|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 288-294
Cerebrovascular Accidents in Sickle Cell Disease: Rates and Risk
Factors
By
Kwaku Ohene-Frempong,
Steven J. Weiner,
Lynn A. Sleeper,
Scott T. Miller,
Stephen Embury,
John W. Moohr,
Doris L. Wethers,
Charles H. Pegelow,
Frances M. Gill, and
the Cooperative Study of Sickle Cell
Disease
From The University of Pennsylvania School of Medicine and the
Division of Hematology, The Children's Hospital of Philadelphia,
Philadelphia, PA; the New England Research Institutes, Watertown, MA;
the Department of Pediatrics, State University of New York Health
Science Center at Brooklyn, Brooklyn, NY; the San Francisco General
Hospital and the University of California, San Francisco, San
Francisco, CA; the Department of Pediatrics, Woodhull Medical and
Mental Health Center, Brooklyn, NY; the Department of Pediatrics,
Columbia University School of Medicine and St Luke's/Roosevelt
Hospital, New York, NY; the Department of Pediatrics, University of
Miami, Miami, FL; and the Department of Pediatrics, The University of
Pennsylvania School of Medicine, Philadelphia, PA.
 |
ABSTRACT |
Cerebrovascular accident (CVA) is a major complication of sickle
cell disease. The incidence and mortality of and risk factors for CVA
in sickle cell disease patients in the United States have been reported
only in small patient samples. The Cooperative Study of Sickle Cell
Disease collected clinical data on 4,082 sickle cell disease patients
enrolled from 1978 to 1988. Patients were followed for an average of
5.2 ± 2.0 years. Age-specific prevalence and incidence rates of CVA
in patients with the common genotypes of sickle cell disease were
determined, and the effects of hematologic and clinical events on the
risk of CVA were analyzed. The highest rates of prevalence of CVA
(4.01%) and incidence (0.61 per 100 patient-years) were in sickle cell
anemia (SS) patients, but CVA occurred in all common genotypes. The
incidence of infarctive CVA was lowest in SS patients 20 to 29 years of
age and higher in children and older patients. Conversely, the
incidence of hemorrhagic stroke in SS patients was highest among
patients aged 20 to 29 years. Across all ages the mortality rate was
26% in the 2 weeks after hemorrhagic stroke. No deaths occurred after
infarctive stroke. Risk factors for infarctive stroke included prior
transient ischemic attack, low steady-state hemoglobin concentration
and rate of and recent episode of acute chest syndrome, and elevated
systolic blood pressure. Hemorrhagic stroke was associated with low
steady-state hemoglobin and high leukocyte count.
| |
INTRODUCTION |
CEREBROVASCULAR accident (CVA) is a
catastrophic complication of sickle cell disease (SCD) and a leading
cause of death in both children1 and adults.2
The reported risk of first CVA in the first 20 years of life is 0.761
per 100 patient-years.3 A cohort study in Jamaica estimated
the prevalence of CVA to be 7.8% among 310 patients of all genotypes
aged 9 to 17 years who were observed since birth.4
Among patients with the common genotypes of SCD, CVA is most frequent
in those with sickle cell anemia (SS).5 The rate of CVA for
patients with other genotypes (SC, S- + thalassemia, and
S-0 thalassemia) has not been reported. The influence of
age, clinical events, and hematologic and genetic factors on the risk
of CVA needs to be clarified so that accurate counseling can be
provided to patients, their families, and couples at risk for producing
children with these genotypes.
To address these and other questions related to CVA, the Cooperative
Study of Sickle Cell Disease (CSSCD) prospectively collected data on
CVA in a large cohort of patients.6,7 These data comprise
the largest series of CVAs in a group of SCD patients. The younger
patients in this cohort were observed since birth and provide the most
accurate rates of CVA in children with SCD living in the United States.
In this report, the prevalence and incidence of CVA and the effects of
age, genotype, and other risk factors are described.
| |
MATERIALS AND METHODS |
The CSSCD, a longitudinal clinical study, observed in its first phase
4,082 patients from 23 clinical centers across the United States
between October 1978 and September 1988. The study was approved by the
Institutional Review Boards of the participating centers. The study
design, recruitment process, and characteristics of patients enrolled
are described in detail elsewhere.6-8 In addition to
newborns, all patients who had visited a participating clinic for any
medical reason between 1975 and 1978 were eligible subjects. Enrollment
was closed in May 1981, except for newborns who were enrolled
throughout the study period. Patients were observed for an average of
5.2 ± 2.0 years. A hemoglobin (Hb) diagnosis was not confirmed for
139 of the 4,082 patients because they were on transfusion therapy; 31
of the 139 and 122 other patients had had at least one CVA before study
entry. An additional 174 patients were observed for routine visits but
not clinical events. Estimates of the incidence of CVA were based on
the remaining 3,647 patients. The genotype distribution of the patient
sample at entry is shown in Table 1.
Laboratory diagnosis.
The Centers for Disease Control (CDC) determined the Hb phenotype by
cellulose acetate and citrate agar electrophoresis methods9
and the presence of -thalassemia by quantification of Hb
A2 levels using column chromatography.10 The
percentage of fetal Hb (Hb F) was measured using the
method of alkali denaturation11 by the CDC for patients
entered at 2 years of age and older and by local centers for younger
patients. Steady-state complete blood counts were performed at local
centers from samples taken during routine clinic visits.  -Globin
gene mapping to determine the presence of a thalassemia was performed
on samples from 2,002 of the 2,675 SS patients (75%) by one of us
(S.E.) using the blot hybridization method.12,13
Definition of clinical syndromes.
CVA was defined as an acute neurologic syndrome secondary to occlusion
of an artery or hemorrhage with resultant ischemia and neurologic
symptoms and signs. In this study, CVA included transient ischemic
attack (TIA), completed infarctive stroke (neurologic deficits lasting
more than 24 hours), and hemorrhagic stroke. TIA was defined as
neurologic signs with vascular distribution that resolve within 24
hours (or 48 hours if basilar system is involved). Strokes were
classified by the investigator at the center as hemorrhagic or
infarctive based on the available clinical and imaging studies.
Ninety-five percent of the patients classified as having infarctive
stroke underwent computer tomography (CT) scan, brain
scan, and/or magnetic resonance imaging (MRI; 1 patient) at the
time of the event. Ninety-three percent of the patients classified as
having hemorrhagic stroke underwent CT scan, brain scan, arteriogram,
and/or autopsy after the event. MRI information was not
collected during the first 8 years of the CSSCD (ie, before December
1986). Studies were performed uniformly across all ages.
The CSSCD definitions of acute anemic episode, acute chest syndrome,
meningitis, and painful event are presented elsewhere.14
Seizure included major or minor motor seizures or psychomotor seizures
that were not secondary to central nervous system infection, tumor, or
stroke. Priapism was defined as a painful erection of the penis lasting
more than 1 hour. Only events severe enough to bring the patient to
seek medical care were recorded.
Statistical analyses.
Crude and age-specific prevalence rates were calculated as the number
of patients with at least one CVA before study entry divided by the
total number of patients in the relevant subgroup. Crude incidence
rates of the first CVA on study were calculated as the number of first
CVAs occurring during the specified time interval divided by the number
of person-years of observation in the relevant subgroup. The direct
method of standardization was used for all age-adjusted rates, with the
age distribution of the entire study sample used as the standard.
Incidence rates were compared using a test of binomial
proportions.15 The SAS macro SMOOTH (Paul
Allison, University of Pennsylvania) was used to obtain kernel-smoothed
hazard estimates for CVA as a function of age.16 Event-free
survival curves were estimated using the Kaplan-Meier method, with
adjustment of the risk sets to account for differing entry
ages,17 and age at CVA used as the time measure. The
proportional hazards model score function test was used to compare
survival curves.
Cox proportional hazards regression with risk set adjustment was used
to determine the risk factors for an initial CVA. Separate models were
fit for hemorrhagic and completed infarctive CVA. For all patients who
did not experience a CVA, observation time was truncated at the
earliest of the following: the end of the study, the time of loss to
follow-up, or the date of death from any cause. Potential covariates
were gender, systolic blood pressure, Hb F level, mean Hb level, mean
leukocyte count, mean platelet count, -thalassemia; history of
meningitis; presentation for seizure, surgery, priapism, acute anemia,
acute chest syndrome, and transfusion within 2 weeks before CVA; and
rates of painful episodes and acute chest syndrome. Mean
values were calculated using all values collected during regular clinic
visits after 1 year of age and before the CVA. Blood pressure was not
averaged; rather, the values were collected over all annual visits
after 2 years of age were incorporated into the model. TIA was examined
also as a risk factor for completed stroke, because, in practice, many
physicians may not consider TIA as a CVA event. Of the 2,436 SS
patients who had no history of CVA before study entry, 36 were excluded
because they were not observed past 1 year of age, leaving 2,400 in the
analysis. A stepwise procedure was used to arrive at a final
multivariate model. -Thalassemia was examined individually but not
included in the stepwise regression due to unknown -globin gene
number for 25% of SS patients.
Descriptive statistics are presented as percentages and means ± 1
standard deviation. All P values are two-sided, and a P
value of .05 is considered significant.
| |
RESULTS |
Prevalence and incidence of CVA.
At entry into the study 153 of 4,082 patients had a history of CVA
resulting in an overall crude prevalence rate of 3.75%. The highest
age-adjusted prevalence estimate, 4.01%, was in patients with SS,
followed in decreasing order by the rates of 2.43% for
S-0 thalassemia, 1.29% for S-+
thalassemia, and 0.84% for SC. One hundred thirty-nine patients had
unknown genotype due to chronic transfusion. Assuming that those
patients are SS results in an age-adjusted prevalence of 4.96% in that
group. The age-specific prevalence rates for each genotype, separating
those with unconfirmed genotype ("unknown"), are shown in Table
2. There was no difference in prevalence
between male and female patients.
During the study, 87 of the 3,647 patients with no history of CVA at
entry had a CVA, yielding an overall incidence rate of 0.46 per 100
patient-years. Age-specific incidence rates for each genotype are shown
in Table 3. The highest incidence of first
CVA was in the SS group, with an age-adjusted rate of 0.61 per 100
patient-years. We compared the incidence rates in broader age groups,
isolating those less than 1 year of age, none of whom had a CVA.
Incidence rates of CVA in SS patients less than 1 year of age, 1 to 9
years of age, 10 to 19 years of age, and 20+ years of age were 0.00,
0.84, 0.41, and 0.59, respectively. When compared with each other, only
the difference in incidence between the 1 to 9 years of age and 10 to
19 years of age groups was statistically significant (P =
.026). The 2 youngest of the 7 SC patients who had first CVA on study
were 5 years of age; they both had TIA. There was no significant
difference in incidence of first CVA between male and female patients
at any age.
Age at first CVA.
Data from the 3,647 patients used to calculate incidence rates were
used to determine CVA-free survival curves. The estimated age at first
CVA was significantly different for SS and SC patients (P <
.001; Fig 1). The chances of having a first
CVA by 20 years of age, 30 years of age, and 45 years of age were
estimated at 11%, 15%, and 24%, respectively, for SS patients and
2%, 4%, and 10%, respectively, for those with SC.
Age and type of CVA in SS patients.
During the study, there were 78 first CVAs in SS patients. The type of
CVA was not available for 2 patients. Forty-one (53.9%) of these CVAs
were infarctive, 26 (34.2%) were hemorrhagic, 8 (10.5%) were TIA, and
1 (1.3%) had both infarctive and hemorrhagic features (Table
4). Although the incidence of infarctive
CVA was highest in SS patients younger than 20 years of age (0.44 per
100 patient-years), adults more than 30 years of age were also found to
be at risk (Fig 2). Conversely, the rate of
hemorrhagic stroke was highest in patients 20 to 29 years of age (0.44
per 100 patient-years) and was low in children and older patients (Fig
2). Eight patients younger than 10 years of age experienced hemorrhagic
stroke (0.17 per 100 patient-years).
View larger version (12K):
[in this window]
[in a new window]
| Fig 2.
Smoothed hazard rates of infarctive and hemorrhagic
stroke in SS patients by age. ( ) Infarctive stroke; (---) hemorrhagic
stroke.
|
|
Recurrence of CVA.
Among 72 SS patients who survived the first day of their initial CVA,
there were 10 recurrences (14%): 6.4 events per 100 patient-years in
patients with initial CVA occurring at less than 20 years of age and
1.6 events per 100 patient-years in patients with initial CVA occurring
at  20 years of age. Two events followed TIA with a mean time to
recurrence of 3.0 months, 2 events followed hemorrhagic stroke with a
mean time to recurrence of 7.2 months, and 6 events followed infarctive
stroke with a mean time to recurrence of 22.2 months. The 2 TIAs were
both followed by infarctive stroke, the 2 hemorrhagic strokes were both
followed by a second hemorrhagic stroke, and the 6 infarctive strokes
were followed by 1 TIA, 4 infarctive strokes, and 1 with mixed
infarctive/hemorrhagic stroke features. One 43-year-old SC patient with
infarctive stroke had a recurrence of unknown type 6 months later. Four
of the 10 SS patients with recurrent CVA received a blood transfusion
within 1 month before the recurrence. However, the CSSCD
did not mandate a transfusion protocol for study participants;
therefore, no definitive statement can be made regarding the
association between transfusion practices and CVA recurrence.
CVA-related mortality.
All deaths occurring less than 14 days after a CVA were considered to
be CVA related. A total of 104 patients (87 first and 17 recurrent
CVAs) had 133 episodes of CVA on study. Eleven (10.6%) of the 104
patients died, 9 after hemorrhagic stroke and 2 after strokes of
unidentified type. Seven of the 11 deaths resulted from the first CVA;
of these, 6 had a hemorrhagic stroke and 1 had stroke of unidentified
type. All 11 patients were in the SS group (11.7% of SS CVA patients)
and ranged in age from 12 to 58 years. Six died on the day of the CVA,
whereas the others died within 1 week after the CVA. The mortality rate
for hemorrhagic stroke was 24% overall and 26% for SS patients. No
deaths occurred within 14 days after 62 infarctive strokes.
-Thalassemia and CVA.
Of 2,436 SS patients with no history of CVA at study entry, 1,833 had
-globin gene mapping data: 573 (31%) had -thalassemia (48 with 2
and 525 with 3 -globin genes) and 1,260 (69%) had 4 (n = 1,242) or
5 (n = 18) -globin genes. The incidence of CVA of all types for
patients with -thalassemia (0.32 per 100 patient-years) was lower
than that for patients without -thalassemia (0.74 per 100
patient-years), yielding a relative risk of 0.44 (95% confidence
interval, 0.23 to 0.85; P = .011). There were no CVA observed
in the 48 patients with 2 -globin genes. The incidence of infarctive
stroke was 0.21 per 100 patient-years in those with -thalassemia and
0.81 per 100 patient-years in those without -thalassemia (P
= .079). The incidence of hemorrhagic stroke was 0.06 per 100
patient-years versus 0.23 per 100 patient-years in those with and
without -thalassemia (P = .076).
Risk factors for CVA.
Risk factors were evaluated separately for first infarctive and
hemorrhagic strokes because the two types of strokes may have different
pathophysiologies. For these analyses, TIA was considered as a risk
factor for having a subsequent completed infarctive or hemorrhagic
stroke. No patients experienced seizures, surgical procedures, or acute
anemic events within 2 weeks before CVA.
Completed infarctive stroke.
Univariate analyses of the risk of completed infarctive stroke (age at
first CVA) identified eight risk factors. Prior TIA, history of
meningitis (any type), history of bacterial meningitis, systolic blood
pressure, steady-state leukocyte count, acute chest syndrome within 2
weeks before stroke, and rate of acute chest syndrome were positively
related to infarctive stroke, whereas steady-state Hb concentration was
negatively related; ie, patients with lower steady-state Hb are at
greater risk of infarctive stroke (P < .05). The rate of
severe painful episodes (P = .671), Hb F level (P =
.106), blood transfusion within 2 weeks before stroke (P =
.077), and platelet count (P = .097) were not significantly
related to occurrence of first completed infarctive stroke.
The final multivariate model for risk of completed infarctive stroke
included five variables: prior TIA, steady-state Hb concentration,
acute chest syndrome within 2 weeks before CVA, rate of acute chest
syndrome, and systolic blood pressure (Table
5A). The most significant predictor of
completed infarctive stroke was prior TIA; however, the majority of
patients had stroke without prior TIA. In this study, 2 of 42 completed
infarctive strokes were preceded by TIA, compared with 6 TIA in 2,394
patients who did not experience any stroke. Similarly, 4 of the 42
completed infarctive strokes were preceded within 2 weeks by acute
chest syndrome. An additional 3 patients had acute chest syndrome on
the same day as the completed infarctive stroke, but these patients
were excluded from the analysis because timing of the acute chest
syndrome event relative to the onset of infarctive stroke was not
documented.
Hemorrhagic stroke.
Univariate analyses of the risk of hemorrhagic stroke (age at first
CVA) identified three significant risk factors: steady-state leukocyte
count and rate of acute chest syndrome were positively related to risk
of hemorrhagic stroke, whereas steady-state Hb concentration was
negatively related (P < .05). The presence of -thalassemia
provided a marginally significant protection against hemorrhagic stroke
in SS patients (P = .054). Unlike infarctive stroke, history of
meningitis and systolic blood pressure were not significant univariate
predictors; none of the 28 patients with first hemorrhagic stroke on
study had had meningitis.
The final multivariate model for risk of hemorrhagic stroke included
two significant variables: low steady-state Hb concentration and high
leukocyte count (Table 5B).
| |
DISCUSSION |
This report represents larger numbers of SCD patients with CVA than any
previous study. As expected, the highest incidence rate was found in SS
patients. Although SS patients are at the greatest risk of stroke,
clinicians and others counseling about SCD should note that strokes
occurred also in patients with other genotypes. Children less than 2
years of age had the lowest CVA incidence, suggesting that there may be
a protective mechanism operative in early life or that, in SCD, the
pathology responsible for CVA develops over time. However, we found the
incidence of CVA to be higher in the 1 to 9 years of age group than in
the 10 to 19 years of age group. This finding suggests that a subset of
patients may have additional risk factors for early stroke.
The type of stroke may be due to different pathophysiologic mechanisms
or to progressive cerebrovascular damage. The notion that infarctive
strokes occur more commonly in children whereas hemorrhagic strokes
occur more frequently in adults is supported partly by this study.
Infarctive stroke was more common in SS patients less than 20 years of
age than in those older, but patients more than 30 years of age were
also at risk. Interestingly, the period of lowest risk for infarctive
stroke (20 to 29 years of age) was the period of highest risk for
hemorrhagic stroke. However, it should be noted that children less than
10 years of age experienced a higher rate of hemorrhagic stroke (0.17
per 100-patient-years) than reported previously.
Some of our data may be useful in identifying patients at high risk for
completed CVA. History of TIA was a strong risk factor for completed
infarctive stroke. This fact should alert clinicians to regard TIA as a
sign of cerebrovascular disease, use definitive diagnostic studies, and
initiate aggressive management to prevent occurrence of completed
stroke. However, infarctive strokes are often not preceded by TIA, and
in young children mild TIA is likely to go unnoticed.
The temporal association of episodes of acute chest syndrome and CVA
found in this study has not been reported previously. It is possible
that in patients with damaged cerebral vessels, CVA may be precipitated
by hypoxia associated with pulmonary disease. Alternatively, these
strokes may be related to the fat embolization syndrome.18
We did not find an association between first CVA and
priapism19 or transfusion therapy occurring within 2 weeks
before the CVA.
Anemia in SCD is a reflection of overall severity of SCD. Patients with
the milder genotypes are less anemic than those with more severe
genotypes. However, within each genotype, an association between the
severity of anemia and major complications of SCD is not always
apparent. In SS patients, a high Hb level is related to increased rates
of severe pain20 and acute chest syndrome.21
Severe anemia may pose an added risk for CVA. It has been suggested
that the increased cerebral blood flow and flow velocity associated
with chronic anemia22 cause flow disturbances that may lead
to cerebrovascular damage.23
A high leukocyte count appears to be a risk factor for many severe
complications of SCD: rates of severe pain,20 acute chest
syndrome,21 and mortality.2 Association of
increased white blood cell count with CVA has been
reported4; our data show such a correlation only for
hemorrhagic CVA. The contribution of leukocytes, if any, and the
various vaso-active and cytoadhesive molecules produced by leukocytes
to vasoocclusion has not been defined.
The lack of a protective effect of increased Hb F levels on CVA was
surprising, given reports of its inhibiting effect on CVA risk in other
series.3,4 Hb F has been inversely correlated with rates of
other major vasoocclusive manifestations of sickle cell disease such as
severe pain and acute chest syndrome. It remains to be seen whether the
ameliorating effect of hydroxyurea therapy on rates of severe pain and
acute chest syndrome will be shown with CVA also.24
The effect of -thalassemia on the incidence of CVA is controversial;
whereas some studies have found that it reduces the risk of
CVA,14,25,26 others have not.4,27 This study
provides some evidence to support earlier reports that -thalassemia
protects SCD patients from CVA.14,25,26 We observed a
significant association when all types of CVA were combined, but the
effect was marginal (.05 < P < .10) when infarctive and
hemorrhagic strokes were considered separately, in part due to the
smaller number of events in each subgroup. Nevertheless, it should be
noted that the effect of -thalassemia appears to be similar for
infarctive and hemorrhagic strokes. Based on additional multivariate
analysis, we conclude that the protective effect of -thalassemia is
largely due to the improvement in Hb concentration. We did not find
-thalassemia to be a significant predictor of CVA after adjusting
for Hb.
SCD patients who suffer CVA have a high risk of recurrence that is
reduced but not abolished by chronic transfusion
therapy.28-32 We were unable to assess the impact of
chronic transfusion on CVA recurrence because the study did not mandate
any transfusion regimen for patients with CVA.
We observed no mortality after 62 infarctive strokes, but there was a
24% mortality rate after 38 hemorrhagic strokes within 2 weeks after
the event. Mortality related to hemorrhagic stroke was rapid, with 6 of
the 11 CVA-related deaths occurring on the day of the event.
For the last 2 decades, management of CVA in SCD has been directed
mainly towards prevention of recurrence. There is now strong interest
in preventing the occurrence of the first CVA. The CSSCD and others are
involved in prospective studies using magnetic resonance technology and
extensive neuropsychological testing to look for evidence of
intracranial pathology that may be predictive of CVA. Cerebral
infarcts33,34 and cerebrovascular disease35
have been demonstrated in SS patients with no history of CVA.
Transcranial Doppler ultrasonography has been shown to be able to
select patients at high risk of stroke,36 and a national
collaborative study in which patients with abnormal flow velocities are
randomized to transfusion or observation has shown recently the risk of
first CVA can be reduced significantly with chronic transfusion
therapy. Patients with the risk factors described in this study should
be particularly evaluated for evidence of cerebrovascular disease.
Caretakers of young children with SCD should be educated about signs of
TIA and advised to report them. Furthermore, patients with clinical and
hematologic risk factors who are found to have cerebrovascular disease
should be considered seriously for intervention studies and therapy.
| |
FOOTNOTES |
Submitted January 31, 1997;
accepted August 25, 1997.
Supported by the Division of Blood Diseases and Resources of the
National Heart, Lung, and Blood Institute of the National Institutes of
Health.
Address reprint requests to Kwaku Ohene-Frempong, MD, Division of
Hematology, Children's Hospital of Philadelphia, 34th St and Civic
Center Blvd, Philadelphia, PA 19104.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. section 1734 solely
to indicate this fact.
| |
ACKNOWLEDGMENT |
The authors thank Sergio Piomelli, Orah Platt, Samuel Charache, William
Mentzer, Rebecca Stellato, and Dale Usner for their thoughtful review
and helpful comments regarding this manuscript.
| |
APPENDIX |
The following were senior investigators in the CSSCD: Clinical Centers:
R. Johnson, Alta Bates Hospital (Berkeley, CA); L. McMahon, Boston City
Hospital (Boston, MA); O. Platt, Children's Hospital (Boston, MA); F.
Gill and K. Ohene-Frempong, Children's Hospital (Philadelphia, PA); G.
Bray, J. Kelleher, and S. Leikin, Children's National Medical Center
(Washington, DC); E. Vichinsky and B. Lubin, Children's Hospital
(Oakland, CA); A. Bank and S. Piomelli, Columbia Presbyterian Hospital
(New York, NY); W. Rosse, J. Falletta, and T. Kinney, Duke University
(Durham, NC); L. Lessin, George Washington University (Washington, DC);
J. Smith and Y. Khakoo, Harlem Hospital (New York, NY); R. Scott, O.
Castro, and C. Reindorf, Howard University (Washington, DC); H. Dosik,
S. Diamond, and R. Bellevue, Interfaith Medical Center (Brooklyn, NY);
W. Wang and J. Wilimas, LeBonheur Children's Hospital (Memphis, TN);
P. Milner, Medical College of Georgia (Augusta, GA); A. Brown, S.
Miller, R. Rieder, and P. Gillette, State University of New York Health
Science Center at Brooklyn (Brooklyn, NY); W. Lande, S. Embury, and W.
Mentzer, San Francisco General Hospital (San Francisco, CA); D. Wethers
and R. Grover, St Luke's-Roosevelt Medical Center (New York, NY); M.
Koshy and N. Talishy, University of Illinois (Chicago, IL); C. Pegelow,
P. Klug, and J. Temple, University of Miami (Miami, FL); M. Steinberg,
University of Mississippi (Jackson, MS); A. Kraus, University of
Tennessee (Memphis, TN); H. Zarkowsky, Washington University (St Louis,
MO); C. Dampier, Wyler Children's Hospital (Chicago, IL); H. Pearson
and A.K. Ritchey, Yale University (New Haven, CT); Statistical
Coordinating Centers: P. Levy, D. Gallagher, A. Koranda, Z.
Flournoy-Gill, and E. Jones, University of Illinois School of Public
Health (Chicago, IL; 1979-89); S. McKinlay, O. Platt, D. Gallagher, D.
Brambilla, and L. Sleeper, New England Research Institutes (Watertown,
MA; 1989-1997); M. Espeland, Bowman-Gray School of Medicine
(Winston-Salem, NC); Program Administration: M. Gaston, C. Reid, and J.
Verter, National Heart, Lung, and Blood Institute (Bethesda,
MD).
| |
REFERENCES |
1.
Leikin SL,
Gallagher D,
Kinney TR,
Sloane D,
Klug P,
Rida W:
Mortality in children and adolescents with sickle cell disease.
Pediatrics
84:500,
1989[Abstract/Free Full Text]
2.
Platt OS,
Brambilla DJ,
Rosse WF,
Milner PF,
Castro O,
Steinberg MH,
Klug PP:
Mortality in sickle cell disease: Life expectancy and risk factors for early death.
N Engl J Med
330:1639,
1994[Abstract/Free Full Text]
3.
Powars D,
Wilson B,
Imbus C,
Pegelow C,
Allen J:
The natural history of stroke in sickle cell disease.
Am J Med
65:461,
1978[Medline]
[Order article via Infotrieve]
4.
Balkaran B,
Char G,
Morris JS,
Thomas PW,
Serjeant BE,
Serjeant GR:
Stroke in a cohort of patients with homozygous sickle cell disease.
J Pediatr
120:360,
1992[Medline]
[Order article via Infotrieve]
5.
Ohene-Frempong K:
Stroke in sickle cell disease: Demographic, clinical and therapeutic considerations.
Semin Hematol
28:213,
1991[Medline]
[Order article via Infotrieve]
6. Gaston M, Smith J, Gallagher D, Fluornoy-Gill Z, West S, Bellevue
R, Farber M, Grover R, Koshy M, Ritchey AK, Wilimas J, and the CSSCD
Group: Recruitment in the Cooperative Study of Sickle
Cell Disease (CCSCD). Controlled Clin Trials 8:131S, 1987
7. Gaston M, Rosse WF, and the Cooperative Study of Sickle Cell
Disease: The Cooperative Study of Sickle Cell Disease: Review of study
design and objectives. Am J Pediatr Hematol Oncol 4:197, 1982
8.
Farber MD,
Koshy M,
Kinney TR:
Cooperative Study of Sickle Cell Disease: Demographic and socioeconomic characteristics of patients and families with sickle cell disease.
J Chronic Dis
38:495,
1985[Medline]
[Order article via Infotrieve]
9. Adams JG III: Clinical laboratory diagnosis, in Embury SH, Hebbel
RP, Mohandas N, Steinberg MH (eds): Sickle Cell Disease: Basic
Principles and Clinical Practice. New York, NY, Raven, 1994, p 457
10.
Wrightstone RN,
Huisman TH:
On the levels of hemoglobins F and A2 in sickle cell anemia and some related disorders.
Am J Clin Pathol
61:375,
1974[Medline]
[Order article via Infotrieve]
11.
Betke K,
Marti HR,
Schlicht I:
Estimation of small percentages of foetal haemoglobin.
Nature
184:1877,
1959
12.
Embury SH,
Lebo RV,
Dozy AM,
Kan YW:
Organization of the single -globin genes in the Chinese -thalassemia syndromes.
J Clin Invest
63:1307,
1979
13.
Embury SH,
Miller JA,
Dozy AM,
Kan YW,
Chan V,
Todd D:
Two different molecular organizations account for the single -globin gene in the -thalassemia-2 genotype.
J Clin Invest
66:1319,
1980
14.
Gill FM,
Sleeper LA,
Weiner SJ,
Brown AK,
Bellevue R,
Grover R,
Pegelow CH,
Vichinsky E:
Clinical events in the first decade in a cohort of infants with sickle cell disease.
Blood
86:776,
1995[Abstract/Free Full Text]
15. Kleinbaum DG, Kupper LL, Morgenstern H: Epidemiologic Research:
Principles and Quantitative Methods. Belmont, CA, Lifetime Learning,
1982, p 284
16. Allison PD: Survival Analysis Using the SAS System: A Practical
Guide. Cary, NC, SAS, 1995, p 259
17.
Cnaan A,
Ryan L:
Survival analysis in natural history studies of disease.
Stat Med
8:1255,
1989[Medline]
[Order article via Infotrieve]
18.
Horton DP,
Ferriero DM,
Mentzer WC:
Nontraumatic fat embolism in sickle cell anemia.
Pediatr Neurol
12:77,
1995[Medline]
[Order article via Infotrieve]
19.
Racoff WR,
Ohene-Frempong K,
Month S,
Scott JP,
Neahring B,
Cohen AR:
Neurologic events after partial exchange transfusion for priapism in sickle cell disease.
J Pediatr
120:882,
1992[Medline]
[Order article via Infotrieve]
20.
Platt OS,
Thorington BD,
Brambilla DJ,
Milner PF,
Rosse WF,
Vichinsky E,
Kinney TR:
Pain in sickle cell disease: Rates and risk factors.
N Engl J Med
325:11,
1991[Abstract]
21.
Castro O,
Brambilla DJ,
Thorington B,
Reindorf CA,
Scott RB,
Gillette P,
Vera JC,
Levy PS:
The acute chest syndrome in sickle cell disease: Incidence and risk factors.
Blood
84:643,
1994[Abstract/Free Full Text]
22.
Prohovnik I,
Pavlakis SG,
Piomelli S,
Bello J,
Mohr JP,
Hilal S,
De Vivo DC:
Cerebral hyperemia, stroke and transfusion in sickle cell disease.
Neurology
39:344,
1989[Abstract/Free Full Text]
23. Adams RJ: Neurologic complications, in Embury SH, Hebbel RP,
Mohandas N, Steinberg MH (eds): Sickle Cell Disease: Basic Principles
and Clinical Practice. New York, NY, Raven, 1994, p 599
24.
Charache S,
Terrin ML,
Moore RD,
Dover GJ,
Barton FB,
Eckert SV,
McMahon RP,
Bonds DR:
Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia.
N Engl J Med
332:1317,
1995[Abstract/Free Full Text]
25.
Adams RJ,
Kutlar A,
McKie V,
Carl E,
Nichols FT,
Liu JC,
McKie K,
Clary A:
Alpha thalassemia and stroke risk in sickle cell anemia.
Am J Hematol
45:279,
1994[Medline]
[Order article via Infotrieve]
26. Piomelli S, Seaman C, Cirella B, Ince C, Meyer P, Paulakis S,
Schaefer-Rego K, Bank A, Mears G: Does -thalassemia
protect from early stroke in sickle cell anemia? Pediatr Res 10:285A,
1986
27.
Miller ST,
Rieder RF,
Rao SP,
Brown AK:
Cerebrovascular accidents in children with sickle-cell disease and alpha-thalassemia.
J Pediatr
113:847,
1988[Medline]
[Order article via Infotrieve]
28.
Russell MO,
Goldberg HI,
Hodson A,
Kim HC,
Halus J,
Reivich M,
Schwartz E:
Effect of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease.
Blood
63:162,
1984[Abstract/Free Full Text]
29.
Sarnaik S,
Soorya D,
Kim J,
Ravindranath Y,
Lusher J:
Periodic transfusions for sickle cell anemia and CNS infarction.
Am J Dis Child
133:1254,
1979[Abstract/Free Full Text]
30. Moohr JW, Wilson H, Pang EJM: Strokes and their management in
sickle cell disease, in Fried W (ed): Comparative Clinical Aspects of
Sickle Cell Disease. New York, NY, Elsevier North Holland, 1982, p 101
31.
Wang WC,
Kovnar EH,
Tonkin IL,
Mulhern RK,
Langston JW,
Day SW,
Schell MJ,
Wilimas JA:
High risk of recurrent stroke after discontinuance of five to twelve years of transfusion therapy in patients with sickle cell disease.
J Pediatr
118:377,
1991[Medline]
[Order article via Infotrieve]
32.
Pegelow CH,
Adams RJ,
McKie V,
Abboud M,
Berman B,
Miller ST,
Olivieri N,
Vichinsky E,
Wang W,
Brambilla D:
Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions.
J Pediatr
126:896,
1995[Medline]
[Order article via Infotrieve]
33.
Pavlakis SG,
Bello J,
Prohovnik I,
Sutton M,
Ince C,
Mohr JP,
Piomelli S,
Hilal S,
De Vivo DC:
Brain infarction in sickle cell anemia: Magnetic resonance imaging correlates.
Ann Neurol
23:125,
1988[Medline]
[Order article via Infotrieve]
34.
Moser FG,
Miller ST,
Bello JA,
Pegelow CH,
Zimmerman RA,
Wang WC,
Ohene-Frempong K,
Schwartz A,
Vichinsky EP,
Gallagher D,
Kinney TR:
The spectrum of central nervous system abnormalities in sickle cell disease as defined by magnetic resonance imaging: A report from the Cooperative Study of Sickle Cell Disease.
Am J Neuroradiol
17:965,
1996[Abstract]
35.
Wiznitzer M,
Ruggieri PM,
Masaryk TJ,
Ross JS,
Modic MT,
Berman B:
Diagnosis of cerebrovascular disease in sickle cell anemia by magnetic resonance angiography.
J Pediatr
17:551,
1990
36.
Adams R,
McKie V,
Nichols F,
Carl E,
Zhang DL,
McKie K,
Figueroa R,
Litaker M,
Thompson W,
Hess D:
The use of transcranial ultrasonography to predict stroke in sickle cell disease.
N Engl J Med
326:605,
1992[Abstract]
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. B. Bailey Jr, F. D. Armstrong, A. R. Kemper, D. Skinner, and S. F. Warren
Supporting Family Adaptation to Presymptomatic and "Untreatable" Conditions in an Era of Expanded Newborn Screening
J. Pediatr. Psychol.,
July 1, 2009;
34(6):
648 - 661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. R. Kirk, M. R. Haynes, S. Palasis, C. Brown, T. G. Burns, M. McCormick, and R. A. Jones
Regionally Specific Cortical Thinning in Children with Sickle Cell Disease
Cereb Cortex,
July 1, 2009;
19(7):
1549 - 1556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Silva, P. Vicari, M. S. Figueiredo, H. Carrete Junior, M. H. Idagawa, and A. R. Massaro
Brain Magnetic Resonance Imaging Abnormalities in Adult Patients With Sickle Cell Disease: Correlation With Transcranial Doppler Findings
Stroke,
July 1, 2009;
40(7):
2408 - 2412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Armstrong-Wells, B. Grimes, S. Sidney, D. Kronish, S. C. Shiboski, R. J. Adams, and H. J. Fullerton
Utilization of TCD screening for primary stroke prevention in children with sickle cell disease
Neurology,
April 14, 2009;
72(15):
1316 - 1321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Debette and S. Seshadri
Genetics of Atherothrombotic and Lacunar Stroke
Circ Cardiovasc Genet,
April 1, 2009;
2(2):
191 - 198.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Amlie-Lefond, T. J. Bernard, G. Sebire, N. R. Friedman, G. L. Heyer, N. B. Lerner, G. deVeber, H. J. Fullerton, and for the International Pediatric Stroke Study Group
Predictors of Cerebral Arteriopathy in Children With Arterial Ischemic Stroke: Results of the International Pediatric Stroke Study
Circulation,
March 17, 2009;
119(10):
1417 - 1423.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-S. Kim, E. Nur, E. J. van Beers, J. Truijen, S. C.A.T. Davis, B. J. Biemond, and J. J. van Lieshout
Dynamic Cerebral Autoregulation in Homozygous Sickle Cell Disease
Stroke,
March 1, 2009;
40(3):
808 - 814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hryniewicz-Jankowska, P. K. Choudhary, L. P. Ammann, C. T. Quinn, and S. R. Goodman
Monocyte Protein Signatures of Disease Severity in Sickle Cell Anemia
Experimental Biology and Medicine,
February 1, 2009;
234(2):
210 - 221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Gladwin and E. Vichinsky
Pulmonary Complications of Sickle Cell Disease
N. Engl. J. Med.,
November 20, 2008;
359(21):
2254 - 2265.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Bernaudin, S. Verlhac, S. Chevret, M. Torres, L. Coic, C. Arnaud, A. Kamdem, I. Hau, M. Grazia Neonato, and C. Delacourt
G6PD deficiency, absence of {alpha}-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia
Blood,
November 15, 2008;
112(10):
4314 - 4317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. d. Montalembert
Management of sickle cell disease
BMJ,
September 8, 2008;
337(sep08_1):
a1397 - a1397.
[Full Text]
|
|
|
|
|
|
|
E. S. Roach, M. R. Golomb, R. Adams, J. Biller, S. Daniels, G. deVeber, D. Ferriero, B. V. Jones, F. J. Kirkham, R. M. Scott, et al.
Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young
Stroke,
September 1, 2008;
39(9):
2644 - 2691.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Rees, M. C. Dick, S. E. Height, S. O'Driscoll, K. R.E. Pohl, D. E. Goss, and C. R. Deane
A Simple Index Using Age, Hemoglobin, and Aspartate Transaminase Predicts Increased Intracerebral Blood Velocity as Measured by Transcranial Doppler Scanning in Children With Sickle Cell Anemia
Pediatrics,
June 1, 2008;
121(6):
e1628 - e1632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. van Beers, C. F.J. van Tuijn, M. R. Mac Gillavry, A. van der Giessen, J.-J. B. Schnog, B. J. Biemond, and on behalf of the CURAMA study group
Sickle cell disease-related organ damage occurs irrespective of pain rate: implications for clinical practice
Haematologica,
May 1, 2008;
93(5):
757 - 760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. D. Pashankar, J. Carbonella, A. Bazzy-Asaad, and A. Friedman
Prevalence and Risk Factors of Elevated Pulmonary Artery Pressures in Children With Sickle Cell Disease
Pediatrics,
April 1, 2008;
121(4):
777 - 782.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Fabry
Arterial access for sickle stroke predictors
Blood,
April 1, 2008;
111(7):
3310 - 3311.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Chang Milbauer, P. Wei, J. Enenstein, A. Jiang, C. A. Hillery, J. P. Scott, S. C. Nelson, V. Bodempudi, J. N. Topper, R.-B. Yang, et al.
Genetic endothelial systems biology of sickle stroke risk
Blood,
April 1, 2008;
111(7):
3872 - 3879.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R Deane, D. Goss, S. O'Driscoll, S. Mellor, K. R E Pohl, M. C Dick, S. E Height, and D. C Rees
Transcranial Doppler scanning and the assessment of stroke risk in children with haemoglobin sickle cell disease
Arch. Dis. Child.,
February 1, 2008;
93(2):
138 - 141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Lefevre, D. Dufour, B. Gulbis, P.-Q. Le, C. Heijmans, and A. Ferster
Use of hydroxyurea in prevention of stroke in children with sickle cell disease
Blood,
January 15, 2008;
111(2):
963 - 964.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. Quinn, N. J. Lee, E. P. Shull, N. Ahmad, Z. R. Rogers, and G. R. Buchanan
Prediction of adverse outcomes in children with sickle cell anemia: a study of the Dallas Newborn Cohort
Blood,
January 15, 2008;
111(2):
544 - 548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Schatz, C. B. McClellan, E. S. Puffer, K. Johnson, and C. W. Roberts
Neurodevelopmental Screening in Toddlers and Early Preschoolers With Sickle Cell Disease
J Child Neurol,
January 1, 2008;
23(1):
44 - 50.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Mazumdar, M. M. Heeney, C. M. Sox, and T. A. Lieu
Preventing Stroke Among Children With Sickle Cell Anemia: An Analysis of Strategies That Involve Transcranial Doppler Testing and Chronic Transfusion
Pediatrics,
October 1, 2007;
120(4):
e1107 - e1116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Sebastiani, V. G. Nolan, C. T. Baldwin, M. M. Abad-Grau, L. Wang, A. H. Adewoye, L. C. McMahon, L. A. Farrer, J. G. Taylor IV, G. J. Kato, et al.
A network model to predict the risk of death in sickle cell disease
Blood,
October 1, 2007;
110(7):
2727 - 2735.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Bernaudin, G. Socie, M. Kuentz, S. Chevret, M. Duval, Y. Bertrand, J.-P. Vannier, K. Yakouben, I. Thuret, P. Bordigoni, et al.
Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease
Blood,
October 1, 2007;
110(7):
2749 - 2756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Francis, S. Raghunathan, and P. Khanna
The role of genetics in stroke
Postgrad. Med. J.,
September 1, 2007;
83(983):
590 - 595.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Telfer, P. Coen, S. Chakravorty, O. Wilkey, J. Evans, H. Newell, B. Smalling, R. Amos, A. Stephens, D. Rogers, et al.
Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London
Haematologica,
July 1, 2007;
92(7):
905 - 912.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Austin, H. Cohen, and N. Losseff
Haematology and neurology
J. Neurol. Neurosurg. Psychiatry,
April 1, 2007;
78(4):
334 - 341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Sachdev, R. F. Machado, Y. Shizukuda, Y. N. Rao, S. Sidenko, I. Ernst, M. St. Peter, W. A. Coles, D. R. Rosing, W. C. Blackwelder, et al.
Diastolic Dysfunction Is an Independent Risk Factor for Death in Patients With Sickle Cell Disease
J. Am. Coll. Cardiol.,
January 30, 2007;
49(4):
472 - 479.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. DeBaun and J. J. Field
Limitations of Clinical Trials in Sickle Cell Disease: A Case Study of the Multi-center Study of Hydroxyurea (MSH) Trial and the Stroke Prevention (STOP) Trial
Hematology,
January 1, 2007;
2007(1):
482 - 488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. Quinn, E. P. Shull, N. Ahmad, N. J. Lee, Z. R. Rogers, and G. R. Buchanan
Prognostic significance of early vaso-occlusive complications in children with sickle cell anemia
Blood,
January 1, 2007;
109(1):
40 - 45.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Day and E. Chismark
The Cognitive and Academic Impact Of Sickle Cell Disease
The Journal of School Nursing,
December 1, 2006;
22(6):
330 - 335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Strouse, M. L. Hulbert, M. R. DeBaun, L. C. Jordan, and J. F. Casella
Primary Hemorrhagic Stroke in Children With Sickle Cell Disease Is Associated With Recent Transfusion and Use of Corticosteroids
Pediatrics,
November 1, 2006;
118(5):
1916 - 1924.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Valadi, G. S. Silva, L. S. Bowman, D. Ramsingh, P. Vicari, A. C. Filho, A. R. Massaro, A. Kutlar, F. T. Nichols, and R. J. Adams
Transcranial Doppler ultrasonography in adults with sickle cell disease.
Neurology,
August 22, 2006;
67(4):
572 - 574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Lee, S. Piomelli, S. Granger, S. T. Miller, S. Harkness, D. J. Brambilla, R. J. Adams, and for the STOP Study Investigators
Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results
Blood,
August 1, 2006;
108(3):
847 - 852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Strouse, C. S. Cox, E. R. Melhem, H. Lu, M. A. Kraut, A. Razumovsky, K. Yohay, P. C. van Zijl, and J. F. Casella
Inverse correlation between cerebral blood flow measured by continuous arterial spin-labeling (CASL) MRI and neurocognitive function in children with sickle cell anemia (SCA)
Blood,
July 1, 2006;
108(1):
379 - 381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al.
Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.
Circulation,
June 20, 2006;
113(24):
e873 - e923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. E. Lezcano, N. Odo, A. Kutlar, D. Brambilla, and R. J. Adams
Regular Transfusion Lowers Plasma Free Hemoglobin in Children With Sickle-Cell Disease at Risk for Stroke
Stroke,
June 1, 2006;
37(6):
1424 - 1426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al.
Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.
Stroke,
June 1, 2006;
37(6):
1583 - 1633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Sacco, R. Adams, G. Albers, M. J. Alberts, O. Benavente, K. Furie, L. B. Goldstein, P. Gorelick, J. Halperin, R. Harbaugh, et al.
Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.
Circulation,
March 14, 2006;
113(10):
e409 - e449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Manci, C. A. Hillery, C. A. Bodian, Z. G. Zhang, G. A. Lutty, and B. S. Coller
Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease
Blood,
February 15, 2006;
107(4):
1651 - 1658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Sacco, R. Adams, G. Albers, M. J. Alberts, O. Benavente, K. Furie, L. B. Goldstein, P. Gorelick, J. Halperin, R. Harbaugh, et al.
Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.
Stroke,
February 1, 2006;
37(2):
577 - 617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Kral, R. T. Brown, J. K. Cure, N. Besenski, S. M. Jackson, and M. R. Abboud
Radiographic Predictors of Neurocognitive Functioning in Pediatric Sickle Cell Disease
J Child Neurol,
January 1, 2006;
21(1):
37 - 44.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Sanefuji, S. Ohga, R. Kira, and T. Yoshiura
Moyamoya Syndrome in a Splenectomized Patient With {beta}-Thalassemia Intermedia
J Child Neurol,
January 1, 2006;
21(1):
75 - 77.
[Abstract]
[PDF]
|
|
|
|
|
|
|
O. S. Platt
Prevention and Management of Stroke in Sickle Cell Anemia
Hematology,
January 1, 2006;
2006(1):
54 - 57.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
The Optimizing Primary Stroke Prevention in Sickle
Discontinuing Prophylactic Transfusions Used to Prevent Stroke in Sickle Cell Disease
N. Engl. J. Med.,
December 29, 2005;
353(26):
2769 - 2778.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. G. Nolan, D. F. Wyszynski, L. A. Farrer, and M. H. Steinberg
Hemolysis-associated priapism in sickle cell disease
Blood,
November 1, 2005;
106(9):
3264 - 3267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Routhieaux, S. Sarcone, and K. Stegenga
Neurocognitive Sequelae of Sickle Cell Disease: Current Issues and Future Directions
Journal of Pediatric Oncology Nursing,
May 1, 2005;
22(3):
160 - 167.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. Gulbis, D. Haberman, D. Dufour, C. Christophe, C. Vermylen, F. Kagambega, F. Corazza, C. Devalck, M.-F. Dresse, K. Hunninck, et al.
Hydroxyurea for sickle cell disease in children and for prevention of cerebrovascular events: the Belgian experience
Blood,
April 1, 2005;
105(7):
2685 - 2690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Steen, T. Emudianughe, M. Hunte, J. Glass, S. Wu, X. Xiong, and W. E. Reddick
Brain Volume in Pediatric Patients with Sickle Cell Disease: Evidence of Volumetric Growth Delay?
AJNR Am. J. Neuroradiol.,
March 1, 2005;
26(3):
455 - 462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Steen, C. Fineberg-Buchner, G. Hankins, L. Weiss, A. Prifitera, and R. K. Mulhern
Cognitive Deficits in Children With Sickle Cell Disease
J Child Neurol,
February 1, 2005;
20(2):
102 - 107.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. D. Villella
Declining Stroke Rates in Children with Sickle Cell Disease
AAP Grand Rounds,
January 1, 2005;
13(1):
1 - 2.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. F. Meschia, T. G. Brott, and R. D. Brown Jr
Genetics of Cerebrovascular Disorders
Mayo Clin. Proc.,
January 1, 2005;
80(1):
122 - 132.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. Monagle, A. Chan, P. Massicotte, E. Chalmers, and A. D. Michelson
Antithrombotic Therapy in Children*: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Chest,
September 1, 2004;
126(3_suppl):
645S - 687S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Fullerton, R. J. Adams, S. Zhao, and S. C. Johnston
Declining stroke rates in Californian children with sickle cell disease
Blood,
July 15, 2004;
104(2):
336 - 339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. Stegenga, P. Ward-Smith, P. S. Hinds, J. A. Routhieaux, and G. M. Woods
Quality of Life Among Children With Sickle Cell Disease Receiving Chronic Transfusion Therapy
Journal of Pediatric Oncology Nursing,
July 1, 2004;
21(4):
207 - 213.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. L. Jison, P. J. Munson, J. J. Barb, A. F. Suffredini, S. Talwar, C. Logun, N. Raghavachari, J. H. Beigel, J. H. Shelhamer, R. L. Danner, et al.
Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease
Blood,
July 1, 2004;
104(1):
270 - 280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. Quinn, Z. R. Rogers, and G. R. Buchanan
Survival of children with sickle cell disease
Blood,
June 1, 2004;
103(11):
4023 - 4027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Adams, D. J. Brambilla, S. Granger, D. Gallagher, E. Vichinsky, M. R. Abboud, C. H. Pegelow, G. Woods, E. M. Rohde, F. T. Nichols, et al.
Stroke and conversion to high risk in children screened with transcranial Doppler ultrasound during the STOP study
Blood,
May 15, 2004;
103(10):
3689 - 3694.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Kral and R. T. Brown
Transcranial Doppler Ultrasonography and Executive Dysfunction in Children with Sickle Cell Disease
J. Pediatr. Psychol.,
April 1, 2004;
29(3):
185 - 195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Goyal, S. T. Miller, M. R. Hammerschlag, M. Gelling, C. A. Gaydos, J. Hardick, B. J. Wood, T. Reznik, and S.P. Rao
Is Chlamydia pneumoniae Infection Associated With Stroke in Children With Sickle Cell Disease?
Pediatrics,
April 1, 2004;
113(4):
e318 - e321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Abboud, J. Cure, S. Granger, D. Gallagher, L. Hsu, W. Wang, G. Woods, B. Berman, D. Brambilla, C. Pegelow, et al.
Magnetic resonance angiography in children with sickle cell disease and abnormal transcranial Doppler ultrasonography findings enrolled in the STOP study
Blood,
April 1, 2004;
103(7):
2822 - 2826.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Hoppe, W. Klitz, S. Cheng, R. Apple, L. Steiner, L. Robles, T. Girard, E. Vichinsky, and L. Styles
Gene interactions and stroke risk in children with sickle cell anemia
Blood,
March 15, 2004;
103(6):
2391 - 2396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Henry, M. C. Driscoll, M. Miller, T. Chang, and C. P. Minniti
Pseudotumor Cerebri in Children With Sickle Cell Disease: A Case Series
Pediatrics,
March 1, 2004;
113(3):
e265 - 269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Gladwin, V. Sachdev, M. L. Jison, Y. Shizukuda, J. F. Plehn, K. Minter, B. Brown, W. A. Coles, J. S. Nichols, I. Ernst, et al.
Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease
N. Engl. J. Med.,
February 26, 2004;
350(9):
886 - 895.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. R. Buchanan, M. R. DeBaun, C. T. Quinn, and M. H. Steinberg
Sickle Cell Disease
Hematology,
January 1, 2004;
2004(1):
35 - 47.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. T. Miller, S. P. Rao, J. H. Boyd, and M. R. DeBaun
Acute chest syndrome, transfusion, and neurologic events in children with sickle cell disease
Blood,
August 15, 2003;
102(4):
1556 - 1557.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Kral, R. T. Brown, P. J. Nietert, M. R. Abboud, S. M. Jackson, and G. W. Hynd
Transcranial Doppler Ultrasonography and Neurocognitive Functioning in Children With Sickle Cell Disease
Pediatrics,
August 1, 2003;
112(2):
324 - 331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Steen, G. M. Hankins, X. Xiong, W. C. Wang, K. Beil, J. W. Langston, and K. J. Helton
Prospective Brain Imaging Evaluation of Children with Sickle Cell Trait: Initial Observations
Radiology,
July 1, 2003;
228(1):
208 - 215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Steinberg, F. Barton, O. Castro, C. H. Pegelow, S. K. Ballas, A. Kutlar, E. Orringer, R. Bellevue, N. Olivieri, J. Eckman, et al.
Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia: Risks and Benefits Up to 9 Years of Treatment
JAMA,
April 2, 2003;
289(13):
1645 - 1651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Hoppe, W. Klitz, J. Noble, L. Vigil, E. Vichinsky, and L. Styles
Distinct HLA associations by stroke subtype in children with sickle cell anemia
Blood,
April 1, 2003;
101(7):
2865 - 2869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Driscoll, A. Hurlet, L. Styles, V. McKie, B. Files, N. Olivieri, C. Pegelow, B. Berman, R. Drachtman, K. Patel, et al.
Stroke risk in siblings with sickle cell anemia
Blood,
March 15, 2003;
101(6):
2401 - 2404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Steen, M. A. Miles, K. J. Helton, S. Strawn, W. Wang, X. Xiong, and R. K. Mulhern
Cognitive Impairment in Children with Hemoglobin SS Sickle Cell Disease: Relationship to MR Imaging Findings and Hematocrit
AJNR Am. J. Neuroradiol.,
March 1, 2003;
24(3):
382 - 389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. T. VI, D. C. Tang, S. A. Savage, S. F. Leitman, S. I. Heller, G. R. Serjeant, G. P. Rodgers, and S. J. Chanock
Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease
Blood,
December 15, 2002;
100(13):
4303 - 4309.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Helton, W. C. Wang, L. W. Wynn, R. B. Khan, and R. G. Steen
The Effect of Hydroxyurea on Vasculopathy in a Child with Sickle Cell Disease
AJNR Am. J. Neuroradiol.,
November 1, 2002;
23(10):
1692 - 1696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K A Anie, A Steptoe, S Ball, M Dick, and B M Smalling
Coping and health service utilisation in a UK study of paediatric sickle cell pain
Arch. Dis. Child.,
May 1, 2002;
86(5):
325 - 329.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Dobson, K. R. Holden, P. J. Nietert, J. K. Cure, J. H. Laver, D. Disco, and M. R. Abboud
Moyamoya syndrome in childhood sickle cell disease: a predictive factor for recurrent cerebrovascular events
Blood,
May 1, 2002;
99(9):
3144 - 3150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. Pegelow, E. A. Macklin, F. G. Moser, W. C. Wang, J. A. Bello, S. T. Miller, E. P. Vichinsky, M. R. DeBaun, L. Guarini, R. A. Zimmerman, et al.
Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease
Blood,
April 15, 2002;
99(8):
3014 - 3018.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. B. Segel, M. G. Hirsh, and S. A. Feig
Managing Anemia in a Pediatric Office Practice: Part 2
Pediatr. Rev.,
April 1, 2002;
23(4):
111 - 122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Kean, M. M. Durham, A. B. Adams, L. L. Hsu, J. R. Perry, D. Dillehay, T. C. Pearson, E. K. Waller, C. P. Larsen, and D. R. Archer
A cure for murine sickle cell disease through stable mixed chimerism and tolerance induction after nonmyeloablative conditioning and major histocompatibility complex-mismatched bone marrow transplantation
Blood,
March 1, 2002;
99(5):
1840 - 1849.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Walters, A. W. Nienhuis, and E. Vichinsky
Novel Therapeutic Approaches in Sickle Cell Disease
Hematology,
January 1, 2002;
2002(1):
10 - 34.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
L. C. Boni, R. T. Brown, P. C. Davis, L. Hsu, and K. Hopkins
Social Information Processing and Magnetic Resonance Imaging in Children With Sickle Cell Disease
J. Pediatr. Psychol.,
July 1, 2001;
26(5):
309 - 319.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Wandersee, J. C. Lee, S. A. Deveau, and J. E. Barker
Reduced incidence of thrombosis in mice with hereditary spherocytosis following neonatal treatment with normal hematopoietic cells
Blood,
June 15, 2001;
97(12):
3972 - 3975.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. T. W. Cheung, P. Harmatz, T. Wun, P. C. Y. Chen, E. C. Larkin, R. J. Adams, and E. P. Vichinsky
Correlation of abnormal intracranial vessel velocity, measured by transcranial Doppler ultrasonography, with abnormal conjunctival vessel velocity, measured by computer-assisted intravital microscopy, in sickle cell disease
Blood,
June 1, 2001;
97(11):
3401 - 3404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ferster, P. Tahriri, C. Vermylen, G. Sturbois, F. Corazza, P. Fondu, C. Devalck, M. F. Dresse, W. Feremans, K. Hunninck, et al.
Five years of experience with hydroxyurea in children and young adults with sickle cell disease
Blood,
June 1, 2001;
97(11):
3628 - 3632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Adams
Stroke Prevention and Treatment in Sickle Cell Disease
Arch Neurol,
April 1, 2001;
58(4):
565 - 568.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Schmugge, H. Frischknecht, Y. Yonekawa, R. W. Baumgartner, E. Boltshauser, and J. Humbert
Stroke in hemoglobin (SD) sickle cell disease with moyamoya: successful hydroxyurea treatment after cerebrovascular bypass surgery
Blood,
April 1, 2001;
97(7):
2165 - 2167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Wandersee, A. N. Roesch, N. R. Hamblen, J. de Moes, M. A. van der Valk, R. T. Bronson, J. A. Gimm, N. Mohandas, P. Demant, and J. E. Barker
Defective spectrin integrity and neonatal thrombosis in the first mouse model for severe hereditary elliptocytosis
Blood,
January 15, 2001;
97(2):
543 - 550.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Goldstein, R. Adams, K. Becker, C. D. Furberg, P. B. Gorelick, G. Hademenos, M. Hill, G. Howard, V. J. Howard, B. Jacobs, et al.
Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association
Circulation,
January 2, 2001;
103(1):
163 - 182.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Goldstein, R. Adams, K. Becker, C. D. Furberg, P. B. Gorelick, G. Hademenos, M. Hill, G. Howard, V. J. Howard, B. Jacobs, et al.
Primary Prevention of Ischemic Stroke : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association
Stroke,
January 1, 2001;
32(1):
280 - 299.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Adams, K. Ohene-Frempong, and W. Wang
Sickle Cell and the Brain
Hematology,
January 1, 2001;
2001(1):
31 - 46.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Wayne, S. E. Schoenike, and C. H. Pegelow
Financial analysis of chronic transfusion for stroke prevention in sickle cell disease
Blood,
October 1, 2000;
96(7):
2369 - 2372.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Abstract
Introduction
Abstract
