Anemia 101- Case Studies Peter A. Kouides MD Associate Professor of Medicine, University of Rochester School of Medicine Attending Physician, The Rochester General Hospital

Anemia classification based on the mechanism Kinetic Classification (based on retic count) Decreased production Morpholgical classification (based on MCV) Microcytic Normocytic Macrocytic Increased destruction Immunological classification (based on Coomb’s test) Immune-mediated Non-immune mediated

The Medical Student’s Approach to Anemia Check the reticulocyte count to determine if the anemia is from decreased production (“hypoproliferative”, “reticulocytopenic”) or increased destruction (“hemolytic”)/acute blood loss (“reticulocytosis”) 2. If decreased production, narrow down the causes in terms of the MCV- If the MCV is low, then do iron studies then Hb electropheresis If the MCV is normal, check the serum creatinine and TSH, if they are WNL then consider bone marrow exam If the MCV is high check a folate and vitamin B12 level 3. If the the reticulocyte count is increased- Check a direct Coomb’s test 4. Look at the peripheral blood smear to confirm/support the diagnosis

Anemia Algorithm Patient with anemia and decreased reticulocyte count- What is the MCV ?? Microcytic Normocytic Macrocytic: Vitamin-related B12, Folate Non-vitamin: MDS EtOH/Liver Disease Hypothyroidism Fe def. Systemic Diseases Thal Diseases in Bone Marrow MDS Solid Tumor Myeloma Aplastic anemia Renal vs. Liver vs. Endocrine vs. Anemia of Inflammation Other: sideroblastic anemia (meds,PB,Zn excess,Cu def)

Anemia Algorithm, continued Patient with anemia and increased reticulocyte count= HEMOLYTIC ANEMIA

Anemia Algorithm, continued Patient with anemia and increased reticulocyte count- What is the result of a Coomb’s test ?? Negative Positive (autoimmune hemolytic anemia) Intrinsic red cell defect Extrinsic red cell defect “Warm” “Cold” Membrane Cytoplasm Vessel Valve Hemoglobin Toxin

The Attending’s Approach to Anemia 1. Stool guiacs x 3 2. If the MCV is low, then prescribe iron 3. If the MCV is high, then check a folate level and vitamin B12 level if folate level returns low or “indeterminate”, then begin folic acid 1 mg po qd if B12 level returns low or “indeterminate”, then begin IM vitamin B12

The Pharmacologist’s Approach to Anemia

Case #1-A 67-year-old man is referred for evaluation of dyspnea Case #1-A 67-year-old man is referred for evaluation of dyspnea. The hematocrit is 28%, white blood cell count 4500/mm3, platelet count 550,000/mm3, and reticulocyte count 4%. The MCV is 78 and the blood smear reveals basophilic stippling and a small population of hypochromic microcytic red cells. Serum Fe 225, TIBC 260, Ferritin 490

Case #2-Patient H.M. A 57-year-old woman presents to the clinic for evaluation of ataxia, weakness, and parathesias. The patient has been taking a multivitamin preparation. Hematocrit is 38% white blood cell count 4,000; platelet count 100,000 What tests would you order next ?

Case #3- A 65-year-old man with a Hematocrit of 33% and a reticulocyte count of 7% is admitted to the hospital with right upper quadrant abdominal pain. Peripheral blood smear reveals occasional spherocytes.

Case #4- Patient R.B. A 26-year-old woman presents to the hospital with pleuritic chest pain. She gives a history of episodic arthralgias for a number of months, plus one episode of frank arthritis involving the small joints of both hands occurring 2 months prior to admission. The patient has a hematocrit of 29%, a white blood cell count of 4000, and a reticulocyte count of 12%. The smear reveals normocytic, normochromic red blood cells with polychromatophilia, and occasional spherocytes, occaisonal NRBC.

Case #5- Patient F.D. A 60-year-old woman is hospitalized because of severe fatigue and dyspnea of 2 weeks' duration. Five years ago, the patient had a total hysterectomy and bilateral salpingo-oophorectomy for ovarian adenocarcinoma. She received a course of oral melphalan as adjuvant chemotherapy.

Patient F.D. continued Three years ago a restaging laparotomy reveals no evidence of tumor, and blood counts were normal. Now, except for a temperature of 38.4°C (101.1°F) and pallor, she has normal findings. Laboratory studies: Hematocrit 17%, MCV 108 fL. , WBC 4,500, platelet count 50,000, reticulocyte count 0.8%

MDS vs. Folate/B12 Deficiency Think of MDS when the anemic patient is elderly and the MCV is increased in one study of the elderly, MDS was the fourth most common cause of anemia after: acute blood loss/Fe Deficiency anemia of chronic disease anemia of renal insufficiency the B12 level can be borderline low in elderly patients but it is not true B12 deficiency if- a serum total homocysteine level is normal a urine methylmalonic acid level is normal

Case #6- Patient G.D. A 28 year-old black man plans a trip to India and is advised to take prophylaxis for malaria. Three days after beginning treatment, he develops dark urine, pallor, fatigue, and jaundice Hematocrit is 26% (it had been 43%), MCV 100; WBC 3.4, Platelets 199,000

Patient G.D. continued Reticulocyte count 13% What test should be diagnostic? And, why do I say “should” instead of “is diagnostic”?

Drugs Causing Anemia LESS COMMON- MORE COMMON- Decreased Production: Anti-Tb drugs= Sideroblastic Anemia Chloramphenicol, Valproic acid= Pure Red Cell Aplasia AZT, Dilantin= Macrocytic Anemia MORE COMMON- Increased Destruction (Hemolytic): Qunidine, PCN, Aldomet= Auto-immune Hemolytic Anemia Primaquine,Nitrofurantoin, Dapsone, Pyridium= G6PD Deficiency

Case # 7 A 21-year-old woman with sickle cell anemia has had a fever and severe pain in the right shin for 3 weeks. The painful area is hot, swollen, tender and indurated.

Case #8 A 66-year-old-man presents with increased fatigue and anemia. Hypothyroidism was detected 3 years ago and thyroid hormone therapy was administered. Anemia was diagnosed 2 years ago, but findings on bone marrow examination were normal, and there was no response to oral therapy with iron. Sexual function has diminished during the last 2 years. He has a blood pressure of 90 Hg systolic and 60 mm Hg diastolic, pallor, absence of axillary hair, and sparse pubic hair. There is no gynecomastia, but the testicles are soft, and the prostate gland is small. The result of an examination of the stool for occult blood is negative. Laboratory studies: hematocrit 36%, leukocyte count 5800/µL, platelet count 255,000/µL, peripheral blood film - normochromic normocytic erythrocytes with anisocytosis or poikilocytosis, MCV: 86 fl, serum creatinine - normal.