How I treat and manage strokes in sickle cell disease

Abstract

Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD.

© 2015 by The American Society of Hematology.

Figures

Figure 1

MRI in SCD: spectrum of abnormality in SCD as illustrated by different imaging examples. Axial DWI (A) and apparent diffusion coefficient (ADC) (B) map of the brain demonstrating multiple foci of restricted diffusion along bifrontal regions (corresponding to the short arrows in A), along the internal watershed zone most consistent with acute strokes. (C) Axial fluid attenuation inversion recovery (FLAIR) image in a different patient with SCD demonstrate areas of old (silent) infarctions in a similar internal watershed distribution. (D) Axial T2 image shows a large area of right occipital cystic encephalomalacia resulting from prior infarction. (E) Axial T2 image from another patient shows diffuse volume loss, sulcal prominence, and an old right basal ganglia infarct from sickle cell-associated vasculopathy. (F) Maximum intensity projection image from the MRA shows nonvisualization of the left MCA with multiple collateral in the left lenticulostriate distribution (long arrow), consistent with moyamoya collaterals.

Figure 2

Acute arterial ischemic and hemorrhagic stroke, PRES and CSVT. Axial DWI and ADC (shown in A-B and C-D in each of the 4 sets of images, respectively) MRIs of the brain demonstrate increased DWI signal with corresponding decreased ADC signal, consistent with restricted diffusion along the left MCA territory most consistent with acute arterial ischemic stroke. Axial T1-weighted MRI (E), axial T2-weighted MRI (F), axial FLAIR (G), and axial GRE (H) images in patients with SCA demonstrate ill- defined mixed intensity focus within the right basal ganglia region with surrounding vasogenic edema. The lesion demonstrates T1 hyperintensity with hypointensity on axial T2 and GRE consistent with hemorrhage. Also seen is intraventricular extension of blood (F, arrow). GRE MR sequences are most sensitive for the detection of intracranial hemorrhage and may demonstrate more diffuse signal loss than the actual lesion, also known as blooming, as seen in this case. Axial FLAIR (I) and coronal FLAIR images MR (J-K) of the brain demonstrates bilateral near symmetric hyperintense signal involving the parieto-occipital lobes with superior frontal involvement, in a distribution and pattern most consistent with PRES. There is both subcortical (I, K arrows) and cortical involvement. Axial DWI (L) demonstrates no corresponding increased signal to suggest for restricted diffusion. Transverse (M) and coronal (N), maximum intensity projection images from a phase contrast MRV. There is no signal within the right transverse sinus due to thrombosis. Axial T1-weighted MRI (O) demonstrates a small well-defined hyperintense focus within the right occipital white matter with hypointensity on axial GRE (P), consistent with hemorrhagic venous infarction secondary to thrombosis.

Figure 3

Schema for the management of a patient with SCD presenting with focal neurologic deficit. Asterisk (*) denotes when an initial blood transfusion (simple followed quickly by an exchange transfusion) is recommended if the Hb is <10 gm/dL; an exchange transfusion is preferred when it can be expedited, or when Hb >10 gm/dL. CTA, computed tomography angiogram; HSCT, hematopoietic stem cell transplant.

Figure 4

Incidence rates of recurrent stroke in individuals with SCD receiving either hydroxyurea therapy, blood transfusion therapy, or no therapy for secondary stroke prevention in published studies since 1995. The expected incidence rates of stroke recurrence while on regular blood transfusion therapy, hydroxyurea therapy, or no therapy were found to be 1.9 (95% CI, 1.0-2.9), 3.8 (95% CI, 1.9-5.7), and 29.1 (95% CI, 19.2-38.9) events per 100 patient years, respectively.