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This article discusses three different case studies related to anemia, including iron deficiency, anemia of chronic disease, and erythrocytosis. The article explores the symptoms, diagnoses, and treatment options for each case.
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Patient Problems in Anemia Mary S. Muscato, M.D., FACP Missouri Cancer Associates
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.
Physical Exam • Mildly weak, VS normal • Pale conjunctivae • Several actively inflamed joints • Stool heme (+)
59 y/o woman with RA • Retic count 0.7% • WESR 64 • CRP 1.05 (elevated) • LDH 140
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
More Data • Ferritin 36 • Fe 6, TIBC 224, Sat 3% • Upper endo: gastritis • Soluble Transferrin Receptor (STfR) 6.1 (normal <4.5)
Diagnoses • Iron deficiency (low normal ferritin, but elevated STfR) • Anemia of chronic disease • Gastritis • Are we done?
Try Not to Make Assumptions! • Colonoscopy: Large adenocarcinoma in the ascending colon
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).
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.
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
16 y/o girl with rapid-onset anemia • Moderately pale young woman • VS T=100.6, pulse 110 • No adenopathy, splenomegaly • Petechiae on LE’s • Mildly lethargic
16 y/o girl with rapid-onset anemia • Creatinine 1.3 • LDH 2,800 • Retic 18% • PT, PTT, fibrinogen normal • Haptoglobin absent • Bili 2.3, mostly indirect • U/A 2+ protein
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.
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.
Alcoholic with Anemia • 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 (+)
Alcoholic with Anemia • Retic 1.6% • Ferritin 133 • Folate 2.6 • RBC Folate 122 (nl 200-700) • Creat 1.3 • Bili 1.8 • LDH 1100
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
Alcoholic with Anemia • Colonoscopy normal • B12 level 153 (nl 211-911) • 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!
57 y.o. Man with Erythrocytosis • 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.
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)
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
56 y/o with intermittent anemia • 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.
Peripheral Smear • Some polychromasia seen. Hematologist noted normocytic spherocytes. No poikilocytosis.
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
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!)
29 y.o. G3P2 woman with anemia • 29 y.o. African-American woman is referred during the 5th month of her 3rd 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.