1. Approach to Anemias

2. Objectives At the end of this session you should be able to: describe history and physical examination findings pertinent to anemia describe the basic diagnostic tests used in working- up anemia describe an approach to classification of anemias Use this approach to arrive at underlying etiology of anemia in various clinical scenarios

3. Definition Decrease in circulating RBC mass Decrease in hemoglobin or hematocrit Affected by plasma volume

4. General Symptoms and Signs Vary with Age Degree rapidity of onset presence of other illness

5. Symptoms Shortness of breath ‘palpitations’ – ‘heart racing’ dizziness headache fatigue

6. http://www.medexpressrx.com/blog/anemia-symptoms-and- causes-for-anemia.aspx

7. www.confidentielles.com/.../10/fatigue_982.jpeg

8. 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 ~250 million Hb molecules in one RBC

9. signs Pallor (skin, palms, oral and conjunctival mucosa, nail beds) dyspnea Tachycardia ejection systolic murmur wide pulse pressure hypotension

10. History: getting at the root cause Duration, time of onset family history previous transfusion blood loss drug exposure other illnesses abdominal pain Diet, EtOH

11. Physical Exam: Getting at the root cause Vital signs Jaundice, pallor splenic enlargement Lymphadenopathy nail beds tongue neurologic changes

12. Basic laboratory exam CBC Reticulocyte count Peripheral blood smear/film

13. Electron Microscopy Facility at The National Cancer Institute at Frederick (NCI-Frederick)

14. Basic Lab Exam: CBC Hemoglobin MCV Hematocrit RDW WBC, platelets

15. Basic Lab Exam – Initial Approach Hb – reduction defining anemia Mean corpuscular volume (MCV)  Size Reticulocyte count – young RBCs Film – details on morphology

16. MCV MCV < 80 microcytic anemia MCV 80-100 normocytic anemia MCV >100 macrocytic anemia MCV

18. Microcytic anemias iron deficiency chronic disease hemoglobinopathy sideroblastic anemia MCV < 80 microcytic anemia MCV 80-100 normocytic anemia MCV >100 macrocytic anemia MCV

19. Macrocytic anemias MCV < 80 microcytic anemia MCV 80-100 normocytic anemia megaloblastic anemias, alcholism, drugs, liver disease, primary marrow disorder, hypothyroidsm, high reticulocyte count MCV >100 macrocytic anemia MCV

20. Normocytic anemias MCV MCV < 80 microcytic anemia MCV 80-100 normocytic anemia reticulocyte count increased evidence of hemolysis (morphology, biochemistry, Coombs test) yes immunenon immune no recent bleed normal or decreased renal, endocrine or chronic disease? yes anemia of chronic inflammation no primary marrow problem MCV >100 macrocytic anemia

21. A little help from a friend: The Kidneys Erythropoietin A natural hormone that stimulates the marrow to produce more RBCs as they are needed Produced by the kidneys Kidney disease Lowered production of erythropoietin  anemia

22. Reticulocyte count endocrine failure, microcyticnormocyticmacrocytic MCV bone marrow problem anemia of chronic inflamation evidence of renal failure, or chronic inflammation? low or normal blood loss or hemolysis high reticulocyte count

23. 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

24. 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

25. Anemia Easy to identify Present with associated symptoms or signs Complete blood count (CBC): low Hb/RBC count Anemia is not a disease itself A condition caused by some other problem Diagnosis of the underlying cause may be difficult  referral to a hematologist Treatment: Sometimes easy Nutrient deficiencies Depends on underlying cause

26. Case presentation#1 74 year old male presents with fatigue, SOB, weakness History: diet is good, no medications, no previous history of anemia, no family history of anemia Physical exam shows: pallor, no jaundice, tachycardia, cachexia CBC: Hb 65, WBC 5.8, plt 487 What do you want to know next? MCV: 75, low reticulocyte count

27. Peripheral blood film

28. Case # 1 continued What other lab tests would you order? Low serum iron, high TIBC, low ferritin Diagnosis?

29. Case #2 45 year old female presents with fatigue and jaundice History: mechanical mitral valve, on warfarin, no other medications, no previous history of anemia, no family history Physical exam shows: scleral icterus, hr 125, bp 102/65, loud holosystolic murmur

30. Case # 2 continued CBC: Hb 56, WBC 6.4, plt 432 What do you want to know next? MCV 102, reticulocyte count high

31. Peripheral blood film

32. Case #2 continued What other lab tests would you order? Haptoglobin low, indirect bilirubin high, Coomb’s test negative Echocardiogram shows large circumferential paravalvular leak around the mechanical valve

33. Case # 3 24 year old female presents with fatigue and joint pain History: previously well, no medications, no family history, 6 weeks of finger, wrist, and ankle pain, associated with joint stiffness and swelling Physical exam: swelling of all MCP and PIP joints, swollen ankles, joints tender to touch, vitals normal

34. Case # 3 continued CBC: Hb 108, WBC 4.5, plt 684 What do you want to know next? MCV is 87, reticulocyte count is low

35. Peripheral blood film

36. Case # 3 continued What other tests might be useful? ESR is 45, ferritin is 364, TIBC is low, serum iron is low, RF is high

37. Questions?

38. Case #4  60 year-old male presents with worsening fatigue, palpitations, shortness of breath with minimal exertion  CBC: Hb 50, WBC 7.0, platelets 400,  MCV 100  High reticulocyte count

39. Peripheral blood film

40. Case #4 continued  What is the differential diagnosis?  What other tests would you order?  Haptoglobin low, indirect bilirubin high  Direct antibody test (Coomb’s test) positive  Antibody specification: non-specific IgG autoantibody  Diagnosis?

41. Objectives At the end of this session you should be able to: describe history and physical examination findings pertinent to anemia describe the basic diagnostic tests used in working- up anemia describe an approach to classification of anemias Use this approach to arrive at underlying etiology of anemia in various clinical scenarios

42. Discovered how blood is truly amazing!