Cerebral vasculopathy, elevated transcranial Doppler velocities and stroke are linked to excessive intravascular haemolysis in sickle cell anaemia. This study determined the prevalence and pattern of abnormal blood flow velocities in children with sickle cell anaemia from Northern Nigeria using transcranial Doppler and to correlate transcranial Doppler velocities with haematological and biochemical markers of haemolysis.
Methods
Full blood count, reticulocyte count, fetal haemoglobin and some selected biochemical markers of haemolysis of 100 children with sickle cell anaemia were determined at steady state. The time-averaged mean of maximal velocities in four major intracranial blood vessels was measured using non-imaging transcranial Doppler, which were then classified according to the stroke prevention in sickle cell disease trial protocol. A simple linear correlation between time-averaged mean of maximal velocities in the four major intracranial vessels as the dependent variable and haematological and biochemical markers of haemolysis as independent variables was also determined at the significance level of 0.05.
Results
Abnormal transcranial Doppler velocities, classified as high risk, were found in 3% of the studied patients; 11% had intermediate risk while 84% had standard risk. Most high velocities were detected in the middle cerebral artery. The time-averaged mean of maximal velocities of middle cerebral artery positively correlated with total white blood cell count, absolute neutrophil count, platelet count, reticulocyte count, serum lactate dehydrogenase and total bilirubin, while it was negatively correlated with haematocrit and fetal haemoglobin levels.
Conclusion
Our study showed low prevalence of abnormal transcranial Doppler velocities and low prevalence is unrelated to low markers of haemolysis in our study population.
HowardJDaviesS. Sickle cell disease in North Europe. Scand J Clin Lab Invest2007; 67: 2738.
2.
WHO. Sickle cell disease and other haemoglobin disorders. Facts sheet no. 308. Geneva: WHO, 2011.
3.
WHO. Management of birth defects and haemoglobin disorders. Report of a joint WHO-March of Dimes meeting. Geneva: WHO, 2006.
4.
WeatherallDAkinyanjuOOFucharoenSet al., Inherited disorders of haemoglobin. In: JamisonD (ed). Disease control priorities in developing countries, 2nd ed. New York: Oxford University Press, 2006, pp. 663–680. .
5.
TaiwoIOloyedeODosumuO. Frequency of sickle genotype among the Yorubas of Lagos: implications for the level of awareness and genetic counselling for sickle cell disease in Nigeria. J Community Genet2011; 2: 13–18.
6.
KinneyTSleeperLWangWet al.Silent cerebral infarcts in sickle cell anaemia: a risk factor analysis. Paediatrics1999; 103: 640–645.
7.
BarosLThomasCWeinerW. Large cerebral vessel disease in sickle cell anaemia. J Neurol Neurosurg Psychiatry1976; 39: 1236–1239.
8.
AdamsRJ. TCD in sickle cell disease: an important and useful test. Pediatr Radiol2005; 35: 229–234.
9.
JefferiesBLipperMKinshoreP. Major intracranial arterial involvement in sickle cell disease. Surg Neurol1980; 14: 291–295.
10.
KatoGHsiehMMachadoRet al.Cerebrovascular disease associated with sickle cell pulmonary hypertension. Am J Haematol2006; 81: 503–510.
11.
KirkhamFDattaA. Hypoxic adaptation during development: relation to pattern of neurological presentation and cognitive disability. Dev Sci2006; 9: 411–427.
12.
RotherRBellLHillmenPet al.The clinical sequelae of intravascular haemolysis and extracellular plasma haemoglobin: a novel mechanism of human disease. JAMA2005; 293: 1653–1662.
13.
ZimmermanSSchultzWBurgettSet al.Hydroxyurea therapy lowers transcranial Doppler flow velocities in children with sickle cell anaemia. Blood J2007; 110: 1043–1047.
14.
LagunjuISodeindeOTelferP. Prevalence of transcranial Doppler abnormalities in Nigerian children with sickle cell disease. Am J Hematol2012; 87: 544–547.
15.
OniyangiOAkanoAOWakamaTTet al.Transcranial Doppler ultrasound studies for primary prevention of strokes among children with sickle cell disease in Nigeria - a single centre experience. Research2014; 1: 825.
16.
OniyangiOAhmedPOtuneyeOet al.Strokes in children with sickle cell disease at the National Hospital Abuja Nigeria. Niger J Paed2013; 40: 158–164.
17.
BallasSKLieffSBenjaminLet al.Definitions of the phenotypic manifestations of sickle cell disease. Am J Hematol2009; 85: 6–13.
18.
BallasSK. More definitions in sickle cell disease: steady state versus baseline data. Am J Hematol2012; 87: 338–338.
19.
Ohene-FrmpongKWeinerWSleeperLet al.Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood1998; 91: 288–294.
WildBBainBJInvestigation of abnormal haemoglobins and thalassaemia. In: LewisSBainBJBatesI (eds). Dacie and Lewis practical hematology, 10th edn. Philadelphia, PA: Churchill Livingstone, 2006, pp. 273–307.
22.
WroblewskiFLaDueJ. UV kinetic method for the determination of LDH activity in serum. Proc Soc Exp Biol Med1955; 90: 210.
23.
JendrassikLGroffP. Simplified photometric method for determination of blood bilirubin. Biochem J1938; 297: 81–89.
24.
BathalaLMehndirattaMMSharmaVK. Transcranial Doppler: technique and common findings. Ann Indian Acad Neurol2013; 16: 174–179.
25.
AdamsRMcKieVBrambillaDet al.Stroke Prevention Trial in sickle cell anaemia (STOP): study design. Control Clin Trials1998; 19: 110–129.
26.
AdamsRMcKieVHsuLet al.Prevention of a first stroke by transfusions in children with sickle cell anaemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med1998; 339: 5–11.
27.
AbdullahiSUHassan-HangaFIbrahimM. Ultrasonographic spleen size and haematological parameters in children with Sickle Cell Anaemia in Kano, Nigeria. Niger Postgrad Med J2014; 21: 165–170.
28.
OmotiC. Haematological values in sickle cell anaemia in steady-state and during vaso-occlusive crisis in Benin City, Nigeria. Ann Afr Med2005; 4: 62–67.
29.
OkpalaI. The intriguing contribution of white blood cells to sickle cell disease – a red cell disorder. Blood Rev2004; 18: 65–73.
30.
OkpalaI. Leukocyte adhesion and the pathophysiology of sickle cell disease. Curr Opin Hematol2006; 13: 40–44.
31.
BalkaranBCharGMorrisJet al.Stroke in a cohort of patients with homozygous sickle cell disease. J Paediatr1992; 120: 360–366.
32.
MeierEByrnesCLeeY. Increased reticulocytosis during infancy is associated with increased hospitalizations in sickle cell anemia patients during the first three years of life. PLoS One2013; 8: e70794.
33.
MeierEWrightEMillerJ. Reticulocytosis and anaemia are associated with an increased risk of death and stroke in the newborn cohort of the Cooperative Study of Sickle Cell Disease. Am J Hematol2014; 89: 904–906.
34.
LebensburgerJMillerSHowardTet al.Influence of severity of anaemia on clinical findings in infants with sickle cell anaemia: analyses from the BABY-HUG Study. Pediatr Blood Cancer2012; 59: 675–678.
35.
AmbeJPMavaYChamaRet al.Clinical features of sickle cell anaemia in northern Nigerian children. West Afr J Med2012; 31: 81–85.
36.
SteinbergMLuZBartonFet al.Fetal haemoglobin in sickle cell anaemia: determinants of response to hydroxyurea. Blood1997; 89: 1078–1088.
37.
GabrielAPrzybylskiJ. Sickle cell anaemia: a look at global haplotype distribution. Nat Educ2010; 3: 2.
38.
AdekileAYacoubFGuptaRet al.Silent brain infarcts are rare in Kuwaiti children with sickle cell disease and high HbF. Am J Hematol2002; 70: 228–231.
39.
ThomasPHiggsDSerjeantG. Benign clinical course in homozygous sickle cell disease: a search for predictors. J Clin Epidemiol1997; 50: 121–126.
40.
Taylor VIJNolanVMendelsonLet al.Chronic hyper-haemolysis in sickle cell anaemia: association of vascular complications and mortality with less frequent vasoocclusive pain. PLoS One2008; 3: e2095.
41.
NdukaNKazemYSalehB. Variation in serum electrolytes and enzyme concentrations in patients with sickle cell disease. J Clin Pathol1995; 48: 648–651.
42.
AkinolaNStevensSFranklinIet al.Subclinical ischaemic episodes during the steady state of sickle cell anaemia. J Clin Pathol1992; 45: 902–906.
43.
JuwahAINlemadimAKaineW. Clinical presentation of severe anaemia in pediatric patients with sickle cell anaemia seen in Enugu, Nigeria. Am J Hematol2003; 72: 185–191.
44.
BernaudinFVerlhacSChevretS. 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 anaemia. Blood2008; 112: 4314–4317.
45.
ArkuszewskiMKrejzaJChenRet al.Sickle cell disease: reference values and interhemispheric differences of non-imaging transcranial Doppler blood flow parameters. Am J Neuroradiol2011; 32: 1444–1450.
46.
ZetolaVF. Role of TCD in sickle cell disease: a review. Perspect Med2012; 1: 265–268.
47.
McCarvilleMLiCXiongXet al.Comparison of transcranial Doppler sonography with and without imaging in the evaluation of children with sickle cell anaemia. Am J Roentgenol2004; 183: 1117–1122.
48.
PadayacheeSThomasNArnoldAet al.Problems with implementing a standardised transcranial Doppler screening programme: impact of instrumentation variation on STOP classification. Pediatr Radiol2012; 42: 470–474.
49.
AdamsRMcKieVCarlEet al.Long-term stroke risk in children with sickle cell disease screened with transcranial Doppler. Ann Neurol1997; 42: 699–704.
50.
MakaniJKirkhamFKombaA. Risk factors for high cerebral blood flow velocity and death in Kenyan children with Sickle Cell Anaemia: the role of haemoglobin oxygen saturation and febrile illness. Br J Haematol2009; 145: 529–532.
51.
PavlakisSReesRHuangX. Transcranial Doppler ultrasonography (TCD) in infants with sickle cell anaemia: baseline data from the BABY HUG Trial. Pediatr Blood Cancer2010; 54: 256–259.
52.
SilvaIReisAPalarMet al.Sickle cell disease in children: chronic complications and search of predictive factors for adverse outcomes. Eur J Haematol2014; 94: 157–161.
53.
PadayacheeSTThomasNArnoldAJet al.Problems with implementing a standardised transcranial Doppler screening programme: impact of instrumentation variation on STOP classification. Pediatr Radiol2012; 42: 470–474.
54.
TzengYCWillieCKAtkinsonG. Cerebrovascular regulation during transient hypotension and hypertension in humans. Hypertension2010; 56: 268–273.
