A 19 year old male presents with two weeks of non-bloody, non-bilious vomiting and two episodes of non-bloody diarrhea. He is unable to eat but is tolerating fluids. His urine is dark and he is febrile to 101.7. He was seen the day before in the ED, discharged with the diagnosis of gastroenteritis, before returning with worsening diffuse lower abdominal pain. He denies any other symptoms and the rest of the history is unremarkable.
Past medical history: ADHD, hypothyroidism, depression.
Medications: bupropion, fluoxetine, levothyroxine, lamotrigine, mirtazapine
Past surgical history: None
Family History: Adopted
Social history: Past tobacco smoker, now vapes, smokes marijuana, occasional alcohol
Vitals: T 38.1, HR 93, BP 109/47, SpO2 93%
Physical exam: Crackles at the left lower base, otherwise unremarkable
Labs: WBC 14 with neutrophilic predominance, no blasts, Total Bili 1.9, Direct Bili 0.9, Hgb 8.8, MCV 90, Haptoglobin 472 (high), LDH 301 (high), ferritin 507 (high), TIBC 123 (low), iron 12 (low), Rhino-Enterovirus positive, Mycoplasma PCR negative, HIV negative, blood cultures and urine cultures negative
Imaging: CT chest shows multifocal pneumonia, CT abdomen shows nonspecific hepatomegaly
Hospital course: The patient was admitted to the pediatric floor, became a rapid response for tachypnea and hypoxemia, and eventually upgraded to PICU on high flow nasal cannula. Pediatric hematology and GI were consulted for the anemia and elevated bilirubin. All his labs improved and he was eventually discharged. His final diagnosis was multifocal pneumonia and anemia of inflammation.
Take Away #1
What is the differential for normocytic anemia?
What tests do you need to order?
What other tests can help you confirm the diagnosis?
CT chest and abdomen to rule out intrathoracic and intra abdominal hemorrhage, haptoglobin and LDH for hemolysis, iron studies to differentiate between iron deficiency and anemia of chronic disease/inflammation
How do you rule out each diagnosis on the differential?
G6PD: peripheral smear (bite cells, Heinz bodies), physical (jaundice)
Acute blood loss from a GI bleed or trauma: guaiac, history and physical, +/- CT chest and abdomen
Anemia of chronic disease: diagnosis of exclusion +/- iron studies
Anemia of inflammation: diagnosis of exclusion +/- iron studies
Chronic renal insufficiency: Chem 8
Bone marrow suppression: CBC
Hemolysis: CBC +/- haptoglobin and LDH
Aplastic anemia: CBC
Take Away #2
The CBC gives you a lot of useful information and can help you avoid unnecessary work-up and tests. The MCV tells you this is a normocytic anemia, the reticulocyte count and differential tell you whether the bone marrow is working properly. Iron studies help you to confirm the diagnosis.
Reticulocyte count - In this case the reticulocyte count was 0.9 (normal range is 1% to 3%). Reticulocytes are red blood cells that still contain RNA. After losing RNA they become mature red blood cells. The rate of production of reticulocytes is equal to the rate of destruction of old red blood cells in a healthy person. If there is a process that speeds up the destruction of red blood cells (hemolysis), the bone marrow will try to catch up by producing more reticulocytes. On the other hand a very low reticulocyte count in the setting of anemia points to the bone marrow as the culprit. In anemia of chronic disease/inflammation, the reticulocyte count is normal to slightly low.
Ferritin - In this case it was elevated to 507. Ferritin is a circulating iron storage protein that is increased in proportion to body iron stores. It is low in iron deficiency, but increased in cases of inflammation and infection because it’s an acute phase reactant.
Serum Iron - In this case it was 12, which is low (normal range 30-160). Serum iron is low in iron deficiency and anemia of chronic disease/inflammation. Not very specific because the levels can fluctuate even in the absence of anemia.
TIBC (aka Transferrin) - In this case it was 123, which is low (normal range 236-448). Transferrin is a protein that carries iron. It is increased in the setting of iron deficiency anemia and can be decreased in anemia of chronic disease/inflammation.
Transferrin saturation - In iron deficiency anemia, the transferrin saturation is decreased because there is low levels of iron and high levels of transferrin.
Haptoglobin - In this case it was 472, which is high (normal range 8-234) indicating that hemolysis is unlikely. Haptoglobin is an acute phase reactant.
Take Away #3
This patient's case shows you that with a few blood tests you can get to the correct diagnosis. At the same time ordering a seemingly unnecessary test like a chest x-ray was crucial and possibly life saving for this patient.
When the patient presents multiple times for the same complaint without a clear diagnosis, broaden your differential and work up.
Philip Siva Vittozzi Wong, MD is a current third year resident at Stony Brook Emergency Medicine.
Fraenkel PG. Anemia of Inflammation: A Review. Med Clin North Am. 2017 Mar;101(2):285-296
Rosen's Emergency Medicine : Concepts and Clinical Practice. St. Louis :Mosby, 2002. Print. See Figure 112.1 page 1466 from Rosen’s
Edited by Bassam Zahid, MD