(P-TS-7) Acquiring Red Blood Cells from Japan for a Patient with Anti-Hr0/Rh17 Requiring Surgery

The Rh blood group system is highly polymorphic, and mutations in the RHCE gene can cause null phenotypes of the RhCE protein. Patients with these null phenotypes can form alloantibodies to high-incidence RhCE antigens, making compatible RBCs extremely difficult to procure. This case report describes a 66-year-old woman with a history of anti-Hr0/Rh17, anti-E, and anti-c who presented to a U.S. hospital with a proximal femur fracture requiring surgical intervention. Hr0 represents multiple high-incidence epitopes found on RhCE and is not expressed in people with null RhCE phenotypes. This report outlines the molecular testing performed to characterize the patient’s null RHCE mutation and the management needed to provide compatible RBCs for her surgery.

Study

Design/Methods:

Molecular testing by a reference laboratory was performed to identify the patient’s RHCE alleles. Initial testing was performed using the PreciseType Human Erthryocyte Antigen (HEA) assay (Immucor). Medium-resolution genotyping was done using multiplex PCR, PCR-restriction fragment length polymorphism, and RHCE BEADCHIP (Immucor). High-resolution genotyping was performed using genomic DNA sequencing of the RCHE gene.

Results/Findings:

Results from PreciseType HEA falsely predicted the patient to be positive for c and E antigens, which was discrepant with the patient’s known alloantibodies and her C-c-E-e- RBC phenotype. Medium-resolution genotyping also yielded a false-positive phenotype prediction for c and E antigen expression. High-resolution genotyping identified 907delC (L303stop) mutation (RHCE*cE907delC homozygous or hemizygous) in the RHCE gene and determined that the patient had a rare single nucleotide deletion that is associated with a null phenotype.

Due to lack of compatible RBCs, surgery was deemed too risky, and the patient received an external fixator placement as a temporizing measure. Her family members were tested to be incompatible, and a national search did not find any compatible units or donors in the United States. The blood center escalated to an international search and identified a compatible donor in Japan. In order to import these RBC units, a monocyte monolayer assay was performed to confirm the clinical significance of the patient’s anti-Hr0, and the medical director applied for FDA approval for international import. Approximately 3 weeks later, two units of compatible blood were available, and the patient underwent an open reduction internal fixation of her femur without incident.

Conclusions:

Patients with rare mutations associated with null Rh phenotypes can have alloantibodies to high-incidence antigens. High-resolution genotyping can be necessary to interrogate these rare mutations. Finding compatible RBCs for these patients is challenging and can require international searches for suitable donors.