Haemoglobin oxygen saturation is a determinant of cerebral artery blood flow velocity in children with sickle cell anaemia
Hematology-Oncology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX 75390-9063, USA. British Journal of Haematology
(Impact Factor: 4.71).
04/2009; 145(4):500-5. DOI: 10.1111/j.1365-2141.2009.07652.x
Steady-state haemoglobin (Hb) desaturation is a common finding in sickle cell anaemia (Hb SS) that could predispose to stroke by limiting oxygen delivery to the brain. To determine its association with the risk of overt stroke, we examined the relationship between daytime Hb saturation measured by pulse oximetry (SpO(2)) and cerebral artery blood flow velocity measured by transcranial Doppler ultrasonography (TCD), an established risk factor for overt stroke in Hb SS. We studied 181 children using multivariate models to control for known determinants of TCD velocity, including age, haematocrit, and a measure of stenosis. We found that SpO(2) correlated significantly and inversely with TCD velocity in both the right and left middle cerebral arteries. Hb desaturation was associated with increased cerebral artery blood flow velocities and increased odds of abnormal TCD velocities, hence increased risk of stroke. About 5% of the variation in TCD velocity could be ascribed to Hb saturation while controlling for other determinants of TCD velocity. In conclusion, Hb saturation is a determinant of TCD velocity and a risk factor for stroke in children with Hb SS.
Available from: Charles Newton
- "Hemoglobin oxygen desaturation in the absence of acute illness is common in children with Sickle Cell Anemia (SCA), and is associated with higher cerebral blood flow velocities  , and with risk of complications including stroke . The underlying mechanisms of hemoglobin oxygen desaturation in SCA are poorly understood but may involve the severity of anemia  as well as differences in hemoglobin oxygen affinity compared to hemoglobin A (HbA), with increased expression of 2.3 DPG in hemoglobin S (HbS) resulting in a right-shifted hemoglobin oxygen affinity curve and other differences in red cell physiology . "
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ABSTRACT: Low hemoglobin oxygen saturation (SpO2) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO2 in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO2 was 97% (IQ range 94-99%) in SCA (N = 458), lower (P < 0.0001) than non-SCA (median 99%, IQ range 98-100%; N = 394). Within SCA, associations with SpO2 were observed for hematological variables, transferrin saturation, body-mass-index z-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (P < 0.001, Adj r (2) = 0.09). In non-SCA only age correlated with SpO2. α-thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient -0.60, P < 0.0001). In multivariable models, lower SpO2 correlated with higher MCH (β-coefficient -0.32, P < 0.001) or with decreased copies of α-thalassemia 3.7 deletion (β-coefficient 1.1, P < 0.001), and independently in both models with lower HbF% (β-coefficient 0.15, P < 0.001) and Glucose-6-Phosphate Dehydrogenase genotype (β-coefficient -1.12, P = 0.012). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO2 in children with SCA. Potential mechanisms and implications are discussed.
Available from: Julie Makani
- "In SS disease, normal adult haemoglobin is replaced with sickle haemoglobin, which polymerizes when deoxygenated, distorting the red cells into a sickle shape that can occlude the microvasculature. The aetiology of the wide range of acute and chronic complications of SS disease remains unexplained, but there is an association with the degree of haemoglobin oxygen desaturation (Quinn et al. 2009), and alterations in the peripheral vasculature may be involved (Mohan et al. 1998, 2011; Sangkatumvong et al. 2011). Exposure to cold, fever and dehydration increase the risk of painful vaso-occlusive episodes, a common complication in SS disease, possibly because of increased sympathetic drive in response to these environmental triggers causing vasoconstriction. "
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ABSTRACT: New Findings
• What is the central question of this study?
Autonomic nervous dysfunction is implicated in complications of sickle cell anaemia (SCA). In healthy adults, a deep inspiratory breath hold (IBH) elicits rapid transient SNS- mediated vasoconstriction detectable using Laser Doppler Flux (LDF) assessment of the finger-tip cutaneous micovasculature.
• What is the main finding and its importance?
We demonstrate significantly increased resting peripheral blood flow and sympathetic activity in African children with SCA compared to sibling controls and increased sympathetic stimulation in response to vasoprovocation with DIG.
This study is the first to observe an inverse association between resting peripheral blood flow and haemoglobin oxygen saturation (SpO2). These phenomena may be an adaptive response to the hypoxic exposure in SCA.
There is increasing evidence that autonomic dysfunction in adults with homozygous sickle cell (haemoglobin SS) disease is associated with enhanced autonomic nervous system-mediated control of microvascular perfusion. However, it is unclear whether such differences are detectable in children with SS disease. We studied 65 children with SS disease [38 boys; median age 7.2 (interquartile range 5.1–10.6) years] and 20 control children without symptoms of SS disease [8 boys; 8.7 (5.5–10.8) years] and recorded mean arterial blood pressure (ABP) and daytime haemoglobin oxygen saturation (). Cutaneous blood flux at rest (RBF) and during the sympathetically activated vasoconstrictor response to inspiratory breath hold (IBH) were measured in the finger pulp of the non-dominant hand using laser Doppler fluximetry. Local factors mediating flow motion were assessed by power spectral density analysis of the oscillatory components of the laser Doppler signal. The RBF measured across the two study groups was negatively associated with age (r=−0.25, P < 0.0001), ABP (r=−0.27, P= 0.02) and daytime (r=−0.30, P= 0.005). Children with SS disease had a higher RBF (P= 0.005) and enhanced vasoconstrictor response to IBH (P= 0.002) compared with control children. In children with SS disease, higher RBF was associated with an increase in the sympathetic interval (r=−0.28, P= 0.022). The SS disease status, daytime and age explained 22% of the variance in vasoconstrictor response to IBH (P < 0.0001). Our findings suggest that blood flow and blood flow responses in the skin of young African children with SS disease differ from those of healthy control children, with increased resting peripheral blood flow and increased sympathetic stimulation from a young age in SS disease. They further suggest that the laser Doppler flowmetry technique with inspiratory breath hold manoeuvre appears to be robust for use in young children with SS disease, to explore interactions between , ABP and autonomic function with clinical complications, e.g. skin ulceration.
Available from: Lori Chaffin Jordan
- "Specifically, TCD screening should not be performed during an acute illness to assess baseline stroke risk, as co-morbidities may alter the baseline measurements(Bulas 2005, Nichols, et al 2001). Hypoxia, fever, hypoglycaemia and worsening anaemia can also increase cerebral blood flow and flow velocity(Quinn, et al 2009). Although it is tempting to perform TCD examinations while a patient is in the hospital for a medical illness, the results might not be valid, if velocities fall in the abnormal or conditional range. "
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ABSTRACT: This review will focus on the strengths and limitations associated with the current standard of care for primary prevention of ischaemic strokes in children with sickle cell anaemia (SCA) - transcranial Doppler ultrasound (TCD) screening followed by regular blood transfusion therapy when TCD measurement is above a threshold defined by a randomized clinical trial (RCT). The theoretical basis for potential alternative strategies for primary prevention of neurological injury in SCA is also discussed. These strategies will include, but will not be limited to: immunizations to prevent bacterial infections, particularly in low income countries; management of elevated blood pressure; and targeted strategies to increase baseline haemoglobin levels with therapies such as hyroxycarbamide or potentially definitive haematopoietic stem cell transplant.
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