Fat embolism syndrome (FES) is characterized by the onset of respiratory, neurological, cutaneous, and hematologic manifestations and is thought to be related to intravascular embolization of fat. FES has been associated with bone marrow necrosis in patients with hemoglobinopathies; however, it is often not considered in the primary differential diagnosis of acute complications with hemoglobin SC disease.
Report of a case
The patient was a 36-year-old female with hemoglobin SC disease. Her past medical history was significant for migraines, bipolar disorder, tobacco abuse, and asthma. She presented to an outside hospital with headache, nausea, and photophobia. Four days later she started becoming hypoxic and was subsequently intubated. She became febrile, and her hemoglobin trended down from 12 to 10g/dL with associated thrombocytopenia (platelets of 37×109/L) and elevation in her total bilirubin. Upon transfer to our institution, laboratory studies revealed hematocrit of 20%, platelets of 27×109/L, lactate of 6.3mmol/L, and acidosis with bicarbonate of 13mmol/L. Ultrasound showed no acute bleeding via Focused Assessment with Sonography in Trauma (FAST) protocol and a limited echocardiogram showed an ejection fraction of 70% and no wall motion abnormalities. Her condition further deteriorated and she twice went into pulseless electrical activity and expired within 24h of arrival.
Post-mortem examination revealed a bilateral, diffuse involvement of the pulmonary vasculature by numerous small fat emboli seen on Oil Red O stains (Figs. 1 and 2). In addition, there were bilateral pleural effusions with left lung adhesions to the A-769662 and pleural cavity wall; the right lower lobe of the lung showed a focal hemorrhagic lesion. The spleen showed splenomegaly and siderofibrotic plaques (Fig. 3) consistent with the patient’s history of hemoglobin SC disease. Leptomeningeal blood vessels and microvasculature in the gray and white matter showed congestion and circular clearings within the blood-filled vessels, suspicious for fat emboli, which were confirmed using Oil Red O stain (Figs. 4 and 5). The gastrointestinal tract showed multiple scattered hemorrhagic and infarct regions in the small bowel and peritoneal sanguineous fluid. The bone marrow showed erythroid hyperplasia.
This patient’s pulmonary and central nervous system symptoms were due to the widespread capillary embolization of fat in the lungs and brain. This is a known complication of sickle disease with marrow infarction. There are two theories – mechanical theory and metabolic theory- to explain the pathogenesis of fat embolism. The mechanical theory postulates direct embolization of fat liberated from the marrow of injured bones. The fat is driven out by an increased intramedullary pressure, transmits via the draining veins and lodges the pulmonary capillaries. The metabolic theory suggests that emboli arise in the plasma by agglutination of pre-existing tiny chylomicrons in physiological suspension. The agglutination possibly due to some biochemical change initiated by tissue damage, such as increased C-reactive protein.
In sickle cell disorders the fat emboli are thought to arise from bone marrow necrosis. Bone marrow necrosis was described for the first time in literature, in 1941, in a patient with sickle cell disease who died of cerebral infarction. Later reports suggest bone marrow necrosis is a relatively common event in the painful crises of the sickle cell disorders and usually has a full recovery after the end of the hemolytic crisis. Mechanical obstruction of the microcirculation is proposed as the mechanism for bone marrow necrosis in sickle cell disease. Aggregates of deformed sickle cells occlude the bone marrow capillaries during crisis.
Patients with hemoglobin SC disease have higher incidence of fat embolism syndrome than patients with hemoglobin SS disease. The reason has been suggested due to the higher hematocrit level in SC disease leads to larger number of sickled cells per unit volume and greater increase in blood viscosity, which predispose the patient to bone marrow necrosis. The high incidence in hemoglobin SC disease is also attributed to the increased amount of fat cells in bone marrow of SC disease patients.