P-TS-39: Red Blood Cell Alloimmunization in Hyper-Inflammatory States: A Study on Hemophagocytic Lymphohistiocytosis

Document Type

Conference Proceeding

Publication Date


Publication Title

Association for the Advancement of Blood & Biotherapies


Background/Case Studies: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation resulting in hyper-inflammatory response. We have previously reported on the high transfusion needs in HLH. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization as in sickle cell disease. With HLH being a hyper-inflammatory disease with increased blood transfusion needs, we wanted to assess if HLH patients are at increased risk of alloimmunization to RBC antigens.

Study Design/Methods: We identified all adult patients (age ≥18 years) with a diagnosis of HLH managed at our institution between April 2010 and February 2020. The Institutional Review Boards approved this retrospective chart review study. HLH diagnosis was established based on the 2004 Histiocyte Society Criteria (HLH-2004). The following exclusion criteria were applied: 1- Patients clinically diagnosed with HLH, but did not meet the HLH-2004 criteria, 2- Patients who received packed RBCs in an outside institution before their admission to our institution, 3- Patients not transfused with packed RBCs at our institution, and 4- Patients without a follow up antibody screen. Serologic testing was performed using standard immunohematology techniques following our blood bank procedures. All our blood components were pre-storage leukoreduced.

Results/Findings: Forty-four adult patients with HLH fulfilled the inclusion criteria. The median age of patients was 57.1 years (range 18.2 - 77.6 years); 27 (61%) were male. Patients received a median of 8 RBC units (range 2 - 38 units) during admission when HLH diagnosis was established. The median serological follow up after the first transfused RBC unit was 22.5 days (range 3 days - 108.1 months). After a median follow up of 43 days (range 8 days - 122 months), 14 (31.8%) were alive. We only had one patient who developed a new anti-E antibody that was identified 13 days after transfusion of an E-positive RBC unit. The patient was a 27-year-old Caucasian male with no history of previous transfusions. At the time of alloimmunization, his DAT was negative and hemolysis workup was unremarkable.

Conclusions: The rate of alloimmunization (2.3%) in our cohort was not increased compared to that of the general population (3-5%). The patient who had alloimmunization seemed to have had a primary immune response based on negative transfusion history and absence of delayed hemolytic transfusion reaction. However, his alloimmunization was detected after only 13 days from transfusion of the involved RBC unit which was earlier than the usual window period for primary immune responses following transfusion. This early primary response might be due to the hyper-inflammatory state of HLH. RBC alloimmunization in HLH warrants further investigation.