Cerebral vessel stenosis in sickle cell disease: criteria for detection by transcranial Doppler

Ischemic stroke is a common and disabling complication of sickle cell disease (Hb SS). Most infarctions occur in the presence of intracranial stenotic lesions of the large vessels of the circle of Willis. Transcranial Doppler (TCD), by measuring flow velocity in these arterial segments, can detect focal stenosis on the basis of elevated flow velocity. We report the preliminary results of a prospective study to develop criteria for detection of stenotic lesions based on TCD and identification of patients with Hb SS at risk for stroke. Comparing the TCD findings from six patients with lesions demonstrated by angiography to those from 115 Hb SS children without stroke, we conclude: (a) middle cerebral (MCA), anterior cerebral (ACA), or internal carotid (ICA) artery mean velocities greater than 190 cm/s strongly suggest focal stenosis; (b) MCA or ACA mean velocities of 150 to 190 cm/s suggest abnormality but at present cannot be considered diagnostic of stenosis; (c) mean velocities up to 150 cm/s are possibly due to the effects of low hematocrit and/or young age, and cannot as yet be distinguished from velocity elevations due to vessel stenosis.     

Can peak systolic velocities be used for prediction of stroke in sickle cell anemia?

Background and purpose Ischemic stroke occurs in at least 11% of patients with homozygous sickle cell anemia (SCD) by the time they turn 20 years old. High risk associated with distal intracranial internal carotid (ICA) and proximal middle cerebral artery (MCA) stenosis can be detected by transcranial Doppler (TCD). TCD screening offers the possibility of reducing the risk of first stroke significantly based on a paradigm tested and proven to be effective in a stroke prevention trial in sickle cell anemia (STOP). Children with high flow velocity in the ICA and MCA of 200 cm/s time average mean of the maximum (TAMM) or higher had a 10% per year risk of first stroke that was reduced to <1% with regular red cell transfusion (reduction of hemoglobin S <30%). The clinical application of the STOP results could be enhanced if criteria for treatment could be found that are based on peak systolic velocity (PSV), the measure more commonly used in vascular ultrasound practice.Objective To compare PSV and end diastolic velocity (EDV) with TAMM for prediction of stroke and to derive PSV cutpoints for STOP protocol definitions of conditional and abnormal TCD. Using the STOP TCD and stroke outcome data to compare PSV and TAMM in terms of stroke prediction, PSV cutpoints comparable to those based on TAMM and used in STOP were derived. Because of their familiarity to the vascular ultrasound community, PSV cutpoints should be an important alternative to TAMM and may increase availability of screening and risk stratification for children with this disease.Materials and methods Data from 1,937 baseline TCD studies from STOP were correlated with stroke outcome in those not treated with transfusion. Stroke prediction was assessed with survival analysis using TAMM, PSV and EDV as continuous variables individually and then pair-wise in the same model, which contained 53 stroke events.Results PSV and EDV were highly correlated to the TAMM velocity (r=0.94). The multivariate model for prediction indicated that TAMM velocity was a better predictor than EDV, and PSV and TAMM were approximately equivalent. PSV cutpoints defining the two relevant STOP risk categories—conditional, which should lead to increased TCD surveillance, and abnormal, which should lead to strong consideration for treatment according to STOP—were derived taking into consideration known differences in measurements between the dedicated Doppler systems (TCD) used in STOP and the transcranial Doppler imaging (TCDI) systems commonly used in clinical practice. The recommended PSV cutpoint for conditional TCD is 200 cm/s, and for abnormal TCD triggering consideration for treatment is 250 cm/s.Conclusion Assuming TCDI equipment is used and the STOP protocol is applied, a PSV cutpoint of 200 cm/s is recommended as the threshold for increased TCD surveillance (comparable to a TCD TAMM of 170 cm/s in STOP); a PSV of 250 cm/s is recommended as the cutpoint at which, if confirmed in a second examination, chronic transfusion should be considered. Assuming the STOP scanning protocol is used, PSV is at least as good as TAMM and can be used to select children with SCD for treatment or increased surveillance to prevent first stroke.     

Detection of cerebrovascular disease in patients with sickle cell disease using transcranial Doppler sonography: correlation with MRI,MRA and conventional angiography

A prospective study of 58 patients with sickle cell disease (SCD) by transcranial Doppler sonography (TCD) included both MRI and MRA in patients over 7 years of age and those with abnormal TCD. Arteriography was performed in cases where a stenosis was suspected on TCD. Middle cerebral artery (MCA) and basilar artery (BA) velocities were significantly higher in the sickle cell hemoglobin SS group than in the hemoglobin SC group. Patients with a MCA mean velocity of over 1.90 m/s had stenoses found by arteriography. Patients with unilaterally undetectable MCA flow had experienced a stroke and MCA thrombosis was confirmed at MRA and arteriography. We concluded that TCD is valuable in detecting arterial stenosis in SCD and will lead to consideration of these patients for intensive therapy, such as bone marrow transplantation (BMT) or transfusion regimes.

     

Intra-individual variation in blood flow velocities in cerebral arteries of children with sickle cell disease

BACKGROUND: Children with sickle cell disease (SCD) are at elevated risk of stroke. Risk increases with blood flow velocity in selected cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, and use of TCD to screen these patients is widely recommended. Interpretation of TCD results should be based on knowledge of intra-individual variation in blood flow velocity, information not currently available for sickle cell patients. PROCEDURES: Between 1995 and 2002, 4,141 subjects, 2-16 years old, with homozygous SCD or Sbeta0-thalasemmia and no history of stroke were screened with TCD, including 2,018 subjects screened in one clinical trial (STOP), 1,816 screened in another (STOP 2), and 307 screened in an interim ancillary prospective study. The 812 subjects with >or=2 examinations<6 months apart were selected for analysis, including 242 (29.8%) subjects with normal average velocities (i.e., <170 cm/sec), 350 (43.1%) subjects with conditional velocities (i.e., 170-199 cm/sec), and 220 (27.1%) subjects with abnormal velocities (i.e., >or=200 cm/sec). The intra-subject standard deviation of TCD velocity was estimated from the difference between velocities at the first two interpretable examinations on each subject. RESULTS: An intra-subject standard deviation of 14.9 cm/sec was obtained. Seven (0.9%) subjects had unusually large and unexplained differences between velocities at the two examinations (range of absolute differences: 69-112 cm/sec). CONCLUSIONS: While stroke risk is well demonstrated to increase with increasingly abnormal TCD velocity, given the relatively large intra-subject variability, one TCD examination is generally not sufficient to characterize stroke risk in this patient population.     

Transcranial Doppler, MRA, and MRI as a screening examination for cerebrovascular disease in patients with sickle cell anemia: an 8-year study

Objective. The authors previously reported five transcranial Doppler ultrasonography (TCD) findings as significant in detecting clinical cerebrovascular disease in a 4-year study in patients with sickle cell disease. This is a follow-up to evaluate the validity of the original findings over another 4-year period during which the study population doubled. A clinical follow-up of the original asymptomatic sickle cell patients with positive TCD, MRA, and MRI was also made. Materials and methods. Over an 8-year period TCD, MRI, and MRA were prospectively performed in 90 sickle cell patients who were clinically asymptomatic for stroke and in 27 sickle cell patients with clinical stroke. Results. Of the 4 out of original 46 control patients in 1992 who had positive MRA and TCD, 3 have subsequently had clinical stroke. None of the 9 original patients with positive TCD and positive MRI but negative MRA have developed stroke. All five original TCD indicators of disease were still significant (P < 0.05) for detecting clinical disease: maximum velocity in ophthalmic artery (OA) > 35 cm/s, mean velocity in middle cerebral artery (MCA) > 170 cm/s, resistive index (RI) in OA < 50, velocity in OA greater than in MCA, and velocity in posterior cerebral (PCA), vertebral, or basilar arteries greater than in MCA. Four additional factors were also significant: turbulence, PCA or ACA without MCA, RI < 30, and maximum velocity in MCA > 200 cm/s. Conclusion. Positive MRA with a positive TCD in an asymptomatic patient in long-term follow-up suggests a trend for developing clinical stroke. A 4- to 8-year follow-up of nine patients with positive TCD, positive MRI, but not positive MRA did not show development of clinical stroke. Nine Doppler findings are significant in screening for clinically symptomatic vascular disease in sickle cell patients. It is recommended that children with sickle cell disease be screened for cerebrovascular disease with TCD. If one or two indicators of abnormality are present, MRA is recommended. If the MRA is positive, the patient may be considered for transfusion therapy or other treatment for prevention of stroke. Received: 17 April 1997 Accepted: 7 July 1997     

Hydroxyurea therapy lowers TCD velocities in children with sickle cell disease

INTRODUCTION: Hydroxyurea (HU) improves hematologic parameters and decreases adverse events in patients with sickle cell disease (SCD). HU has been proposed as an alternative to chronic transfusions for secondary stroke prevention. Transcranial doppler (TCD) is an accepted method of stroke risk stratification in patients with SCD. We sought to determine if HU affects TCD velocities in children with SCD. METHODS: A cohort of 24 children with HbSS with a baseline TCDi prior to HU and a follow-up after at least 6 months of therapy was analyzed. Twenty-four age-matched children with HbSS formed the control group. Differences in hematologic parameters before and after HU therapy were evaluated. RESULTS: TCDi velocities decreased in the HU-treated patients. The adjusted mean change in TCDi velocities was -13.0 cm/sec (95% CI -20.19, -5.92) in the HU-treated group and +4.72 cm/sec (95% CI -3.24, 12.69) in the controls. Changes in TCDi between the two groups were statistically significant (P < 0.001). Changes in hematologic parameters were not predictive of changes in TCDi velocities in the treated patients. Four out of five patients with TCDi velocities >170 cm/sec had normalization of TCDi velocities on HU. Mean change was -34.75 cm/sec in this subgroup. No patients experienced cerebrovascular accidents (CVA) while on HU. CONCLUSIONS: HU-treated patients experienced statistically significant decreases in TCDi velocities compared to age-matched controls. Changes in hematologic parameters were not predictive of changes in TCDi velocities in the treated group. The decrease in TCDi velocities is not a consequence of changes in hematologic values in patients treated with HU.     

Transcranial Doppler scanning and the assessment of stroke risk in children with HbSC [corrected] disease.

OBJECTIVE: To assess the role of transcranial Doppler (TCD) scanning in assessing the risk of stroke in children with haemoglobin SC (HbSC) disease. TCD scanning has an established role in primary stroke prevention in sickle cell anaemia but its value in HbSC is unknown. DESIGN: A retrospective audit of routinely performed TCD scans and routinely collected clinical data. SETTING: A paediatric sickle cell clinic in a teaching hospital in south London, UK. PATIENTS: 46 children with HbSC disease who have undergone routinely performed TCD scans and steady-state blood tests. MAIN OUTCOME MEASURES: The time-averaged mean of the maximum velocity (TAMMV) in the middle cerebral artery circulation correlated with clinical and laboratory data. RESULTS: The mean TAMMV was 94 cm/s, with a 98(th) centile of 128 cm/s. This is significantly less than the published ranges for HbSS, with a mean reading of 129 cm/s. One child had a stroke at the age of 5 years, when her TAMMV was measured at 146 cm/s. CONCLUSIONS: Further studies are needed to assess stroke risk in HbSC disease, but we suggest that TCD measurements are potentially useful in this condition, and that readings greater than 128 cm/s are abnormally high and warrant further investigation.     

Reversible posterior leuko‐encephalopathy in children with sickle cell disease

Children with sickle cell disease (SCD) have high risk of neurologic morbidity and mortality, such as strokes, silent infarcts and TIA's. A retrospective review of magnetic resonance imaging and magnetic resonance angiography identified eight children with radiological and clinical characteristics of reversible posterior encephalopathy (RPLS). These patients had no evidence of previous cerebral infarcts or vasculopathy. Three have died during the 5‐year follow up; one developed a stroke and one a conditional TCD. RPLS needs to be considered in the differential diagnosis of children with SCD that present with acute neurological changes, especially if they are already been hospitalized. Pediatr Blood Cancer 2009;52:373–375. © 2008 Wiley‐Liss, Inc.     

Transient stenoses and occlusions of main cerebral arteries in children —diagnosis and control of therapy by transcranial Doppler sonography

Flow disturbances in main cerebral arteries may cause severe neurological symptoms. Using transcranial Doppler sonography (TCD) the blood flow velocities in the basal cerebral arteries (BCA) can be recorded at any age. Transient stenoses or occlusions of main cerebral arteries were detected in 11 children by this method and confirmed by other techniques. Vasospasm produced a marked increase in flow velocities in the affected arteries which was reduced by nimodipine, the calcium channel blocker. Vasospasm also occurred in severe bacterial meningitis. In acute hemiplegia due to cerebral arterial obstruction no flow velocities could be recorded at the corresponding site. If distal branches were obstructed reduced flow velocities were found proximally. Increased flow velocities or reversed flow in anastomoses indicated the collateralization. The transient nature of the occlusions was shown by repcated recordings. TCD is a reliable, noninvasive and rapidly available technique for diagnosing or excluding transient flow disturbances in the main cerebral arteries as the cause of neurological symptoms in children. It indicates the necessity and most advantageous stage for therapy.Abbreviations ACA anterior cerebral artery - BCA basal cerebral artery (-ies) - CT computed tomography - ICA internal carotid artery - MCA middle cerebral artery - MFV mean peak flow velocity - PCA posterior cerebral artery - TCD transcranial Doppler sonography     

Transcranial Doppler changes in children with sickle cell disease on transfusion therapy

Transcranial Doppler (TCD) is an effective method for screening patients with sickle cell disease (SCD) at risk for first stroke. Its usefulness in monitoring children with SCD receiving transfusions has not been established. The authors studied 17 children with SCD evaluated with TCDs and magnetic resonance angiograms (MRAs) while receiving transfusion therapy. Patients with normalized TCDs had normal MRAs that remained normal on transfusions. Patients with persistently abnormal TCDs had abnormal MRAs. In these children, TCD velocities decreased but rarely reverted to normal. Patients with low TCD velocities (<70 cm/s) had corresponding vasculopathy on MRA. Low velocities may be a risk factor for stroke and should be followed. Overall, there was good correlation between TCD velocity changes and MRA analysis.     

Arterial spin-labeled perfusion combined with segmentation techniques to evaluate cerebral blood flow in white and gray matter of children with sickle cell anemia

Background

Changes in cerebral perfusion are an important feature of the pathophysiology of sickle cell anemia (SCA); cerebrovascular ischemia occurs frequently and leads to neurocognitive deficits, silent infarcts, and overt stroke. Non‐invasive MRI methods to measure cerebral blood flow (CBF) by arterial spin labeling (ASL) afford new opportunities to characterize disease‐ and therapy‐induced changes in cerebral hemodynamics in patients with SCA. Recent studies have documented elevated gray matter (GM) CBF in untreated children with SCA, but no measurements of white matter (WM) CBF have been reported.

Procedures

Pulsed ASL with automated brain image segmentation‐classification techniques were used to determine the CBF in GM, WM, and abnormal white matter (ABWM) of 21 children with SCA, 18 of whom were receiving hydroxyurea therapy.

Results

GM and WM CBF were highly associated (R² = 0.76, P < 0.0001) and the GM to WM CBF ratio was 1.6 (95% confidence interval: 1.43–1.83). Global GM CBF in our treated cohort was 87 ± 24 mL/min/100 g, a value lower than previously reported in untreated patients with SCA. CBF was elevated in normal appearing WM (43 ± 14 mL/min/100 g) but decreased in ABWM (6 ± 12 mL/min/100 g), compared to published normal pediatric controls. Hemispheric asymmetry in CBF was noted in most patients.

Conclusions

These perfusion measurements suggest that hydroxyurea may normalize GM CBF in children with SCA, but altered perfusion in WM may persist. This novel combined approach for CBF quantification will facilitate prospective studies of cerebral vasculopathy in SCA, particularly regarding the effects of treatments such as hydroxyurea. Pediatr Blood Cancer 2009;52:85–91. © 2008 Wiley‐Liss, Inc.     

Pulsed Doppler sonographic measurement of normal values for the flow velocities in the intracranial arteries of healthy newborns

121 healthy premature born infants and full term newborns (corrected gestational age 29 to 45 weeks, weight at investigation 1070 to 3750 g) were investigated by pulsed Doppler sonography with a 5 MHz transducer. In all infants pulsed Doppler recordings were obtained from the internal carotid arteries (ICA), the basilar artery (BA) and both anterior cerebral arteries (ACA). From the flow profile the maximal systolic velocity (V_s), the endsystolic velocity (V_es) and the enddiastolic velocity (V_ed), the time average velocity (TAV) and the time average maximal velocity (TAMX) as well as the resistance-index (RI) and the pulsatility-index (PI) were measured. For all parameters the relationship to the gestational age was analysed and normal values were established. There was a linear increase of all flow velocities with increasing gestational age. V_s in the ICA was about 20% higher than in the ACA and BA whereas V_es and V_ed were not significantly different in the three arteries. The TAV in the ICA was 9% higher than in the ACA and 15% higher than in the BA. The TAMX in the ICA was 10% higher than in the ACA and 14% higher than in the BA. In contrast to the increase of the flow velocities neither the RI nor the PI showed a significant age dependency. For the RI in the ICA 0.77±0.08, in the ACA 0.73±0.08 and in the BA 0.72±0.09 were measured. The PI in the ICA was 3.0±0.08, in the ACA 2.7±0.09 and in the BA 2.7±0.7. Because of the age dependency of the flow velocities in the cerebral arteries the corrected gestational age must be taken into consideration when pathologic flow velocities are analysed. Presented at the ESPR meeting in Montreux 1988. Selected for publication by an International Group of the ESPR.     

Transcranial Doppler (TCD) screening for stroke prevention in sickle cell anemia: pitfalls in technique variation

Background. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) identified children as being at high stroke risk if the time-averaged maximum mean velocity (TAMMV) of the middle cerebral or intracranial internal carotid arteries measured ≥ 200 cm/s. These values were obtained utilizing a 2-mHz dedicated nonimaging pulsed Doppler technique (TCD) and manual measurements. Questions have been raised as to the comparability of results obtained with different ultrasound machines and measurement techniques.¶Objective. The purpose of this study was to compare nonimaging (TCD) and transcranial duplex imaging (TCDI) findings in children potentially at risk for stroke with sickle cell disease.¶Materials and methods. Twenty-two children with sickle cell disease and no history of stroke were evaluated by both TCD and TCDI. Examinations were performed on the same day without knowledge of the other modality results and read independently using manually obtained measurements. Mean velocities, peak systolic velocities, and end diastolic velocities obtained by the two techniques were compared. In a subgroup, manual measurements were compared to electronically obtained measurements. ¶Results. TCDI values were lower than TCD measurements for all vessels. TCDI TAMMV values were most similar to the TCD values in the middle cerebral artery (–9.0 %) and distal internal cerebral artery (–10.8 %), with greater variability in the anterior cerebral artery (–19.3 %), bifurcation (–16.3 %), and basilar arteries (–23.1 %). Risk group placement based on middle cerebral artery TAMMV values did not change when comparing the two techniques. Measurements obtained electronically were lower than those obtained manually. ¶Conclusion. Velocities obtained by TCDI may be lower than TCD measurements, and these differences should be taken into consideration when performing screening for stroke risk and selection for prophylactic transfusion based on the STOP protocol.     

Management of severe chronic pain with methadone in pediatric patients with sickle cell disease

Vasocclusive pain crises are common among pediatric patients with sickle cell disease (SCD). Some patients with repeated pain crises develop chronic pain. We performed a retrospective cohort study of pediatric patients with SCD with chronic pain treated with methadone. We identified a significant reduction in pain hospitalizations following methadone treatment (0.35 ± 0.19 vs. 0.19 ± 0.17 hospitalizations/month, P = 0.016). In addition, we did not observe overt organ toxicity nor symptoms of opioid withdrawal during methadone wean. We suggest that methadone is safe and has some clinical benefit, which should be proven in prospective randomized trials for pediatric patients with SCD and chronic pain.     

Simultaneous acute splenic sequestration and transient aplastic crisis in children with sickle cell disease

Acute splenic sequestration crisis (ASSC) is a hematological emergency in young children with sickle cell disease (SCD), characterized by worsening anemia and splenomegaly, usually with reticulocytosis and thrombocytopenia. Transient aplastic crisis (TAC) due to parvovirus B19 infection occurs in older children with SCD, and typically manifests as worsening anemia with reticulocytopenia and no splenomegaly. Five older children with SCD (4 HbSC, 1 HbSS on hydroxyurea) developed ASSC concurrent with TAC and had a severe clinical course. Our cases suggest that older children with SCD and acute parvovirus infection should be monitored closely for splenomegaly and multi‐system dysfunction. Pediatr Blood Cancer 2009;53:479–481. © 2009 Wiley‐Liss, Inc.     

Elevated tricuspid regurgitation velocity in congenital hemolytic anemias: Prevalence and laboratory correlates

Elevated tricuspid valve regurgitation jet velocity (TRV ≥ 2.5 m/s) is associated with mortality among adults with sickle cell disease (SCD), but correlative biomarkers are not studied according to treatment exposure or genotypes. To investigate the associations between biomarkers and TRV elevation, we examined the relationship between TRV and hemolytic, inflammatory, and cardiac biomarkers, stratified by disease‐modifying treatments and SCD genotype. In total, 294 participants with SCD (mean age, 11.0 ± 3.7 years) and 49 hereditary spherocytosis (HS; mean age, 22.9 ± 19.75 years) were included for comparison and enrolled. TRV was elevated in 30.7% of children with SCD overall: 18.8% in HbSC/HbSβ⁺‐thalassemia, 28.9% in untreated HbSS/HbSβ⁰‐thalassemia, 34.2% in HbSS/HbSβ⁰‐thalassemia hydroxyurea‐treated, and 57% in HbSS/HbSβ⁰‐thalassemia chronic transfusion treated. TRV was elevated in 10.7% and 27.8% in HS children and adults, respectively. In children with SCD, elevated TRV was correlated with hemoglobin (odds ratio [OR] = 0.78, P = 0.004), lactate dehydrogenase (LDH; OR = 2.52, P = 0.005), and N‐terminal pro‐brain natriuretic peptide (NT‐pro BNP; OR = 1.003, P = 0.004). In multivariable logistic regression, adjusting for genotype, sex, hemolytic index, and treatment, hemoglobin concentration remained the only significant variable associated with elevated TRV in untreated HbSS/HbSβ⁰‐thalassemia participants. TRV was not associated with inflammatory markers, other markers of hemolysis, or NT‐pro BNP in untreated HbSS/HbSβ⁰‐thalassemia. Neither hemoglobin nor LDH was associated with TRV in HbSC/HbSβ⁺‐thalassemia. These results suggest that elevated TRV is influenced by the degree of anemia, possibly reflecting sickling as part of the disease pathophysiology. Prospective studies should monitor hemoglobin concentration as children with SCD age into adulthood, prompting initiation of TRV screening and monitoring.     

Diverse manifestations of acute sickle cell hepatopathy in pediatric patients with sickle cell disease: A case series

The hepatic complications of sickle cell disease (SCD) are associated with increased morbidity and mortality in adults; children usually survive but may suffer significant sequelae. Few diagnostic tools differentiate the various hepatic manifestations of SCD. Why patients exhibit one hepatic pathology versus another is unclear. We report four pediatric patients with hemoglobin SS disease with diverse manifestations of acute hepatic involvement including acute sickle hepatic crisis, hepatic sequestration, sickle cell intrahepatic cholestasis, and a non‐SCD cause of hepatopathy in a patient with viral hepatitis. These complications require a systematic approach to extensive evaluation and coordinated multidisciplinary care.     

Chronically Transfused Pediatric Sickle Cell Patients are Protected from Cardiac Iron Overload

Iron overload is a major toxicity of chronic transfusions. Myocardial iron overload is associated with cardiac dysfunction. Cardiac and liver magnetic resonance imaging (MRI) was performed on 14 chronically transfused sickle cell disease (SCD) and non-sickle cell disease (non-SCD) patients seen at Vanderbilt Children's Hospital from 1 January 2000 to 10 March 2010. Retrospective review was conducted to assess cardiac T2*, liver T2*, ventricular dimensions and function, echocardiogram, length of transfusion, hemoglobin, and ferritin measurements. Ten patients had SCD and 4 had non-SCD, including α-thalassemia, β-thalassemia, and Diamond-Blackfan anemia. Cardiac T2* was normal in all SCD patients (mean 39 ± 12 ms), but abnormal in 3 of 4 non-SCD patients (mean 11.8 ± 2.4 ms). Liver T2* was similar between SCD (mean 6.2 ± 1.6 ms) and non-SCD patients (mean 5.9 ± 1.9 ms), and did not correlate with serum ferritin. Comparing SCD and non-SCD patients with similar transfusion duration, SCD patients had normal cardiac T2* and non-SCD patients had abnormal cardiac T2*. No patients had cardiomyopathy, but ventricular dilatation was common among SCD patients. Chronically transfused pediatric SCD patients are relatively spared of myocardial iron overload, which is unlikely to be due to lower total body iron burden in SCD patients than non-SCD patients.     

Long-term follow-up of pediatric sickle cell disease patients with abnormal high velocities on transcranial Doppler

Cerebral arteriopathy can be detected in children with sickle cell disease (SCD) by transcranial Doppler (TCD). Abnormally high velocities are predictive of high stroke risk, which can be reduced by transfusion therapy. We report the results of the screening of 291 SCD children followed in our center, including the clinical and imaging follow-up of 35 children with abnormal TCDs who were placed on transfusion therapy. We postulated that patients with normal MRA findings and abnormal TCD velocities that normalized on a transfusion program could be safely treated with hydroxyurea (HU). We report their outcome (median follow-up of 4.4 years). Of 13 patients with normalized velocities on transfusion, 10 had normal MRAs, and transfusion therapy was stopped and HU begun. Four of these ten patients redeveloped high velocities off transfusion, so currently only six remain transfusion-free. Six other transplanted patients remain transfusion-free. Abnormal TCD velocities detect a high-risk group, justifying the research for suitable transplant donors. Multicenter studies comparing HU therapy to long-term transfusion might help identify which patients can avoid transfusion and its complications while avoiding vasculopathy.