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.