Background/Case Studies: Complications of sickle cell disease (SCD) can be severe and life-threatening and include acute chest syndrome (ACS), cerebrovascular events, and bone marrow necrosis (BMN)/fat embolism syndrome (FES). The use of red cell transfusions as part of early therapeutic intervention has steadily been increasing. Despite the strides made in implementing national blood banking policies, transfusions in SCD continue to pose a greater risk of precipitating reactions. Transfusion-related complications often overlap with the sequelae of sickle cell crisis making transfusion reaction evaluation an especially challenging endeavor.
Study
Design/Methods: We present a 16-year-old female with a medical history of HbSS complicated by 20+ lifetime episodes of ACS and avascular necrosis. She presented to our institution’s emergency department in vaso-occlusive crisis pain with concern for ACS and transient altered mental status. The patient received one crossmatch compatible pRBC unit. Approximately 3 hours after transfusion, she experienced acute respiratory distress requiring intubation. Her cardiopulmonary status precipitously deteriorated and cardiopulmonary resuscitation was unsuccessful. The blood bank was consulted for transfusion reaction evaluation.
Results/Findings: Routine lab workup ruled out hemolytic transfusion reaction. Transfusion-related acute lung injury (TRALI) was the initial impression given the acute onset of respiratory distress within 6 hours of transfusion and worsening pulmonary edema noted on imaging. However, TRALI investigation by the blood supplier, American Red Cross, was negative. Transfusion associated circulatory overload (TACO) was included in the transfusion associated fatality work up. The suspicion was low due to only a mild elevation in pro b-type natriuretic peptide but present given chest x-ray findings. Post mortem examination was performed by our institution revealing extensive alveolar wall and bone marrow necrosis, and innumerable fat and bone marrow emboli in pulmonary and cortical cerebral arteries. Osmium tetraoxide staining confirmed the presence of circulating fat-containing emboli. The findings corroborate a diagnosis of BMN/FES. Conclusions: We present a challenging case in which a patient with HbSS and suspected ACS developed acute respiratory failure and died shortly following red blood cell transfusion. Autopsy findings demonstrated histologically proven bone marrow necrosis and FES. Although the pathogenesis of FES in SCD is still not fully understood, it is thought that fat emboli arise from infarcted bone marrow and enter the circulation through bony venous vessels. The diagnosis of FES is based on clinical grounds since currently no laboratory test is pathognomonic. Non-HbSS genotypes and milder forms of SCD are at the highest risk. Due to the rarity of this syndrome, many cases remain undiagnosed, and transfusion associated fatality was the initial impression.
Importance of research: Our case underscores the importance of autopsy in the workup of possible transfusion-associated fatalities in patients with SCD. The initial impression was TRALI until autopsy revealed FES, a rare and poorly understood entity that develops more often in non-SS genotypes. This case adds to the limited literature on FES, particularly in HbSS disease. We discuss the nebulous nature of its presentation and how it can confound transfusion reaction evaluation.
