LAUSR

Recently, the risks of an Rh(D)-negative female of child-bearing potential (FCP) developing haemolytic disease of the newborn (HDFN) following receipt of Rh(D)-positive red blood cells (RBCs) or low-titre group O whole blood during her trauma resuscitation was modelled using her age at the time of transfusion and several other important societal factors that impact the development of HDFN [1]. In that study, the FCP age range was 18–49 years. Since its publication, questions have arisen about the future HDFN potential following the transfusion of Rh(D)-positive units to injured Rh(D)-negative children. The previously published model was adapted for, and applied to, patients between 0 and 17 years [1]. For this new model, the Rh(D) alloimmunization risk had to be derived for a paediatric population as it has not been published and might be difficult to obtain as it is uncommon to provide Rh(D)-positive RBCs to Rh(D)-negative/type unknown children in trauma. Age-specific paediatric alloimmunization rates to all RBC antigens were obtained from a study of paediatric patients in Japan; these age-specific rates might be different in populations with different antigen frequencies [2]. These age-specific rates were divided by the overall alloimmunization rate to all RBC antigens in adults who received a median of four RBC units (2.2%) [3], then separately multiplied by 7.8% (low estimate) or 42.7% (high estimate) as these rates reflect the ends of the spectrum of Rh(D) alloimmunization that have been reported in trauma populations where the patients’ ages reflected the child-bearing age range [4, 5]. These mathematical manipulations attempted to correct the paediatric-specific overall RBC alloimmunization risk for the adult Rh(D)-alloimmunization risk, although this created the potential for slightly underestimating the paediatric Rh(D)alloimmunization rate. The age-specific Rh(D)-alloimmunization rates are shown in the inset table in the Figure 1. For the current model, 7.8% and 42.7% were also used for the adult (18–49 years) Rh(D)-alloimmunization rates instead of 21.2% from the previous model [1]. The 28-day mortality rate used for injured patients, 0–17 years, was 36% as recently described [6]. Although it is known that injured adult females have lower mortality than males, it is not currently known if this finding also applies to injured girls. All other assumptions were unchanged from the previous model. The model, implemented in Microsoft R Open version 3.5.3 (Microsoft, Redmond, WA), simulated 1 million Rh(D)-negative females from 0 to 49 years of age who received an Rh(D)-positiveunit during trauma resuscitation and estimated her risk of developing HDFN of any severity. The rate of future HDFN increased as the child’s age increased, largely due to the increasing rates of alloimmunization as the child’s age increased, reaching a plateau between approximately 18–20 years (Figure 1); at this age, the alloimmunization rate is at its maximum, and the length of time for future pregnancies is approximately 30 years. These data indicate that if Rh(D)-negative children, especially very young children, are resuscitated with Rh(D)-positive units, the overall risk of developing HDFN is relatively small compared to the mortality reduction of receiving preand early in-hospital transfusions. However, Rh(D)-positive transfusions should only be administered when the Rh(D)-negative patient’s survival would be compromised by waiting for Rh(D)-negative units. F I G U R E 1 Anti-Rh(D)-mediated HDFN risk estimate based on the patient’s age and age-specific RhD alloimmunization rates. The HDFN risk was modelled using Rh(D)-negative alloimmunization rates of 7.8% (low estimate, lower solid line) and 42.7% (high estimate, upper solid line), with an age correction factor for patients between 0 and 17 years of age as described in the text. The hatched area between these lines indicates the range of risk for HDFN as defined by these two Rh(D)-alloimmunization rates. Locally estimated scatterplot smoothing (LOESS) was used for HDFN rates between ages 0 and 17 years Received: 30 March 2021 Revised: 24 May 2021 Accepted: 2 June 2021