Pediatric Radiology

, Volume 35, Issue 1, pp 66–72 | Cite as

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

  • Anne Jones
  • Suzanne Granger
  • Don Brambilla
  • Dianne Gallagher
  • Elliott Vichinsky
  • Gerald Woods
  • Brian Berman
  • Steve Roach
  • Fenwick Nichols
  • Robert J. AdamsEmail author
Original Article


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.


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.


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.


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.


Sickle cell disease Stroke Transcranial Doppler Peak systolic velocity 



The authors wish to thank Dana Eller, Rayna Wright, Judi S. Schweitzer, the STOP study investigative team, the patients who made the stroke prevention program possible, and NHLBI that supported the work.


  1. 1.
    Ohene-Frempong K, Weiner SJ, Sleeper LA, et al (1998) Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 91:288–294PubMedGoogle Scholar
  2. 2.
    Caplan LR, Brass LM, DeWitt LD, et al (1990) Transcranial doppler ultrasound: present status. Neurology 40:696–700PubMedGoogle Scholar
  3. 3.
    Adams RJ, McKie VC, Nichols FT, et al (1992) The use of transcranial ultrasonography to predict stroke in sickle cell disease. N Eng J Med 326:605–610Google Scholar
  4. 4.
    Adams RJ, McKie VC, Carl EM, et al (1997) Long-term stroke risk in children with sickle cell disease screened with transcranial Doppler. Ann Neurol 42:699–704PubMedGoogle Scholar
  5. 5.
    Seibert J, Miller S, Kirby R, et al (1993) Cerebrovascular disease in symptomatic and asymptomatic patients with sickle cell anemia: screening with duplex transcranial Doppler US—correlation with MR imaging and MR angiography. Radiology 189:457–466PubMedGoogle Scholar
  6. 6.
    Verlhac S, Bernaudin F, Tortrat D, et al (1995) Detection of cerebrovascular disease in patients with sickle cell disease using transcranial Doppler sonography: correlation with MRI, MRA and conventional angiography. Pediatr Radiol 25:14–19Google Scholar
  7. 7.
    Adams RJ, Brambilla DJ, McKie VC, et al (1998) Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 339:5–11CrossRefPubMedGoogle Scholar
  8. 8.
    NHLBI Communications Office (1997) Clinical alert from the National Heart, Lung, and Blood Institute. Department of Health and Human Services, National Institutes of Health, Bethesda, MDGoogle Scholar
  9. 9.
    Nichols FT, Jones AM, Adams RJ (2001) Stroke prevention in sickle cell disease (STOP) study guidelines for transcranial Doppler testing. J Neuroimaging 11:354–362PubMedGoogle Scholar
  10. 10.
    Aaslid R, Markwalder TM, Nornes H (1982) Non-invasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 57:769–774PubMedGoogle Scholar
  11. 11.
    Jones AM, Seibert JJ, Nichols FT, et al (2001) Comparison of transcranial color Doppler imaging (TCDI) and transcranial Doppler (TCD) in children with sickle cell anemia. Pediatr Radiol 31:461–469CrossRefPubMedGoogle Scholar
  12. 12.
    Bulas DI, Jones A, Siebert JJ, et al (2000) Transcranial Doppler (TCD) screening for stroke prevention in sickle cell anemia: pitfalls in technique variation. Pediatr Radiol 30:733–738CrossRefPubMedGoogle Scholar
  13. 13.
    Neish A, Blews DE, Sims CA, et al (2002) Screening for stroke in sickle cell anemia: comparison of transcranial Doppler imaging and non-imaging US techniques. Radiology 222:709–714PubMedGoogle Scholar
  14. 14.
    Adams RJ, McKie VC, Brambilla DJ, et al (1997) Stroke prevention trial in sickle cell anemia (“STOP”): study design. Control Clin Trials 19:110–129CrossRefGoogle Scholar
  15. 15.
    Pegelow CH, Adams RJ, McKie V, et al (1995) Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions. J Pediatr 126:896–899PubMedGoogle Scholar
  16. 16.
    Adams RJ, Brambilla DJ, Granger S, et al, for the STOP Study Investigative Team (2004) Stroke and conversion to high risk in children screened with transcranial Doppler ultrasound during the STOP study. Blood 103:3689–3994CrossRefPubMedGoogle Scholar
  17. 17.
    Adams RJ, Nichols FT, Figueroa R, et al (1992) Transcranial Doppler correlation with cerebral angiography in sickle cell disease. Stroke 23:1073–1077PubMedGoogle Scholar
  18. 18.
    Seibert JJ, Glasier CM, Kirby RS, et al (1998) Transcranial Doppler, MRA, and MRI as a screening examination for cerebrovascular disease in patients with sickle cell anemia: an 8-year study. Pediatr Radiol 28:138–142CrossRefPubMedGoogle Scholar
  19. 19.
    Adams RJ, Pavlakis S, Roach ES (2003) Sickle cell disease and stroke: primary prevention and transcranial Doppler. Ann Neurol 54:559–563CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Anne Jones
    • 1
  • Suzanne Granger
    • 2
  • Don Brambilla
    • 2
  • Dianne Gallagher
    • 2
  • Elliott Vichinsky
    • 3
  • Gerald Woods
    • 4
  • Brian Berman
    • 5
  • Steve Roach
    • 6
  • Fenwick Nichols
    • 7
  • Robert J. Adams
    • 1
    Email author
  1. 1.Medical College of GeorgiaAugustaUSA
  2. 2.New England Research InstitutesData Coordinating CenterWatertownUSA
  3. 3.Children’s Hospital of OaklandDepartment of HematologyOaklandUSA
  4. 4.Section of Hematology/OncologyChildren’s Mercy HospitalKansas CityUSA
  5. 5.Pediatric Hematology/OncologyRainbow Babies & Children’s HospitalClevelandUSA
  6. 6.Department of Neurology Medical Center Blvd.Wake Forest University School of MedicineWinston-SalemUSA
  7. 7.Medical College of GeorgiaAugustaUSA

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