TRANSCRANIAL DOPPLER SCREENING FOR STROKE RISK IN CHILDREN WITH SICKLE CELL DISEASE: A SYSTEMATIC REVIEW.

Background Sickle cell disease (SCD) is one of the most common causes of stroke in children worldwide. Based on the results of the Stroke Prevention Trial in Sickle Cell Anemia (STOP), annual transcranial Doppler ultrasound (TCD) screening for affected children is standard practice. However, the need for TCD surveillance programs could override the accuracy of the screening, affecting the correct stratification of stroke risk and subsequent clinical management of the target population. Aims To shed light on this issue, a systematic review of the literature on TCD screening for children and adolescents with SCD was carried out (CRD42016050549), according to a list of clinically relevant questions, with a particular focus on screening practices in European countries. Quality of the evidence was rated using the grading of recommendations assessment, development and evaluation. Summary of review Thirty-three studies published in English or French were included (5 randomized controlled trials, 8 experimental non-randomized, and 20 observational studies). The quality of the retrieved evidence ranged between low and high, but was rated as moderate or high most of the times. TCD is effective as a screening tool for the primary prevention of stroke in SCD children. There is no high-quality evidence on the effectiveness of alternative screening methods, such as imaging-TCD with or without angle correction or magnetic resonance angiography. No evidence was found on effectiveness of the screening on children on hydroxyurea and with genotypes other than HbSS and HbS/β0. No European data were found on screening rates or adherence of screening practices to the STOP protocol. Conclusions High-quality studies on alternative screening methods that are currently used in real-world practice, and on screening applicability to specific subgroups of patients are urgently needed. Considering the low awareness of the disease in European countries and the lack of data on screening practices and adherence, clinicians need up-to-date guidelines for more uniform and evidence-based surveillance of children with SCD.

Download Full-text

Transcranial Doppler scanning and the assessment of stroke risk in children with haemoglobin sickle cell disease

Archives of Disease in Childhood ◽

10.1136/adc.2007.125799 ◽

2007 ◽

Vol 93 (2) ◽

pp. 138-141 ◽

Cited By ~ 16

Author(s):

Colin R Deane ◽

David Goss ◽

Sandra O’Driscoll ◽

Sarah Mellor ◽

Keith R E Pohl ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Transcranial Doppler ◽

Stroke Risk ◽

Cell Disease

Download Full-text

Long-term stroke risk in children with sickle cell disease screened with transcranial doppler

Annals of Neurology ◽

10.1002/ana.410420505 ◽

1997 ◽

Vol 42 (5) ◽

pp. 699-704 ◽

Cited By ~ 242

Author(s):

R. J. Adams ◽

V. C. McKie ◽

E. M. Carl ◽

F. T. Nichols ◽

R. Perry ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Transcranial Doppler ◽

Stroke Risk ◽

Cell Disease

Download Full-text

First Report on Elevated Transcranial Doppler Ultrasound Velocities As First Stroke Risk and Their Association with Hemoglobin F Expression in Saudi Arabian Pediatric Sickle Cell Patients

Blood ◽

10.1182/blood.v128.22.3665.3665 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3665-3665

Author(s):

Khalid Al Jamaan ◽

Saleh Al Oraibi ◽

Giuseppe Saglio ◽

Mudassar Iqbal ◽

Zafar Iqbal

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Transcranial Doppler ◽

Stroke Risk ◽

Protective Role ◽

Cell Disease ◽

Hemoglobin F ◽

Female Ratio ◽

Flow Velocities

Abstract Introduction: Sickle cell disease (SCD) is one of the most common inherited hemoglobinopathies in Middle East and specifically Saudi Arabia which leads to vaso-occlusive, hematological and infectious crises, including stroke as one of the common complications (1,2). Primary prevention of the first stroke is carried out by risk assessment using transcranial Doppler (TCD) ultrasound and providing blood transfusions to SCD patients with higher than 199 cm/sec TCD velocities (3). Furthermore, althoughhigher HbF expression is also associated with less severity of the SCD, no studies are available about association of HbF with TCD flow velocities and hence risk of stroke in SCD (4). This study has been carried out to identify SCD patients at high risk of stroke based on TCD results, and to determine the association between Hb-F levels and blood velocity using TCD results. Patients and Methods: Cross-sectional study included 56 pediatric SCD patients. TCD ultrasounds were performed at diagnosis for assessment of first stroke risk and then after every 6 months for follow-up studies. Patients with elevated TCD velocities given monthly packed RBCs transfusions to have HbS level around 40% (5,6). Data analysis was performed by "Statistical Package for the Social Sciences (SPSS, Version 17.0)". Results: In our patient population, male to female ratio was 1.33:1 (32 males, 24 females) and mean age was 7.5 ± 3.42 years (range: 2-14 years). Seven (12.5%) patients had TCD velocities higher than or equal to 200 cm/second, with mean age of 4.7±1.4 years and mean HbF 7.5±3.8, which were significantly different from patient group with normal flow velocities (mean age of 7.8±3.4 years; mean HbF 20±15.9). Patients with higher TCD velocities receiving blood transfusion got velocities in normal range within 6-12 months. Most importantly, normal TCD flow velocities were significantly associated with higher HbF expression and vice versa. As protective role of HbF in sickle cell patients is well established (11;13) and inducing the HbF expression in such patients using medications like hydroxyurea (20) or by genetically modifying the silencing of fetal γ-globin gene have been long standing goal in treatment of sickle cell disease (21), our findings about correlation of higher TCD flow velocities with lower HbF expression (and vice versa) and hence higher risk of first stroke in sickle cell patients provides a new direction for assessing the risk for vasculopathy in SCD patients. Discussion/Conclusions : Low prevalence of SCD patients with higher TCD velocities in our study population is in accordance with previous studies (5). Risk of first stroke was clinically manageable by 6-12 months of regular PRBCs transfusions, per established clinical practice (6). Moreover, normal TCD flow velocities and hence lower risk of stroke was significantly associated with the higher hemoglobin F expression and vice versa. As protective role of HbF in sickle cell patients is well established (4) and inducing the HbF expression in such patients have been long standing goal in treatment of sickle cell disease (7), our findings about correlation of higher TCD flow velocities with lower HbF expression (and vice versa) and hence higher risk of first stroke in sickle cell patients provides a new direction for assessing the risk for vasculopathy in SCD patients. References: 1. Kato GJ. Curr Opin Hematol. 2016 May;23(3):224-32. 2. Ahmed AE, et al. Health Qual Life Outcomes. 2015 Nov 16;13:183. 3. Lawrence C, Webb J. Curr Neurol Neurosci Rep. 2016 Mar;16(3):27. 4. Liu L, et al. Exp Biol Med (Maywood). 2016 Apr;241(7):706-18. 5. Adams R, McKie V, Hsu L, et al. N Engl J Med. 1998;339: 5-11. 6. Bernaudin F, et al. Blood. 2016 Apr7;127(14):1814-22. 7. Pule GD, et al. Clin Transl Med. 2016 Mar;5(1):15. doi: 10.1186/s40169-016-0092-7. Disclosures Saglio: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria.

Download Full-text

An Educational Study Promoting the Delivery of Transcranial Doppler Ultrasound Screening in Paediatric Sickle Cell Disease: A European Multi-Centre Perspective

Journal of Clinical Medicine ◽

10.3390/jcm9010044 ◽

2019 ◽

Vol 9 (1) ◽

pp. 44

Author(s):

Baba P. D. Inusa ◽

Laura Sainati ◽

Corrina MacMahon ◽

Raffaella Colombatti ◽

Maddalena Casale ◽

...

Keyword(s):

Sickle Cell Disease ◽

Doppler Ultrasound ◽

Sickle Cell ◽

Transcranial Doppler ◽

Stroke Risk ◽

Transcranial Doppler Ultrasound ◽

Ultrasound Screening ◽

Cell Disease ◽

Risk Distribution ◽

The Impact

Background: Effective stroke prevention in sickle cell disease (SCD) is recommended for children with sickle cell anaemia. Effective implementation relies on the correct stratification of stroke risk using Transcranial Doppler Ultrasound (TCD), prior to committing children to long-term treatment with transfusion. Nevertheless, less than 50% of children with SCD in Europe receive annual TCD—one of the reasons being a lack of trained personnel. The present European multi-centre study was designed to promote the standardisation and delivery of effective screening. Methods: Fifty-five practitioners from differing professional backgrounds were recruited to the TCD training program. The impact of the training programme was evaluated in three European haematology clinics by comparing stroke risk classification and middle cerebral artery time-averaged maximum velocity (TAMMV) obtained from a cohort of 555 patients, before and after training. Results: 42% (23/55) of trainees successfully completed the program. The TAMMV, used to predict stroke risk at each Centre, demonstrated the highest values in Centre 3 (p < 0.0001) before training. The imaging-TCD TAMMV was also higher in Centre 3 (p < 0.001). Following training, the TAMMV showed closer agreement between centres for both imaging-TCD and non-imaging TCD. The stroke risk distribution of children at each centre varied significantly before training (p < 0.001), but improved after training (Fisher’s Exact: no treatment = 5.6, p = 0.41, treatment = 13.8, p < 0.01). The same consistency in stroke risk distribution following training was demonstrated with both non-imaging and imaging-TCD data. Conclusion: The attainment of competency in stroke screening using transcranial Doppler scanning (TCD) in sickle cell disease is more feasible for professionals with an ultrasound imaging background. A quality assurance (QA) system is required to ensure that standards are maintained. Further work is in progress to develop an achievable and reproducible QA program.

Download Full-text

Sickle cell disease and stroke

Blood ◽

10.1182/blood-2009-05-220921 ◽

2009 ◽

Vol 114 (25) ◽

pp. 5117-5125 ◽

Cited By ~ 87

Author(s):

Luis A. Verduzco ◽

David G. Nathan

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Oxygen Transport ◽

Transcranial Doppler ◽

Stroke Risk ◽

Association Studies ◽

Fetal Hemoglobin ◽

Genome Wide Association Studies ◽

Cell Disease ◽

Transport Efficiency

Abstract Twenty-four percent of sickle cell disease (SCD) patients have a stroke by the age of 45 years. Blood transfusions decrease stroke risk in patients deemed high risk by transcranial Doppler. However, transcranial Doppler has poor specificity, and transfusions are limited by alloimmunization and iron overload. Transfusion withdrawal may be associated with an increased rebound stroke risk. Extended blood typing decreases alloimmunization in SCD but is not universally adopted. Transfusions for thalassemia begun in early childhood are associated with lower rates of alloimmunization than are seen in SCD, suggesting immune tolerance. Optimal oxygen transport efficiency occurs at a relatively low hematocrit for SCD patients because of hyperviscosity. Consequently, exchange rather than simple transfusions are more effective in improving oxygen transport efficiency, but the former are technically more demanding and require more blood units. Although viscosity is of importance in the noncerebral manifestations of SCD, inflammation may play a larger role than viscosity in the development of large-vessel stroke. The future of SCD stroke management lies in the avoidance of transfusion. Hydroxyurea and anti-inflammatory measures may reduce the need for transfusion. Recent genome-wide association studies may provide methods for modulating fetal hemoglobin production enough to attenuate stroke risk and other complications of SCD.

Download Full-text