Sickle Cell Disease Complicated by Iron Overload: An Under-Recognized Risk Factor for Vibrio vulnificus Infection

Patients with sickle cell disease (SCD) often receive unnecessary red blood cell (RBC) transfusions leading to complications which include alloimmunization, hyperhemolysis, and iron overload [1-3]. An under-recognized risk of iatrogenic iron overload in patients with SCD is an increased susceptibility to infections with siderophilic, or “iron-loving,” bacteria. Here we present a patient with SCD who developed septicemia with Vibrio vulnificus, a previously unreported complication in patients with SCD and acquired iron overload from repeated RBC transfusions.

A 28-year-old African American man with SCD (HbSS), complicated by recurrent vaso-occlusive pain crises as well as hepatic dysfunction and cirrhosis secondary to iron overload, presented to our medical center with acute onset of high-grade fever and worsening abdominal pain. The patient was intermittently compliant with hydroxyurea therapy and had required both simple and exchange RBC transfusion to manage his SCD. He had biopsy-proven hepatic dysfunction and cardiomyopathy due to iron overload. He initially established care at our institution for evaluation of liver transplant. He was receiving dual iron chelation therapy with oral deferiprone and continuous infusion deferoxamine to improve pretransplant organ function. On presentation, the physical examination was remarkable for tachycardia and scleral icterus. His hemoglobin was 3.8 g/dL (baseline 7.0 g/dL, normal range 12.6–17.4), white blood cell count was 25 ×10⁹/L (normal range 4.5–11), and lactic acid was 8.8 mmol/L (normal range 0.5–1.6). He was started on broad-spectrum antibiotics, but rapidly developed respiratory failure and septic shock. Blood cultures grew V. vulnificus. Upon further questioning, the patient’s family reported that he had prepared and eaten crabs a few days prior to the onset of symptoms. His hospital course was complicated by multiorgan dysfunction and death.

In the USA, infection with V. vulnificus is the leading cause of shellfish-associated death [4]. V. vulnificus is a Gram-negative bacterium primarily associated with wound infections and characterized by rapidly progressive hemorrhagic bullae and septicemia with mortality rates as high as 80% [5]. The bacterium is particularly virulent in patients with liver disease, iron storage disorders, human immunodeficiency virus, cancer, diabetes, and thalassemia [6, 7]. Liver disease is a risk factor due to both decreased glutathione and cytokine production, resulting in poor bloodstream clearance of the bacterium [8]. In iron-rich conditions, V. vulnificus grows exponentially, particularly when transferrin exceeds 70% [9]. V. vulnificus can be inhibited by deferiprone or deferasirox; however, it is stimulated by deferoxamine through the outer membrane DesA receptor [10-12].

In patients with SCD complicated by iron overload, infection with V. vulnificus should be suspected if patients present with sepsis, diarrhea, or wound infections following seafood consumption, particularly during warmer seasons. It is imperative to warn patients with SCD regarding the risks of handling and ingesting raw or undercooked shellfish. Providers must be cognizant that iron chelators can potentiate the virulence of V. vulnificus infection. Hematologists caring for patients with SCD complicated by iron overload should include V. vulnificus infection in their differential diagnosis when evaluating patients presenting with septicemia following recent seafood consumption.