Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease

Hulbert, Monica L.; McKinstry, Robert C.; Lacey, JoAnne L.; Moran, Christopher J.; Panepinto, Julie A.; Thompson, Alexis A.; Sarnaik, Sharada A.; Woods, Gerald M.; Casella, James F.; Inusa, Baba; Howard, Jo; Kirkham, Fenella J.; Anie, Kofi A.; Mullin, Jonathan; Ichord, Rebecca; Noetzel, Michael J.; Yan, Yan; Rodeghier, Mark; DeBaun, Michael R.

doi:10.1182/blood-2010-01-261123

Cited by 223 publications

(237 citation statements)

References 18 publications

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“…Even with blood transfusion therapy, children with SCA and overt strokes still have a rate of infarct recurrence as high as 22% over a median of 10 years (overt stroke only) [78], or even 45% over 5.5 years (when both silent infarcts and overt stroke are included) [79]. Further after the first stroke while receiving blood transfusion therapy, 35% had a third stroke while receiving blood transfusion therapy with hemoglobin S levels as low as 1%, 9%, 22%, 25%, 26%, and 55% at the time of the second or third stroke [78,79].…”

Section: Stroke Prevention In Scamentioning

confidence: 99%

“…Further after the first stroke while receiving blood transfusion therapy, 35% had a third stroke while receiving blood transfusion therapy with hemoglobin S levels as low as 1%, 9%, 22%, 25%, 26%, and 55% at the time of the second or third stroke [78,79]. Based on the high rate of infarct recurrence even with rigorous blood transfsuion therapy, HLA-matched sibling hematopoietic stem cell transplantation is now considered the optimal therapeutic option for children with overt strokes.…”

Section: Stroke Prevention In Scamentioning

confidence: 99%

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Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

2015

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Over the past 40 years, public health measures such as universal newborn screening, penicillin prophylaxis, vaccinations, and hydroxyurea therapy have led to an impressive decline in sickle cell disease (SCD)-related childhood mortality and SCD-related morbidity in high-income countries. We remain cautiously optimistic that the next 40 years will be focused on meeting current challenges in SCD by addressing chronic complications of SCD to reduce mortality and improve quality of life in a growing population of adults with SCD in high-income countries, while simultaneously decreasing the disparity of medical care between high and low-income countries.

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Section: Stroke Prevention In Scamentioning

confidence: 99%

Section: Stroke Prevention In Scamentioning

confidence: 99%

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

2015

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“…HU did not prevent secondary stroke in children with SCD when transfusions therapy was switched to HU. A prospective multicentre [27] suggested that new silent cerebral infarction can develop in transfused children with a history of overt stroke. This high incidence of silent cerebral infarction in transfused patients was similar to our observations in HbS-ß thalassemia.…”

Section: E262mentioning

confidence: 99%

Cerebrovascular events in sickle cell‐beta thalassemia treated with hydroxyurea: A single center prospective survey in adult Italians

et al. 2013

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Stroke is a common cause of morbidity and mortality in sickle cell disease (SCD) and silent cerebral infarction is the most common form of neurologic injury. The frequency and risk factors for new silent cerebral infarction are incompletely understood. Moreover, no recommended treatment has been established. Although hydroxyurea (HU) is recommended for SCD, concerns remain regarding its role in the prevention of cerebrovascular events, including silent cerebral infarction. A single center population of 104 Italian patients with HbS-ß thalassemia treated with HU has been followed for a mean of 11 years. Clinical evaluation and brain imaging by Magnetic Resonance Imaging were done before and during HU treatment. During follow-up, the number of sickle cell crises (86%, 7.8 6 6.9 vs. 1.2 6 0.5 per year, P < 0.0001), hospitalizations (2.5 6 2.9 vs. 0.3 6 1.5 per year, P < 0.0001), and days in the hospital (22.4 6 21.9 vs. 0.361.5 per year, P < 0.0001) decreased significantly and HbF increased from a mean of 8-20.8%. Cerebral infarcts occurred in 37.5% of patients. Among these, 6.7% had overt strokes, while 30% had new or progressive silent cerebral infarction. Stroke and silent cerebral infarction were not related to clinical hematologic or HbF response to HU. These findings suggest that in adults, HU treatment does not prevent new cerebrovascular events or the progression of existent silent cerebral infarcts in HbS-b thalassemia. A major benefit of HU is the increase in HbF; the association of high HbF and reduced cerebrovascular disease has been weak. New treatment strategies should be developed for the prevention of sickle cerebrovascular disease. Am. J. Hematol. 88:E261-E264,

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“…18 A more recent report revealed that children with SCD who had overt strokes and were receiving regular blood transfusion continue to experience a high rate of silent cerebral infarcts. 28 The role of transfusion therapy in preventing silent infarcts in children with normal TCD velocities has been questioned. 2 Our study reveals that at least in patients with abnormal TCD velocities who revert to normal with transfusions, discontinuation from the transfusion program will increase the risk of silent infarction.…”

Section: Discussionmentioning

confidence: 99%

“…27 The benefit of transfusion in the prevention of silent cerebral infarction in children with SCD seems to depend on the patient's cerebrovascular status. 28 Analysis of the STOP trial revealed that transfusion therapy lowers the risk Figure 1. Brain MRI findings in the study population at study entry and study end.…”

Section: Discussionmentioning

confidence: 99%

Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II

Abboud

Yim

Musallam

et al. 2011

Blood

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In the STOP II trial, discontinuation of prophylactic transfusions in high risk children with sickle cell disease (SCD) resulted in a high rate of reversion to abnormal blood-flow velocities on transcranial Doppler (TCD) ultrasonography and strokes. We analyzed data from STOP II to determine the effect of discontinuing transfusions on the development or progression of silent brain infarcts on magnetic resonance imaging (MRI). At study entry, 21 of 79 (27%) patients had evidence of silent infarcts. There were no statistically significant differences in baseline characteristics between patients with normal brain MRI or silent infarcts at study entry. At study end, 3 of 37 (8.1%) patients in the continued-transfusion group developed new brain MRI lesions compared with 11 of 40 (27.5%) in the transfusion-halted group (P ‫؍‬ .03). The total number of lesions remained essentially unchanged decreasing from 25 to 24 in the continuedtransfusion group while increasing from 27 to 45 in transfusion-halted patients. Thus, discontinuation of transfusions in children with SCD and abnormal TCD who revert to low-risk increases the risk of silent brain infarction. Together with data from STOP, these findings demonstrate that transfusions prevent the development of silent infarcts in patients with SCD and abnormal TCD but normal MRA. (Blood. 2011;118(4):894-898) IntroductionEstimates of the prevalence of silent brain infarcts, in children with sickle cell disease (SCD) range from 17% to 35%. [1][2][3][4] Despite the terminology, 'silent infarcts' are clinically significant given their association with subsequent overt stroke and neurocognitive deficits in school-aged children. 2,[5][6][7][8][9] Better understanding of the associated risk factors and efforts to optimize prevention remain essential. Reported risk factors for silent infarction are raised white blood-cell count, anemia, severe vasculopathy, and the SEN ␤-globin haplotype. 4,[10][11] Transfusions have been successfully used to prevent initial or recurrent strokes in SCD. [12][13][14][15][16] To prevent first strokes, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) used prophylactic red-cell transfusions in children who were identified by transcranial Doppler (TCD) ultrasonography as being at high risk for stroke. This strategy reduced the incidence of stroke among such children from 10% per year to Ͻ 1% per year. 15 The STOP study led to recommendations for TCD screening and prophylactic transfusion for children with abnormal velocities on ultrasonography. 17 Among patients with MRI evidence of silent infarction and raised velocities by TCD enrolled in STOP, transfusion also diminished the risk of new silent infarcts. 18 Despite the reduced risk of stroke, the potentially indefinite duration of transfusion aroused concern about adverse effects, especially iron overload. In the Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP II) Trial, discontinuation of transfusions in patients whose TCD velocities had normalized (normal TCD) resulted in a hig...

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Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease

Cited by 223 publications

References 18 publications

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

Cerebrovascular events in sickle cell‐beta thalassemia treated with hydroxyurea: A single center prospective survey in adult Italians

Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II

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