Hemoglobin Zurich: A Rare Hemoglobin Anomaly With Hemolytic Crisis in the ICU

Introduction: Unstable hemoglobinopathies are rare and often underrecognized contributors to acute hemolysis in critically ill patients. Hemoglobin Zurich is an unstable β-globin variant that predisposes red blood cells to oxidative denaturation, yet remains clinically silent in the absence of stressors. Phenazopyridine, a commonly used urinary analgesic, has oxidant properties that may provoke hemolysis in susceptible individuals. We present a case illustrating the diagnostic and clinical challenges in managing Hgb Zurich crisis.


Description: A 53-year-old woman with a remote diagnosis of Hemoglobin Zurich and no prior hemolytic episodes presented with acute dyspnea, fatigue, and chest tightness after treatment for a urinary tract infection with nitrofurantoin and over-the-counter phenazopyridine. Initial labs showed hemoglobin 6.7 g/dL (baseline >12), reticulocytosis (17.1%), undetectable haptoglobin, elevated LDH (>1100 IU/L), indirect hyperbilirubinemia, and carboxyhemoglobin of 11.7%. Peripheral smear revealed anisocytosis and acanthocytes. Coombs and cold agglutinin tests were negative; G6PD level was elevated. Hemoglobin electrophoresis revealed 28.9% abnormal β-globin variant, consistent with Hemoglobin Zurich. Imaging showed mild splenomegaly. She was admitted to the ICU for close monitoring, transfused 2 units of packed RBCs, received fluid resuscitation, and was supported with oxygen. Steroids were briefly trialed but discontinued once autoimmune hemolysis was excluded. She recovered uneventfully and was discharged with hemoglobin 13.9 g/dL on follow-up.


Discussion: This case underscores the need to consider unstable hemoglobins in the differential diagnosis of acute hemolysis in the ICU. Carboxyhemoglobin elevation served as a key clue to oxidative stress in Hemoglobin Zurich. Hemoglobin electrophoresis aided in diagnosis, though more specialized tests may be required. Management hinges on early identification, supportive care, transfusions, and avoidance of triggers. In severe or refractory cases, exchange transfusion may be necessary. This case highlights the need for thorough medication review and heightened awareness of oxidant-induced hemolysis. Prompt recognition and targeted supportive care can prevent deterioration, optimize ICU resource use, and improve patient outcomes.