Anemia

Anemia 101Case 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 1.

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 countWhat is the MCV ?? Microcytic

Normocytic

Macrocytic: •Vitamin-related

Fe

Thal

def.

Systemic Diseases

Renal vs. Liver vs. Endocrine vs. Anemia of Other: sideroblastic anemia Inflammation (meds,PB,Zn excess,Cu def)

Diseases in Bone B12 , Folate Marrow •Non-vitamin: •MDS

•Solid Tumor

•MDS

•Myeloma

•EtOH/Liver Disease

•Aplastic

•Hypothyroidism

Anemia Algorithm, continued •

Patient with anemia and increased reticulocyte count= HEMOLYTIC ANEMIA

Anemia Algorithm, continued • Patient with anemia and increased reticulocyte countWhat is the result of a Coomb’s test ??

Negativ Extrinsic red e cell defect

Intrinsic red cell defect

Membrane Vessel

Valve

Cytoplasm Hemoglobin

Toxin

Positive

(autoimmune hemolytic anemia)

“Warm”

“Cold”

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 Pharmcologically Responsive Anemias

Pharmcologically Unresponsive (“refractory”) Anemias

• nutrient-responsive • with cellular marrow ⇒iron deficiency anemia ⇒anemia of chronic disease (inflammation) ⇒B12 deficiency ⇒MDS ⇒folate deficiency ⇒Metastatic tumor ⇒pyridoxine-responsive sideroblastic anemia ⇒Thalassemia trait • erythropoietin• with hypocellular marrow responsive ⇒aplastic anemia ⇒renal failure anemia ⇒hypoplastic AML • synthroid-responsive ⇒hypothyroidism • prednisone-responsive ⇒AIHA

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 salpingooophorectomy 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:

Increased Destruction (Hemolytic):

Anti-Tb drugs= Sideroblastic Anemia Chloramphenicol, Valproic acid= Pure Red Cell Aplasia AZT, Dilantin= Macrocytic Anemia

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.