Anemia. A case-based approach. David B. Sykes, MD, PhD Hematology, MGH Cancer Center June 8, 2017
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1 Anemia A case-based approach David B. Sykes, MD, PhD Hematology, MGH Cancer Center June 8, 2017
2 Recognizing trends Learning Objectives MCV, RDW, Ferritin, LDH, Reticulocytes Managing complex patients 1. When to do nothing 2. When to watch 3. When to test 4. When to refer 2
3 Ask Google about anemia 3
4 Anemia Symptoms 4
5 When does anemia lead to fatigue? 27% 45% Hematocrit 5
6 6
7 67M with erythrocytosis
8 67M with erythrocytosis WBC HGB HCT MCV PLT DEC He feels great Incidentally discovered on routine labs at physical Vitals: HR 65, BP 122/76, O 2 sat 98% PMH: Hypertension (controlled) 8
9 67M with erythrocytosis A. Recheck CBC in 3 months B. Send a serum erythropoietin C. Send him for a sleep study D. Send him for an echocardiogram E. Send iron studies (Ferritin, Fe, TIBC) 9
10 Erythrocytosis Evaluation 10
11 EPO 1.1 (normal 4-20) Highly suppressed Lab Results JAK2V617F POSITIVE A JAK2 mutation is pathognomonic for a myeloproliferative neoplasm ~99% of polycythemia vera ~50% of essential thrombocythemia 11
12 67M with JAK2+ Polycythemia Vera A. Follow until HCT > 60% B. ASA C. ASA + therapeutic phlebotomy to goal HCT<45% D. ASA + hydrea to goal HCT<45% E. ASA + bone marrow transplant evaluation 12
13 He comes back to see me in 2 months WBC HGB HCT MCV PLT DEC FEB Why is the MCV so high!? 13
14 Now on a stable dose of hydrea WBC HGB HCT MCV PLT DEC FEB APR Remember: Polycythemia Vera is a clonal stem cell disorder, thus affecting all lineages 14
15 65F with anemia
16 65F with anemia 16
17 65F with anemia A. Looks like iron deficiency B. Looks like B12 deficiency C. Looks like chronic kidney disease D. Why is the RDW so wide? E. We need some more labs 17
18 65F with anemia CREAT 1.1 BILI 0.1 LDH 282 (normal up to 200) FERRITIN 160 FE 35, TIBC 253 B12 normal FOLATE normal EPO 27 (normal range 3-19) Serum protein electrophoresis: normal 18
19 The trend in the MCV 08/ /
20 65F with anemia and increasing MCV A. Worsening liver disease B. Started a new medication (e.g. methotrexate) C. Drinking more (e.g. toxic effects of alcohol) D. Worsening renal disease despite normal creatinine E. MDS needs a bone marrow biopsy 20
21 Each of us has our own MCV baseline Normocytic is relative to the individual patient Even modest alcohol, especially in older patients, can lead to macrocytosis without anemia
22 34M with a cold
23 34M with a cold Young child in daycare : I caught a cold Felt better, but never quite fully recovered Wife said that he looked a little yellow last week Now in the ED with my heart is racing WBC 7.4, HCT 17.2, MCV 87, PLT 184 BILIRUBIN TOTAL 1.5, DIRECT 0.4 LDH
24 34M with a cold A. Needs a bone marrow biopsy B. Needs a PT, PTT, and Fibrinogen C. Needs a haptoglobin checked D. Expect to see schistocytes on the smear E. Expect to see spherocytes on the smear 24
25 Autoimmune hemolytic anemia BM: would show erythroid hyperplasia PT, PTT, Fibrinogen: should be normal Haptoglobin: would expect it to be low Schistocytes: NO. Spherocytes: YES. 25
26 AIHA A. Start steroids. B. Start steroids and IVIG. C. Check mycoplasma IgG and IgM. D. Send a Coombs test (direct antiglobulin test). E. Check HIV. 26
27 AIHA DAT + : IgG Warm autoantibody IgG Usually idiopathic Can be associated with a lymphoproliferative disease Steroids DAT + : Complement Cold autoantibody IgM Often associated with a mycoplasma infection Self-limited, steroids generally are not helpful 27
28 Trends: LFTs, LDH, WBC, MCV, NRBC, RETIC 3/10 3/3 2/17 2/10 2/1 1/31 1/30 1/29 1/28 1/27 1/25 ALT AST ALKP TBILI DBILI <0.2 <0.2 < LDH WBC HGB HCT MCV PLT RDW NRBC% RETIC >23.0 >
29 A little aside on EPO
30 Erythropoietin Produced in specialized fibroblasts in the kidney Highly responsive to hypoxia Normal range is usually
31
32 HGB=15 HCT=45% EPO=10 32
33 HGB=9 HCT=27% EPO=100 33
34 HGB=6 HCT=18% EPO=
35 What suppresses EPO production? Pretty much everything. Age Renal disease Illness Inflammation Cancer Take care when interpreting an EPO result in a hospitalized patient 35
36 So when is the serum EPO useful? Helpful in the outpatient setting when one is wondering what the contribution of low EPO production is having on the HGB/HCT 81F with CREAT 0.9 and HGB 9.5, HCT 28%, MCV 89 EPO should be If the EPO comes back at 19, though it will be flagged in the normal range, the EPO is actually low given the degree of anemia 36
37 45M with thrombocytopenia
38 45M with thrombocytopenia 38
39 45M with thrombocytopenia A. Probably a transient viral process. B. Probably a medication side-effect. C. Probably ITP (immune thrombocytopenic purpura). D. Probably Aplastic Anemia. E. Probably MDS. F. Probably Acute Leukemia (AML or ALL). 39
40 Context: 45M with thrombocytopenia 45M Time course seems to be going on for a few weeks Concerns: All three lines are low ANC is down Red herrings? Exposures in India 40
41 45M with thrombocytopenia 2-weeks later 41
42 What do we need for work-up? A. HIV, HBC, HCV, CMV, EBV testing. B. Peripheral blood flow cytometry for PNH. C. Coombs test, LDH, Reticulocyte count. D. Bone marrow biopsy. E. Trial of steroids +/- IVIG. 42
43 A D are all correct Suspect aplastic anemia Aplastic anemia is caused by a toxic or autoimmune attack on the hematopoietic stem cell It leads to pancytopenia because of underproduction LDH is typically LOW RETIC is typically <0.5% Rule out destructive processes 43
44 74M with diarrhea and weight loss
45 74M with diarrhea and weight loss CREAT 0.9 BILI 0.6 LDH 260 RETIC 2.4% ALBUMIN 2.9 HIV+ on Rx, suppressed VL and normal CD4 BMI 16 45
46 Anemia is caused by A. Low level of HIV despite treatment B. Co-infection with Hepatitis C C. TTP: Thrombotic Thrombocytopenia Purpura D. Lymphoma infiltration of the bone marrow E. Severe malnutrition 46
47 David BMI 16. Albumin 2.9. Prealbumin 9. Patient 47
48 Marrow aplasia Bone marrow biopsy: <5% cellularity Gelatinous transformation of the bone marrow Seen in cases of AIDS Severe protein malnutrition Anorexia 48
49 56F with anemia and a rejected CBC 49
50 56F with anemia 50
51 56F with anemia
52 What is going on? A. Warm autoimmune hemolytic anemia. B. Paroxysmal Nocturnal Hemoglobinuria. C. Drug-induced hemolytic anemia. D. Cryoglobulinemia. E. Cold agglutinin disease. 52
53 56F with anemia
54
55
56
57 56F with anemia
58 56F with anemia
59 How do you treat cold-agglutinins? A. Steroids. B. IVIG. C. Cytoxan. D. Rituximab. E. Rituximab and Fludarabine. 59
60
61 An intriguing and practical paper on iron absorption 61
62 Recommended daily iron 62
63 Hypothesis: supplemental iron downregulates the body s ability to absorb the next dose of iron Blood. Volume 126(17): October 22, 2015
64 Iron dose vs. Iron absorbed
65 Iron dose vs. Iron absorbed AM Dose PM Dose
66 Feosol Original Ferrous Sulfate 325 mg 20% elemental iron Elemental Fe 65 mg 66
67 Feosol Natural Release Carbonyl iron 100% elemental iron Elemental Fe 45 mg 67
68 Feosol Complete Iron polysaccharide + Heme iron polypeptide Elemental Fe 28 mg 68
69 Ferrous Gluconate Fe Gluconate 240 mg 12% elemental iron Elemental Fe 28 mg 69
70 Ferrous Fumarate Fe Fumarate 54 mg 33% elemental iron Elemental Fe 18 mg 70
71 MegaFood Blood Builder 71
72 So then what to tell our patients? Many of the side effects of iron can be avoided by trying a lower dose formulation Much of the benefit of iron supplementation can be derived from taking them every-other-day I like to start patients on a MON/WED/FRI schedule and see how they do iron of their choice. 72
73 73
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