Severe hemorrhagic coagulopathy with hemophagocytic lymphohistiocytosis secondary to Epstein-Barr virus-associated T-cell lymphoproliferative disorder.

OBJECTIVE: We describe the coagulopathy and hemorrhagic complications associated with fulminant, secondary hemophagocytic lymphohistiocytosis in a cohort of patients with Epstein-Barr virus-associated T-cell lymphoproliferative disorder.

PATIENTS AND METHODS: Institutional Review Board-approved retrospective review of all patients at our children's hospital over 3 years (2008-2010) with hemophagocytic lymphohistiocytosis secondary to acute Epstein-Barr virus-associated T-cell lymphoproliferative disorder.

RESULTS: Four males (2, 3, 17, and 20 yr old) presented with fever, hepatosplenomegaly, and pancytopenia with elevated serum ferritin, and all met clinical and laboratory criteria for secondary hemophagocytic lymphohistiocytosis. d-dimer on admission was elevated in all patients and remained extremely elevated during hospitalization, while the median prothrombin and activated partial thromboplastin times as well as fibrinogen were all in the normal range. Within a few weeks to months following admission, all patients developed multiorgan system failure with episodes of severe, life-threatening hemorrhage; in all four patients, hemorrhage was not associated with a nadir in platelet count. There were no survivors beyond 4 months from diagnosis.

CONCLUSIONS: A coagulopathy characterized by persistent, extreme elevations in plasma d-dimer and severe, life-threatening hemorrhage was noted in association with hemophagocytic lymphohistiocytosis secondary to Epstein-Barr virus-associated T-cell lymphoproliferative disorder. We speculate that this coagulopathy is a marker of severe hemophagocytic lymphohistiocytosis in this setting.