Successful Treatment of Bone Marrow Necrosis and Fat Embolism Syndrome Without Long‐Term Sequelae in a Young Adult with Sickle Cell Disease: A Case Report and Recommendations for Diagnosis and Management

Bone marrow necrosis (BMN) with fat embolism syndrome (FES) is a rare and life-threatening complication of sickle cell disease (SCD). First identified in 1941 [1], this syndrome is often not recognized until it is too late, with more than 50% of cases diagnosed on autopsy, and mortality rates reported as high as 64% [2, 3]. The clinical presentation and laboratory findings overlap with other hematologic complications such as vaso-occlusive episode (VOE), hemophagocytic lymphohistiocytosis (HLH), and thrombotic thrombocytopenic purpura (TTP), further complicating diagnosis. Here, we report a case of a young adult with SCD who developed BMN with FES and despite rapid clinical decompensation, had complete recovery due to early recognition and aggressive multi-modal management. The patient is a 21-year-old male with HbSS disease who immigrated from Ghana 5 years prior, where treatment included whole blood transfusions resulting in red blood cell (RBC) alloimmunization. His SCD was well controlled with hydroxyurea until a recent lapse in adherence resulting in several hospitalizations for painful VOE. He then presented with sudden-onset band-like back, abdominal, and bilateral leg pain described as different and out of proportion to previous VOEs. He was diaphoretic, hypertensive, and tachycardic but afebrile without respiratory findings or chest x-ray abnormalities. Initial labs were consistent with prior uncomplicated VOEs (hemoglobin 8.3 g/dL). He was admitted for pain management with intravenous hydromorphone per his individualized pain management plan with rapidly escalating dose requirements. On hospital day 2 (HD2), he developed fever and oxygen requirement with decline in hemoglobin to 5.1 g/dL, significant decrease in platelet count and absolute reticulocyte count (ARC), and marked increase in nucleated red blood cells (nRBCs), creatinine, ferritin, lactate dehydrogenase (LDH), and direct bilirubin (Figure 1). He had no focal neurologic symptoms but was confused and difficult to communicate with, initially attributed to pain and opioid medications. His clinical presentation and laboratory trends raised early suspicion for BMN/FES, and he was transferred to the pediatric intensive care unit (PICU) for closer monitoring and initiation of bilevel positive airway pressure for respiratory support. Red cell exchange (RCE) transfusion was considered upfront, but due to the severity of his anemia and limited availability of matched RBC units requiring a national search, he was initially managed with simple transfusions, receiving five units PRBCs over 48 hours bringing his HbS to less than 30%. Shortly after PICU transfer, the patient deteriorated and developed multisystem organ failure including respiratory failure requiring intubation, cardiac insufficiency requiring inotropic support, disseminated intravascular coagulation (DIC), severe liver injury (direct bilirubin 21.3 mg/dL), and renal failure requiring dialysis (Figure 1). The diagnosis of FES/BMN was confirmed on pathologic examination of bone marrow biopsy (Figure 2). Soluble IL-2 and ADAMSTS13 were not consistent with alternative diagnoses. His rapid decline prompted an aggressive management approach including simple transfusions followed by RCE to suppress HbS, a 5-day course of therapeutic plasma exchange (TPE), and high-dose corticosteroids (Figure 1). He began to show clinical improvement; however, following completion of TPE and initiation of steroid taper, he re-developed fever and worsening pain, which led to precautionary re-initiation of TPE × 3 days and re-escalation of steroid dosing with prolonged taper. Given the known association of neurologic sequelae from FES, brain imaging was obtained demonstrating subdural and scalp hematomas and marrow necrosis of the calvarium, but no "starfield" pattern classically reported with cerebral FES. The patient continued recovery with extubation to room air on HD9, discontinuation of hemodialysis on HD11, and discharge home on HD25. Monthly RCE transfusions were continued for 3 months, and subsequently discontinued with resumption of hydroxyurea with a complete recovery and no long-term sequelae. This case describes an SCD patient, treated in the pediatric setting, with BMN/FES, and demonstrates the life-saving nature of early recognition followed by aggressive approach to management. Importantly, this patient had several recent admissions for painful VOE, and this presentation initially appeared quite similar highlighting the dangers of attributing all SCD pain to VOE without sufficient consideration of alternative pathologies. Clinical presentation with any of the following should raise suspicion for BMN/FES and prompt rapid action: pain out of proportion to VOE, non-specific neurologic symptoms, acute respiratory decompensation/end-organ damage, elevation in serum ferritin/alkaline phosphatase/LDH, marked increase in nRBCs, relative reticulocytopenia, and mild/moderate thrombocytopenia. As demonstrated, rapid intervention is essential and can be lifesaving. While there are no evidence-based guidelines for the management of BMN/FES, our experience and that of the literature demonstrates emergent transfusion support, specifically RCE, is critical and associated with reduction in mortality [4, 5]. There is significant overlap in the presentation of BMN/FES with conditions such as HLH or TTP, and alternative pathologies should be evaluated without delaying RCE [6]. In addition to transfusion support, our case and published evidence support concurrent TPE, likely addressing the hyperinflammatory effects of this condition [7-10]. The isolated benefits of systemic corticosteroids are not clear, but amidst acute clinical decompensation, the benefits appear to outweigh the risks, as noted in our case, with a careful and slow tapered approach. In summary, BMN with FES is a severe complication of SCD with high morbidity and mortality. This case demonstrates the importance of early recognition and aggressive management to treat this rare complication. The authors declare no conflicts of interest.