Rapidly Progressive Multi-Organ Failure and Fat Embolism Syndrome in Sickle Cell Disease: Use of Exchange Transfusion Followed by Plasma Exchange
Jessica Moore, Cassandra Chua, Amy Sobota, Caitlin Neri, Charlene Sylvestre, Britney Bell, Robyn Cohen, Elizabeth KlingsAbstract
Background
Fat embolism syndrome (FES) is a rare but life-threatening complication of sickle cell disease (SCD) with a mortality rate of 46%. FES is often triggered by extensive bone marrow necrosis during vasoocclusive pain crisis (VOC) leading to rapidly progressive acute chest syndrome (ACS), neurologic impairment, thrombocytopenia, petechial rash, multi-organ failure (MOF) and death. Laboratory testing and radiologic imaging studies are commonly non-specific, but in some cases, brain magnetic resonance imaging (MRI) demonstrates punctate infarcts consistent with FES. Urgent red blood cell (RBC) exchange transfusion is standard practice in the treatment of FES to reduce hemoglobin (Hb) S and improve survival. However, ongoing inflammation-mediated injury may persist. We report the use of therapeutic plasma exchange (PLEX) as an adjunctive therapy for further removal of circulating fat globules and pro-inflammatory mediators.
Methods
Patients with SCD (all Hb genotypes) hospitalized at a single center between January 1, 2021 and September 4, 2025 were identified from the electronic medical record via a clinical data warehouse search based on ICD-10 billing codes for SCD (D57.01, D57.211, D57.411, D57.431, D57.451, D57.811). From this cohort, episodes of FES among hospitalized patients with SCD were identified via retrospective chart review using the search term “fat embolism syndrome”. MOF (e.g. acute respiratory distress syndrome, acute kidney injury) was defined as the presence of two or more organ failures. A diagnosis of FES was presumed in those with MOF, particularly if neurologic dysfunction was present. Data collected included demographics, vital signs, Hb genotype, highest level of oxygen/respiratory support required, laboratory testing, radiologic imaging, therapies administered, time from presentation to FES/MOF diagnosis, and time from FES/MOF diagnosis to PLEX initiation. Descriptive statistics were used to summarize demographic, clinical, and laboratory characteristics. Continuous variables were reported as medians/interquartile ranges (IQR) depending on the distribution, and categorical variables were presented as counts and percentages.
Results
Seven patients with MOF/presumed FES were included (median age 22 years [IQR 17.5–37.5]); the majority were male (71%). Three patients (43%) had HbSS disease; 2 (29%) had HbSC disease and 2 (29%) had HbSβ+ thalassemia. At presentation, median white blood cell count was 19.2 ×10³/µL (IQR 9.3–22.7), hemoglobin 8.7 g/dL (IQR 6.3–10.0), and platelet count 195 ×10³/µL (IQR 92–283). Median lactate dehydrogenase (LDH) was markedly elevated in most cases, with the median being 1,513 U/L (IQR 1,131–1,856). Total bilirubin was elevated in all cases at 3.4 mg/dL (IQR 1.6–6.7). Reticulocyte count was elevated in all cases (3.9% (IQR 3.5–5.8)) except for Case 6 (0.1%), likely due to bone marrow suppression in the setting of Parvovirus infection. Ferritin levels were markedly elevated in 6 patients (range 436–19,701 ng/mL). The median time from presentation to FES/MOSF diagnosis was 2 days (IQR 1–3); PLEX was initiated a median of 1 day post-diagnosis. Red blood cell exchange transfusion was performed in 5 of 7 patients (71%) and all patients completed PLEX. All patients, before receiving PLEX, developed hypoxemia requiring supplemental oxygen; two (29%) required mechanical ventilation. Brain MRI demonstrated cerebral fat embolism in 2 patients (29%). Elevated NRBCs, metamyelocytes, and myelocytes were found in several cases (notably Case 7 had NRBC 105%) supporting a leukoerythroblastic reaction consistent with bone marrow necrosis, a known trigger for FES. All seven patients survived and were discharged to home without sequelae.
Conclusions
FES/MOF remains a rare but highly morbid complication of SCD, often presenting with rapidly progressive ACS, altered mental status, and a mortality rate of 46%. In this case series, early recognition of characteristic clinical and radiographic features prompted urgent exchange transfusion followed by adjunctive PLEX, which was feasible and resulted in clinical improvement. This therapy needs to be evaluated prospectively in a multi-center study to better understand its efficacy in FES/MOF presentations.