Splenectomy Protects Humans from Red Cell Alloimmunization

Background and aim

Being the primary organ that clears and processes ageing and damaged red cells, the spleen has been suggested to play a central role in red cell alloimmunization in mice experiments. We evaluated the effect of splenectomy on the occurrence of red cell alloimmunization in humans.

Methods

We performed a nested case-control study among a source population of 24,063 patients who received their first and subsequent red cell transfusion in one of six participating hospitals in the Netherlands between 2005 and 2013. Cases were defined as patients who developed a first transfusion-induced clinically relevant red cell alloantibody. Each case was matched to two non-alloimmunized control patients, based on the number of (lifetime) transfusions and the hospital. Using multivariate logistic regression analyses, we evaluated the association between (a history of) splenectomy and the risk for alloimmunization.

Results

Among a source population of 24,063 patients, 505 patients (2.1%) developed red cell alloantibodies and were matched to 1,010 controls. Splenectomy had been performed in one case and 19 controls. In 12 patients, splenic injury was caused by severe trauma or complicated abdominal surgery. No patient underwent a splenectomy in the context of an autoimmune disease.

Using multivariate logistic regression analysis with conditioning on identified potential confounders, we found that splenectomized patients had a 20-fold reduced risk of alloimmunization as compared to patients lacking a history of splenectomy (adjusted RR 0.05, 95% confidence interval (CI) 0.01-0.55).

With the assumption that the red cell exposure patterns of the 19 splenectomized controls represented the red cell exposure pattern of all splenectomized patients within the source population we estimated that the total number patients with alloimmunization after splenectomy was 24; yielding a RR of 0.04 which confirms our logistic regression based RR.

Interpretation

In conclusion, in accordance with the findings in mice, our findings suggest that splenectomized patients are strongly protected from primary red cell alloimmunization.