Hemophagocytosis seen within the bone marrow is a rare adult disease, “Peripheral” hemophagocytosis is unique. We present such a case with resultant multi-system organ failure.
A 54 yo WM with significant past medical history of ITP (in his 20s) presented to an outside emergency department (ED) complaining of fatigue and darkening urine. He had been squirrel hunting in North Carolina, and reported a tick exposure (found 4 days after the hunting trip). His review of symptoms was otherwise negative. He reported no recent medication changes. He denied alcohol, drug, or tobacco use. He was a traveling salesman covering the northeast coast.His physical examination was remarkable only for jaundice. Laboratory studies on presentation demonstrated: hemoglobin (Hg) 7.5 g/dl, WBC 19.7, platelet count 214, AST 293 u/dl, ALT 198 u/dl, LDH 1903, and total bilirubin 13.7 g/dl. His prothrombin time and aPTT were normal, but an Iron panel revealed a ferritin of 26,214. The outside ED reported a positive direct antibody test with “cold agglutinins.”Upon transfer to our medical center 8 hours later his Hg had decreased to 4.6 g/dl. Over the next 24 hours he received 8 units of pRBC (packed Red Blood Cells) due to a persistent decline in Hg without clinical evidence of bleeding. He was transferred to the MICU due to respiratory distress, at which time his creatine was 3 mg/dl despite aggressive fluid resuscitation and adequate urine output. ALT and AST were both above 500. At MICU admission the patient was placed in an 85 degree (F) room due to suspected cold antibody mediated hemolysis. Plasmapheresis was initiated. Hemodialysis was scheduled. 40 hours after hospital admission the patient required intubation and mechanical ventilation for worsening mental and respiratory status. 44 hours after admission, despite transfusion of 10 units of PRBC, a Hgb of 2.5 g/dl was reported and 30 minutes later the patient had a PEA cardiac arrest. ACLS was performed for approximately 60 minutes. During this resuscitation the patient received warmed blood products via the plasmapheresis machine totaling 11 units of PRBC, 9 units of FFP, 2 units of platelets, and 4 units of cryoprecipitate. Following return of spontaneous circulation he required vasopressor support, and his Hg one hour later was 7.1 g/dl. Hematologist review of the peripheral blood smear revealed striking hemophagocytosis. Cyclosporine was given for presumptive treatment of hemophagocytic syndrome or hemphagocytic lymphohistiocytosis. Empiric doxycycline and clindamycin were given though a search for an infectious etiology was unrevealing; the patient was HIV negative, and specimens sent for tick-borne illnesses were, unfortunately, agglutinated and not of use. Ultimately, despite plasmapheresis, hemodialysis, 7 more units of pRBC, and continued aggressive respiratory and cardiovascular support, the patient had another cardiac arrest 12 hours after his initial arrest from which he could not be resuscitated. Despite our request, the family declined an autopsy.
Hemphagocytic lymphohistiocytosis (HLH) is a rare disorder thought to be due to dysfunction of NK cells and impaired down-regulation of macrophages. This leads to unregulated macrophage activation, and excessive cytokine and complement activation, resulting in the “hemophagocytic syndrome” characterized by red blood cells within leukocytes most commonly in the bone marrow. To our knowledge this has never been reported in peripheral blood smears. HLH in adults has been associated with a variety of infectious, oncologic, and rheumatologic triggers.
The finding of hemophagocytosis on a peripheral blood smear is noteworthy in this patient. The etiology of the severe hemophagocytosis, cold antibody hemolysis, and the rapid multi-system organ failure in this patient is not known and without a post-mortem examination remains speculative. The differential diagnosis includes a tick-borne illness, a rheumatologic disorder, lymphoma, or a severe viral syndrome.
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