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CQC

. 46 yo FemalePMHDMHTNCirrhosis (NASH), MELD 22OSAUterine FibroidsMorbid Obesity, BMI 57.7PSxHUterine fibroid embolizationSHNo Tob, EtOH, illicitsFHMother breast ca. MedsInsulinLasixLisinoprilProtonixPropanololSpirinolactoneMag oxideTramadolPE:98.8, 120/60, 68, 18Gen: aao

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CQC

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    1. CQC 9/23/08 Matt George

    2. 46 yo Female PMH DM HTN Cirrhosis (NASH), MELD 22 OSA Uterine Fibroids Morbid Obesity, BMI 57.7 PSxH Uterine fibroid embolization SH No Tob, EtOH, illicits FH Mother – breast ca Meds Insulin Lasix Lisinopril Protonix Propanolol Spirinolactone Mag oxide Tramadol PE: 98.8, 120/60, 68, 18 Gen: aaox3, obese, comfortable, conversational HEENT: AT/NC, PERRL, +icteric sclera, TM;s clear, OP clear Neck: no masses, no bruits CV: RRR, no m/r/g Lungs: CTA-B Abd: obese, soft, NT, ND, normoactive BS Ext: 1+ edema b/l, 2+ pulses b/l Neuro: CN II-XII intact, 5/5 strength, normal sensation, no deficits

    3. Alk P 84 ALT 25 AST 41 TB 5.0 TP 6.0 Alb 2.3 INR 1.5 TSH 1.5 B12 1036 Folate 7.5 Abs retic 0.118 (1/07) Uncorr. Retic 3.6 Corr. Retic 2.6

    4. The Question Macrocytosis. What do I do now?

    5. Macrocytosis Defined as MCV > 100 femtoliters Prevalence 1.7 – 3.6% 60% without associated anemia Identified by peripheral blood smear or automated RBC indices Smear is more sensitive in detecting early macrocytic changes and small numbers of macrocytes Cell morphology can aid in determining etiology of macrocytosis

    6. Does Size Matter? Not Exactly No complications arise from macrocytosis as an isolated finding Identifying macrocytosis can provide important information about the presence of an underlying disease state

    7. Common Causes of Macrocytosis

    8. Macrocytosis workup If H&P does not clearly point to a diagnosis, routine lab testing should consist of: Blood smear Retic count Cobalamin Folate TSH LFTs Protein electrophoresis for multiple myeloma

    9. Common Causes – Alcohol Can develop macrocytosis before anemia appears Proposed mechanism is through acetaldehyde interference with cellular division Can be caused by regular ingestion of 80 gm/day (1 bottle of wine) Can occur in patients with normal B12 and folate Abstinence results in correction of macrocytosis in 2-4 months, which confirms the diagnosis

    10. Common Causes – Vitamin B12 Deficiency Mechanism – interference with DNA synthesis Megaloblastic anemia, look for hypersegmented neutrophils Prevalence 1.5 – 4.6% in elderly Requirement: 1 microgram/day, typical diet provides 5-15 micrograms daily and the liver stores 2 -5,000 micrograms, therefore B12 deficiency develops many years after B12 absorption ceases Most commonly caused by pernicious anemia Treatment Cyanocobalamin IM or SQ 1000 micrograms/week for 1 month and monthly thereafter Alternatively, hydroxycobalamin can be given IM every 1-3 months Oral cyanocobalamin can be administered at 1000-2000 micrograms/day for 1 month followed by 125-500 micrograms/day

    11. Common Causes – Folate Deficiency Mechanism – interference with DNA synthesis Megaloblastic anemia, look for hypersegmented neutrophils Requirement: 50-100 micrograms/day Folate stores can become depleted in 2-4 months from onset of dietary deprivation Treatment: Oral folate 1mg daily should replenish stores in about 3 weeks Can produce transient hematologic improvement in patients with B12 deficiency, but neurological manifestations will continue

    12. B12 and Folate treatment and maintenance Recommended that patients receiving tx for B12 deficiency also receive empiric folate supplementation CBC should be checked 10-14 days after initiation of treatment and should reveal an increase in Hgb and decrease in MCV Full response should be achieved in 2 months for both Further monitoring of CBC, B12, or folate levels during treatment in not necessary If patient requires long term treatment for B12 deficiency than an annual CBC is reasonable

    13. Diagnostic Tests and Pitfalls with B12 and Folate deficiency Serum B12 falsely low with folate deficiency, pregnancy, OCP use, MM Serum folate levels can decrease within a few days of dietary insufficiency, and can be replenished by one good meal, so patients should fast prior to testing. High concentration of folate in RBC can give falsely high levels with hemolysis Increased in B12 deficiency RBC folate Remain constant throughout lifespan of the cell Can be low with EtOH, pregnancy, anticonvulsants, and B12 deficiency Methylmalonic Acid (MMA) and Homocysteine Serum Concentrations Conversion of homocysteine to methionine requires both B12 and folate, however, the metabolism of L-methylmalonyl CoA to succinyl CoA only requires B12 Both metabolites are elevated in in B12 deficiency while only homocysteine levels are elevated in folate deficiency MMA will be elevated in patients with renal insufficiency

    14. Common Causes - Medications Chemotheraputics Cyclophosphamide Hydroxyurea Methotrexate Azathioprine Mercaptopurine Cladribine Cyctosine arabinoside 5-fluouracil Antiretroviral Zidovudine Stavudine Hypoglycemic metformin Antimicrobials Pyrimethamine Sulfamethoxazole Trimethoprim Valacyclovir Diuretics Traimterene Anticonvulsants Phenytoin Primidone Valproic acid Anti-inflammatory Sulfasalazine Other Nitrous oxide

    15. Common Causes Hemolysis or Bleeding Smear: Increased polychromasia, nucleated RBCs, spherocytes, or schistocytes Elevated Retic count Liver disease Hepatitis, obstructive jaundice, acute and chronic alcoholism with liver disease Smear: Round target macrocytes characteristic Can cause increased lipid deposition on RBC membranes Primary Bone Marrow Disorder Smear: Disordered maturity, hypogranulated or hyposegmented neutrophils, and cytopenias should be followed by a Bone Marrow biopsy Hypothyroidism Some patients will have macrocytosis w/o megaloblastosis ~10% incidence of pernicious anemia due to chronic autoimmune thyroiditis

    16. Our Patient: Plan by Problem Macrocytosis Macrocytosis likely secondary to liver disease. Will obtain CBC, peripheral smear, reticulocyte count, and LFTs. Expect to see round target appearing cells on smear. Would not expect an elevated retic count in liver disease. Pt with uterine fibroids, could possibly have mixed anemia. Down trending Human Spirit in an older woman Tx: show her two dimples and ask her for a second date in 3 months

    17. References Andres E, Loukili NH, Noel E. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ 2004;3:251-259. Aslinia, Mazza, Yale. Megaloblastic Anemia and Other causes of Macrocytosis. Clinical Medicine and Research. Vol 4 number 3. 2006. Colon-Otero G, Menke D, Hook CC. A Practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia. Med Clin North Am 1992;76:581-597. Davenport, John. Macrocytic Anemia. American Family Physician. January 1996. George, MW. If you are actually reading this I will buy you a drink. Loyola Int Med 2008; 164:896-904. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med 1999;159:1289-1298.

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