5607225 ADDITION OF THERAPEUTIC PLASMA EXCHANGE TO RED CELL EXCHANGE IMPROVES OUTCOMES OF FAT EMBOLISM SYNDROME IN SICKLE CELL DISEASE

Abstract

Background: Fat embolism syndrome (FES) is a severe but possibly underdiagnosed complication of sickle cell disease (SCD) associated with very high mortality and morbidity. It is the result of extensive bone marrow necrosis that leads to release of large amounts of fat droplets in the systemic circulation. These not only cause mechanical obstruction of the microvasculature but also act as a substrate for the generation of various pro-inflammatory cytokines that contribute to the development of multiorgan failure. FES predominantly affects non-homozygous patients and those with a previously mild course of their illness. Immediate red cell exchange (RCE) can be life-saving and it is currently the treatment of choice. However, despite its increasing use in recent years, mortality remains substantial while a large number of survivors is left with significant neurocognitive impairment. With that in mind, we have previously advocated the addition of therapeutic plasma exchange (TPE) to RCE in order to address the inflammatory environment and potentially improve outcomes. Aims: To compare outcomes from FES using standard treatment with RCE and combination of RCE and TPE. Methods: A systematic review of all cases published since 2012 where RCE was employed was performed, and outcomes were compared to cases where a combination of RCE and TPE was used. Results: The systematic review of the literature identified 39 cases treated with RCE since 2012. Mortality was 21%, 33% of patients were left with severe and 13% with mild neurological impairment while only 33% made a complete recovery (CR). We are aware (publications/ personal communication) of 11 cases (separate from the previous 39) treated with combination of RCE and TPE worldwide (8 UK, 2 Canada, 1 USA). 9 patients were adults and 2 patients were children. 5 patients had homozygous Hb SS disease, 5 Hb SC and 1 Hb Sβ+. All patients, irrespective of genotype, had previously a mild course of their illness. The number of TPE procedures performed varied greatly between cases (1-10). There was 1 death (9%), 2 patients (18%) suffered mild/moderate neurological impairment and 8 patients (73%) achieved CR. Both patients reported as suffering mild/moderate neurological impairment are patients who developed the complication recently, have fully recovered cognition but are still in rehabilitation improving from generalised weakness resulting from prolonged hospitalisation and are very likely to achieve CR eventually. One more 13-year old patient (not included in this analysis as the final outcome is yet unknown) is currently recovering in hospital having recently suffered severe FES with multiorgan failure requiring extracorporeal membrane oxygenation now extubated, recovering organ function and able to communicate appropriately. Interestingly, 2 patients had a cytotoxic lesion of the corpus callosum (CLOCC) on brain imaging. This further highlights the role of the inflammatory environment in the pathophysiology of FES as CLOCCs are known to be the result of direct cytotoxicity from proinflammatory cytokines, especially IL-1 and IL-6. TPE was well tolerated with no associated adverse events. Conclusion: These early data suggest a clear benefit from this approach, and as TPE is a low risk intervention, we recommend its addition to RCE as standard management for FES in SCD. Reference 1. Tsitsikas DA, Vize J, Abukar J. Fat Embolism Syndrome in Sickle Cell Disease. J Clin Med. 2020 Nov 8;9(11):3601.