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Fetomaternal hemorrhage occurs when a disruption in the placental barrier allows fetal blood to enter the maternal circulation.[1] This disruption may occur in the placental barrier for many reasons, including intrauterine fetal demise and trauma. Trauma is the leading cause of pregnancy-associated maternal deaths in the United States.[2] Fetomaternal hemorrhage occurs in as many as 40% of trauma cases, increasing in frequency and amount with high-force trauma, blunt-force trauma, abdominal trauma, and anterior placental placement in the uterus. When fetomaternal hemorrhage occurs, fetal hemoglobin (HbF) is mixed with maternal blood. In response to this exposure, the maternal immune system is activated, and isoimmunization (formation of anti-RhD antibodies) may occur if the mother is Rhesus-D protein (RhD) negative and the fetus is RhD positive. Only 0.01 to 0.03 mL of fetomaternal hemorrhage is required to isoimmunize the mother. Future pregnancies may be at risk for RhD disease if the fetus is RhD positive. The maternal antibodies bind to fetal RhD-positive erythrocytes, leading to hemolysis, anemia, hydrops fetalis, and possibly fetal death. To prevent the formation of anti-RhD antibodies, Rho(D) immune globulin is indicated. Before 12 weeks of gestational age, in the setting of an RhD-negative mother and fetomaternal hemorrhage, a mini-dose of 150 mcg Rho(D) immune globulin is given. This dose suppresses the immune response to 2.5 mL of Rh-positive red blood cells. At 12 weeks' gestation, a standard dose of 300 mcg is recommended. This standard dose of Rho(D) immune globulin (300 mcg) covers fetomaternal hemorrhage up to 15 mL of fetal red cells (30 mL of whole fetal blood). However, additional dosing may be necessary in cases of massive red blood cell fetomaternal hemorrhage and the resulting maternal immune response. In these situations, the Kleihauer-Betke test is essential.

The Kleihauer-Betke test is highly specific but has low sensitivity, with a positivity threshold of approximately 5 mL of fetomaternal hemorrhage. By comparison, only 0.01 to 0.03 mL of fetal blood is sufficient to cause isoimmunization. Therefore, the Kleihauer-Betke test is not meant to detect the presence of fetomaternal hemorrhage, but rather to provide a more accurate estimate of its volume. When positive, it guides whether additional doses of Rho(D) immune globulin are required beyond the standard 150 or 300 mcg.