Factors Associated with Elevated Transcranial Doppler Ultrasound Velocities in Children with Sickle Cell Anemia in Mwanza, Tanzania
Georgina George Balyorugulu [Female]
Factors Associated with Elevated Transcranial Doppler Ultrasound Velocities in Children with Sickle Cell Anemia in Mwanza, Tanzania - Mwanza, Tanzania: Catholic University of Health and Allied Sciences [CUHAS - Bugando] : 2020 - xiv; 71 Pages Includes References and Appendices
Abstract:
Background: Sickle cell anemia (SCA) is associated with several major complications including cerebral vascular diseases such as stroke, with 11% being affected before the age of 20 years. In Northwestern Tanzania, the prevalence of stroke among children living with SCA under the age 15 years is 16.9%. Due to the absence of routine screening modalities by using Transcranial Doppler Ultrasound (TCD) and provision of preventive prophylaxis measures such as chronic blood transfusion, a higher risk of stroke might be prevalent in this population in our setting. TCD has led to the reduction of stroke prevalence by 92% following introduction of prophylactic blood transfusion for those with abnormal TCD. Despite the benefits of screening, TCD has low positive predictive value with 60% among those who screened positive for risk of stroke end up not developing stroke. Additional factors such hemoglobin level have been studied for identification of those at risk of stroke which can be used as adjuvant tools for clinical guidance in preventive measures of stroke.
Methods: This was a cross section study, which enrolled 267 SCA children aged 2 to 16 years attending Bugando Medical Centre Pediatric Sickle Cell Clinic from July 2019 to June 2020. Assessment of factors associated with elevated TCD included a clinical history of stroke in sibling, death history in sibling, oxygen saturation in room air, blood pressure (Systolic and Diastolic), hemoglobin level and total white blood cell count. TCD was done by accessing transtemporal window on both sides and recording the highest time average mean of maximum velocity (TAMMV) of major vessels mainly, middle cerebral artery (MCA) and distal internal carotid artery (dICA).
Results: The median age of enrolled was 6.6 (IQR: 4-9) years. The prevalence of elevated TCD (>170cm/s) was found to be 21% (56/267). By multivariate logistic regression, low oxygen saturation in room air, p-value = 0.037, OR 0.92 [95% CI 0.85-0.10] and low hemoglobin level, p-value=0.001, OR 0.57 [95% CI 0.41-0.79] were statistically significantly associated with elevated TCD among children living with SCA.
Conclusion: A proportion of children with elevated TCD were detected, which is associated with low hemoglobin and low oxygen saturation. These factors seen in this study warrants their incorporation in the screening of risk of stroke in children with SCA aged 2 to 16 years.
= OPERATIONAL DEFINITIONS 1. Transcranial Doppler (TCD) ultrasonography velocities findings were defined as adapted from Stroke prevention trial (STOP) in sickle cell disease, as follows; Abnormal TCD velocity ultrasonography findings are defined as either Time Averaged Mean of Maximum Velocity (TAMMV) ≥ 200 cm/s in dICA (distal Internal Carotid Artery) and/ or MCA (Middle Cerebral Artery), Low velocity < 100cm/s or nonvisualization of MCA in a patient with adequate windows. Conditional TCD velocity ultrasonography findings are defined TAMMV >170cm/s but < 200cm/s in the MCA or dICA. In this study, both abnormal and conditional TAMMV were considered as elevated TCD (>170cm/s) findings. Normal findings were defined as TCD ultrasonography with TAMMV ≤170cm/s. Inadequate window is defined as failure to detect the velocity of one of the cerebral vessels; MCA, dICA, the bifurcation (BIF) and the bilateral M1 (the shallowest portion of MCA), by using the TCD non imaging technique through either the left or right transtemporal window. OPERATIONAL DEFINITIONS 2. Sickle Cell Anemia (SCA) patient was defined as a patient with homozygous HbS (Hemoglobin S) resulting into HbSS. 3. Routine TCD is the screening of risk of stroke that is done for SCA children at first visit to the clinic and the following visits according to the results of the previous TCD velocity. For those with normal TCD screened is done annually, conditional TCD screening is repeated 3-6 months depending on the clinical status and abnormal TCD screening is repeated after 2 weeks and patient is the followed monthly. = ABBREVIATIONS ACA Anterior Cerebral Artery BCL11A B-Cell Lymphoma/Leukemia 11A BMC Bugando Medical Centre BMI Body Mass Index CAR Central African Republic Ca++ Calcium ion Cl- Chloride ion dICA Distal Internal Carotid Artery ENPP1 Ectonucleotide Pyrophosphatase/Phosphodiesterase 1gene FBP Full Blood Picture G6PD Glucose 6 Phosphate Dehydrogenase GOLGB1 Golbin B1 Hb Hemoglobin HbF Fetal hemoglobin HbS Hemoglobin S HbSS Hemoglobin SS (Homozygous) HbSβ+ Hemoglobin S/ beta plus thalassemia HbSβ° Hemoglobin S/beta zero thalassemia HED Hemolysis-endothelial dysfunction sub phenotype K+ Potassium ion LDH Lactate Dehydrogenase MCA Middle Cerebral Arteryxi MCHC Mean Corpuscular Hemoglobin Concentration MCV Mean Corpuscular Volume MRA Magnetic Resonance Angiography MRI Magnetic Resonance Imaging mRNA messenger Ribonucleic acid NAD Nicotinamide Adenine Dinucleotide Rh Rhesus factor SCA Sickle Cell Anemia SCD Sickle Cell Disease SCI Silent cerebral infract SCR Sickle cell retinopathy SNP Single nucleotide polymorphism TAMMV Time Average Mean of Maximum Velocity TCD Transcranial Doppler Ultrasound vWF Von Willebrand factor
Wurzburg Road 35, BMC Premises, Post Code: 33102: P. O Box 1464, Mwanza – Tanzania: Phone: +255 28 298 3384: Fax: +255 28 298 3386: Email: vc@bugando.ac.tz : Website: www.bugando.ac.tz
--Pediatrics and Child Health
Factors Associated with Elevated Transcranial Doppler Ultrasound Velocities in Children with Sickle Cell Anemia in Mwanza, Tanzania - Mwanza, Tanzania: Catholic University of Health and Allied Sciences [CUHAS - Bugando] : 2020 - xiv; 71 Pages Includes References and Appendices
Abstract:
Background: Sickle cell anemia (SCA) is associated with several major complications including cerebral vascular diseases such as stroke, with 11% being affected before the age of 20 years. In Northwestern Tanzania, the prevalence of stroke among children living with SCA under the age 15 years is 16.9%. Due to the absence of routine screening modalities by using Transcranial Doppler Ultrasound (TCD) and provision of preventive prophylaxis measures such as chronic blood transfusion, a higher risk of stroke might be prevalent in this population in our setting. TCD has led to the reduction of stroke prevalence by 92% following introduction of prophylactic blood transfusion for those with abnormal TCD. Despite the benefits of screening, TCD has low positive predictive value with 60% among those who screened positive for risk of stroke end up not developing stroke. Additional factors such hemoglobin level have been studied for identification of those at risk of stroke which can be used as adjuvant tools for clinical guidance in preventive measures of stroke.
Methods: This was a cross section study, which enrolled 267 SCA children aged 2 to 16 years attending Bugando Medical Centre Pediatric Sickle Cell Clinic from July 2019 to June 2020. Assessment of factors associated with elevated TCD included a clinical history of stroke in sibling, death history in sibling, oxygen saturation in room air, blood pressure (Systolic and Diastolic), hemoglobin level and total white blood cell count. TCD was done by accessing transtemporal window on both sides and recording the highest time average mean of maximum velocity (TAMMV) of major vessels mainly, middle cerebral artery (MCA) and distal internal carotid artery (dICA).
Results: The median age of enrolled was 6.6 (IQR: 4-9) years. The prevalence of elevated TCD (>170cm/s) was found to be 21% (56/267). By multivariate logistic regression, low oxygen saturation in room air, p-value = 0.037, OR 0.92 [95% CI 0.85-0.10] and low hemoglobin level, p-value=0.001, OR 0.57 [95% CI 0.41-0.79] were statistically significantly associated with elevated TCD among children living with SCA.
Conclusion: A proportion of children with elevated TCD were detected, which is associated with low hemoglobin and low oxygen saturation. These factors seen in this study warrants their incorporation in the screening of risk of stroke in children with SCA aged 2 to 16 years.
= OPERATIONAL DEFINITIONS 1. Transcranial Doppler (TCD) ultrasonography velocities findings were defined as adapted from Stroke prevention trial (STOP) in sickle cell disease, as follows; Abnormal TCD velocity ultrasonography findings are defined as either Time Averaged Mean of Maximum Velocity (TAMMV) ≥ 200 cm/s in dICA (distal Internal Carotid Artery) and/ or MCA (Middle Cerebral Artery), Low velocity < 100cm/s or nonvisualization of MCA in a patient with adequate windows. Conditional TCD velocity ultrasonography findings are defined TAMMV >170cm/s but < 200cm/s in the MCA or dICA. In this study, both abnormal and conditional TAMMV were considered as elevated TCD (>170cm/s) findings. Normal findings were defined as TCD ultrasonography with TAMMV ≤170cm/s. Inadequate window is defined as failure to detect the velocity of one of the cerebral vessels; MCA, dICA, the bifurcation (BIF) and the bilateral M1 (the shallowest portion of MCA), by using the TCD non imaging technique through either the left or right transtemporal window. OPERATIONAL DEFINITIONS 2. Sickle Cell Anemia (SCA) patient was defined as a patient with homozygous HbS (Hemoglobin S) resulting into HbSS. 3. Routine TCD is the screening of risk of stroke that is done for SCA children at first visit to the clinic and the following visits according to the results of the previous TCD velocity. For those with normal TCD screened is done annually, conditional TCD screening is repeated 3-6 months depending on the clinical status and abnormal TCD screening is repeated after 2 weeks and patient is the followed monthly. = ABBREVIATIONS ACA Anterior Cerebral Artery BCL11A B-Cell Lymphoma/Leukemia 11A BMC Bugando Medical Centre BMI Body Mass Index CAR Central African Republic Ca++ Calcium ion Cl- Chloride ion dICA Distal Internal Carotid Artery ENPP1 Ectonucleotide Pyrophosphatase/Phosphodiesterase 1gene FBP Full Blood Picture G6PD Glucose 6 Phosphate Dehydrogenase GOLGB1 Golbin B1 Hb Hemoglobin HbF Fetal hemoglobin HbS Hemoglobin S HbSS Hemoglobin SS (Homozygous) HbSβ+ Hemoglobin S/ beta plus thalassemia HbSβ° Hemoglobin S/beta zero thalassemia HED Hemolysis-endothelial dysfunction sub phenotype K+ Potassium ion LDH Lactate Dehydrogenase MCA Middle Cerebral Arteryxi MCHC Mean Corpuscular Hemoglobin Concentration MCV Mean Corpuscular Volume MRA Magnetic Resonance Angiography MRI Magnetic Resonance Imaging mRNA messenger Ribonucleic acid NAD Nicotinamide Adenine Dinucleotide Rh Rhesus factor SCA Sickle Cell Anemia SCD Sickle Cell Disease SCI Silent cerebral infract SCR Sickle cell retinopathy SNP Single nucleotide polymorphism TAMMV Time Average Mean of Maximum Velocity TCD Transcranial Doppler Ultrasound vWF Von Willebrand factor
Wurzburg Road 35, BMC Premises, Post Code: 33102: P. O Box 1464, Mwanza – Tanzania: Phone: +255 28 298 3384: Fax: +255 28 298 3386: Email: vc@bugando.ac.tz : Website: www.bugando.ac.tz
--Pediatrics and Child Health