Hemolytic disease of the fetus and newborn due to alloanti‐M: three Chinese case reports and a review of the literature

Abstract

BACKGROUND: Alloanti-M was once regarded as not clinically significant, with a few exceptions in extremely rare cases. However, an increasing number of cases of severe hemolytic disease of the fetus and newborn (HDFN), resulting in fetal hydrops and recurrent abortion caused by alloanti-M, have been reported mainly in the Asian population. STUDY DESIGN AND METHODS: Three pregnantChinese women with a history of abnormal pregnancy with hydrops fetalis were encountered. During this pregnancy, a series of clinical examinations and an alloantibody identification against RBCs and platelets were conducted. Intrauterine transfusion and postnatal transfusion were then performed in the fetuses. In addition, the HDFN cases caused by alloanti-M reported in different ethnic groups as well as their clinical and serologic features are also summarized. RESULTS:Three pregnant women were identified with an M-N+ phenotype and IgM mixed with IgG alloanti-M in serum. Their fetuses were found by ultrasound examination and cord blood testing to have severe anemia. Additionally, an M+N+ phenotype and IgG alloanti-M were detected in the cord blood of the three fetuses with titers ranging from 1:1 to 1:128. Moreover, low reticulocyte counts and negative direct antiglobulin tests were also shown in two of the fetuses. After receiving intrauterine transfusions and postnatal transfusions several times, these three fetuses eventually survived and then healthfully developed in the follow-up tracking. CONCLUSION: Alloanti-M immunization can cause severe HDFN with hyporegenerative anemia, often seen in the Asian population, and suppression of erythropoiesis might account for it. ABBREVIATIONS: DAT = direct agglutination test; HDFN = hemolytic disease of the fetus and newborn; IAT = indirect antiglobulin test; IUT = intrauterine transfusion; MCA-PSV = middle cerebral artery peak systolic velocity; MoM = multiple of median; RPI = reticulocyte production index. From the

Red blood cell alloimmunization prevalence and hemolytic disease of the fetus and newborn in Israel: A retrospective study

“…21,22 However, several cases of anti-M, mostly IgG, causing severe HDFN, have been reported. [23][24][25] In our study anti-M was found in 86 of 769 (11%) women as a single alloantibody and in six women with multiple antibodies. Data on IgM/IgG subtypes and titers in these women were not available.…”

Distribution of maternal red cell antibodies and the risk of severe alloimmune haemolytic disease of the foetus in a Chinese population: a cohort study on prenatal management

“…In addition, the antibody titre of anti-M was significantly lower than that of anti-D, indicating that anti-M can cause severe HDF even at low titres. The lower reticulocyte count indicated incompatible erythropoiesis with severe anaemia [21], which was also found in neonatal cases [19]. These results might be explained by the suppression of red cell development from erythroid precursor cells [22,23].…”

“…Very few reports have causally linked anti-M antibody positivity with HDFN in a Caucasian population [18]. Over the past two decades, anti-M-related HDFN has mostly been reported in Asian ethnic groups, especially in Japanese [19] and Chinese populations [20,21], and it has been reported to result in severe foetal anaemia, hydrops fetalis, stillbirth and neonatal death. A previous study found that 88.6% of anti-M-related HDFN cases occurred in Asian populations [21], indicating the high pathogenicity of IgG anti-M in Chinese people.…”

“…Over the past two decades, anti-M-related HDFN has mostly been reported in Asian ethnic groups, especially in Japanese[ 19 ] and Chinese populations[ 20 , 21 ], and it has been reported to result in severe foetal anaemia, hydrops fetalis, stillbirth and neonatal death. A previous study found that 88.6% of anti-M-related HDFN cases occurred in Asian populations[ 21 ], indicating the high pathogenicity of IgG anti-M in Chinese people. Even though our tertiary prenatal centre provided a relatively higher incidence of HDF due to anti-M, our results suggested that the risk of anti-M-associated severe HDFN in the Chinese population might be high, with 60.0% (6/10) receiving IUTs and 2 cases of intrauterine demise due to the lack of timely treatment.…”

Different distribution of maternal red cell antibodies and risk on the severe alloimmune haemolytic disease of the foetus in a Chinese Population: a retrospective cohort study on prenatal management

“…There were very few reports that causally link anti-M antibody positivity with HDFN in a Caucasian population [14]. Over the past two decades, anti-M-related HDFN has mostly been reported in the Asian ethnic group, especially in Japanese [15] and Chinese populations [16,17], [17] which was also found in neonatal cases [15]. These might be explained by the suppression of red cell development from the erythroid precursor cell [18,19].…”