Double-filtration plasmapheresis as an adjunct to therapy for severe early-onset maternal erythrocyte alloimmunization

Erythrocyte alloimmunization is an important cause of hemolytic disease in fetuses and newborn (HDFN). Intrauterine blood transfusion (IUT) is the standard treatment for anemic fetuses, but there are adverse reactions, especially before 20 weeks of gestation. Here, we used double filtration plasmapheresis (DFPP) as an adjunct therapy to prolong the time to receive IUT safely. The aim of this study was to determine the safety and efficacy of DFPP for early-onset HDFN during pregnancy. We recruited pregnant women with a high risk of early-onset HDFN. The DFPP procedure was performed by a plasmapheresis machine using a plasma separator and a plasma component separator. A 5% albumin solution served as the replacement fluid. A central venous catheter was used for DFPP. The blood flow rate was 120–150 ml/min, and the plasma separation rate was 1200–1500 ml/h. The rates of discarding the plasma and replenishing the plasma were 150–200 ml/h. The plasma volume to treat each patient was calculated via the Kaplan formula. Anticoagulation was achieved with low-molecular-weight heparin. The treatment goal was to reduce the ratio of antibodies to less than 1:32 or to maintain fetal MCA-PSV < 1.5 MoM, thereby prolonging pregnancy to allow safe IUT when necessary. Epidemiological data and hematological parameters as well as side effects were evaluated before and after DFPP. A total of 6 patients, including 5 with Rh and 1 with MN-associated maternal–fetal hemolysis, were analyzed. DFPP was initiated at a median gestational age of 14 weeks (range: 12–18). Patients received a median of 8 sessions (range: 3–9) over 4 weeks (range: 2– 5), with 3000 mL (range: 2000–3250) of plasma processed per session. A total of 40 procedures were performed. Anti-D/M antibody titers decreased by a median of 50% after each session . Other proteins, such as albumins, globulins, and complement and coagulation factors, also decreased significantly after DFPP treatment, whereas white blood cells, neutrophil and hemoglobin increased after DFPP treatment. However, coagulation factor levels returned to normal levels the next day. No obvious side effects were observed during the entire treatment period. Five women successfully prolonged pregnancy until 20 weeks of gestation and underwent IUTs, whereas one woman failed at 15 weeks of gestation due to severe fetal anemia and underwent induced labor. The cohort received a total of 26 transfusions, with a median of 5 procedures (range: 1–6) per patient over a median treatment duration of 9.5 weeks (range: 1–14). These favorable results indicate that DFPP is an effective and safe rescue therapy for pregnant women with maternal incompatible hemolytic anemia. However, more clinical trials with larger sample sizes, long-term follow-up, and cost‒benefit analyses are needed to better evaluate its application value and prospects.