In 1998 the STOP study3 changed the outlook for children (and all people who have sickle cell disease as children eventually become adults) with sickle cell disease. This study showed that with transcranial Doppler stroke could be predicted and prevented with chronic blood transfusion. Screening can be started as young as 2 years old and continues annually until the age of 16. The prevalence of stroke risk was 8% in the 1990’s leading up to the STOP study. The study was ended early when it was found that it had reached statistical significance in only 18 months. A later study, the STOP II study4, showed that you could not abruptly stop transfusion therapy without significantly increasing the risk of stroke. Transcranial Doppler screening significantly decreased the incidence of stroke in children with sickle cell disease. Unfortunately, even today not all children who have sickle cell disease have screening, there are still preventable strokes occurring in the United States. It should be noted that only ischemic strokes are prevented by transcranial Doppler screening.
The prospect of lifelong transfusions for stroke is a huge burden for people who are at risk of stroke. It requires transfusion every three to four weeks, there can be antibodies made to blood and it can be difficult to find appropriately matched blood for transfusion. If the transfusion is simple (Intravenous line that transfuses whole units of blood monthly) there is the inevitable increase in total body iron which requires daily oral therapy to remove or there can be liver damage or cardiac damage from the excess iron. The transfusion can be done by exchange (removing blood and replacing it with donate blood) which reduces the amount of iron with each transfusion. Occasionally this can prevent increased iron or make the excess iron easier to manage.
In 2016 a study was published5 that showed in children who had been transfused for a year, who did not have cerebral vascular disease could be weaned from transfusion to hydroxyurea without an increase in stroke risk. This is now standard of care, though stopping hydroxyurea could increase the risk of stroke in the future. Still a potential lifelong therapy. Though hydroxyurea has other benefits besides preventing stroke in children and adults who have sickle cell disease.
It has been shown that progenitor cell transplant can prevent stroke in children who have abnormal transcranial Doppler studies and may even improve blood flow in some patients with abnormal cerebral vessels.6
What about “silent infarcts”? In 2014 a study was published that showed silent infarcts were common in children and that they could be decreased with chronic blood transfusion.7 The blood transfusions did not completely eliminate silent infarcts, but they were decreased with five silent infarcts in the transfused group and seven in the untransfused group. It also showed that strokes occurred in children who had silent infarcts and were more common in the untransfused group than the transfused group, one stroke in the transfused group and seven strokes in the untransfused group. It has been shown that silent infarcts are not silent and there is measurable cognitive decline with increased numbers of these small infarcts.
Recently there have been developed standards of care for cerebrovascular disease in people who suffer from sickle cell disease by the American Society of Hematology.8 This is in the open journal Blood Advances and is available for free online.