific tests follow morphology

35. What is the abnormality ? Spherocytes

36. What is the abnormality ? Bite cells Oxidative hemolysis

37. What is the abnormality fragment

38. Which anemia is this ?

39. Common anemias Iron deficiency Megaloblastic anemias Secondary anemias of chronic diseases Hemolytic anemias: immune, non-immune Spherocytic fragmentation

40. PRINCIPLES Anemia is not a disease There is usually a cause investigation should be logical Start with CBC and Blood film Leads to other tests – non specific – specific Guides therapy