Researchers suggest the possibility of an association between haptoglobin (Hp) polymorphism and the incidence of stroke in patients with sickle cell disease (SCD), as published in Genes.

The review examined published studies on Hp, SCD, and strokes from 2010 to 2022. The authors said that further research is warranted into a potential advantage of the Hp 1-1 genotype compared with Hp 2-2 in terms of therapy and Hp blood infusions for patients with SCD.

Due to the excess rate of hemolysis in patients with SCD, Hp, which facilitates the breakdown and excretion of toxic hemoglobin dimer products of hemolysis, has been identified as a key indicator of disease progression. Previous studies have found an association between SCD symptom severity and Hp concentrations and activity.

“Our group has also previously reviewed the role of Hp polymorphism in subarachnoid hemorrhage (SAH). We found strong evidence that Hp 1-1 can be taken up by cells faster, as well as cross the blood-brain barrier, which may ameliorate secondary injury after SAH,” the authors said.

Read more about SCD experimental therapies

Furthermore, the 3 main genotypes of the Hp glycoprotein, Hp 1-1, Hp 2-1, and Hp 2-2 have been reported to differentially affect the incidence of cardiovascular events such as strokes in patients with diabetes. This inspires the researchers’ current assessment of the potential impact of Hp genotype on other populations that are susceptible to strokes, such as patients with SCD.

The authors found no clear evidence of an association between Hp genotype and outcomes in SCD. However, in patients with SCD, blood exchange infusions have been shown to reduce symptoms of anemia and pain crises as well as lower the incidence of stroke.

The authors raised the possibility of screening blood donors for Hp genotype with the aim of achieving optimal treatment results.


Edwards O, Burris A, Lua J, et al. Influence of haptoglobin polymorphism on stroke in sickle cell disease patients. Genes. 2022;13(1):144. doi:10.3390/genes13010144