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Patient Problems in Anemia Mary S. Muscato, M.D., FACP Missouri Cancer Associates Mary S. Muscato, M.D., FACP Missouri Cancer Associates.

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Presentation on theme: "Patient Problems in Anemia Mary S. Muscato, M.D., FACP Missouri Cancer Associates Mary S. Muscato, M.D., FACP Missouri Cancer Associates."— Presentation transcript:

1 Patient Problems in Anemia Mary S. Muscato, M.D., FACP Missouri Cancer Associates Mary S. Muscato, M.D., FACP Missouri Cancer Associates

2 59 y/o woman with RA 59 y/o woman with a 4-year history of RA was referred for persistent anemia. She has been treated with NSAIDs, Plaquenil and methotrexate. She complains of fatigue and epigastric burning. She denied any change in bowel habits.

3 Physical Exam Mildly weak, VS normal Pale conjunctivae Several actively inflamed joints Stool heme (+) Mildly weak, VS normal Pale conjunctivae Several actively inflamed joints Stool heme (+)

4 WBC 4.1 Hb 8.3 Hct 24.6 MCV 78 Plt 528 Neut77 Bands Lymph15 Mono6 Eos2 Baso Other Morph Aniso, poik, hypo 59 y/o woman with RA

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6 Retic count 0.7% WESR 64 CRP 1.05 (elevated) LDH 140 Retic count 0.7% WESR 64 CRP 1.05 (elevated) LDH 140

7 How Should we Look at this Problem? Technically, hypochromic, “normocytic” anemia, but slide shows poik, aniso MCV a little on the small side: consistent with iron deficiency and anemia of chronic disease (ACD) Heme(+) stool Known RA, CRP elevated On methotrexate Technically, hypochromic, “normocytic” anemia, but slide shows poik, aniso MCV a little on the small side: consistent with iron deficiency and anemia of chronic disease (ACD) Heme(+) stool Known RA, CRP elevated On methotrexate

8 More Data Ferritin 36 Fe 6, TIBC 224, Sat 3% Upper endo: gastritis Soluble Transferrin Receptor (STfR) 6.1 (normal <4.5) Ferritin 36 Fe 6, TIBC 224, Sat 3% Upper endo: gastritis Soluble Transferrin Receptor (STfR) 6.1 (normal <4.5)

9 Diagnoses Iron deficiency (low normal ferritin, but elevated STfR) Anemia of chronic disease Gastritis Are we done? Iron deficiency (low normal ferritin, but elevated STfR) Anemia of chronic disease Gastritis Are we done?

10 Try Not to Make Assumptions! Colonoscopy: Large adenocarcinoma in the ascending colon

11 59 y/o woman with RA The patient underwent a right colectomy and no other cancer was found. She did not require adjuvant chemotherapy. She was treated with four months of oral iron on an empty stomach. Her repeat Hb rose to 10.4 and the MCV was now 85. She still has active RA; she was started on infliximab (Remicade). The patient underwent a right colectomy and no other cancer was found. She did not require adjuvant chemotherapy. She was treated with four months of oral iron on an empty stomach. Her repeat Hb rose to 10.4 and the MCV was now 85. She still has active RA; she was started on infliximab (Remicade).

12 59 y/o woman with RA Infliximab is a monoclonal antibody that binds to α-TNF (tumor necrosis factor). Her inflammatory arthritis rapidly improved. Over the next 2 months her Hb rose to 13.1, The MCV rose to 91, her platelets fell to 320,000, WESR and CRP fell to normal. Infliximab is a monoclonal antibody that binds to α-TNF (tumor necrosis factor). Her inflammatory arthritis rapidly improved. Over the next 2 months her Hb rose to 13.1, The MCV rose to 91, her platelets fell to 320,000, WESR and CRP fell to normal.

13 ANEMIA OF CHRONIC DISEASE ACD is Cytokine Driven Production of pro-inflammatory cytokines, like TNF and gamma interferon, damage erythroid progenitors Changes in iron homeostasis Decreased proliferation of erythroid progenitor cells Decreased production of Epo and shortened lifespan of RBC’s Production of pro-inflammatory cytokines, like TNF and gamma interferon, damage erythroid progenitors Changes in iron homeostasis Decreased proliferation of erythroid progenitor cells Decreased production of Epo and shortened lifespan of RBC’s

14 Changes in Hb with Remicade

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16 16 y/o girl with rapid-onset anemia

17 Moderately pale young woman VS T=100.6, pulse 110 No adenopathy, splenomegaly Petechiae on LE’s Mildly lethargic Moderately pale young woman VS T=100.6, pulse 110 No adenopathy, splenomegaly Petechiae on LE’s Mildly lethargic

18 WBC12.3 Hb7.1 Hct22.7 MCV103 Plt14 Neut79 Bands10 Lymph6 Mono3 Eos1 Baso1 Other 3 NRBC 2 metas Morph Poik, aniso, 2+ schisto 16 y/o girl with rapid-onset anemia

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20 Creatinine 1.3 LDH 2,800 Retic 18% PT, PTT, fibrinogen normal Haptoglobin absent Bili 2.3, mostly indirect U/A 2+ protein Creatinine 1.3 LDH 2,800 Retic 18% PT, PTT, fibrinogen normal Haptoglobin absent Bili 2.3, mostly indirect U/A 2+ protein

21 Diagnosis: Thrombotic Thrombocytopenic Purpura (TTP) Treatment begun with emergent daily plasmapheresis, aspirin, folic acid Mental status deteriorated initially, minimal seizure activity LDH & retic gradually dropped, plt count improved, remained with significant hemolysis After two weeks, plasmapheresis switched to every other day. She eventually recovered and made it to the prom. Treatment begun with emergent daily plasmapheresis, aspirin, folic acid Mental status deteriorated initially, minimal seizure activity LDH & retic gradually dropped, plt count improved, remained with significant hemolysis After two weeks, plasmapheresis switched to every other day. She eventually recovered and made it to the prom.

22 TTP TTP is caused by a deficiency of ADAMTS-13, a metalloprotease which normally cleaves the large multimers of VWF. The enzyme deficiency (often acquired) results in an overabundance of ultralarge VWF multimers (ULVWF). These ULVWF bind platelets to endothelium, leaving platelet-rich microvascular thrombosis unchecked, leading to micro- thrombi and intravascular hemolysis. TTP is caused by a deficiency of ADAMTS-13, a metalloprotease which normally cleaves the large multimers of VWF. The enzyme deficiency (often acquired) results in an overabundance of ultralarge VWF multimers (ULVWF). These ULVWF bind platelets to endothelium, leaving platelet-rich microvascular thrombosis unchecked, leading to micro- thrombi and intravascular hemolysis.

23 Alcoholic with Anemia

24 42 y.o. man, alcoholic, history of GI bleeds Recently drinking, presents with abd pain PMH: total gastrectomy 20 years before for hemorrhagic gastritis PE: Anicteric, spiders, liver 14 cm, spleen down 3 cm Stool heme (+) 42 y.o. man, alcoholic, history of GI bleeds Recently drinking, presents with abd pain PMH: total gastrectomy 20 years before for hemorrhagic gastritis PE: Anicteric, spiders, liver 14 cm, spleen down 3 cm Stool heme (+)

25 WBC 3.4 Hb 9.8 Hct 30 MCV 94 Plt 71 Neut67 Bands3 Lymph18 Mono10 Eos2 Baso Other Morph Macro, aniso, targets CBC

26 Alcoholic with Anemia Retic 1.6% Ferritin 133 Folate 2.6 RBC Folate 122 (nl ) Creat 1.3 Bili 1.8 LDH 1100 Retic 1.6% Ferritin 133 Folate 2.6 RBC Folate 122 (nl ) Creat 1.3 Bili 1.8 LDH 1100

27 Alcoholic with Anemia Because of the pancytopenia, confusing MCV, and concern re mixed anemia, a bone marrow aspirate and biopsy was done. Bone marrow showed –megaloblastic changes –absent iron stores –normal megakaryocytes Because of the pancytopenia, confusing MCV, and concern re mixed anemia, a bone marrow aspirate and biopsy was done. Bone marrow showed –megaloblastic changes –absent iron stores –normal megakaryocytes

28 Alcoholic with Anemia Colonoscopy normal B12 level 153 (nl ) Causes of anemia: –History of bleeding: iron loss –Gastrectomy: loss of IF, loss of iron absorption, change in mucosa –Folate lack from not eating broccoli RX: B12, folate, iron and stop drinking! Colonoscopy normal B12 level 153 (nl ) Causes of anemia: –History of bleeding: iron loss –Gastrectomy: loss of IF, loss of iron absorption, change in mucosa –Folate lack from not eating broccoli RX: B12, folate, iron and stop drinking!

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32 57 y.o. Man with Erythrocytosis

33 A 57 y.o. man is referred for erythrocytosis. His history is pertinent for malaise and pruritis. His wife has noticed that he appears plethoric. He has smoked 1 ½ ppd for 35 years. P.E. Plethoric. Decreased breath sounds. Cardiac exam normal. No hepato- splenomegaly. A 57 y.o. man is referred for erythrocytosis. His history is pertinent for malaise and pruritis. His wife has noticed that he appears plethoric. He has smoked 1 ½ ppd for 35 years. P.E. Plethoric. Decreased breath sounds. Cardiac exam normal. No hepato- splenomegaly.

34 WBC 13.1 Hb 19.8 Hct 59.5 MCV 91 Plt 450 Neut78 Bands1 Lymph12 Mono4 Eos2 Baso3 Other MorphNormal CBC

35 57 y.o. Man with Erythrocytosis Retic 2.3% ABG: pH 7.41, pO2 85, pCO2 38, O2 sat 94% B12 level 1235 LAP 112 Red cell mass: 34 ml/kg, plasma volume normal Erythopoetin: 2 (nl 4-19) Retic 2.3% ABG: pH 7.41, pO2 85, pCO2 38, O2 sat 94% B12 level 1235 LAP 112 Red cell mass: 34 ml/kg, plasma volume normal Erythopoetin: 2 (nl 4-19)

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38 57 y.o. Man with Erythrocytosis Diagnosis: Polycythemia Vera Confirmatory genetic testing: JAK2, positive (Official Symbol: JAK2 and Name: Janus kinase 2 (a protein tyrosine kinase) - Chromosome: 9; Location: 9p24) Treatment: phlebotomy to normal hematocrit, aspirin, possibly hyrdoxyurea Diagnosis: Polycythemia Vera Confirmatory genetic testing: JAK2, positive (Official Symbol: JAK2 and Name: Janus kinase 2 (a protein tyrosine kinase) - Chromosome: 9; Location: 9p24) Treatment: phlebotomy to normal hematocrit, aspirin, possibly hyrdoxyurea

39 56 y/o with intermittent anemia

40 A 56 y/o woman presents with a mild anemia. History reveals that she was once told by a doctor that she might have had some jaundice. Generally healthy, no infections. FH + for her 86 y/o mother diagnosed last year with massive splenomegaly and Hb 6. Thought to be MDS, but she clinically improved. PE normal except spleen tip palpable. A 56 y/o woman presents with a mild anemia. History reveals that she was once told by a doctor that she might have had some jaundice. Generally healthy, no infections. FH + for her 86 y/o mother diagnosed last year with massive splenomegaly and Hb 6. Thought to be MDS, but she clinically improved. PE normal except spleen tip palpable.

41 WBC 4.6 Hb 10.7 Hct 33.1 MCV 104 Plt 152 Neut67 Bands Lymph18 Mono10 Eos3 Baso2 Other Morph Macro, polychromasia CBC

42 Peripheral Smear Some polychromasia seen. Hematologist noted normocytic spherocytes. No poikilocytosis.

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44 56 y/o with intermittent anemia Retic count 11.2% MCHC elevated Bili 2.2, 1.8 Indirect LDH 317 Haptoglobin normal Nuclear Medicine liver-spleen scan shows only minimal splenomegaly Direct Coombs negative Retic count 11.2% MCHC elevated Bili 2.2, 1.8 Indirect LDH 317 Haptoglobin normal Nuclear Medicine liver-spleen scan shows only minimal splenomegaly Direct Coombs negative

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46 56 y/o with intermittent anemia Osmotic fragility ordered. Returns showing increased osmotic fragility, consistent with hereditary spherocytosis. The patient’s mother had come with her; she was re- examined. Spleen now only 6 cm and Hb back up to 11.0! Peripheral smear: spherocytes. Her son was also in the exam room. His smear also showed spherocytes. (This is a true story!) Osmotic fragility ordered. Returns showing increased osmotic fragility, consistent with hereditary spherocytosis. The patient’s mother had come with her; she was re- examined. Spleen now only 6 cm and Hb back up to 11.0! Peripheral smear: spherocytes. Her son was also in the exam room. His smear also showed spherocytes. (This is a true story!)

47 29 y.o. G3P2 woman with anemia

48 29 y.o. African-American woman is referred during the 5 th month of her 3 rd pregnancy. Pregnancy has been uncomplicated, as have her previous pregnancies. She has been faithfully taking her prenatal vitamins. P.E. normal; uterine size 22 weeks. 29 y.o. African-American woman is referred during the 5 th month of her 3 rd pregnancy. Pregnancy has been uncomplicated, as have her previous pregnancies. She has been faithfully taking her prenatal vitamins. P.E. normal; uterine size 22 weeks.

49 WBC 6.5 Hb 8.8 Hct 24 MCV 78 Plt 340 Neut65 Bands Lymph24 Mono9 Eos2 Baso Other Morph Micro, targets CBC

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51 29 y.o. G3P2 woman with anemia Retic 2.1% Ferritin 140 Fe/TIBC 110/290 STfR 2.9 (normal) Hb electrophoresis normal: A2 and F not elevated Cord blood at time of delivery showed Hb Bart’s (tetramers of γ-chains) Retic 2.1% Ferritin 140 Fe/TIBC 110/290 STfR 2.9 (normal) Hb electrophoresis normal: A2 and F not elevated Cord blood at time of delivery showed Hb Bart’s (tetramers of γ-chains)

52 Globin Chain Dimers A1A1 A2A2 F α β γ δ

53 Summary: Anemia for M3s Always pay attention to: –History, PE: do they fit? –Peripheral smear –Retic –MCV –LDH, bili –Blood in stool or urine Always pay attention to: –History, PE: do they fit? –Peripheral smear –Retic –MCV –LDH, bili –Blood in stool or urine


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