Therapy Insight: Stroke Risk and Its Management in Patients With Sickle Cell Disease

Fenella J. Kirkham


Nat Clin Pract Neurol. 2007;3(5):264-278. 

In This Article

Stroke Prevention in Patients With Sickle Cell Disease

The Royal College of Physicians (UK) has recently published guidelines on the management of stroke in childhood, which address the issues of primary and secondary prevention of stroke in SCD ( Box 1 ).[95]

If no treatment was offered after a first ischemic stroke in children with sickle cell anemia, the risks of recurrence documented by cohort studies have been between 20% and 92%.[27,96,97,98,99] Two studies found a high risk of recurrence in children who had arteriographic abnormalities.[99,100] Ever since transfusion therapy was shown to be effective at reducing recurrent events,[99,100] it has been the mainstay of treatment for stroke in SCD.[101] The aim of transfusion is to reduce the percentage of HbS and increase levels of HbA, thereby reducing the deleterious effects of sickling while improving tissue oxygenation. For acutely sick patients, such as those with severe chest crisis or neurological symptoms, treatment is usually simple or partial exchange blood transfusion.[101] Although there has never been a controlled trial of transfusion, a chronic intermittent transfusion program, aiming to keep the HbS level below 30%, decreases the risk of stroke recurrence to between 10% and 20%.[2,101,102] There is ongoing controversy over whether allowing the HbS percentage to drift up towards 50% with less-frequent blood transfusions,[101] or switching to hydroxyurea[101,103,104] after a few years, is safe. Moyamoya syndrome is a risk factor for stroke recurrence despite regular transfusion,[48,54] although this risk seems to be reduced after extracranial-intracranial bypass or indirect revascularization.[101,105] Bone marrow or cord blood transplantation is an option for children with a matched sibling donor.[101,106,107,108] These procedures might, however, result in acute neurological complications including subarachnoid hemorrhage[109] and border zone edema in the context of hypertensive encephalopathy,[109] and serial MRI scans in individuals with pre-existing cerebral damage might show new lesions as well as extension of existing abnormality.[109] Further studies of these procedures are needed as some researchers have not found progression,[107] and the cerebrovascular disease can stabilize as demonstrated on both MRA[110] and TCD.[111]

The peak age for hemorrhage in SCD is 20-30 years, and these young adults usually have aneurysms,[47] which are amenable to extirpation by coil embolization or surgery;[112] these procedures reduce the risk of recurrence. By contrast, aneurysms and other cerebrovascular diseases are rarely found in children with SCD and intracranial or subarachnoid hemorrhage—conditions that seem to be common in those exposed to corticosteroids and rapid blood transfusion.[20] Care with corticosteroid use and judicious blood transfusion to achieve small increases in hemoglobin without acute hypertension might reduce the incidence of hemorrhagic stroke.[20]

There is Class A evidence for the role of blood transfusions in preventing first stroke in children with sickle cell anemia and high blood flow velocities on TCD. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) showed a clear benefit for prophylactic transfusion in children with blood flow velocities of more than 200 cm/s.[113] A large proportion of the treated patients apparently received unnecessary transfusion, however, as only 15% of the nontransfused children went on to have a stroke despite very high velocities. This is an important issue, as transfusion is associated with risks of infection and alloimmunization,[114] and many children and their families find regular blood transfusion and chelation therapy burdensome. The subsequent STOP II has, however, shown that it is essential to continue to transfuse long-term even if TCD velocities return to the normal range, as the risks of stroke or reversion to high-risk TCD velocities are unacceptably high.[115] Reductions in the incidence of stroke in SCD recorded in California[116] and East London[117] are probably related to the introduction of TCD screening and prophylactic transfusion. TCD screening is currently not universally available, however, and cannot, therefore, be mandated at present.[117,118] In addition, there is evidence that adults with SCD do not have high TCD velocities, and programs of TCD screening and prophylactic transfusion are probably not appropriate for older age groups.


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