ANEMIA

² Definition: decrease in red cells or hemoglobin concentration in peripheral venous blood. For women, hemoglobin < 12 g/dL or hematocrit < 36%; for men, hemoglobin < 14 g/dL or hematocrit <41%.

² Symptoms: fatigue, headache, lightheadedness, dyspnea.

² Signs: hypotension, tachycardia, blood loss, pallor, jaundice, petechiae, purpura, flow murmur, splenomegaly.

Evaluation of Anemia

1. Start with reticulocyte count. Reticulocytes are immature red blood cells seen on peripheral smear that indicate increased bone marrow activity. Correct for the degree of anemia using the reticulocyte production index (RPI). A low retic count (< 1%) or RPI < 3 in the face of anemia indicates that production of red blood cells or hemoglobin is deficient. A high retic count (> 4%) or RPI > 3 shows that the bone marrow is working to replace blood lost through hemolysis or bleeding.

2. If the reticulocyte count is low, there must be a defect in the production of red blood cells or hemoglobin. Check the MCV.

a. MCV < 80 à Microcytic Anemia – a problem making hemoglobin.

i. Fe deficiency anemia: check ferritin. A ferritin < 20 indicates iron deficiency, and a ferritin > 100 rules it out. A ferritin between 20 and 100 is indeterminate – check the bone marrow.

ii. Anemia of chronic inflammation: in cases of microcytic anemia with a ferritin > 100, check the TIBC. A low TIBC and a high ferritin is seen in states of chronic disease. A normal or high TIBC and a high ferritin warrants examination of the bone marrow.

iii. Thalassemia: check the Hgb/MCV ratio (high in thalassemia and low in iron deficiency).

iv. Sideroblastic anemia: check for sideroblasts in the bone marrow.

b. MCV 80-94 à Normocytic Anemia – often due to stem cell failure, as in aplastic anemia.

c. MCV > 94 à Macrocytic Anemia – a problem making DNA.

i. Liver disease: check the peripheral smear. Target cells are indicative of liver disease.

ii. B₁₂/Folate deficiency: on the peripheral smear, hypersegmented neutrophils and macro-ovalocytes will be present. Check serum B₁₂ and folate levels.

iii. Drugs: check for medications like methotrexate, phenytoin, phenobarbital, hydroxyurea, colchicine, pyrimidine antagonists (zidovudine, fluorouracil), sulfonamides, alkylating agents, OCPs, and triamterene. Also, alcoholism can result in macrocytic anemia.

3. If the reticulocyte count is high, the patient is either losing blood through hemolysis or bleeding. It is important to rule out bleeding first – ask the patient about hematemesis, hemoptysis, hematuria, melena, etc. and check hemoccult and urinalysis. Many hemolytic anemias are hereditary, so find out if the patient has any family history of bleeding problems or anemia.

a. Positive family history à Check the peripheral smear.

i. Sickle cell anemia: patients will have sickle cells on peripheral smear. Check hemoglobin electrophoresis, which will help identify sickle cell anemia and other hemoglobinopathies.

ii. Hereditary spherocytosis: spherocytes will be seen. Test osmotic fragility.

iii. Hereditary elliptocytosis: again, the peripheral smear will demonstrate elliptocytes.

iv. Enzyme deficiencies (G6PD Deficiency, PK Deficiency): peripheral smear will be normal, but specific enzyme assays are available to test for these conditions.

b. Negative family history à These are acquired hemolytic anemias. The peripheral smear is still important, as is the Coombs test.

i. Autoimmune hemolytic anemias: these can be due to autoantibodies, transfusion reactions, or drugs. Coombs test will be positive in these patients. It is important to work up possible causes for the autoimmune reactions (check ANA, evaluate medications, etc.)

ii. Microangiopathic hemolytic anemia (MAHA): schistocytes will often be seen on peripheral smear. Coombs test will be negative. Check a coagulation profile to evaluate for potential causes, like DIC, TTP, and HUS.

iii. Paroxysmal nocturnal hemoglobinuria (PNH): the peripheral smear will be normal, and Coombs test will be negative. These patients will have a history of having brown or red urine in the morning. Check a sucrose lysis test to diagnose this condition.

APPROACH TO THE PATIENT WITH ANEMIA

		Reticulocyte count
	Low (< 1%) Decreased production					High (> 4%) Hemolysis / Bleeding
	MCV					Hemolysis?
					(ü IBili, LDH, hemoglobinuria, ¯haptoglobins)
Microcytic (< 80)	Normocytic (80-94)	Macrocytic (>94)
			No = Bleeding			Yes = Hemolysis
¯ Hgb synthesis	¯ demand or stem cell failure	defective DNA synthesis
							Family History
Iron deficiency	Bleeding	Liver disease
(¯Fe, TIBC, ¯Ferritin) Chronic disease	Dilution Hypothyroidism	B12 deficiency Folate deficiency	No = Acquired extrinsic defect					Yes = Inherited intrinsic defect
(¯Fe, ¯TIBC, Ferritin)	Chronic renal failure
Sideroblastic Thalassemias	Aplastic anemia Marrow replacement			Direct Coombs’ Test				Membrane defects Hemoglobinopathies
	Chronic disease							Enzyme deficiencies
			(+) = Immune			( – ) = Non-immune
			Transfusion reaction Autoimmune hemolysis Drug induced			Hypersplenism MAHA PNH Malaria