Case Presentation: 85-year-old male with history of Myasthenia Gravis who presented with shortness of breath and back pain after a fall. Presenting vitals were as follows: heart rate of 80, respiratory rate of 20, afebrile and normotensive. Exam was negative for scleral icterus, jaundice, rashes, or petechia. Significant labs included Hgb 8.7 g/dL (baseline 13 g/dL) and MCV 108 fL. Indirect bilirubin was elevated to 2.5 mg/dL which was present for 2 months prior to presentation. Computerized tomography angiography of the chest was notable for new segmental pulmonary embolus. Therefore, patient was started on a heparin drip. During admission, patient’s hemoglobin continued to drop with a nadir of 7.0 g/dL. Patient continued to deny signs of overt bleeding. Given recent fall and initiation of anticoagulation, there was concern for intrabdominal or retroperitoneal blood loss. CT abdomen and pelvis was negative for any source of bleeding. Given persistent indirect hyperbilirubinemia, hemolysis workup was initiated which was notable for LDH 460 mg/dL, haptoglobin < 30 units/L, INR within normal limits, absolute reticulocyte count of 247. Direct antiglobulin test was negative. Hematology was consulted, and peripheral blood smear was obtained which showed bite cells and Heinz bodies. Further chart review revealed that patient was started on dapsone for Pneumocystis Jiroveci pneumonia prophylaxis in the setting of high dose prednisone for Myasthenia Gravis flare two months ago. Given this clinical presentation, patient was diagnosed with Heinz body hemolytic anemia triggered by dapsone in setting of likely Glucose 6-phosphate dehydrogenase deficiency (G6PD deficiency). G6PD level came back normal, but likely falsely normal in setting of acute hemolysis. Dapsone was discontinued. Hemoglobin improved to 8.5 g/dL with simultaneous decrease in LDH and increase in haptoglobin at time of discharge.
Discussion: Worsening anemia after initiation of anticoagulation is a problem commonly seen by hospitalists. In cases such as this, patients often undergo extensive GI evaluation with imaging and endoscopy to identify a source of bleeding. In this patient’s case, his worsening anemia and anticoagulation start were only coincidental. The only initial clue to the underlying hemolytic process was a mildly elevated indirect bilirubin, which led to further investigation to identify the cause. Therefore, this case represents the importance of maintaining a broad differential diagnosis during the workup of anemia and further pursing lab abnormalities that do not fit the initial clinical picture.
Conclusions: This is an interesting presentation of an elderly patient with worsening anemia after being started on anticoagulation. The patient was found to have Heinz body hemolytic anemia secondary to dapsone and underlying G6PD deficiency, which is rarely first identified so late in life. Dapsone can induce a hemolytic anemia due to increased oxidative stress and formation of Heinz bodies, which can be worsened in patients with G6PD deficiency. The only treatment is cessation of the offending drug, so a high index of suspicion is necessary to make the diagnosis.