What is the appropriate work‑up and management for anemia in a pregnant patient?

Work-up for Anemia During Pregnancy

Screen all pregnant women with a complete blood count (CBC) at the first prenatal visit and repeat at 24-28 weeks gestation, using trimester-specific hemoglobin thresholds (<11 g/dL in first trimester, <10.5 g/dL in second/third trimester) to diagnose anemia. 1, 2

Initial Screening Protocol

• Obtain CBC at first prenatal visit to establish baseline hemoglobin, hematocrit, and mean corpuscular volume (MCV). 1, 2
• Repeat CBC at 24-28 weeks gestation as physiologic hemodilution peaks during this period and may unmask iron deficiency. 1, 2
• Use trimester-specific diagnostic thresholds: hemoglobin <11.0 g/dL defines anemia in the first trimester, while <10.5 g/dL (or <11.0 g/dL depending on guideline) defines anemia in the second and third trimesters. 1, 2

Diagnostic Algorithm Based on Initial CBC Results

Mild Anemia (Hemoglobin ≥10.0 g/dL) with Normal or Mildly Low MCV

• Presume iron deficiency anemia and initiate empiric oral iron therapy at 60-120 mg elemental iron daily without waiting for confirmatory testing. 1, 2
• Reassess hemoglobin after 4 weeks of treatment, expecting an increase of ≥1 g/dL or hematocrit increase of ≥3%. 1, 2
• If no response occurs after 4 weeks despite confirmed compliance, perform additional testing including MCV, red cell distribution width (RDW), and serum ferritin. 1, 2

Mild Anemia with Very Low MCV (<80 fL)

• Obtain additional testing before starting treatment: serum ferritin, iron studies, and hemoglobin electrophoresis to evaluate for thalassemia or other hemoglobinopathies. 2, 3
• Consider coeliac serology if there is family history of gastrointestinal disease or coeliac disease. 1

Macrocytic Anemia (MCV >100 fL)

• Measure serum vitamin B12 and folate levels to identify megaloblastic anemia. 4, 3
• Evaluate for underlying causes including dietary deficiency, malabsorption, or medications affecting folate metabolism. 4

Moderate Anemia (Hemoglobin 7.0-9.9 g/dL)

• Perform comprehensive work-up before initiating treatment: CBC with differential, reticulocyte count, peripheral blood smear, serum ferritin, iron studies, vitamin B12, and folate. 2, 3
• Evaluate for hemolysis: lactate dehydrogenase (LDH), indirect bilirubin, haptoglobin, and direct antiglobulin test (Coombs). 3, 5
• Consider referral to hematology or a physician experienced in managing anemia during pregnancy. 1, 2

Severe Anemia (Hemoglobin <7.0 g/dL or <9.0 g/dL with symptoms)

• Immediately refer to a physician familiar with anemia in pregnancy or hematology specialist. 1, 2
• Perform urgent comprehensive laboratory evaluation: CBC with differential, reticulocyte count, peripheral smear, iron studies, hemolysis markers, vitamin B12, folate, and hemoglobin electrophoresis. 2, 3
• Prepare for potential intravenous iron therapy or transfusion depending on clinical status and gestational age. 1, 6

Important Limitations of Laboratory Testing in Pregnancy

• Serum ferritin has limited diagnostic utility in pregnancy because ferritin concentrations fall in late pregnancy even with adequate iron stores and may be falsely elevated by inflammation. 7
• Hemoglobin and hematocrit alone are imprecise for diagnosing iron deficiency due to physiologic hemodilution, which normally reduces these values by up to 20% during pregnancy. 7, 2
• Do not rely solely on ferritin levels to diagnose or exclude iron deficiency; clinical response to empiric iron therapy is often more informative. 7

Additional Testing for Specific Clinical Scenarios

Suspected Inherited Hemoglobinopathy

• Obtain hemoglobin electrophoresis if MCV is very low (<80 fL) or if there is family history or ethnicity suggesting thalassemia or sickle cell disease. 3, 5
• Test partner for hemoglobinopathy carrier status if patient is confirmed carrier to assess fetal risk. 5

Suspected Hemolytic Anemia

• Order reticulocyte count, peripheral blood smear, LDH, indirect bilirubin, haptoglobin, and direct antiglobulin test if hemoglobin is dropping rapidly or there are signs of hemolysis. 3, 5
• Evaluate for microangiopathic hemolytic anemia (HELLP syndrome, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome) if platelet count is low or there are signs of preeclampsia. 3

Non-Response to Oral Iron After 4 Weeks

• Verify compliance first—gastrointestinal side effects frequently lead to treatment discontinuation without patient disclosure. 1
• Perform MCV, RDW, and serum ferritin to confirm iron deficiency and exclude other causes. 1, 2
• Do not attribute iron deficiency solely to aspirin or proton pump inhibitors without completing appropriate investigations, as these do not reduce the likelihood of underlying gastrointestinal pathology. 1
• Consider upper gastrointestinal endoscopy and duodenal biopsy if coeliac disease is suspected; these procedures can be performed safely in pregnancy. 1

Critical Pitfalls to Avoid

• Never assume compliance without verification—frequent gastrointestinal side effects (constipation, nausea, abdominal pain) often lead to discontinuation. 1
• Do not wait for confirmatory testing to start treatment in mild anemia with normal or mildly low MCV; empiric oral iron is both diagnostic and therapeutic. 1, 2
• Do not overlook physiologic anemia—hemoglobin naturally decreases during pregnancy due to plasma volume expansion, but this does not require treatment unless iron deficiency is present. 2, 8
• Do not use serum ferritin as the sole diagnostic criterion for iron deficiency in pregnancy due to its poor sensitivity and specificity in this population. 7