Transfusion Dependence Is Common in Adults with Hemophagocytic Lymphohistiocytosis (HLH) and Is Associated with EBV Viremia

Introduction:HLH in adults is a fulminant, often fatal hyperinflammatory disorder that often mimics sepsis and is associated with significant cytopenias, primary and secondary infections, immunosuppression, and bleeding. The etiologies in adults are typically autoimmune disease or lymphoma. As a result, HLH patients are immunocompromised hosts who represent a distinct group of high blood product users. Importantly, the need for adequate blood product support can obligate care in tertiary or quaternary settings. The literature lacks sufficient description of transfusion need patterns and the factors associated with blood product use in HLH. This IRB approved resource utilization study investigates this unique group of patients' transfusion needs and seeks to identify factors associated significant cytopenias that result in transfusion dependence.

Methods: We retrospectively identified and reviewed the charts of 59 HLH patients diagnosed between January 2012 and May 2017 at Stanford Health Care system. Patients were identified by search of the ICD9 code 288.4, ICD 10 76.1, 76.2 and associated keyword searches Hemophagocytic Syndromes in the EPIC electronic medical record system and by a similar keyword permutation search in PowerPath, the pathology department database. Data collected and evaluated included the patients' demographics, causes of HLH, transfusion requirements, primary and secondary infections, Charleston comorbidity index, SOFA score, times to diagnosis and therapy, HLH therapy, lengths of hospital stay, and survivorship. Data related to transfusion therapy was restricted to active HLH episodes only and was not collected after remission. Statistical analysis utilized Fisher exact test or 2 tailed t-test.

Results: The median age of the patients was 52 (range 18-96; SD +/- 19). The majority of the patients had either malignancy or autoimmune disease: 56% had underlying malignancy with lymphoma in 88%; 22% had an underlying autoimmune disease. A concurrent infectious component was common and found in 17/33 of malignancy and 9/14 autoimmune patients. Eighty-five (85) % (50/59) of the patients received blood products, with the transfusion requirements per hospitalization as following, in units: PRBC , mean 7, median 4 (range 0-68); platelets, mean 7, median 2 (range 0-37); FFP mean 2, median 0 (range 0-13), and pooled cryoprecipitate mean 2, median 0 (range 0-13). Adult patients with EBV viremia (24/59) showed the highest rate of transfusion (92%), with a statistically significant increase in platelet and cryoglobulin usage amongst transfused patients (p = 0.008 and p = 0.04, respectively).

Conclusions: This analysis finds that a high percentage of adult patients with HLH require transfusions. Our data suggests that adult HLH secondary to an infectious etiology, in particular EBV viremia, correlates with higher blood product usage. Further multi-center studies with larger number of patients are needed to further characterize and optimize transfusion therapy in the management of adults with HLH, as well as to establish the potential role of transfusion therapy of these immunocompromised hosts in the need to provide tertiary or quaternary care.