RHD Genotype Matching for Anti-D

This is a pilot study to evaluate the feasibility and safety of providing RH genotype matched D+ Red Blood Cells (RBCs) to chronically transfused patients with sickle cell disease (SCD) who type D+ but have formed anti-D and are currently transfused with D- RBC (Red Blood Cell) units.

Red blood cell transfusion remains a critical therapy for patients with sickle cell disease (SCD). A major problem is the high rate of alloimmunization (antibody formation against transfused red cells) that occurs in patients with SCD. Recent studies performed by Investigators and others demonstrate RH genetic variants in patients and donors is a major risk factor leading to Rh alloimmunization. Anti-D formation in D+ patients occurs frequently, and once identified, providing D- cells for all subsequent transfusions can be challenging. These anti-D antibodies in D+ patients suggest exposure to different or variant D protein on donor cells. Investigators will test whether transfusion of patients with anti-D with RHD genotyped matched red cells is feasible, safe and can decrease D- donor unit demand.

Investigators will provide one red cell unit of D+ RH genotype matched RBCs at the first transfusion study visit. The remainder of units will be provided per clinical standard of care, i.e. D-, CEK-matched, and negative for all other antigens the patient is alloimmunized against. If laboratory monitoring shows no reappearance of anti-D and no signs of increased red cell hemolysis, the patient will receive one unit of D+ RH genotype matched RBCs at the 2nd transfusion study visit, and if tolerated, D+ red cell exposures will increase by one unit per study visit until all units required are D+.

Chronically transfused patients with SCD and anti-D will receive D+ RH genotyped matched red cell units for transfusion in addition to standard C, E, and K antigen matching and being hemoglobin S negative, which is the Children's Hospital of Philadelphia institutional standard of care for patients with SCD. RH genotyping of donor units will be performed by the New York Blood Center (NYBC) Immunogenetics laboratory.

Feasibility and safety of providing RH genotype matched D+ RBCs to patients with SCD who type D+ but have formed anti-D

To determine feasibility of identifying sufficient RH genotype matched units (identifying sufficient RH genotype match red cells without delays in transfusion), and safety (no anti-D reappearance or evidence of hemolysis of transfused red cells).

Inclusion Criteria: Subjects age > 8 years old Diagnosis of SCD, all genotypes Require chronic red cell transfusion therapy History of anti-D RH genotype predicts D+ expression Exclusion Criteria: Rare RH genotype that would preclude sufficient RBC units Antigen negative requirements due to alloimmunization that would preclude sufficient RBC units

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