An Approach to the “Untransfusable” Patient

Abstract 4385

The multiply alloimmunized patient poses a difficult predicament for clinicians, the hospital blood bank and duty hematologist. Whilst parallels may be drawn between patient blood management strategies used in the setting of blood refusal, others are unique to alloimmunization. There is limited literature guiding the management of the multiply alloimmunized patient requiring transfusion.

We describe a 54-year-old lady who presented with symptomatic anaemia due to a delayed haemolytic transfusion reaction from an unidentifiable antibody. She had been transfused 2 units of red cells 13 days earlier in the setting of gastrointestinal bleeding. At this time she was found to have an anti- Fy^a antibody and was transfused with Rh matched, K negative, Fy(a-) and indirect anti-globulin test (IAT) cross-match compatible red cells. Her history included previous transfusions in the setting of bleeding, but no pregnancies. On admission hemoglobin (Hb) was 69 g/L [115 – 165], reticulocyte count 237× 10⁹/L [20 – 100], bilirubin 33 μmol/L [<20] and haptoglobin <0.1 g/L [0.3 – 2.0]. Her blood film showed moderate polychromasia and nucleated red cells. A direct antiglobulin test was weakly positive (3/12) for IgG and C3d. Antibody investigations revealed a weakly positive auto-control and a new unidentifiable antibody. Subsequent testing identified 2 heterozygous mutations in exon 13 of the Lutheran gene: 1742A>T, encoding Gln581Leu and a silent 1671C>T, not affecting Ser557. These mutations are 2 out of the 3 mutations describing the LU- 13 genotype¹. Our patient lacks the third mutation 1340C>T previously described.

The patient's Hb dropped to 42 g/L and her treatment included bed-rest, intravenous iron, intramuscular vitamin B12, oral folate and erythropoietin. Whilst she had no active gastrointestinal bleeding she was given pantoprazole infusions and had a capsule endoscopy. She had a history of menorrhagia so was started on norethisterone and tranexamic acid to suppress menstrual loss. No first degree relatives were available for directed donation. She was transfused with 1 unit of IAT cross match compatible red cells together with 100mg prednisolone orally daily and 1g/kg intravenous immunoglobulin in an attempt to suppress immune haemolysis. She tolerated the transfusion well; however there was no increment in her Hb. Avoidance of unnecessary blood testing and pediatric collection tubes were used to reduce phlebotomy related loss. Over the next 10 days her Hb incremented without further transfusion to 78 g/L and had normalized by 4 weeks. Due to the need for future gastrointestinal surgery, on recovery of her Hb she had 5 autologous units of blood collected and frozen. Patient blood management strategies in the patient where the risk of potentially significant haemolytic reactions to transfusion is high must focus on minimizing blood loss, maximizing tissue oxygenation, promoting erythropoiesis and reducing metabolic needs. Approaches to lessen blood loss include early radiologic or surgical intervention to stop active bleeding, cessation or reversal of anticoagulants or aspirin and avoidance of medications or supplements associated with increased bleeding risk. Reducing phlebotomy-based blood loss includes minimizing the number of blood tests, using pediatric collection tubes and point of care devices. In our patient we investigated for ongoing bleeding sources, utilised proton pump inhibitors and used hormonal control for cessation of menstruation. Erythropoiesis was stimulated by the delivery of iron, folate, vitamin B12 and erythropoietin. Early investigation for associated coagulopathy or thrombocytopenia and early treatment with vitamin K, fresh frozen plasma and cryoprecipitate ensures that red cell volume is optimised.

In a patient with multiple alloantibodies, the hospital blood bank should screen their inventory of donated red cells and consult with local and regional blood authorities. The blood typing of family members may allow for identification of potential donors. In the acute setting with an unstable haemorrhaging patient, the decision to transfuse the least incompatible blood may need to be considered. Long-term management plans may include autologous unit collection and identification of alloantibodies at a molecular level.