Autoimmune hemolytic anemia (AIHA) during pregnancy and puerperium is severe, requires treatment with corticosteroids and/or intravenous immunoglobulin (IVIg) in almost all women, and necessitates blood transfusions in about half of all patients, according to findings from an international multicenter study published in the journal Blood.

Cold agglutinin disease (CAD) is a rare subtype of AIHA characterized by the premature destruction of red blood cells (ie, hemolysis), in which the autoantibody is IgM. De novo or relapsing AIHA during pregnancy or puerperium is extremely rare, with reports mainly describing cases of the warm IgG type.

Recognizing that relapsing or occurring de novo AIHA during pregnancy or puerperium has been poorly delineated, the researchers sought to describe the severity, treatment need, and impact on fetal and maternal outcomes of AIHA.

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In the current analysis, patients were retrospectively obtained from 12 tertiary hematology centers with expertise in the diagnosis and management of AIHA. The centers were located in Denmark, France, the Netherlands, Spain, the United Kingdom, and the United States.

Study inclusion criteria were diagnosis of AIHA, according to current guidelines, in women of childbearing potential who had (1) AIHA diagnosed prior to pregnancy and (2) de novo AIHA that occurred during pregnancy or puerperium. The study period was between 1997 and 2022.

All clinical and hematologic parameters were collected during AIHA flares either during pregnancy or postpartum/ puerperium. All AIHA therapies carried out prior to or following a pregnancy were registered. Response to treatment was categorized as “partial” (ie, hemoglobin [Hb] ≥10 g/dL or increase of ≥2 g/dL from baseline) or “complete” (ie, Hb ≥12 g/dL). All pregnancy outcomes were systematically registered and compared with those from a control group of 56 healthy pregnant women.

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The current report discusses 45 pregnancies that occurred in 33 women who were evaluated at 1 of the 12 centers. Among the 20 women who had an AIHA diagnosis prior to pregnancy, 10 experienced a relapse. An additional 13 women developed de novo AIHA during gestation/puerperium (2 women experienced an AIHA relapse during a second pregnancy).

Among 24 reported hemolytic events, patients’ anemia was uniformly severe (median HB, 6.4 g/dL; range, 3.1 to
8.7 g/dL) and required treatment in all women (96% treated with corticosteroids and/or IVIg; 58% receiving transfusions). A response was achieved in all women, with a complete response reported in 65% of them.

Antithrombotic prophylaxis was given to 8 women. Rituximab was administered in 4 patients, and cyclosporine was received by 1 woman following delivery. The rate of maternal complications reported was 15%; they included premature rupture of the membranes, placental detachment, and preeclampsia. Early miscarriages were observed in 13% of the pregnancies.

Fetal adverse events were reported in 22% of the newborns, including respiratory distress, fetal growth restriction, preterm birth, and AIHA in the newborn. There were 2 perinatal deaths reported as well.

The authors concluded that the current study “provides insight into pregnancy outcomes in AIHA, suggesting that the occurrence of AIHA does not preclude the ability to carry a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications [take place].”


Fattizzo B, Bortolotti M, Fantini NN, et al. Autoimmune hemolytic anemia during pregnancy and puerperium: an international multi-center experience. Blood. Published online January 27, 2023. doi:10.1182/blood.2022018890