CAD Can Lead to Serious Complications During Pregnancy, Case Study Says

Cold agglutinin disease can lead to serious complications during pregnancy, according to a case study of two women with autoimmune hemolytic anemia (AIHA).

The study’s researchers emphasized the importance of a complete molecular diagnosis of AIHA to estimate maternal and fetal risks, and to establish appropriate treatment plans.

The study, “Autoimmune hemolytic anemia in pregnancy: a challenge for maternal and fetal follow-up,” was published in The Journal of Maternal-Fetal & Neonatal Medicine.

AIHA is an autoimmune disease in which the body mistakenly attacks its own red blood cells (RBCs) by producing self-reacting antibodies that target these cells. The antibodies are classified as warm, cold, or mixed, based on the temperature at which they react and attack RBCs.

As its name suggests, cold agglutinin disease (CAD) occurs at lower temperatures, between 32 and 50 degrees Fahrenheit. At these temperatures, antibodies called cold agglutinins destroy RBCs, resulting in anemia. Immunoglobulin M (IgM) is one such antibody.

AIHA is estimated to affect one in 100,000 people in the general population. However, its incidence in pregnant women is unclear due to the scarcity of published studies.

“Identification of the etiology [origin] of anemia and the antibody type is essential to establish the potential risk for both the mother and the fetus as well as to determine their monitoring and treatment,” the investigators wrote.

To shed more light on this subject, researchers in Spain described and analyzed two cases of pregnant women with AIHA.

The first case was a 35-year-old woman who was referred to the University Hospital of Girona, Spain, for severe treatment-resistant (refractory) anemia when she was 17 weeks pregnant.

After a blood transfusion failed to resolve her symptoms, more extensive lab testing revealed she had AIHA, for which she was prescribed the steroid prednisone. A direct antiglobulin test (DAT) — which detects antibodies attached to RBCs — then revealed the presence of cold-reacting antibodies (IgM), confirming the diagnosis of CAD.

Middle cerebral artery (MCA) peak systolic velocity, a common and accurate parameter that is often used to diagnose fetal anemia, showed nothing unusual in the fetus.

Although the patient appeared to respond well to therapy and her prednisone dose was halved, she was later hospitalized and put on methylprednisolone after her symptoms worsened when she was 27 weeks pregnant. By then, she also started undergoing more intensive fetal monitoring.

Despite treatment, her condition continued to deteriorate, with her hemoglobin levels falling to 5.4 g/dL (the normal range for women is from 12.0 to 15.5 g/dL). This prompted physicians to adopt more aggressive measures to stabilize the patient and ensure healthy development of the fetus. The mother’s hemoglobin levels improved, but her baby was stillborn.

Doctors found nothing unusual after examining the fetus. The mother’s physical condition continued to improve with gradual tapering of prednisone and immunoglobulin therapy.

The second case was a 42-year-old woman, who was referred to hospital for anemia at 30 weeks pregnant.

Her pregnancy had been normal up to that point, and she had no relevant medical history. DAT was positive for IgG, a warm agglutinin, prompting the diagnosis of warm antibody AIHA.

As in the other woman’s case, she was treated with prednisone and MCA peak systolic velocity was analyzed to identify any signs of fetal anemia. At 38.5 weeks, she had a natural (unassisted) delivery without complications and was discharged from hospital with decreasing doses of prednisone.

The researchers noted that in CAD, the IgM antibody is an activator of a component of the immune system, called the complement system, which enhances the ability of antibodies to target and destroy cells.

Even though IgM cannot cross the placental barrier and directly harm the fetus, it can indirectly cause blood to coagulate, resulting in blood clots. The researchers said that the absence of fetal abnormalities in the first case report raises the possibility that a blood clot related to the complement system may have caused the stillbirth.

“During pregnancy, identification of the type antibodies in AIHA is crucial to estimate the potential maternal and fetal risks and to establish [adequate] follow-up [procedures],” they wrote.