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IgA Deficiency, Immune Globulin Treatment, and Pregnancy

Dr. Xu Han

David Daniel, MD

Clinical Fellow
Department of Transfusion Medicine
National Institutes of Health
Bethesda, MD

The patient was a 32-year-old G1P0 woman with a history of infertility and IgA deficiency undergoing in vitro fertilization. She had undergone five prior implantation attempts without success, had never received transfusions of any blood products, and did not have a history of anaphylactic reactions. Her blood group is O, RhD-negative, and her fertility specialists wanted to know whether she could be considered a candidate for Rho(D) immune globulin (RhIG) treatment and how to approach RBC transfusion if required during her delivery.

 Quantitative Immunoglobulin Levels (reference range)
 IgG  582mg/dL (586-1,602 mg/dL)
 IgA  <5mg/dL (87-352 mg/dL)
 IgM  96mg/dL (26-217 mg/dL)

Question: What is the most appropriate approach to the use of RhIG and RBC transfusions in this patient?

  • A. The patient has never had a history of anaphylactic reaction. No special precautions are required for RhIG and RBC administration.
  • B. The patient has an absolute IgA deficiency. RhIG is contraindicated since it is derived from pooled alloimmunized plasma donors. RBCs should be washed prior to transfusion to remove IgA that may be present in the residual plasma of the RBC unit.
  • C. The patient has an absolute IgA deficiency. Given the concern for potential RhD alloimmunization, any available RhIG should be given. Only IgA negative blood should be transfused to mitigate possible transfusion reactions.
  • D. The patient should be tested for anti-IgA antibodies. If anti-IgA is present, then most RhIG preparations are contraindicated, and RBCs should be washed.

Answer: D

IgA deficiency is a common human immunodeficiency that can be subclassified into relative (<5 mg/dL) or absolute (<0.05 mg/dL) deficiency, depending on the plasma concentration of IgA. The majority of patients with IgA deficiency are asymptomatic. However, if a patient with an absolute IgA deficiency is exposed to blood products containing IgA, anti-IgA antibodies may develop, placing the patient at risk of an anaphylactic reaction when given future blood products containing even small amounts of IgA.

The typical transfusion management strategy for patients with a history of IgA deficiency and anaphylactic reaction is to provide washed blood products or blood products collected from IgA-deficient donors, as this will aid in preventing future anaphylactic reactions. Given that RBCs and platelets have a short shelf life, maintaining an inventory of IgA-deficient products is challenging. Most commonly, washing is available for RBCs and platelets from routine donors, with the aim of removing as much IgA-containing plasma as possible. Plasma cannot be washed, and if indicated, would need to be collected from an IgA-deficient donor. Frozen plasma has a shelf life of 12 months, allowing many blood centers to maintain a sufficient supply as needed. It is important to note that the presence of even some IgA (a relative but not absolute deficiency) would denote an inability to produce an anti-IgA antibody, and transfusion of IgA-containing blood products or any RhIG would be safe.

This patient had a history of IgA deficiency with quantitative immunoglobulin testing demonstrating a selectively low IgA level (<5 mg/dL). Even though the patient has never had an anaphylactic reaction (Answer A), this low IgA level should raise concern for the possibility of an absolute IgA deficiency. Therefore, washing of blood products, issuing only IgA-negative blood, and a restriction on receiving RhIG should be considered.

RhIG must be considered when pregnant, RhD-negative patients may have an RhD-positive fetus (Answer B). If D alloimmunization prophylaxis is required, most RhIG is contraindicated for patients with anti-IgA, since traditional formulations of RhIG utilize the cold ethanol fractionation method of production, resulting in the presence of small amounts of IgA (usually less than 15 µg per dose) in the product. Fortunately, preparations of RhIG developed using ion exchange chromatography isolation, such as Rh0(D) Immune Globulin Intravenous, should be preferentially considered as there is no contraindication for this preparation per the package insert (Answer C). Another option to consider would be testing the RhD status of the father to rule out the need for RhD alloimmunization prophylaxis. Additionally, cell-free DNA testing can be used to assess the RhD status of the fetus and the need for D alloimmunization prophylaxis.

Most quantitative assays that are available for clinical use have a limit of detection of approximately 5 mg/dL, which is not sensitive enough to exclude a small amount of IgA and therefore cannot reliably diagnose an absolute IgA deficiency. If there is some IgA present in the patient’s plasma, she would not be able to form anti-IgA and would be eligible for any RhIG and routine blood products. The presence of some IgA would indicate that washed products and an RhIG restriction would not be necessary. A more fruitful test would be checking for the presence of an IgA antibody (Answer D), an assay that is not routinely run in hospitals but is readily available at many reference laboratories.

Acknowledgement: This article was edited by Eric Vick, MD, and Alfred Lee, MD.


  1. Sandler SG. How I manage patients suspected of having had an IgA anaphylactic transfusion reaction. Transfusion. 2006;46(1):10-13.
  2. Khandelwal A, Clarke G, Goldman M. Anaphylactic transfusion reactions and IgA deficiency [Internet]. Ottawa: Canadian Blood Services; 2021 [cited 12/27/2022]. Available from: professionaleducation.blood.ca/en/transfusion/publications/anaphylactic-transfusion-reactions-and-iga-deficiency
  3. Rhophylac [package insert]. Bern, Switzerland: CSL Behring AG; 2008.
  4. RhoGAM Ultra-Filtered PLUS [package insert]. Melville, NY; Kedrion Biopharma Inc.; 2018

Dr. Daniel indicated no relevant conflicts of interest.