HDFN Therapeutic treatment

Intrauterine transfusions: In the presence of severe fetal anemia, valuated measuring the peak velocity of the systolic blood flow of the median cerebral artery, if the fetus did not reach a reasonable gestational age to born and if the hematocrit is <30% there’s the indication to use intrauterine transfusions. These are performed directly into the fetal circulation through the umbilical vein under the ultrasound guide. The infusion is made with O Rh negative group concentrated red blood cells, CMV negative and irradiated.

It must be highlighted that such transfusions may be burdened with sometimes severe complications: fetal asphyxia, procedural lesions (umbilical cord rupture, arterial spasms, hematoma spasm or excessive bleeding), fluid overload, amniotic fluid infection (coronamnionitis), premature breakage of the amniotic membranes and premature delivery. From scientific literature data, the risk of abortion, following this intervention, varies from 0.9% to 4.9% depending from the center in which is performed, and is more frequently observed in hydrops fetuses and when intrauterine transfusion is performed at a particularly low gestational age(Lindenburg et al., 2014).

With the remarkable reduction in cases of RhD alloimmunization only a few centers retained the ability to carry out this technique with a proper expertise and good results, therefore it is advisable to concentrate the treatment of pregnant women, with higher risk alloimmunization only in these referenced centers.

Delivery is recommended at 37-38 weeks, but with severe forms of HDFN it should be anticipated.

Over the years, technology has produced different phototherapy luminaires with LED lamps and/or a combination of blue and green lights for intensive phototherapy.

Exchange-transfusion: introduced in the 1950s, is a life-saving technique since lowering the serum bilirubin level of the infant it prevents bilirubinic encephalopathy and subsequent kernicterus. It is based on the exchange of the sensitized red cells of the infant, bounded with maternal antibodies, with Rh negative red blood cells of a donor. This procedure reduces the level of bilirubin, of circulating antibodies and corrects any anemia. The exchange transfusion uses reconstituted blood (ie fresh red blood cells, filtered and CMV free, with plasma at hematocrit of 50-55%). The blood, before the use, is irradiated to prevent donor transplanted immune cells from inducing graft-versus-host disease.

Exchange transfusion, carried out using approximately twice the volume of blood that circulates, removes about 90% of the sensitized red blood cells and about 50% of the circulating serum bilirubin. It can then be assisted after exchange transfusion to a rebound for the passage of bilirubin from tissues to the bloodstream.

Exchange transfusion is performed using a catheter placed in the umbilical vein (Girelli, 2015).

The most frequent complications of exchange transfusion are: decreased number of platelets, hypocalcemia, electrolytic alterations and necrotizing enterocolitis. The risk of death following this procedure is calculated between 0.5 and 2% (Falciglia, 2013).

Intravenous immunoglobulins have been introduced in the last years in the therapy. Their mechanism of action is not entirely clear, but they often limit hemolysis and reduce the use of exchange transfusion. Further studies are needed to better define the newborns population that can benefit most of this therapy and at what levels of bilirubin should be performed.

Newborns with HDFN should be periodically checked after hospital dismission because they have a higher risk of late anemia, especially after 4-6 weeks. Infants who received intrauterine or multiple blood transfusions, may develop, between two and six weeks of life, a late hyporegenerative anemia (with a small number of reticulocytes). This status can be treated  with recombinant human erythropoietin, which, in about two weeks, is capable to significantly  increase the reticulocytes, and to reduce the need for transfusions. In addition to the condition of late anemia, the follow-up of these newborns over the first few years of life, promptly identifies possible neuro-behavioral disorders caused, in particular, by hyperbilirubinemia and anemia.

References
Lindenburg ITM, van Kamp IL, Oepkes D. Intrauterine blood transfusion: current indications and associated risks. Fetal Diagn Ther 2014; 36: 263–271
Girelli G, Antoncecchi S, Casadei AM et al. Recommendations for transfusion therapy in neonatology. Blood Transfus 2015; 13; 484-97
Falciglia HS, Greenwood CS. Double volume exchange transfusion: A Review of the “Ins and Outs”. Neoreviews 2013; 14: e513-520