Hemoglobinopathies and Stroke: Strategies for Prevention and Treatment

Noorjahan Ali, Rothtida Srey, Steven Pavlakis

Current treatment options for stroke in sickle cell disease (SCD) and thalassemia are limited. Hypercoagulation occurs in both diseases partly due to activated platelets and red blood cell dysmorphology and dysfunction, resulting in chronic anemia. This overlapping pathophysiology of the nervous system promotes the role of some common treatment modalities for these similar diseases. The current evidence suggests that chronic exchange transfusion and stem cell transplantation/bone marrow transplant (BMT) can be used in both diseases. Exchange transfusion is the mainstay of therapy of acute stroke in SCD whereas blood transfusions and hydroxyurea appear to be the most effective current treatments. However, evidence suggests that exchange transfusion should be initiated in acute ischemic stroke (AIS) and chronic transfusion continued in both diseases after AIS. Exchange transfusion can also be used acutely in AIS with thalassemia as this disorder is also associated with hypervolemia at baseline, occurring secondary to chronic anemia. The ideal length of chronic transfusions for both primary and secondary stroke prevention still needs to be better defined. Stem cell transplant or BMT is the only curative treatment for both diseases. However, timing needs to be further investigated. If transplantation is effective, it may need to be done before the child with SCD expresses disease, such as in infancy. However, in infancy, we cannot predict the severity of the phenotype in SCD with certainty, so an individual decision about transplantation is difficult to make. In thalassemia, transplantation may be effective later because vasculopathy is not the problem as in SCD. Furthermore, cerebrovascular disease occurs later in thalassemia than in SCD. Finally, aspirin is a treatment modality that also warrants further investigation. There are limited studies on the effectiveness of aspirin in SCD and thalassemias. Few studies have demonstrated clinical improvement of stroke in patients with hemoglobinopathies. Given the successful use of aspirin in the treatment and prevention of recurrent cardioembolic events in patients without hemoglobinopathies, diseases with hypercoagulability, such as SCD and thalassemia, may also benefit from the use of aspirin for treatment and prevention. However, the evidence available is based on case and retrospective studies, necessitating future larger and more valid studies to evaluate safety and effectiveness.