Sickle Cell Anemia Blood Transfusions

Silent Cerebral Infarcts Occur Despite Regular Blood Transfusion Therapy After First Strokes in Children with Sickle Cell Disease

By: Monica Hulbert, Robert McKinstry, Joanne Lacey, Alexis Thompson et al

Results

• Blood Transfusion Therapy

1) The mean of all patients' HbS levels (pretransfusions) was 26.9% and the mean levels for patients who had second overt strokes was 25.0%.

2) For patients who had SCIs pretransfusions the mean was 27.2% and the mean for patients who had no cerebral infartcs pretransfusion the mean was 27.4%.

Results

Data Analysis

Introduction

Purpose

• SCIs during Transfusion

1) New or enlarging SCIs were identified in 18 (out of 40) patients (45%).

2) 7 of the 18 patients had second overt strokes and 11 had new SCIs.

3) 7 out of 40 patients (during the transfusion process) had a second overt stroke. 4 out of the 7 patients had HbS levels less than 30% . In the remaining 3 patients, 2 had HbS concentrations of 38% and 48%.

4) Out of these 7 patients with a second overt stroke, 3 had a third stroke, and one had a fourth stroke.

• TIAs

1) Four patients without recurring strokes experienced TIAs (one had a single event, three had repeated TIAs).

2) Overall, a total of 25% (10 out of 40) had neurologic symptoms, and radiographic evidence of regressive infarcts, either second overt strokes (n=7) or TIA plus an SCI (n=3).

There were 2 goals for this experiment/trial:

1) To determine the incidence of silent cerebral infarcts in children with SCD that receive regular blood transfusions for secondary overt stroke prevention.

2)To validate and extend previous retrospective findings using the hypothesis that overt strokes occur in children receiving regular blood transfusion therapy and is associated with cerebral vasculopathy (damage to the blood cells).

• Sickle cell anemia is a hereditary genetic disease where the blood cells become sickled and sticky due to a mutation in the victim's hemoglobin genes.

• As a result, patients are likely to have silent cerebral infarcts, which are small 3mm abnormalities on an MRI T2 weighted image which could grow and develop into an overt (symptomatic) stroke.

Materials and Methods

• When only reports, (no images), were available, neuroradiologists would determine if a SCI had occurred (yes or no).

• Statistical Analysis

1) The Kaplan Meier Method was used to estimate event free intervals with respect to second overt strokes and/or silent cerebral infarcts.

2) Other statistical events, such as HbS concentration or overt stroke occurrence was analyzed using the PASW Statistics system.

• Inclusion Criteria

1) Patient had to be diagnosed with sickle cell anemia and have a first overt stroke after January 1, 1996.

2) Patient also had to have proof of being treated with blood transfusion therapy for secondary prevention.

3) Patients consented to have MRI and MRA screenings every 12 to 24 months and to have regular blood transfusions.

• Data Collection

1) Data extracted included initial stroke(symptoms), treatment of stroke, occurrence of a second stroke (if any), HbS concentration during the second stoke, and other neurological events such as TIAs.

2) The studies were transmitted electronically to the Electronic Radiology Laboratory at Washington University and images of the MRIs were viewed using the Pacs system.

Discussion

• Previous analysis of children with SCI and progressive cerebral infarction did not include discussion of regular blood transfusion therapy so it is not clear if progressive infarction occurred due to the blood transfusion therapy.

• A factor that may play a role in the enlarging of SCIs are associated with the increased burden of cognitive deficits in children with a history of overt strokes.

Review of Literature

Limitation

Discussion

Conclusion

Future

In the future, studies should be conducted to test whether or not adults respond to blood transfusions in regards to treating overt strokes and/or SCIs.

• Small sample size (only 40 patients).
• MRI and MRA information was not always available or reviewed for every subject.
• Participants who didn't have MRA or MRI data were reported as having no progressive infarction and no vasculopathy.

• Overall this study demonstrates the idea that regular blood transfusions are not as effective in preventing recurrent cerebral infarction or progression of cerebral vasculopathy in children with SCD.
• This study also highlights the importance of having children undergo MRI and MRA evaluations when diagnosed with SCD.

• SCIs are associated with a decrease of 8 points on the intelligence scale (Armstrong FD, 1996).

• Also by using MRA instead of angiography, the progression of vasculopathy and other neurological abnormalities could be detected more efficiently.

Delimitation

• This study included had 7 experienced hematologists, 3 neuroradiologists and a pediatric neuroradiologist that helped to analyze the data.
• This study also included multiple hosptials and universities in may parts of the U.S. and the United Kingdom.

• Overt strokes occur in 11% of children with the homozygous SS sickle cell gene before the age of 20 (Weiner SJ et al, 1998).

• Secondary overt stroke prevention, for patients with sickle cell disease, consists of regular blood transfusions are utilized to suppress the synthesis of hemoglobin S (Price C et al, 2002).

Review of Literature

• Without transfusion therapy, approximately 67% of children with sickle cell anemia will have overt strokes (Wilson B et al 1978).

• However 20% of children who undergo blood transfusion therapy still have overt strokes (Brook CG et al, 1987).

Review of Literature

• Silent cerebral are almost undetectable on most neurological exams like MRI on a T1 weighted scale (Lee BC, 1995).

• Children with SCIs are at a higher risk of having more infarcts or overt strokes (Moser FG, 2002) (Miller ST, 2001).

Review of Literature

• Silent cerebral infarcts are also known to decrease cognitive function and intelligence quotient scores (IQ) (Armstrong M 2002).

• Moyamoya collateral blood vessels have been described as a risk factor for recurrent overt strokes and TIAs in children receiving regular blood transfusions (Holden KR, 2002).