Anemia is a common finding in primary care. Patients may present with weakness, dizziness, syncope, fatigue, dyspnea or palpitations. Low hemoglobin on routine screening tests must be evaluated to determine the cause. A careful history and physical examination are always the next step, but if they are noncontributory, the laboratory examination should narrow down the cause. The first tests in the anemic patient work-up are:

• The complete blood count (CBC)
• Corrected reticulocyte count (corrected for the patient’s hemoglobin level)
• Red cell morphology or a review of the blood smear by a trained technologist
• Chemistry profile including renal, hepatic, lactate dehydrogenase (LDH) and Bilirubin values
• Urinalysis for protein and hemoglobin levels

If the corrected reticulocyte percentage is over 2.0 then the anemia cause is usually blood loss from hemolysis or bleeding. Hemolysis can be confirmed if the indirect bilirubin and LDH are increased. The patient may also have hemogobinuria, but no red cells in the urine. The work-up of hemolysis should indclude:

• Coombs test is to check for antibody-antigen autoimmune reactions
• Hemoglobin electrophoresis to diagnose hereditary hemoglobinopathies like thalassemia and sickle cell disease
• Heinz body stain to diagnose G6PD deficiency. “Bite” cells may be present on the red cell morphology
• Review the red cell morphology for malaria, babesiosis, spherocytosis and eliptocytosis. Schistocytes may be present in patients with valvular prosthesis or coagulopathies such as DIC, TTP or HUS

If the corrected reticulocyte percentage is less than 2.0, the problem is lack of bone marrow red cell production. The mean corpuscular volume or MCV value from the CBC will help guide the laboratory tests to order. If the MCV is under 80 fl, then the red cells are microcytic and the following tests should be ordered:

• Iron studies including serum iron, total iron binding capacity or TIBC, percent saturation and ferritin. The best indicator of iron deficiency is a serum ferritin less than 20 in a male and under 10 in a female. If Iron deficiency is diagnosed, the cause should be differentiated from poor nutrition, GI or menstrual bleeding.

If the Iron studies are normal, the following lab tests should be completed depending on the patient’s history:

• C-Reactive protein will be elevated if inflammatory block is the cause
• Hemoglobin electrophoresis will demonstrate a decreased hemoglobin A and elevated A2 in beta thalassemia. There may be target cells reported on the red cell morphology
• Lead level – to rule out lead poisoning which may also have basophilic stippling on the red cell morphology

If the patient’s MCV is between 80 – 100fl, they have a normocytic anemia and the following tests may make the diagnosis:

• C-Reactive protein will be elevated if inflammatory block is the cause.
• Pregnancy test in females as this can cause a dilutional normocytic anemia.
• BUN, and Creatinine levels are elevated in renal failure. Proteinuria may also be present.
• TSH may be elevated in hypothyroidism

If the MCV is greater than 100 fl, the patient has a macrocytic anemia and the first tests should be the following:

• Serum folate and RBC folate are low and serum homocyteine levels are elevated in folate deficiency
• Serum B12 level is low and methylmalonic acid level is elevated in vitamin B12 deficiency. To identify the reason, order intrinsic factor antibodies, which are present in pernicious anemia

If these tests do not point to the cause, the next step is referring your patient to a hematologist for a probable bone marrow biopsy to take a look inside the red cell factory.

Allan Platt will be speaking at the GAPA summer meeting on “Blood – too little, too much, too thick and too thin”. A 60 min streaming video of a “Review of Hematology” which include more details about the anemia work-up is located at http://emorypa.org/electronic_board_review_2010.htm There are links to PDF articles and free Differential Diagnosis Mnemonics electronic handbook.

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