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Citation Information : Immunohematology. Volume 33, Issue 4, Pages 152-154, DOI: https://doi.org/10.21307/immunohematology-2019-021
License : (CC-BY-NC-ND 4.0)
Published Online: 16-October-2019
Only rare cases of anti-Vel–associated mild-to-moderate hemolytic disease of the fetus and newborn have been previously reported. No case of fetal anemia requiring prenatal therapy has been noted to date. We report such a case recently encountered at our Fetal Center. Strategies are discussed for managing pregnancy complicated with alloimmunization to an antibody to a high-prevalence antigen, including sources of red blood cells for intrauterine transfusions.
The Vel red blood cell (RBC) antigen was first described in 1952.1 The antigen is ubiquitous in the general population, with only 0.04 percent of Caucasian individuals failing to exhibit expression.2 Only rare cases of anti-Vel–associated mild-to-moderate hemolytic disease of the fetus and newborn (HDFN) have been previously reported.3–7 The neonatal manifestation of HDFN in these cases was limited to hyperbilirubinemia requiring only phototherapy. No case of fetal anemia requiring prenatal therapy has been noted to date. We report such a case recently encountered at our Fetal Center.
The patient was a 31-year-old woman (gravida/para/abortus [GPA] = G2P1000) who was referred to our Fetal Center from a neighboring state for evaluation of Vel alloimmunization. Her past history was significant, with the finding of a positive antibody detection test and identification of anti-Vel during her previous pregnancy. Based on literature reports of only mild-to-moderate HDFN in association with Vel alloimmunization, the patient’s obstetrician had elected to follow the previous pregnancy conservatively. The patient was delivered by vaginal birth at 39 6/7 weeks of gestation. The neonate was noted to exhibit severe anemia and was transferred to a tertiary level nursery. After a stormy neonatal course that was complicated by pulmonary hypertension, the neonate died on day 13 of life.
In the patient’s current pregnancy, her anti-Vel titer was 32 at 11 weeks of gestation. A repeat at our regional blood center indicated a titer of 4. Consideration was given to begin a plasmapheresis/intravenous immune globulin treatment; given the patient’s low titer, however, this was not felt to be indicated. The patient returned to her local maternal-fetal medicine specialist and was followed with weekly middle cerebral artery Doppler ultrasounds to measure the peak systolic velocity (MCA-PSV). She was encouraged to donate autologous RBC units in anticipation of a possible need for intrauterine transfusion later in gestation. The patient was able to donate 4 units; these were kept refrigerated for 3–5 days and then frozen at the local blood center. At 24 weeks of gestation, the MCA-PSV became elevated to 1.89 multiples of the median (MoM), and the patient was referred back to our Fetal Center (>1.5 MoM is indicative of severe fetal anemia8). A repeat MCA-PSV was 2.0 MoM, and the repeat maternal anti-Vel titer was 16. A decision was made to proceed with intrauterine transfusion. Arrangements were made for transport of the previously donated frozen maternal RBC units to our regional blood center. Initial sampling at the time of cordocentesis at 24 1/7 weeks of gestation revealed a fetal hematocrit (Hct) of 11.8 percent (normal 36%) with a reticulocyte count of 14.7 percent (normal <2%). RBC typing indicated the fetus to be Vel+. One unit of maternal autologous RBCs was deglycerolized, irradiated, washed, and reconstituted with normal saline to achieve an Hct of 72 percent in the final blood product. A 60-mL intravascular transfusion combined with a 40-mL intraperitoneal transfusion was performed successfully. A total of five intrauterine transfusions were subsequently undertaken (Fig. 1). The patient donated 3 additional RBC units during the remainder of the pregnancy and maintained an Hct above 32 percent, with oral iron and folate supplementation. The additional RBC units for intrauterine transfusion came from a single local blood donor (2 frozen, 1 fresh) and another rare registry donor (1 fresh). The patient was delivered uneventfully by repeat caesarean section at 37 6/7 weeks of gestation of a 4235-gram male infant with Apgar scores of 8 and 9. The infant was noted to have an Hct of 46.2 percent (normal 53%) with a reticulocyte count of 2 percent (normal <7%) and a Kleihauer-Betke stain indicating 3.7 percent fetal cells remaining in the infant’s circulation (normal 100%). The neonatal course was benign and required only treatment with bili light therapy for 3 days; the maximum total bilirubin was 10.6 mg/dL (normal 6.5 mg/dL). He was discharged on day 7 of life. The infant was followed weekly by a local pediatric hematologist. He required one top-up transfusion at 5 weeks of age and was released by the pediatric hematologist at 9 weeks of age.
Our case illustrates at least three important points. Vel is expressed on fetal RBCs as early as 12 weeks of life; its strength appears to be equivalent to that on adult RBCs.9 Because alloimmunization to this antigen is so rare and only a few case reports of HDFN have been reported to date, it is difficult to determine a “critical titer” for this entity. Often, anti-Vel is only IgM, which would not present a risk for HDFN because transplacental passage cannot occur. Linz et al.10 recommended treatment with 2-mercaptoethanol or dithiothreitol to determine whether an IgG component is present. Both IgG and IgM had been detected in our case. A predominance of IgG in our case may well explain the severe degree of HDFN. One should assume that a paternal Vel antigen will be inherited by the fetus, given that Vel is a high-prevalence antigen. Thus, it would appear prudent to institute serial MCA-PSV determinations in the early second trimester in the rare case that anti-Vel is detected during pregnancy.
The strategy in obtaining sufficient RBC units for intrauterine transfusion to treat the HDFN is also an essential element of our case. The high prevalence of Vel makes finding Vel– donors extremely difficult. The patient was evaluated before pregnancy, and no sibling or family member was identified as a potential donor. A search by our regional blood center found only one eligible donor locally. The patient was instructed to undergo autologous donations in the early part of pregnancy and was able to donate 4 units. Iron and folate supplementation was initiated in advance. We previously reported a series of 21 patients who donated 77 units of autologous blood as a source of RBCs for intrauterine transfusion in the pre-HIV testing era.11 Three of the patients in that series were able to donate 6 units with maintenance of their baseline Hct levels. In our case, we were able to have our patient donate 7 units while maintaining her Hct with hematopoietic pharmacologic supplementation. Because freshly donated RBCs are typically preferred as a source for intrauterine transfusion, we defined the specific time for the final 3 units of autologous donation and arranged allogeneic donation times so that fresh blood was used for the scheduled intrauterine transfusions. Our experience in timed blood preparation would be useful in managing similar patients.
Finally, at delivery, we had multidisciplinary communication. To prepare for the urgent need for blood as well as to prevent wasting the rare blood product, we secured 2 frozen autologous compatible RBC units in our regional blood center before the scheduled caesarean delivery. In the event of an acute postpartum hemorrhage, we developed a plan with our blood bank for the emergency release of ABO-compatible RBCs pending the deglycerolization of these frozen units.