There are many causes of anemia. Anemia can, at times, be multifactorial and in some cases, anemia may even be an early presentation of cancer. Learn more about the diagnostic workup for anemia and when to refer these patients to hematology.
Blood Tests to Run for an Anemia Workup
When evaluating a patient for anemia, start with a complete blood count (CBC) to check for other concurrent cytopenias, as more than one cytopenia may indicate a more serious disease. If there is only one major cell line that is mildly decreased or increased, it is reasonable to wait a couple of weeks and then repeat the CBC to see if the affected cell line has normalized. For patients with more than one cell line out of range, it is best to refer the patient to hematology for further evaluation.
Within the CBC results, you should evaluate the mean corpuscular volume (MCV), which measures the average size of the patient’s red blood cells. For patients with an MCV below normal range, it is important to evaluate for iron deficiency or inheritable thalassemia. For patients with an increased MCV, considerations might include Vitamin B12 or folate deficiency, medication effect, increased reticulocytes, or other multifactorial processes including a bone marrow disorder, alcohol intake, liver disease, or hypothyroidism. In patients with a normocytic anemia there can be multiple etiologies, including hemolysis, and further testing should be pursued.
Below is a non-exhaustive list of laboratory studies that can aid in determining the cause of a patient’s anemia:
- Ferritin test: This test is used to evaluate iron stores within the body. Given that ferritin is also an acute phase reactant, elevated levels should be interpreted in conjunction with complete iron studies and within the context of the patient’s overall clinical picture. Significantly low ferritin confirms iron deficiency. Referral to Rocky Mountain Cancer Centers (RMCC) for intravenous iron replacement should be considered in patients with severely low ferritin levels (<20) or in cases that have proven refractory or intolerant to oral replacement.
- Kidney function (BUN, Serum creatinine, and Glomerular Filtration Rate): These basic markers of kidney function can be used to identify patients with kidney disease, which can lead to insufficient erythropoietin and, in turn, reduced RBC production. In cases where abnormal renal function is a suspected cause of anemia, it may be beneficial to evaluate a serum erythropoietin level as well.
- Peripheral blood smear: This test can evaluate for other cytopenias and characterize abnormal red blood cell morphology to help guide evaluation. The presence of spherocytes may be indicative of hemolysis and a direct antiglobulin test should be ordered.
- Reticulocyte count: This test can evaluate if the patient’s bone marrow is appropriately responding to the anemia by increasing production of red blood cells. Reticulocytes may be appropriately elevated following blood loss or red blood cell destruction in the setting of hemolysis. Be sure to assess your patient for any evidence of gastrointestinal or abnormal gynecological sources of blood loss.
- Folate & Vitamin B12: These basic nutritional markers are particularly important to assess in patients with dietary restrictions (i.e. vegetarian or vegan) or those who have undergone gastric bypass. Replacement to normal range should correct the patient’s anemia. If a provider is concerned about the patient’s ability to absorb nutrients by mouth, referral to RMCC can be made for intramuscular injections.
- Serum protein electrophoresis (SPEP): A small percentage of patients may have anemia (often accompanied by macrocytosis) as a result of monoclonal gammopathy (MGUS) or multiple myeloma. Concern for multiple myeloma is higher in the setting of concurrent hypercalcemia, renal insufficiency, or recent fractures. If the patient is found to have a detectable paraprotein (also called a monoclonal protein or “M-Spike”), a referral should be placed to hematology for further characterization and workup.
Patients should be referred to hematology if the above work up does not readily identify a cause for anemia, if multiple abnormalities are identified, or if the treatment for the patient’s anemia extends beyond the scope of primary care. If you feel more comfortable referring your patient for the workup, RMCC hematologists are equipped to handle your request.
Iron Deficiency Anemia Evaluation and Management Considerations
Clinical History and Iron Stores
When evaluating the many causes of anemia in patients, peripheral blood results are only part of the picture. A complete clinical history should be obtained to help guide the anemia work up. It is important to ask about your patient’s diet to evaluate for risk of nutritional deficiencies. You should inquire about their routine health maintenance studies, including the date of their most recent colonoscopy and any reported concerns from previous gerontologic studies. Be certain to maintain an updated medication list so that any changes secondary to medications or supplements can be identified. This is especially important for patients who are taking blood thinners, as this may help the provider concentrate on blood loss as an etiology for anemia. For female patients of reproductive age with anemia, always inquire about the duration, frequency, and flow of menses.
Oral Iron vs. IV Iron Treatments
Iron deficiency is often identified as a cause of anemia. Correction of iron deficiency anemia may involve collaboration with GI or GYN specialists. If the iron deficiency is mild, it is reasonable to proceed with oral iron replacement. Generally, we recommend over-the-count “slow Fe” as the sustained release tends to be better tolerated. To ensure best absorption of oral iron, patients should be educated on the importance of taking vitamin C with iron each day. Furthermore, as dairy can interfere with the absorption of iron, patients should avoid taking iron supplements within two hours of dairy product consumption. Oral iron should also be separated by at least two hours from proton pump inhibitor or H2 blockers, which lower stomach acid and interfere with absorption.
If the iron deficiency is significant, it may be best to send the patient to hematology for replacement with intravenous iron infusions. Additionally, some patients may not be able to tolerate oral iron. Common complaints include upset stomach and constipation. Finally, certain patient populations may be unable to absorb oral iron, including those with a history of gastric bypass or chronic inflammatory disorders such as Ulcerative Colitis or Crohn’s Disease. These patients are also excellent candidates to receive intravenous iron, which is readily bioavailable and has fewer side effects. It should be discussed with patients that intravenous iron infusions are not entirely without risk. In fact, a small percentage of patients can have infusion reactions. For this reason, infusion are managed by RMCC registered nurses under the supervision of physicians and advanced practice providers with rescue medications available for any concerns.
To refer an anemia patient to Rocky Mountain Cancer Centers, use our Patient Referral Form.