3.3 Red Blood Cell Molecular Testing

NC Medicaid should expand required newborn traditional blood testing.

Implementation: • NC Medicaid should cover red blood cell (RBC) molecular testing (“genotyping”) for patients with SCD.

Background

RBC transfusion is a mainstay of SCD treatment. It is recommended preoperatively and to treat acute SCD complications like acute chest syndrome, stroke and organ failure.251 However, for patients with SCD, RBC transfusion carries a high risk of alloimmunization, a serious complication in which the patient’s own immune system destroys newly-transfused RBCs that do not match the patient’s blood type.252 Alloimmunization can also cause delayed hemolytic transfusion reactions (DHTRs), an extreme, life-threatening reaction to mismatched blood.253 Patients with SCD have the highest alloimmunization rate of any transfused patient population.254 One study estimated that about 50 percent of patients with SCD suffer alloimmunization.255

RBC molecular antigen testing beyond traditional serological testing can ensure that transfused blood is a proper match for a recipient, thereby avoiding these dangerous and costly complications in the future. The traditional serological tests used to match donor and recipient red blood are insufficient. They do not test for RBC antigens that are most frequently implicated in alloimmunization (i.e., C/c, E/e and K antigens), and they carry significant risk of error for patients transfused in the past three months.256 NC Medicaid covers traditional blood testing as part of newborn screens for SCD, but a 2018 NC Medicaid bulletin suggests that NC Medicaid does not cover RBC molecular antigen testing.257 However, Blue Cross Blue Shield of North Carolina (Blue Cross NC) covers such testing under its private plans and considers it medically necessary for SCD treatment.258 Patients with SCD receiving blood transfusions are at significant risk of complications like alloimmunization and DHTRs without properly matched donor blood.

Evidence

RBC molecular testing is a once-in-a-lifetime test.259 ASH strongly recommends RBC genotyping for patients with SCD at the earliest opportunity, optimally before the first transfusion, to ensure that donor blood is safe to transfuse.260 It has near-perfect concordance with traditional serological testing, but it is insensitive to prior transfusions and provides additional, clinically significant antigen information to improve blood matching.261 In one survey of hospitals, 37 percent of respondent hospitals indicated that they obtain RBC molecular tests for all new patients with SCD.262

Alloimmunization and DHTRs are potentially deadly and very costly transfusion complications, requiring extended hospitalizations and risky treatments. Genotyping to prevent these complications would save lives and reduce morbidity. At the same time, genotyping is likely cost-justified.263 Physicians from the UNC Comprehensive Sickle Cell Disease Program estimate that preventing even one DHTR would likely pay for genotyping for 1000 patients with SCD. Further, molecular antigen testing can save time in transfusion management during acute situations.264