It happens all the time. You’re flipping through a patient’s labs before knocking on the exam room door, and — bam — anemia. Maybe they’re here for fatigue. Maybe it’s a routine visit. Either way, the lab is nudging you toward a bigger question: why?
Anemia is defined as a hemoglobin <13.6 g/dL or a hematocrit < 40% in men and a hemoglobin<11.9 g/dL or a hematocrit < 35% in women.
Anemia isn’t a single diagnosis: it’s a breadcrumb trail. Our job is to follow it thoughtfully, resisting the urge to jump to conclusions or brush it off as “just a little low.” The workup begins with the CBC and one of its most underappreciated gems: the MCV. This simple measurement gives you a head start, sorting anemia into three broad categories based on red blood cell size.
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Microcytic (MCV <80 fL)
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Iron deficiency anemia (IDA), alpha thalassemia, beta thalassemia, lead poisoning
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Normocytic (MCV 80-100 fL)
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Nutrient deficiency (esp early stages of Fe, B12, folate, copper def), combination of microcytic and macrocytic anemias, anemia of chronic disease, CKD, heart failure, hemolysis, malignancy, hypothyroidism, medication induced, liver disease/ETOH use, clonal hematopoietic stem cell disorders (MDS, aplastic anemia), early blood loss, pure red cell aplasia, partially treated anemia
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Macrocytic (MCV >100 fL)
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Folate deficiency, B12 deficiency, medication induced, liver disease, ETOH abuse, copper deficiency, myelodysplastic syndrome (MDS), aplastic anemia, hypothyroidism, reticulocytosis, multiple myeloma
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From there, patient context is everything. Age matters — new anemia in someone over 55 deserves a malignancy workup until proven otherwise. Sex assigned at birth? Think IDA in menstruating patients, and normocytic anemia in adult men or postmenopausal folks. Past medical history can be loaded with clues: gastric bypass raises suspicion for B12 and folate deficiency; CKD, liver disease, and hypothyroidism all carry their own anemia risks. Even social history deserves a fresh look. Alcohol use? Vegan diet? Smoking? Travel? They all shape your differential. And don’t sleep on the medication list — NSAIDs, metformin, anticonvulsants, and chemotherapy agents can all cause anemia.
While anemia often shows up as a lab surprise, the vitals can steer you toward urgency. Hypotension and tachycardia in an anemic patient should set off alarms for acute blood loss. Stable vitals let you dive deeper into the story. And though many patients with anemia are asymptomatic, others will report vague but telling complaints: fatigue, dizziness, reduced exercise tolerance, maybe a hint of pallor. Don’t forget to ask about pica, beeturia, bleeding symptoms, or dark urine — they’re subtle but specific, especially in iron deficiency or hemolysis.
The physical exam may not scream “aha!” but it can still whisper clues. Think glossitis, cheilitis, and koilonychia in iron deficiency. Or symmetric paresthesias and gait disturbances with B12 deficiency. Cognitive changes? Could be folate or B12.
After a thorough history and physical exam, ordered additional labs to determine the underlying cause of the patient’s anemia. Consider the following labs using the MCV as a guide:
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Anemia Type
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Next Steps
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Microcytic (MCV <80 fL)
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- Iron studies (serum Fe, TIBC, ferritin)
- If normal iron studies → hematology referral to assess for thalassemia
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Normocytic (MCV 80-100 fL)
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- Reticulocyte count, peripheral blood smear and CMP
- Iron studies (serum Fe, TIBC, ferritin)
- Hematology referral if the initial workup is inconclusive
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Macrocytic (MCV >100 fL)
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- Serum B12, folate first, then methylmalonic acid (MMA) if either borderline
- If normal, ✔️ TSH, serum cooper, LFTs
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Sometimes the diagnosis is obvious. Sometimes it’s a journey. Either way, you can land on a presumptive diagnosis and move forward with confidence, or bring in hematology when the path gets murky. The beauty of anemia is that it asks us to slow down, think broadly, and consider the whole patient.
Want more step-by-step guidance on walking through the most common undifferentiated chief complaints, like abdominal pain, headache, and pediatric fever? Check out our NP Clinical Resource Guide.
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