Discussion:
Hereditary spherocytosis results in an increased risk of hemolysis with cellular stress and splenic clearance. Patients can develop significant intermittent hemolysis and splenomegaly or have baseline chronic hemolysis which occasionally necessitates splenectomy for control of severe chronic anemia. Patients and care providers are educated on the importance of monitoring for hemolysis during febrile episodes to avoid an array of complications from acute anemia. While hemolysis in patients with HS and viral infection is a well-known complication of this disorder, it has only been described in the context of hydroxychloroquine toxicity in subjects with COVID-19.13
Our patient, with underlying HS with COVID-19 infection and hemolysis, emphasizes the necessity to follow patients at risk for hemolysis closely in the setting of COVID-19. There have been reports about patients with sickle cell disease who were infected with COVID-19, however no case report has addressed the risk of hemolysis in patients with hemolytic anemias.14-16
Splenectomy is often thought of as “curative” in patients with HS as the site of red cell clearance is in the spleen. However, the red cell membrane defect is not corrected with splenectomy and as such patients remain at an increased risk of hemolysis with significant cellular stress.17 Patients who have previously had an anatomic splenectomy may have a milder course of hemolysis due to removal of the red cell clearance organ.
There are numerous hemolysis markers that can be followed during a hemolytic crisis. Bilirubin levels are an important marker of hemolysis and elevation is due to the breakdown of the protoporphyrin IX ring of heme.18 In our patient it was reassuring to note the down trending bilirubin value prior to discharge. Ferritin is another hemolytic marker; however, it is also an acute phase reactant and has been found to rise in patients with severe COVID-19 infection who develop cytokine storm.18,19 In the setting of recent transfusions and an acute illness, a ferritin level could be elevated and not offer insight to acute hemolysis. Lastly, we followed lactate dehydrogenase (LDH) while hospitalized. LDH increases with hemolysis as LDH-1 and LDH-2 are isoenzymes present in red blood cells and released during a hemolytic event.18 We noted in our patient that LDH trended down as the hemolytic event was resolving. This trend has additional utility in the setting of COVID-19 in that severe infections can progress to a cytokine storm with elevated LDH as one potential marker.
This case highlights the importance of monitoring hemoglobin and hemolytic markers in patients with hemolytic disorders who are infected with COVID-19. If widespread COVID-19 testing with nasopharyngeal swabs is initiated, children with positive results and underlying hemolytic disorders should be screened for hemolysis. HS has a varying severity of hemolysis and it is possible that the first hemolytic event could take place in the setting of a COVID-19 infection. Due to this, it is important for any provider to keep an open differential when noticing hemolysis in the setting of COVID-19.
Conflict of Interest: The authors have no conflicts of interest relevant to this article to disclose.
Acknowledgements: We have no additional acknowledgements to share