Transfusion confusion: hemolysis or eltrombopag?

Abstract

A 71-year-old female with severe aplastic anemia developed nausea, abdominal/back pain, chest tightness, dyspnea, chills, headache, and blood pressure elevation after transfusion of 270 mL red blood cells. The transfusion was stopped and a reaction work-up initiated. The post-transfusion sample visual check was reported as "markedly hemolyzed," raising concern for a hemolytic transfusion reaction. However, a sample drawn 3 hours prior to this transfusion showed a similar appearance (see figure). Discussion with the referring physician and review of the patient's clinical history and labs confirmed she did not have pre-existing hemolysis. The post-transfusion direct antiglobulin test was negative, hemolysis labs (plasma free hemoglobin, lactate dehydrogenase, total and direct bilirubin) were within reference range, and her hemoglobin showed appropriate increment, ruling out a hemolytic transfusion reaction. The patient's symptoms resolved with systemic steroids and diphenhydramine. The reaction was signed out with a category of "unknown" given the findings did not fit case definitions for any other reaction as defined by the National Healthcare Safety Network (NHSN) hemovigilance module. 1 Further investigation revealed the patient was on 150 mg/day eltrombopag, which was causing the

Interference of eltrombopag with bilirubin measurements on the Vitros 5600 analyzer

“…As the utility of eltrombopag continues to expand for a broad range of thrombocytopenias and other diseases, understanding its interference with laboratory tests that rely on absorbance measurements, including bilirubin tests, becomes crucial in the interpretation of results and clinical management. Furthermore, increased awareness of how this drug affects the physical appearance of the plasma can help avoid confusions with hemolysis, which could impact the handling of the specimen in laboratory testing 15,16 …”

Hemolysis in the plasma of a specimen? Add a drop to clarify it

“…Eltrombopag has been reported to cause a dark brown coloration in plasma at high doses (150 mg/day), like those taken for aplastic anemia. 1,2 This oral thrombopoietin receptor agonist is a diacid with carboxyl and phenolic functional groups, whose color in solution varies by pH, from yellow at acid pH to reddish brown at basic pH. 3 In an experiment in our lab, a drop of acid was added to one tube of the patient's plasma and a drop of base was added to another (see figure, right-plasma of the patient; middle, after adding a drop of 6 M HCl solution; and left, after adding a drop of 6 M NaOH solution).…”

“…The unusual plasma color was attributed to eltrombopag. Eltrombopag has been reported to cause a dark brown coloration in plasma at high doses (150 mg/day), like those taken for aplastic anemia 1,2 . This oral thrombopoietin receptor agonist is a diacid with carboxyl and phenolic functional groups, whose color in solution varies by pH, from yellow at acid pH to reddish brown at basic pH 3 .…”