Anemia In Pregnancy

A 29-year-old G2P1 woman at 20 weeks’ gestation is seen for her second prenatal visit. Her antenatal history is unremarkable except for a urinary tract infection treated with an antibiotic 2 weeks ago. The patient was noted to be anemic on her prenatal screen with a hemoglobin level of 9.5 g/dL, and a mean corpuscular volume (MCV) of 70 fL. On examination, her blood pressure (BP) is 100/60 mm Hg, heart rate (HR) 80 beats per minute (bpm), and she is afebrile. The thyroid gland appears normal on palpation. The heart and lung examinations are unremarkable. The fundus is at the umbilicus. The fetal heart tones are in the 140- to 150-bpm range. The evaluation of the anemia includes: ferritin level: 90 mcg/L (normal 30-100); serum iron 140 mcg/dL (normal 50-150); hemoglobin electrophoresis: Hb A1 of 95% and Hb A2 of 5.5% (normal 2.2% to 3.5%)

1.  What is the most likely diagnosis?
2. What is the underlying mechanism?

Case Discussion And Answers:


• Most likely diagnosis: Anemia due to β-thalassemia minor.
• Underlying mechanism: Decreased β-globin chain production.

This pregnant patient has a mild anemia, since the hemoglobin level is less than 10.5 g/dL. The red blood cell (RBC) indices give an indication of the etiology. In this case, the MCV is low, microcytic. The most common cause of microcytic anemia is iron deficiency. Typically, with a mild microcytic anemia in the absence of risk factors for thalassemia (such as Southeast Asian ethnicity), a trial of iron supplementation and recheck of the hemoglobin in 3 weeks would be the next step. This is called a therapeutic trial of iron. If the hemoglobin level improves, the evidence supports iron deficiency. If the hemoglobin level does not improve, then iron studies and a hemoglobin electrophoresis would be the next step. In this case, iron studies were performed which were normal/high normal, thus eliminating iron deficiency as a cause. The hemoglobin electrophoresis studies strongly suggest β-thalassemia trait (heterozygous for β-thalassemia) with the elevated A2 hemoglobin. If the patient had β-thalassemia homozygous disease, there would have been complications and clinical manifestations since childhood. The patient should now be counseled about her laboratory findings, and referred for genetic counseling, and instructed that her baby has a 1 in 4 risk for β-thalassemia disease if the father of the baby also has β-thalassemia trait. Extra iron should not be given, since these patients can be prone to iron overload.

DEFINITIONS

Anemia: A hemoglobin level of less than 10.5 g/dL in the pregnant woman.

Iron Deficiency Anemia: A fall in hemoglobin level that is due to insufficient iron to meet the increased iron requirements in pregnancy.

Thalassemia:A decreased production of one or more of the peptide chains (most common are the α and β chains) that make up the globin molecule. This process may result in ineffective erythropoiesis, hemolysis, and varying degrees of anemia.

Hemolytic Anemia: An abnormally low hemoglobin level due to red blood cell destruction, which may be divided into congenital causes and acquired causes.

Glucose-6-Phosphate Dehydrogenase Deficiency:  An X-linked condition whereby the red blood cells may have a decreased capacity for anaerobic glucose metabolism. Certain oxidizing agents, such as nitrofurantoin, can lead to hemolysis.

Important Clinical Points:

• The most common cause of anemia in pregnancy is iron deficiency. 
•  The two most common causes of microcytic anemia are iron deficiency and thalassemia.
• An elevated A2 hemoglobin level is suggestive of β-thalassemia disorder, whereas an elevated hemoglobin F level is suggestive of α-thalassemia. 
•  For mild anemias, it is acceptable to initiate a trial of iron supplementation and reassess the hemoglobin level. 
•  The most common cause of megaloblastic anemia in pregnancy is folate deficiency.
•  Hemolysis in individuals with glucose-6-phosphate dehydrogenase deficiency may be triggered by sulfonamides, nitrofurantoin, or antimalarial agents.