Anemia A case-based approach David B. Sykes, MD, PhD Hematology, MGH Cancer Center June 8, 2017
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
Ask Google about anemia 3
Anemia Symptoms 4
When does anemia lead to fatigue? 27% 45% Hematocrit 5
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67M with erythrocytosis
67M with erythrocytosis WBC HGB HCT MCV PLT DEC 9.9 19.0 59.2 86 358 He feels great Incidentally discovered on routine labs at physical Vitals: HR 65, BP 122/76, O 2 sat 98% PMH: Hypertension (controlled) 8
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
Erythrocytosis Evaluation http://www.mayomedicallaboratories.com/ 10
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
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
He comes back to see me in 2 months WBC HGB HCT MCV PLT DEC 9.9 19.0 59.2 86 358 FEB 3.8 10.9 33.0 132 234 Why is the MCV so high!? 13
Now on a stable dose of hydrea WBC HGB HCT MCV PLT DEC 9.9 19.0 59.2 86 358 FEB 3.8 10.9 33.0 132 234 APR 6.0 14.0 43.3 118 270 Remember: Polycythemia Vera is a clonal stem cell disorder, thus affecting all lineages 14
65F with anemia
65F with anemia 16
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
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
The trend in the MCV 08/2015 03/2017 19
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
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 90 86 2011 2017 21
34M with a cold
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 684 23
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
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
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
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
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 19 21 52 348 511 586 680 380 321 321 427 AST 19 18 33 56 94 113 201 118 94 94 84 ALKP 66 66 77 133 126 133 155 133 135 135 153 TBILI 0.7 0.8 1 1.2 0.7 0.9 1.2 1.3 1.8 1.8 1.5 DBILI <0.2 <0.2 <0.2 0.3 0.3 0.4 0.4 0.4 LDH 206 234 290 246 373 415 467 844 813 684 WBC 4.35 4.83 6.17 8.07 4.9 6.24 6.55 8.94 10.29 20.01 30.23 HGB 11.4 11.1 11.3 10.7 8.5 8.6 8 8.2 9.6 5.2 6.1 HCT 32.4 31.2 33.3 32.6 27.5 27.1 24.7 24.4 28.8 15.4 17.2 MCV 86.2 87.4 94.3 100.9 102.6 100.7 99.2 95.3 93.8 89 85.6 PLT 172 214 246 165 112 96 97 110 137 142 184 RDW 13.8 14.1 15.6 22.6 24.9 25.1 23.6 20.7 19.8 16.9 16.2 NRBC% 0 0 0 0 1.2 1.3 2.2 3.6 5.4 8.7 7 RETIC 4.1 5.5 5.4 >23.0 >23.0 23 17.4 10.1 5.6 3.8 28
A little aside on EPO
Erythropoietin Produced in specialized fibroblasts in the kidney Highly responsive to hypoxia Normal range is usually 4-20 30
1000 100 10 31
HGB=15 HCT=45% EPO=10 32
HGB=9 HCT=27% EPO=100 33
HGB=6 HCT=18% EPO=1000 34
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
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 50-100 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
45M with thrombocytopenia
45M with thrombocytopenia 38
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
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
45M with thrombocytopenia 2-weeks later 41
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
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
74M with diarrhea and weight loss
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
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
David BMI 16. Albumin 2.9. Prealbumin 9. Patient 47
Marrow aplasia Bone marrow biopsy: <5% cellularity Gelatinous transformation of the bone marrow Seen in cases of AIDS Severe protein malnutrition Anorexia 48
56F with anemia and a rejected CBC 49
56F with anemia 50
56F with anemia
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
56F with anemia
56F with anemia
56F with anemia
How do you treat cold-agglutinins? A. Steroids. B. IVIG. C. Cytoxan. D. Rituximab. E. Rituximab and Fludarabine. 59
An intriguing and practical paper on iron absorption 61
Recommended daily iron 62
Hypothesis: supplemental iron downregulates the body s ability to absorb the next dose of iron Blood. Volume 126(17):1981-1989. October 22, 2015
Iron dose vs. Iron absorbed
Iron dose vs. Iron absorbed AM Dose PM Dose
Feosol Original Ferrous Sulfate 325 mg 20% elemental iron Elemental Fe 65 mg 66
Feosol Natural Release Carbonyl iron 100% elemental iron Elemental Fe 45 mg 67
Feosol Complete Iron polysaccharide + Heme iron polypeptide Elemental Fe 28 mg 68
Ferrous Gluconate Fe Gluconate 240 mg 12% elemental iron Elemental Fe 28 mg 69
Ferrous Fumarate Fe Fumarate 54 mg 33% elemental iron Elemental Fe 18 mg 70
MegaFood Blood Builder 71
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
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