Very small volumes of blood cells commonly escape from the fetal intravascular compartment across the placental barrier into the maternal intervillous space and thus into the maternal circulation. Although the incidence of fetal-to-maternal hemorrhage in each trimester is high, the volume transfused from fetus to mother is very small (see Figure 27-1). Large hemorrhages are uncommon, and 2 to 4 percent of women will have fetal hemorrhage exceeding 30 mL. A number of events may cause sufficient fetal-to-maternal hemorrhage to incite isoimmunization in the mother (see Table 27-1).
FIGURE 27-1 Incidence of fetal-to-maternal hemorrhage during pregnancy. The numbers at each data point represent total volume of fetal blood estimated to have been transferred into the maternal circulation. (Reproduced, with permission, from Cunningham FG, Leveno KJ, Bloom SL, et al (eds). Williams Obstetrics. 23rd ed. New York, NY: McGraw-Hill; 2010. Data from Choavaratana R, Uer-Areewong S, Makanantakocol S: Fetomaternal transfusion in normal pregnancy and during delivery. J Med Assoc Thai 80:96, 1997.)
TABLE 27-1. Causes of Fetomaternal Hemorrhage That May Incite Red Cell Antigen Isoimmunization
Placental abruption does not commonly cause appreciable fetal-to-maternal hemorrhage, unless it is due to trauma, where the likelihood is increased due to placental fracture.
Fetal red cells in the maternal circulation can be identified by use of acid elution, which is the basis of the Kleihauer–Betke test. This test is based on the fact that fetal erythrocytes contain hemoglobin F, which is more resistant to acid elution than hemoglobin A. After exposure to acid, only fetal hemoglobin remains. Fetal red cells can then be identified by uptake of a special stain and quantified on a peripheral smear (see Figure 27-2).
FIGURE 27-2 Massive fetal-to-maternal hemorrhage. After acid elution treatment, fetal red cells rich in hemoglobin F stain darkly, whereas maternal red cells with only very small amounts of hemoglobin F stain lightly. (Reproduced, with permission, from Cunningham FG, Leveno KJ, Bloom SL, et al (eds). Williams Obstetrics. 23rd ed. New York, NY: McGraw-Hill; 2010.)
The presence of D-positive fetal red blood cells in maternal blood can also be determined by the rosette test. In this test, maternal red cells are mixed with anti-D antibodies, which coat any fetal D-positive cells in the sample. Indicator red cells bearing the D antigen are then added, and “rosettes” form around the fetal cells as the indicator cells are attached to them by the antibodies. The presence of rosettes indicates that fetal D-positive cells are present in the maternal circulation. The fetus that is severely anemic is more likely to demonstrate a sinusoidal heart rate pattern (see Chapter 13). In general, anemia occurring gradually or chronically, as in isoimmunization, is better tolerated by the fetus than anemia that develops acutely. Chronic anemia may not produce fetal heart rate abnormalities until the fetus is moribund. In contrast, acute anemia may cause profound neurological fetal impairment due to hypotension, diminished perfusion, ischemia, and cerebral infarction. Unfortunately, after an acute hemorrhage, subsequent obstetrical management usually will not change the outcome.
QUANTIFICATION OF THE EXTENT OF FETAL HEMORRHAGE
In addition to recognizing fetal-to-maternal hemorrhage, it is important to try to quantify the volume of fetal blood lost. The volume may influence obstetrical management, and is essential to determining the appropriate dose of D-immunoglobulin when the woman is D-negative. Using basic physiological principles, the amount of fetal hemorrhage may be calculated from the results of a Kleihauer–Betke (KB) stain using the formula:
where MBV = maternal blood volume (about 5000 mL in normal-sized normotensive women at term) and Hct = hematocrit. Thus, for 1.7 percent positive Kleihauer–Betke-stained cells in a woman of average size with a hematocrit of 35 percent giving birth to an infant weighing 3000 g:
The normal fetal–placental blood volume at term is about 125 mL/kg, and the hematocrit is about 50 percent. Thus, this fetus has lost 60 mL of whole blood over time into the maternal circulation. This amount represents approximately 15 percent of the fetal–placental blood volume and would require two 300-μg doses of anti–D immunoglobulin to prevent isoimmunization (one 300-μg dose of anti-D immunoglobulin neutralizes 30 cc of fetal Rh+ whole blood).
For further reading in Williams Obstetrics, 23rd ed.,
see Chapter 29, “Disease and Injuries of the Fetus and Newborn.”