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In hemolytic disease of the newborn, fetal red cells become coated with IgG alloantibody of maternal origin, directed against an antigen on the fetal cells that is of paternal origin and absent on maternal cells. The IgG-coated cells undergo accelerated destruction, both before and after birth. The clinical severity of the disease can vary from intrauterine death to hematological abnormalities detected only if blood from an apparently healthy infant is subject to serologic testing.
Pregnancy causes immunization when fetal red cells possessing a paternal antigen foreign to the mother enter the maternal circulation, an event described as fetomaternal hemorrhage (FMH). FMH occurs in up to 75% of pregnancies, usually during the third trimester and immediately after delivery. Delivery is the most common immunizing event, but fetal red cells can also enter the mother's circulation after amniocentesis, spontaneous or induced abortion, chorionic villus sampling, cordocentesis, or rupture of an ectopic pregnancy, as well as blunt trauma to the abdomen.(1)
Rh immune globulin (RhIG, anti-D antibody) is given to Rh-negative mothers who are pregnant with an Rh-positive fetus. Anti-D antibody binds to fetal D-positive red cells, preventing development of the maternal immune response. RhIG can be given either before or after delivery. The volume of FMH determines the dose of RhIG to be administered.
Determining the volume of fetal-to-maternal hemorrhage for the purposes of recommending an increased dose of the Rh immune globulin
Greater than 15 mL of fetal red blood cells (RBC) (30 mL of fetal whole blood) is consistent with significant fetomaternal hemorrhage (FMH).
A recommended dose of Rh immune globulin (RhIG) will be reported for all specimens. One 300 mcg dose of RhIG protects against a FMH of 30 mL of D-positive fetal whole blood or 15 mL of D-positive fetal RBCs. Recommended standard of practice is to administer RhIG within 72 hours of the fetomaternal bleed for optimal protective effects. The effectiveness of RhIG decreases beyond 72 hours post-exposure but may still be clinically warranted. This assay has been validated out to 5 days post collection.
Clinical conditions exist that may result in an increased level of fetal hemoglobin-containing red cells, including hereditary persistence of fetal hemoglobin and thalassemia. Such red cells (also referred to as F cells) are detected by this assay. Results must be interpreted with caution in these situations.
This test is not used to detect the hereditary persistence of fetal hemoglobin (see HPFH / Hemoglobin F, Red Cell Distribution, Blood).
< or =1.5 mL of fetal RBCs in normal adults
1. Technical Manual. Sixteenth edition. Edited by J Roback, MR Combs, B Grossman, C Hillyer. Bethesda, MD, AABB Press, 2008, pp 625-637, pp 888
2. Iyer R, McElhinney B, Heasley N, et al: False positive Kleihauer tests and unnecessary administration of anti-D immunoglobulin. Clin Lab Haematol 2003;25:405-408