Stroke in Sickle Cell Anemia After Excellent Response to Hydroxyurea.

Strokes occur in about 10% of children with sickle cell anemia (SS) less than 10 years old. These strokes are usually ischemic in nature. Stroke due to SS in adults is less common and is usually hemorrhagic in nature. We wish to report an unusual adult patient with SS and excellent response to HU who developed a stroke that was unrelated to SS.

A 35-year-old female with sickle cell anemia had mitral valve prolapse and migraine headaches presented 2 days after developing abrupt bilateral blurry vision, left facial numbness and weakness of her left leg. Her SS has been complicated by acute chest syndrome, bilateral hip avascular necrosis and frequent painful crises prior to hydroxyurea (HU) therapy. She was enrolled in the multicenter study of hydroxyurea (MSH) in SS and has been on 2500mg of HU per day for the past 13 years. She had an excellent response to HU with no recurrent acute chest syndrome and decreased need for blood transfusion. After starting HU, the frequency of crises requiring hospital admission decreased from 1 admission every 1 to 2 months to less than 1 admission per year except when hydroxyurea was discontinued for pregnancy. Her fetal hemoglobin increased from 6.1 % before HU to a maximum of 45%. Her MCV increased from 96 fl to a maximum of 132 fl and Hb from 8.0 g/dl to 9.8 g/dl Her exam was remarkable for left lower extremity weakness which was more pronounced proximally. All cranial nerves were intact and there was normal sensation bilaterally. CT scan of the brain showed three foci of hypodensity and MRI of the brain showed increased signal on T2, FLAIR and diffusion weighted images within the frontoparietal deep white matter consistent with infarction in the border zone of the middle cerebral artery (MCA)-anterior cerebral artery (ACA). MR angiography of the intracerebral and extracerebral vessels demonstrated focal narrowing of the right MCA at the trifurcation suggesting an embolic cause. Common causes of stroke were ruled out with routine studies. Her hemoglobin electrophoresis after admission but before blood exchange transfusion showed HbS of 55% and HbF of 45%. She underwent exchange transfusion 2 days after admission and was started on chronic blood exchange transfusions with the assumption that she had ischemic stroke due to SS. Initial transthoracic echocardiogram with contrast injection did not show an atrial shunt. Follow-up transesophageal echocardiogram after discharge showed a secundum atrial septal defect with a defect size of 1.4 cm. Right heart catheterization was performed and the pulmonary flow to systemic flow (Qp/Qs) was 1.7:1. An Amplatzer atrial septal defect (ASD) closure device was deployed with transesophageal echocardiographic guidance and a large thrombus was removed from the right atrium. At the patient's request exchange red cell transfusions were discontinued. The patient has continued treatment with hydroxyurea and aspirin.

Young patients with cryptogenic stroke have a much higher prevalence of atrial shunts and in particular patent foramen ovale than patients with other forms of stroke and therefore a cause-effect association is suggested. Young adults with stroke should be evaluated for common and reversible causes of stroke including paroxysmal emboli. Transesophageal echocardiography is the gold standard for diagnosing atrial shunts. Strokes in patients younger than age 55 are related to paroxysmal emboli and have a risk of recurrence of approximately 30% within one year. High risk features for stroke recurrence with an atrial shunt include hypercoagulable states, large opening and presence of an atrial septal aneurysm. Optimal management of patients with a stroke and an atrial shunt is unknown. Options include surgical closure, percutaneous device closure, anticoagulation and antiplatelet therapy. Patients with sickle cell disease and stroke should receive long term blood transfusions to reduce HbS below 30% if the stroke is felt to be related to sickle cell disease vasculopathy. The patient described with SS had a stroke and had an atrial septal defect that was repaired. The MRI/MRA findings are consistent with paroxysmal emboli. The patient is receiving treatment with hydroxyurea and aspirin having discontinued red cell exchange transfusions and at two years of follow-up has not had a recurrent stroke.

No relevant conflicts of interest to declare.