Correspondence

Case 23-1998: Fat Embolism

N Engl J Med 1999; 340:393-394February 4, 1999

Article

To the Editor:

Rosen and Mark (July 23 issue)1 did not include dose-intensive chemotherapy or treatment with granulocyte colony-stimulating factor (G-CSF) among the possible causes of atraumatic fat embolism syndrome. We describe two patients with atraumatic fat embolism in whom symptoms developed suddenly and were rapidly fatal.

Patient 1 was a 59-year-old-woman with recurrent diffuse large-cell lymphoma who received a second course of therapy consisting of 60 mg of etoposide per kilogram of body weight intravenously on day 1, 3 g of cyclophosphamide per square meter of body-surface area intravenously on day 2, 200 mg of paclitaxel per square meter intravenously on day 3, 5 μg of G-CSF per kilogram per day intravenously beginning on day 4, and 40 mg of prednisone orally twice daily beginning on day 8 for stem-cell mobilization and tumor cytoreduction. She was admitted to the hospital on day 11 with febrile neutropenia and treated with empirical antibiotic therapy. On day 14, excruciating, diffuse skeletal pain suddenly developed, followed rapidly by hypoxemia, obtundation, and cardiac arrest. Laboratory findings included a white-cell count of 1×10⁹ per liter, a serum lactate dehydrogenase level of 503 U per liter (normal range, 81 to 175), a total cholesterol level of 163 mg per deciliter (normal range, 0 to 200), and a triglyceride level of 235 mg per deciliter (normal range, 58 to 219). Autopsy findings included extensive fat emboli in the lungs, kidneys (Figure 1Figure 1Kidney Specimen from Patient 1 and Lung Specimen from Patient 2 (Hematoxylin and Eosin, ×250).), and brain but no viable tumor.

Patient 2 was a 54-year-old man with recurrent diffuse large-cell lymphoma who was treated with the same regimen used for Patient 1. He was admitted on day 11 with excruciating, diffuse skeletal pain of sudden onset. Since the white-cell count was 2.4×10⁹ per liter, treatment with G-CSF was discontinued. On day 13, obtundation and hypoxemia developed and intubation was required. On day 16, the serum lactate dehydrogenase level was 3290 U per liter, the total cholesterol level was 178 mg per deciliter, and the triglyceride level was 164 mg per deciliter. Life support was withdrawn because of the lack of clinical improvement. Autopsy findings included fat emboli in the lungs (Figure 1), kidneys, brain, and skeletal muscles but no viable tumor.

The pathogenesis of atraumatic fat embolism syndrome is unclear. It has been suggested that chylomicrons exist as an emulsion in the bloodstream and that unidentified substances elaborated in a variety of diseases destabilize this emulsion.2 One such substance, C-reactive protein, an acute-phase reactant seen in patients with cancer and sepsis, agglutinates chylomicrons and very-low-density lipoproteins, yielding fat emboli.3 Moreover, elevated levels of free fatty acids resulting from lipolysis of mobilized neutral fat,4 hypoalbuminemia,4 or stress-induced hypercatecholaminemia5 may also lead to the formation of fat macroglobules (globules larger than 8 μm), which obstruct the pulmonary microvasculature and induce capillary leakage and inflammation by interacting with platelets and releasing vasoactive cytokines.5 A diagnosis of fat embolism syndrome should be considered whenever characteristic symptoms develop in patients after chemotherapy with growth factor support during rebound from pancytopenia.

Syed Bilgrami, M.D.
Jack Hasson, M.D.
Peter J. Tutschka, M.D.
University of Connecticut Health Center, Farmington, CT 06030

5 References

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   Case Records of the Massachusetts General Hospital (Case 23-1998). N Engl J Med 1998;339:254-261
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   Lehman EP, Moore RM. Fat embolism including experimental production without trauma. Arch Surg 1927;14:621-662
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   Hulman G. Pathogenesis of non-traumatic fat embolism. Lancet 1988;1:1366-1367
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   Moylan JA, Birnbaum M, Katz A, Everson MA. Fat emboli syndrome. J Trauma 1976;16:341-347
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Citing Articles (2)

Citing Articles

1. 1

   Martina Montagnana, Gianfranco Cervellin, Massimo Franchini, Giuseppe Lippi. (2011) Pathophysiology, clinics and diagnostics of non-thrombotic pulmonary embolism. Journal of Thrombosis and Thrombolysis 31:4, 436-444
   CrossRef

2. 2

   &NA;. (1999) Antineoplastics/granulocyte colony-stimulating factor. Reactions Weekly &NA;:738, 6
   CrossRef