Diagnosis of hypersplenism with the epinephrine stimulation test

Abstract

PRINCIPLES: Hypersplenism can be defined by thrombocytopenia and/or neutropenia resulting from blood cell sequestration in an enlarged spleen. In multimorbid patients the differential diagnosis of cytopenia is challenging and currently there is no established test for diagnosing hypersplenism. METHODS: The epinephrine stimulation test (EST) measures changes in platelets, neutrophil counts and spleen size following a subcutaneous epinephrine injection. We retrospectively analysed the results of EST in 228 patients. RESULTS: Increases in neutrophils and platelets after epinephrine injection were significantly greater in patients with enlarged than in patients with normal size spleens. Using cutoffs of low, intermediate and high confidence EST was positive in 69.8% vs. 41.3% (low confidence), 49.6% vs. 17.4% (intermediate confidence) and 38.8% vs. 10.9% (high confidence) in patients with enlarged vs. normal size spleens. Changes in platelet and neutrophil counts correlated with each other and with changes in spleen size, confirming cell release from the spleen during EST. When stratified according to the underlying diagnosis, patients with liver disease had the strongest response to EST, patients with malignant haematological diseases the weakest. In addition the response to EST was significantly related to changes in platelet and neutrophil counts after splenectomy, confirming the validity of our test. No serious side effects occurred during EST. CONCLUSION: When used in a large patient cohort, EST is a safe and simple diagnostic test. In this exploratory study EST is of value in evaluating patients with cytopenia and a positive EST argues strongly for hypersplenism. Future studies should prospectively evaluate EST for the management of patients with splenomegaly.