Discussion:
Hyperhemolysis is a hematologic emergency with limited options for treatment. Hyperhemolysis in individuals with β-thalassemia presents additional challenges, as they are unable to effectively compensate for the hemolysis due to dysfunctional erythropoiesis. In this case presentation, initial immunosuppression slowed the hemolysis, but was insufficient to allow for the resumption of necessary transfusions. His hgb reached a critically low level and his condition was tenuous while waiting for immunosuppression to take effect.
Complement plays a crucial role in red blood cell hemolysis in the hyperhemolytic crisis. In one study, an in vitro model demonstrated complement deposition on healthy cells, sickle cells and cells lines of patients with PNH.4 In this model, hemolysis was only seen among the PNH cell lines, despite evidence that the sickle cells were similarly decorated.4 Increased concentrations of complement were seen in the setting of simulated infection supporting that infections and inflammation can trigger complement activation on the RBC surface leading to hemolysis.4
Complement mediated hyperhemolysis in β-thalassemia may share similar features to hemolysis in PNH. PNH results from a structural defect in the red cell membrane resulting in a lack glycosyl-phosphatidyl inositol (GPI) anchor protein synthesis. This results in a chronic hemolytic anemia. The anemia in patients with PNH is less severe because they are able to effectively synthesize their own red cells. The downstream effect is a lack of CD55 (Decay Accelerating Factor) and CD59 (Membrane Inhibitor of Reactive Lysis) protection from red cell complement-mediated hemolysis.10 Decreased expression of CD55 and CD35 has also been demonstrated in patients with β-thalassemia major, suggesting that these cells may exhibit a similar mechanism of red cell lysis during a hyperhemolysis episode.11
Thus, complement blockade with eculizumab, through the binding of complement component 5 (C5), was a logical choice for managing this condition. In this case, the use of eculizumab successfully slowed the hemolysis and allowed for safe transfusion. After recovery from the acute episode, hemolysis recurred while his immunosuppression was being managed solely with corticosteroids. He required resumption of complement blockage with eculizumab. This blunted the hemolytic process before it resulted in a critical degree of anemia.
This case demonstrates that ongoing complement blockade with eculizumab allowed for successful resumption of immunosuppression with a prednisone taper and maintenance sirolimus without recurrence of hemolysis. Additionally, this can serve as a model for the successful management of this rare, potentially fatal syndrome in individuals with β-thalassemia.
Conflict of Interest Disclosures : The authors have no conflicts of interest relevant to this article to disclose.
Disclaimer: The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Defense or the U.S. Government.