Abstract
Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591). A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140) were tested for IgM memory B cells. We also determined a) changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b) the kinetics of changes in haematological markers associated with splenectomy(n = 45). Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001) reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB), occurred early (median 25 days) and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.
Highlights
The most clinically significant complication of splenectomy is overwhelming post-splenectomy infection (OPSI) which occurs in about 1 in 500 patients per annum and has a mortality of 50% [1,2,3]
We showed that the kinetics of loss of IgM memory B cells after splenectomy was delayed compared to the earlier onset of lymphocytosis, thrombocytosis and appearance of red cell changes including appearance of HJBs
The main finding in these populations was a significant decrease in total CD27+ memory B cells and in the IgM+IgD+CD27+IgM memory B cells compared to normal controls
Summary
The most clinically significant complication of splenectomy is overwhelming post-splenectomy infection (OPSI) which occurs in about 1 in 500 patients per annum and has a mortality of 50% [1,2,3]. Risk of OPSI has been thought to be highest in the first two years following splenectomy it may occur at any time [2,4] and can occur even in those who have been managed with an appropriate immunization regimen. Prophylactic antibiotics have been shown in a randomized controlled trial to be of clear benefit in children with sickle cell anemia [5] and are advised for adults following splenectomy in particular during the first 2 years postsplenectomy [6,7,8]. An assay that would better stratify risk of OPSI would provide a useful measure to determine those in whom prophylactic antibiotics could be discontinued without significant risk
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