Pial synangiosis for moyamoya syndrome in children with sickle cell anemia: a comprehensive review of reported cases

2014 ◽  
Vol 36 (1) ◽  
pp. E12 ◽  
Author(s):  
Benjamin C. Kennedy ◽  
Michael M. McDowell ◽  
Peter H. Yang ◽  
Caroline M. Wilson ◽  
Sida Li ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Brain Ischemia ◽  
Sickle Cell Anemia ◽  
Transcranial Doppler ◽  
Pediatric Patients ◽  
Significant Risk ◽  
Moyamoya Syndrome ◽  
Transfusion Therapy ◽  
Comprehensive Review

Object Pediatric patients with sickle cell anemia (SCA) carry a significant risk of developing moyamoya syndrome (MMS) and brain ischemia. The authors sought to review the safety and efficacy of pial synangiosis in the treatment of MMS in children with SCA by performing a comprehensive review of all previously reported cases in the literature. Methods The authors retrospectively reviewed the clinical and radiographic records in 17 pediatric patients with SCA treated at the Morgan Stanley Children's Hospital of New York (MSCHONY) who developed radiological evidence of MMS and underwent pial synangiosis between 1996 and 2012. The authors then added any additional reported cases of pial synangiosis for this population in the literature for a combined analysis of clinical and radiographic outcomes. Results The combined data consisted of 48 pial synangiosis procedures performed in 30 patients. Of these, 27 patients (90%) presented with seizure, stroke, or transient ischemic attack, whereas 3 (10%) were referred after transcranial Doppler screening. At the time of surgery, the median age was 12 years. Thirteen patients (43%) suffered an ischemic stroke while on chronic transfusion therapy. Long-term follow-up imaging (MR angiography or catheter angiography) at a mean of 25 months postoperatively was available in 39 (81%) treated hemispheres. In 34 (87%) of those hemispheres there were demonstrable collateral vessels on imaging. There were 4 neurological events in 1590 cumulative months of follow-up, or 1 event per 33 patient-years. In the patients in whom complete data were available (MSCHONY series, n = 17), the postoperative stroke rate was reduced more than 6-fold from the preoperative rate (p = 0.0003). Conclusions Pial synangiosis in patients with SCA, MMS, and brain ischemia appears to be a safe and effective treatment option. Transcranial Doppler and/or MRI screening in asymptomatic patients with SCA is recommended for the diagnosis of MMS.

scholarly journals Effectiveness of surgical revascularization for stroke prevention in pediatric patients with sickle cell disease and moyamoya syndrome

2017 ◽  
Vol 20 (3) ◽  
pp. 232-238 ◽  
Author(s):  
Wuyang Yang ◽  
Risheng Xu ◽  
Jose L. Porras ◽  
Clifford M. Takemoto ◽  
Syed Khalid ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Pediatric Patients ◽  
Moyamoya Syndrome ◽  
Cell Disease ◽  
Surgical Revascularization ◽  
Transfusion Therapy ◽  
Indirect Revascularization

OBJECTIVESickle cell disease (SCD) in combination with moyamoya syndrome (MMS) represents a rare complication of SCD, with potentially devastating neurological outcomes. The effectiveness of surgical revascularization in this patient population is currently unclear. The authors’ aim was to determine the effectiveness of surgical intervention in their series of SCD-MMS patients by comparing stroke recurrence in those undergoing revascularization and those undergoing conservative transfusion therapy.METHODSThe authors performed a retrospective chart review of patients with MMS who were seen at the Johns Hopkins Medical Institution between 1990 and 2013. Pediatric patients (age < 18 years) with confirmed diagnoses of SCD and MMS were included. Intracranial stroke occurrence during the follow-up period was compared between surgically and conservatively managed patients.RESULTSA total of 15 pediatric SCD-MMS patients (28 affected hemispheres) were included in this study, and all were African American. Seven patients (12 hemispheres) were treated with indirect surgical revascularization. The average age at MMS diagnosis was 9.0 ± 4.0 years, and 9 patients (60.0%) were female. Fourteen patients (93.3%) had strokes before diagnosis of MMS, with an average age at first stroke of 6.6 ± 3.9 years. During an average follow-up period of 11.6 years, 4 patients in the conservative treatment group experienced strokes in 5 hemispheres, whereas no patient undergoing the revascularization procedure had any strokes at follow-up (p = 0.029). Three patients experienced immediate postoperative transient ischemic attacks, but all recovered without subsequent strokes.CONCLUSIONSIndirect revascularization is suggested as a safe and effective alternative to the best medical therapy alone in patients with SCD-MMS. High-risk patients managed on a regimen of chronic transfusion should be considered for indirect revascularization to maximize the effect of stroke prevention.

scholarly journals Encephaloduroarteriosynangiosis and encephalomyoarteriosynangiosis for treatment of moyamoya syndrome in pediatric patients with sickle cell disease

2015 ◽  
Vol 16 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Christoph J. Griessenauer ◽  
Jeffrey D. Lebensburger ◽  
Michelle H. Chua ◽  
Winfield S. Fisher ◽  
Lee Hilliard ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Stroke Prevention ◽  
Pediatric Patients ◽  
Case Series ◽  
Secondary Stroke Prevention ◽  
Moyamoya Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
The Mean

OBJECT Pediatric patients with sickle cell disease (SCD) and moyamoya syndrome (MMS) are at significant risk for cerebrovascular accidents despite chronic transfusion therapy. Encephaloduroarteriosynangiosis (EDAS) and encephalomyoarteriosynangiosis (EMAS) are additional therapeutic options for these patients. To date, the incidence of complications after and efficacy of EDAS and EMAS in stroke prevention in this population have been described in several institutional case series reports, but no randomized prospective trials have been reported. METHODS The authors retrospectively reviewed the cases of all pediatric patients at the University of Alabama at Birmingham with a history of homozygous hemoglobin S (HbS) and sickle cell/β-thalassemia (SB0 thalassemia) and on chronic transfusion therapy, including 14 patients with MMS who underwent EDAS or EMAS. RESULTS Sixty-two patients with SCD and on chronic transfusion therapy were identified. After exclusion of patients on chronic transfusion therapy for indications other than stroke prevention, 48 patients (77.4%) remained. Of those patients, 14 (29.1%) underwent EDAS or EMAS. Nine (18.8%) and 25 (52.1%) patients were on chronic transfusion therapy for primary or secondary stroke prevention, respectively, but did not undergo EDAS or EMAS. The 14 patients with SCD and radiological evidence of MMS and on chronic transfusion therapy for primary or secondary stroke prevention underwent 21 EDAS or EMAS procedures for progressive vascular disease (92.9% of patients), stroke (71.4%), and/or seizure (7.1%). The mean (± SD) time from initiation of chronic transfusion therapy to EDAS or EMAS was 76.8 ± 58.8 months. Complications included 1 perioperative stroke, 1 symptomatic subdural hygroma, 1 postoperative seizure, and 1 case of intraoperative cerebral edema that required subsequent cranioplasty. Before EDAS or EMAS, the stroke rate was calculated to be 1 stroke per 7.8 patient-years. One additional stroke occurred during the follow-up period (mean follow-up time 33.7 ± 19.6 months), resulting in a post-EDAS/EMAS stroke rate of 1 stroke per 39.3 patient-years, a 5-fold reduction compared with that in the pre-EDAS/EMAS period. The patients’ mean pre-EDAS/EMAS HbS level of 29.5% ± 6.4% was comparable to the mean post-EDAS/EMAS HbS level of 25.5% ± 6.1% (p = 0.104). CONCLUSIONS The results of this retrospective case series in a large cohort of pediatric patients with SCD and MMS suggest that EDAS/EMAS provides a stroke-prevention benefit with an acceptably low morbidity rate. Given the combined experience with EDAS and EMAS for this indication at this and other institutions, a prospective clinical trial to assess their efficacy compared with that of chronic transfusion therapy alone is warranted.

Surgical treatment of moyamoya syndrome in patients with sickle cell anemia: outcome following encephaloduroarteriosynangiosis

2008 ◽  
Vol 1 (3) ◽  
pp. 211-216 ◽  
Author(s):  
Todd C. Hankinson ◽  
Leif-Erik Bohman ◽  
Geoffrey Heyer ◽  
Maureen Licursi ◽  
Saadi Ghatan ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Significant Risk ◽  
Moyamoya Syndrome ◽  
Effective Treatment Option ◽  
Left Lower Extremity ◽  
Cerebrovascular Complications ◽  
Period 2 ◽  
Ischemic Attack

Object Children with sickle cell anemia (SCA) and moyamoya syndrome carry a significant risk of ischemic stroke. Given the success of encephaloduroarteriosynangiosis (EDAS) or pial synangiosis in the treatment of moyamoya disease, the purpose of this study was to examine whether it reliably and durably protected children with SCA and moyamoya syndrome against cerebrovascular complications. Methods The authors retrospectively reviewed a series of 12 patients with SCA who developed clinical and/or radiological evidence of moyamoya syndrome and underwent EDAS. Results Eleven patients (92%) presented following a cerebrovascular accident (CVA), transient ischemic attack (TIA), or seizure. Magnetic resonance (MR) imaging or angiography suggested moyamoya vascular changes, and cerebral angiography confirmed the diagnosis in all 12 patients. At the time of surgery, the median age was 12.3 years (range 6.8–19.4 years). Ten (83%) of 12 patients had a history of CVA, and 4 of these patients were compliant with a transfusion protocol at the time of their CVA. Bilateral (7 patients) or unilateral (5 patients) EDAS was performed without complications. The mean follow-up period was 46.8 months (range 8.1–106 months). During the follow-up period, 2 patients (16.7%) suffered cerebrovascular events. One patient, who was stroke-free preoperatively, suffered a CVA 3 weeks after the procedure. The other patient suffered a single left lower-extremity TIA 18 months following right-sided EDAS. She returned to her neurological baseline condition and remains stable 53 months postoperatively. Seven patients underwent follow-up angiography or MR angiography, and evidence of revascularization was noted in all cases. At this time, no patient has developed progressive disease requiring a contralateral procedure after unilateral EDAS. Conclusions The EDAS procedure is a safe and effective treatment option in patients with SCA who develop moyamoya syndrome.

Transcranial Doppler in Sickle Cell Anemia Adult Patients: Brazilian Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3736-3736
Author(s):  
Gisele S. Silva ◽  
Maria S. Figueiredo ◽  
Perla Vicari ◽  
Airton R. Massaro ◽  
Adauto Castelo Filho ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transcranial Doppler ◽  
Stroke Risk ◽  
Arterial Disease ◽  
Neurological Complications ◽  
Adult Patients ◽  
History Of ◽  
The Mean

Abstract Sickle cell anemia (SCA) may cause a variety of neurological complications, including stroke and headaches. Stroke occurs in up to 9% of children with SCA, and transcranial Doppler (TCD) studies have demonstrated that increased velocities are related to higher stroke risk. Throbbing headache occurs in SCA but its cause, frequency, and relationship to TCD velocities have received little attention. On the other hand, there are few TCD studies in adult patients. Our aims were: 1) to describe the main features of TCD in adult SCA patients, and 2) to investigate if there were correlation between TCD features and presence of headache. TCD was performed in 56 adult SCA patients (≥ 16 years old) and in 56 healthy individuals (HI), matched by age and race. There were 6 patients with a remote history of stroke but none were on chronic transfusion. The SCA group was submitted to a neurological evaluation and specifically asked about the occurrence of headache and its characteristics. The highest flow velocity (maxFV) recorded for each artery was considered the most representative. We analyzed the frequency of FV asymmetry (side-to-side difference > 20%) and focal FV changes. The mean maxFV was significantly higher in patients (117.7 ± 21.6 cm/s) than in HI (72.45 ± 11.48 cm/s) (p<0.005). Only one patient had maxFV higher than 170 cm/s. The frequencies of asymmetry and of focal FV changes were significantly higher in SCA. Forty-one patients (73.2%) reported having headaches. Twenty-eight patients (50%) had severe (= 5 for pain intensity at a 1–10 scale) and frequent headaches (at least once a month). This group of patients presented TCD velocities significantly higher than patients without or with milder headaches (p=0.035). In conclusion, TCD maxFV was significantly higher in adult patients with SCA than HI, however, only one patient was considered at risk of stroke according to TCD criteria described in children. FV asymmetry and focal FV changes may be markers for arterial disease in adult SCA patients, and need to be further confirmed by neuroimaging and clinical follow up studies. The patients with severe headaches presented TCD velocities significantly higher than patients without or with milder headaches, but this finding needs to be confirmed by more and larger studies.

scholarly journals Outcomes in Children with Severe Vasculopathy from Sickle Cell Anemia after Treatment with Chronic Transfusion, Surgical Revascularization and/or Allogenic Hematopoetic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1098-1098
Author(s):  
Courtney W. Johnson ◽  
Suvankar Majumdar ◽  
Andrew D. Campbell ◽  
Suresh Magge ◽  
Deepika S. Darbari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Research Funding ◽  
Moyamoya Syndrome ◽  
Surgical Revascularization ◽  
Advisory Committees ◽  
Time Of Intervention

Abstract Background: Cerebral vasculopathy is a frequent complication of sickle cell anemia (SCA) and is associated with a high risk for stroke. This vasculopathy seen in SCA can be progressive and severe. Sickle cell patients with severe vasculopathy, including Moyamoya syndrome are at increased risk for neurological disabilities and death. While chronic transfusions decrease the risk of stroke in SCA; unfortunately, progression of vasculopathy can occur despite treatment. Limited data exists regarding long term outcomes for this population. We evaluated effectiveness of three treatment approaches at our center, namely chronic transfusions, surgical revascularization plus chronic transfusions and allogenic hematopoietic stem cell transplant (HSCT). Methods: A retrospective chart review was preformed to identify patients with SCA (hemoglobin SS, Sβ0) and severe vasculopathy including Moyamoya syndrome between 1986 to 2017. Severe vasculopathy was defined as having at least one cerebral artery with > 70% stenosis and/or occlusion as seen on MR angiogram (MRA), CT angiogram (CTA) or conventional angiogram (DSA) as determined by a neuroradiologist at our institution. Patients were identified from an institutional stroke database. Patients were included for analysis if they received at least one of the following: chronic transfusions, surgical revascularization (i.e. encephalo-duro-arterio-synagiosis (EDAS) plus chronic transfusions or HSCT. For HSCT, all graft types (bone marrow, peripheral blood stem cells, umbilical cord blood), conditioning regimens and donor types (related, unrelated and haploidentical) were included. Time to event analyses were performed from the time of intervention (transfusion, HSCT, EDAS/chronic transfusions) using overt clinical stroke, new silent infarcts, progression of vasculopathy or new vasculopathy. Survival curves were analyzed using the log-rank (Mantel-Cox) test. Results: Of 35 patients identified, 54% (n =19) underwent chronic transfusions, 23% (n=8) of patients underwent HSCT after being on chronic transfusions, 23% (n=8) underwent EDAS with chronic transfusions and 1 patient underwent each of the above three modalities (Table 1). Median age at time of intervention was similar for all three cohorts (Table 1). Males were overrepresented in all treatment arms (62.5-79% of patients). Average hemoglobin level prior to intervention was also similar: 7.6 g/dL (IQR 7.1-8.3) for the chronic transfusion cohort, 7.3 gm/dL (IQR 6.3-8.2) for the HSCT cohort, and 7.5 gm/dL (IQR 7.2-8) for the EDAS/chronic transfusion cohort. Absolute reticulocyte count was 492.9 K/ul (IQR 358.4-550) for the chronic transfusion group, 389.4 (IQR 174.3-449) for HSCT, and 250.2 (IQR 107.3-393) for EDAS/chronic transfusions (p=0.08). One patient died of overt stroke in the chronic transfusion cohort. The median follow-up times for the transfusion, HSCT and EDAS plus transfusion groups were 4.4, 2.4 and 6 years respectively. Time from date of intervention (transfusion, HSCT, EDAS) to overt clinical or silent stroke was evaluated (Fig 1). Two of the nineteen patients in the chronic transfusion cohort suffered an overt stroke, while one of eight and two of eight had strokes in the post-HSCT and EDAS plus chronic transfusion cohorts respectively. Fourteen of nineteen (74%) in the chronic transfusion cohort had progression of severe vasculopathy after being on transfusions while two of eight (25%) in the HSCT and four of the eight (50%) patients in the EDAS plus chronic transfusion cohorts had progression. The one patient with all three different interventions did not have additional infarction (clinical or silent) or vasculopathy progression during 1.5 years of follow-up. Conclusions: The risk for cerebral infarction and/or vasculopathy progression after initiation of treatment with either chronic transfusion, HSCT or EDAS is still a major concern. Our data suggest HSCT and surgical revascularization with chronic transfusion provide the greatest benefit in reducing stroke risk and HSCT reduces risk for progression of a severe vasculopathy. Additional, large population studies are needed to clarify the risk. Disclosures Majumdar: NIMHD: Research Funding. Campbell:Functional Fluitics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Variations in the Use of Transcranial Doppler and Chronic Transfusion Therapy for Stroke Prevention in Pediatric Populations at Sickle Cell Centers.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1214-1214
Author(s):  
Andrew E. Mulberg ◽  
Martin Behm ◽  
Catherine Magia ◽  
Robert Adams ◽  
Richard Drachtman ◽  
...  
Keyword(s):  
High Risk ◽  
Sickle Cell ◽  
Transcranial Doppler ◽  
Stroke Prevention ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Transfusion Therapy ◽  
Pediatric Hematology ◽  
Blood Institute ◽  
American Society

Abstract The Stroke Prevention Trial in Sickle Cell Anemia (STOP I) demonstrated a 90% risk reduction of first stroke in high-risk pediatric patients with sickle cell disease (SCD) receiving chronic transfusion therapy (CTT) (Adams RJ et al. N Engl J Med1998;339:5–11). Transcranial Doppler (TCD) is key in assessing the need for CTT in children with SCD. A survey of the American Society of Pediatric Hematology/Oncology found wide variation in how hematologists are managing children with SCD (Lane PA et al. Blood2001;98:784a). Recent recommendations by the National Heart, Lung and Blood Institute (NHLBI) suggest TCD and CTT for stroke prevention in high-risk children with SCD; however, there are no data on the utilization of these guidelines in clinical practice. Therefore, we conducted a telephone survey of Sickle Cell Centers to assess the clinical use of TCD and CTT for stroke prevention in pediatric patients with SCD. Invitations to participate were mailed to Directors of 70 centers; interviews were conducted between December 7, 2005 and February 10, 2006. Results from 25 participating centers were analyzed for trends related to use of TCD and CTT in the care of children with SCD. Questions included frequency of TCD based on velocity: &lt;170 cm/sec, 170–200 cm/sec, and &gt;200 cm/sec (Table). Because some participants could not provide an accurate response, responses are not available for all 25 centers in some cases. Frequency of TCD Sickle Cell Centers N = 25 TCD &lt;170 cm/sec Repeat every 6 mo 4 Repeat yearly 13 Repeat every 1–2 y 4 Repeat every 2 y 1 TCD 170–200 cm/sec Repeat every mo 7 Repeat every 2 mo 3 Repeat every 3 mo 6 Repeat every 4–5 mo 3 Repeat every 6 mo 6 TCD &gt;200 cm/sec Repeat every mo 14 Repeat every 2 mo 1 Repeat every 3 mo 3 Based on clinical observations, participants estimated the percentage of patients with eventual worsening of TCD velocity to &gt;200 cm/sec and the approximate number of months to reach that endpoint. Responses indicated an average of 23% and 11.3 months, respectively. Of the 25 centers, all but one indicated that patients with an abnormal TCD (&gt;200 cm/sec) were typically placed on CTT. Four participants stated that results from the STOP trial were the basis for their decision. Fifteen centers indicated that the youngest age they would initiate CTT was 1–2 years. Only 2 directors would consider CTT in children &lt;1 year, and 3 would not initiate CTT until age 5. Although the NHLBI guidelines suggest a hemoglobin S (Hb S) target of &lt;30%, only 5 directors stated that this was their primary factor in determining frequency of CTT. In terms of typical CTT duration, 68% said therapy was indefinite or lifelong, 20% said &lt;1 year, 4% said 2 years, and 4% said until age 18. Although the number of participants was limited, responses indicate there is a relatively wide variation in the application of the NHLBI recommendations for TCD use and CTT in pediatric patients with SCD. The importance of these findings should be correlated both with a more extensive sample of SCD centers and the reported incidence of stroke in the pediatric population.

Transcranial Doppler Screening Program Is Effective in Preventing Stroke in Children with Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 714-714 ◽  
Author(s):  
Henrietta Enninful-Eghan ◽  
Renee H Moore ◽  
Rebecca Ichord ◽  
Janet L Kwiatkowski
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Transcranial Doppler ◽  
Screening Program ◽  
Treatment Protocol ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Neurological Event ◽  
The Impact

Abstract In the Cooperative Study of Sickle Cell Disease the incidence of stroke in SCD-SS was estimated to be 0.61 per 100 patient-years. Since that study, the use of transcranial Doppler ultrasonography (TCD) has become routine to detect children at high risk of stroke and regular transfusions have been shown to reduce the risk of stroke by over 95% in those with abnormal TCD studies. The impact of TCD screening on the overall incidence of stroke in children with SCD has not been studied extensively. We sought to determine the impact of our TCD screening and treatment protocol on the incidence of first stroke in a cohort of children followed at our Sickle Cell Center. Routine TCD screening was instituted at our Center in Oct, 1998. Our protocol includes annual TCD studies for children with normal TCD results (<170 cm/s), repeat study every 3 to 6 months in those with conditional results (170–199 cm/s), and within 1–4 weeks for children with abnormal results (≥200 cm/s). Chronic transfusion therapy is recommended for patients with confirmed abnormal TCD velocities. In the current study, the rate of stroke in the 8-y period prior to TCD screening (Sept 1, 1990-Aug 31, 1998 – Pre-TCD) was compared to the rate in the 8-y period after TCD screening began (Sept 1, 1998 – Aug 31, 2006 – Post TCD). Eligible subjects were patients less than 22 years old with a diagnosis of SCD-SS or SCD-Sβ0-thalassemia. Subjects with a history of stroke prior to Sept, 1990 or before enrollment in our Center were excluded. Cases of stroke or other neurological event were identified from our clinical database. The study neurologist reviewed all clinical data and radiological studies for each neurological event and classified events into one of the following categories: overt stroke - ischemic (neurological deficit conforming to a vascular territory with neuroimaging studies corresponding to the clinical deficit) or hemorrhagic not overt stroke (other neurological event), and indeterminate. Incidence rates for stroke were calculated and compared between the Pre and Post TCD groups using a test of binomial proportions. Subjects were followed until they had a stroke or neurological event, turned 22 years old, the end of the 8-y period or until the last clinic date. The pre-TCD group included 475 children with a total follow-up time of 3,137 person-years. Twenty-one patients had overt stroke, 3 had other neurologic events (1-seizure, 1-transient ischemic attack/syncope, 1-behavioral changes) and 2 were indeterminate. The post-TCD group included 530 children with 3,578 person-years follow-up. Two patients had overt stroke, 6 had other neurological events [1-diffuse encephalopathy with viral syndrome, 1-febrile seizure, 3-dizzy and/or syncope (one with hgb=2.7), 1-headache with <30 min arm/leg weakness – all with acute punctate infarcts whose location did not correspond to clinical presentation], and 1 was indeterminate. The incidence of overt stroke in the pre-TCD period was 0.67 per 100 person-years, compared with an incidence of 0.06 per 100 person-years in the post-TCD period (p < 0.001). The first stroke case in the post-TCD period was a 3.4 year-old with ACA velocities > 200 cm/s but no abnormal velocities in the ICA/MCA and the second occurred in a 1.2 year-old, prior to the age that screening is started. Thus, our TCD screening and treatment program has been successful in reducing the rate of first overt stroke, although small vessel ischemia, particularly in the setting of an additional insult such as severe anemia, may not be prevented. Further modifications such as the addition of ACA velocity to treatment criteria, earlier screening, or the addition of other neuroimaging studies might further reduce the risk of first stroke.

Hydroxyurea Reduces Conversion From Conditional to Abnormal TCD Velocities In Children with Sickle Cell Anemia (SCA)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 270-270 ◽  
Author(s):  
Jennifer Rothman ◽  
Shelly Burgett ◽  
Russell E. Ware ◽  
Courtney Thornburg
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
Normal Range ◽  
Original Cohort ◽  
Transfusion Therapy ◽  
Hydroxyurea Treatment ◽  
The Mean ◽  
Flow Velocities

Abstract Abstract 270 The use of transcranial Doppler ultrasound (TCD), a non-invasive imaging technique, is now clearly established for detecting high risk of stroke in children with sickle cell anemia (SCA). Children with TCD flow velocities ≥200 cm/s have a 10% risk of primary stroke per year. For these children, chronic blood transfusions (CBT) are recommended and have been shown to reduce the risk of primary stroke by up to 90%. The incidence of stroke has decreased to 0.06–0.17 per 100 patient-years since the institution of TCD screening (Fullerton et al. Blood 2004; Enningul-Egham et al., J Pediatr 2010). Although patients with conditional TCDs (flow velocities 170–199 cm/s) have an estimated stroke risk of 2–5% annually, and their rate of conversion from conditional to abnormal is 23% over an 18 month period (Hankins JS et al., BJH 2008), there are no clinical guidelines for primary stroke prevention in this group. We previously conducted a prospective cohort study of hydroxyurea in 37 children with SCA and TCD velocities >140 cm/sec, and demonstrated that TCD velocities decreased significantly after starting hydroxyurea (Zimmerman et al., Blood 2007; NCT00402480). In order to determine if hydroxyurea provided sustained reductions in TCD velocities, we conducted a retrospective review of these 37 children in this original cohort who had elevated TCD velocities and long-term hydroxyurea treatment. The following data were abstracted from the medical record between April 2000 and September 2009: treatment with hydroxyurea and CBT; adherence with treatments; stroke and non-stroke neurological events; and TCD time-averaged mean velocities (TAMV) immediately prior to initiation of hydroxyurea and at the end of extended follow-up. The primary outcome was comparison of pre and post TCD TAMV using a paired t-test. The mean age of enrollment on the original study was 6.8 years (1.8-14.8) and the mean age at follow-up was 12.9 years (5.3-18.5). The mean follow-up was 5.8 years (0.8-8.5) with an overall follow up of 215.1 patient years. Twenty males and 17 females were enrolled. The mean hydroxyurea dose was 25.2 ± 5.6 mg/kg/day, with one patient discontinuing therapy after 15 months. At follow-up, the mean hemoglobin was 8.9 ± 1.2 g/dL and mean HbF was 16 ± 7.2%. Sustained decreases were observed in both the right MCA (164.8 ± 25.5 cm/s to 124.9 ± 35 cm/s, p<0.001) and left MCA (167.9 ± 25.2 cm/s to 126.9 ± 30 cm/s, p<0.001) for all 37 patients. For the 15 patients with conditional TCD velocities at enrollment, 13 had maximal TAMV that reverted to and were sustained in the normal range (185.8 ± 10.0 cm/s to 132.9 ± 14.5 cm/s, p<0.001). Two converted to abnormal TCD velocities at 1.6 years and 4.5 years for a conversion rate of 13%; one was non-adherent but the other was adherent with hemoglobin of 10.8 g/dL and HbF of 23.5%. These two patients were started on CBT and remain stroke free. There were no primary stroke events observed in the 15 subjects with conditional TCD velocities over a total of 78.1 patient years. Of the 5 patients who had abnormal TCD velocities on enrollment and whose parents refused CBT, 1 patient had a stroke after 0.8 years of hydroxyurea therapy. This was the only patient who continued to have abnormal TCD velocities at MTD, 7 months after starting hydroxyurea. The remaining 4 patients continued to have TCD velocities in the normal range off transfusion therapy over 26.3 patient years. Overall, these data illustrate that treatment with hydroxyurea at MTD in children with SCA and elevated TCD velocities resulted in significantly lower and sustained improvements in TCD velocities. Additionally, for children with conditional TCD velocities, hydroxyurea resulted in a lower than expected conversion to abnormal values, thereby sparing many children from CBT without any noted increase risk of stroke. Hydroxyurea did not, however, protect fully against stroke in one patient who had persistently abnormal TCD velocities and therefore CBT remains the standard of care in this population until larger randomized trials are conducted. Further studies are required to evaluate hydroxyurea for primary stroke prevention in children prior to conversion to abnormal TCD and in children who already have abnormal TCD. The currently funded TCD With Transfusions Changing to Hydroxyurea (TWiTCH) clinical trial, which is scheduled to begin enrollment in late 2010, will help answer this important clinical question. Disclosures: Off Label Use: Hydroxyurea is used to reduce complications of sickle cell anemia.

Academic Community Standards for Chronic Transfusion Therapy In Children with Sickle Cell Anemia and Abnormal Transcranial Doppler Velocities

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2643-2643
Author(s):  
Banu Aygun ◽  
Lisa Wruck ◽  
William Herbert Schultz ◽  
Isaac Odame ◽  
R. Clark Brown ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transcranial Doppler ◽  
Hemoglobin Concentration ◽  
Transfusion Practice ◽  
Academic Community ◽  
Eligibility Criteria ◽  
Transfusion Therapy ◽  
Number Of Patients ◽  
Community Standards

Abstract Abstract 2643 Children with sickle cell anemia (SCA) and abnormal transcranial Doppler (TCD) velocities receive chronic transfusion therapy in an effort to prevent a primary stroke. Typically the goal is maintaining sickle hemoglobin (HbS) <30%, however this goal may be difficult to achieve in actual clinical practice. The NHLBI-sponsored TCD With Transfusions Changing to Hydroxyurea (TWiTCH) trial will compare standard therapy (transfusions) with alternative therapy (hydroxyurea) for the prevention of primary stroke. The transfusions will be given according to current transfusion practices at the participating academic sites. To determine the current academic community standards for primary stroke prophylaxis in children with SCA, 32 potential clinical sites collected data for children with abnormal TCD velocities who are receiving chronic transfusion therapy to prevent a primary stroke. The eligibility criteria included all children with SCA, age 4.0–15.9 years who were on chronic transfusion therapy to prevent a primary stroke due to previous abnormal TCD examination. After IRB-approval, subject and transfusion-related data were collected for all TWiTCH-eligible patients over the 12-month period from 9/1/2008 to 8/31/2009. Variables included year of birth, gender, year chronic transfusions began, TCD velocities that led to transfusion therapy, weight, %HbS transfusion goal, type and volume, pre-transfusion hemoglobin concentration and %HbS, and interval between transfusions. Data were analyzed both “per transfusion” and “per patient.” A total of 3970 transfusions were administered to 340 pediatric patients (mean approximate age at time of survey 10.2 ± 4.1 years, M: F = 0.9:1) over the 12-month period, with a mean of 11.6 ± 2.8 transfusions per patient. The average of the highest TCD velocity that led to transfusion therapy was 221 ± 27 cm/sec. Maximum velocities for right and left hemispheres were 201.2 ± 35.3 and 207.7 ± 31.8 cm/sec, respectively, supporting equal susceptibility. The mean approximate age at the start of transfusion therapy was 6.2 ± 2.6 years with average transfusion duration of 4.0 years. Most children (79%) received primarily simple transfusions, while 19% had primarily exchange transfusions (11% manual and 8% automated), and 2% multiple transfusion types. The transfusion goal was HbS <30% at almost all sites (84%). An equal number of patients developed erythrocyte alloantibodies (13.6%) and autoantibodies (13.7%). Transfusions were considered late if administered later than 7 days beyond the scheduled date. On average, late transfusions were given 1.3 ± 5.5 days after the 7 day allowable window. The average pre-transfusion hemoglobin concentration was 9.0 ± 0.9 gm/dL. The average pre-transfusion %HbS was 34.1 ± 11.2%, with a median value of 32.9%. The 75th percentile for HbS values was 40.9%, while the 90th percentile was 49.5%. There were profound differences among institutional pre-transfusion %HbS values, ranging from 23 ± 14% HbS at one institution where 103 transfusions were given to 9 patients during the 12-month period to 48 ± 15% at another institution where 95 transfusions were administered to 9 patients during the same time frame. These data indicate that current transfusion practice to prevent primary stroke varies among academic pediatric institutions, and 30%HbS is not an easily attainable goal for the TWiTCH study that includes chronic transfusion therapy within the Standard Arm. As a result of this analysis, the TWiTCH study will recommend chronic transfusions with the goal of maintaining HbS <30%, but only record a protocol violation when the HbS value exceeds 45%. Disclosures: Off Label Use: It will include the use of hydroxyurea in children with sickle cell anemia.

Sign in / Sign up

Export Citation Format

Share Document