Residual risk of D alloimmunization: is it time to feel safe about platelets from D+ donors?

T ransfusion of D+ blood components, predominantly red blood cells (RBCs) and platelets (PLTs), to Dindividuals, especially females of childbearing potential, has been a longstanding concern due to the possibility of D sensitization, which may result in hemolytic transfusion reactions and/or hemolytic disease of the fetus and newborn. In this issue of TRANSFUSION, Cid and colleagues report a D sensitization rate of 3.8% in 1014 patients secondary to D-incompatible PLTs in a 10-year retrospective study, which is significantly lower than incidences up to almost 20% reported in the literature. In addition, Cid and colleagues determined that multiple factors did not correlate with increased risk of antibody formation, including type of PLT product, number of products transfused, patient and product ABO compatibility, patient gender, and patient immunosuppression. This study addresses an important issue because it provides significant data on the low risk of alloimmunization from a D+ PLT product to a Dindividual, thus enabling the transfusion community to provide these D+ PLT products to Dindividuals routinely. The potential exception is in females less than 50 years old with childbearing potential because of the potential morbidity as a result of D sensitization resulting in hemolytic disease of the fetus and newborn. The incidence of D sensitization after D-incompatible transfusion varies in the reported literature; indeed, the incidence is lower after D-incompatible PLT transfusion compared to RBC transfusion. Recent data for risk of D sensitization after D-incompatible RBC transfusion suggests incidence of close to 20%, which is substantially lower than 80% determined over 40 years ago. Cid and colleagues previously published a prospective pilot study determining the incidence of D sensitization in patients with malignant hematologic diseases transfused with D-incompatible PLTs derived from whole blood using the buffy coat (BCP) method; none of the 22 patients developed anti-D after median follow-up of 8 weeks (range, 1-37 weeks). Anti-D formation after D-incompatible PLT transfusion reported in the literature up to this time included rates ranging from 0% to 18.7%, studies included 16 to 102 patients with hematologic or oncologic disease or who were immunosuppressed. When the data are analyzed together for patients who did not receive Rh immune globulin the sensitization rate was 7.5% (21/280). The lower incidence of D sensitization in the current study than previously reported may be attributable to multiple factors. A primary factor is decrease in RBC contamination in PLT products due to improved apheresis technology and blood component processing. Cid and colleagues report a RBC volume in apheresis products as 0.00043 mL and in whole blood–derived products as 0.036 mL (prepared as BCP, pooled, leukoreduced, and stored in additive solution). This volume of RBCs is more than 50 times less than the volume of RBCs in a whole blood–derived PLT concentrate using the PLT-rich plasma method (WBDP). In 1971, a study reported a RBC volume as up to 0.42 mL per concentrate (up to 2.1 mL per pooled dose of five concentrates) and an anti-D formation rate of 7.8% in 102 immunosuppressed patients. In 1983, a study reported RBC contamination of WBDP as 0.53 mL on average (range, 0.21-0.74 mL) and of apheresis PLTs as 3.0 mL on average (range, 2.1-5.0 mL), with instances of anti-D formation in 30 oncology patients. Notably all of these reported sensitization rates are significantly less than the normal volunteer studies; for example, one study had four of five volunteers (80%) form anti-D after a single exposure of 0.5 mL of D+ RBCs, detected 63-130 days after exposure. Given the low RBC contamination volume in apheresis compared to WBDP or BCP, particularly using the PLTrich plasma method, then the D sensitization rate should be lower with apheresis compared to PLT concentrates. To date no study determining the D sensitization rate of apheresis only PLT products has been published. Some studies have a high proportion, but not all, of the transfused PLT products as apheresis products. For example, in a recent study, six of 67 (9%) patients received WBDP, 61 of 67 (91%) received only apheresis products, and none formed anti-D after a mean of 13 units (range, 1-109 units). In the study in this issue of TRANSFUSION, 722 of 1014 (71%) of the patients received only BCP and 32 of 1014 (3%) received only apheresis PLTs; 50 of 722 (7%) patients who received PLT concentrates only versus 28 of 260 (11%) who received both versus none of 32 (0%) patients who received apheresis only PLTs formed RBC antibodies upon follow-up. Another study demonstrated lack of D sensitization after PLT concentrates from buffy coat method while another study demonstrated higher immunization rates (8/59 [13.5%] in nonhematologic TRANSFUSION 2011;51:1132-1135.