Relationships Between Transcranial Doppler Velocity, Von Willebrand Factor, Factor VIII, and Hematological Parameters in Children with Sickle Cell Anemia: A Comparative Cross-Sectional Study Eniola Kehinde Enifeni, MD, FMCPath1, Ann Abiola Ogbenna, MD, FMCPath2, Alaba Olanrewaju Daramola, MD, FMCPath1, Ademola Samson Adewoyin, MD, FMCPath2, Oladele Simeon Olatunya, MD, FMCPaed, PhD3 and Edamisan Temiye, MD, FWACPaed4 1Department of Hematology and Blood Transfusion, Ekiti State University, Ado Ekiti, Nigeria 2Department of Hematology and Blood Transfusion, University of Lagos, Lagos, Nigeria 3Department of Paediatrics, Ekiti State University, Ado Ekiti, Nigeria 4Department of Paediatrics, University of Lagos, Lagos, Nigeria ABSTRACT BACKGROUND AND OBJECTIVES: Sickle cell anemia (SCA) is associated with recurrent acute inflammatory processes. These inflammatory processes could lead to elevation of Factor VIII and Von Willebrand Factor levels, thereby increasing the risk of stroke in SCA children. This study aims to determine vWF/FVIII levels in children with SCA and their association with abnormal transcranial Doppler (TCD). SUBJECTS AND METHODS: This study enrolled 75 children, including 24 SCA cases with normal TCD, 27 SCA cases with abnormal TCD, and 24 Hb AA controls, all aged between 2 and 16 years. Transcranial Doppler (TCD) ultrasound was performed to measure the cerebral blood vel- ocity. Venous blood drawn from each participant was used to determine the levels of von Willebrand Factor Antigen (vWF: Ag) and Factor VIII (FVIII) and the complete blood count (CBC). Relationships among the measured parameters were determined using SPSS version 25. Statistical significance was set at P< .05. RESULTS: FVIII and vWF levels were significantly higher among children with SCA compared to the Hb AA controls (P< .001). Although SCA patients with abnormal TCD tended to have higher levels of FVIII and vWF, this result did not attain statistical significance (P> .05). There was a moderate negative correlation between the left middle cerebral artery and FVIII, (r=−0.332; P= .017). Children with SCA showing an abnormal TCD velocity had significantly higher platelet count compared to those with normal TCD (P= .018). CONCLUSION: Children with SCA have elevated levels of FVIII and vWF, and an abnormal TCD velocity is associated with elevated platelet count. KEYWORDS: Sickle cell disease, Von Willebrand factor, factor VIII, TCD, stroke RECEIVED: December 2, 2021. ACCEPTED: September 15, 2022 TYPE: Original Research Article CORRESPONDING AUTHOR: Eniola Kehinde Enifeni, Department of Haematology and Blood Transfusion, Ekiti State University, Ado Ekiti 360101, Nigeria. Email: enisabis@gmail.com Introduction Sickle cell disease (SCD) is one of the most prevailing severe monogenic disorders worldwide.1 The most severe and fre- quently observed variant of SCD is sickle cell anemia (SCA) characterized by a homozygous point mutation in the β globin gene (GAG- GTG) at the sixth codon of β globin gene. The manifestation of SCD includes hemolytic anemia, recurrent vaso-occlusive crisis, recurrent infections, and stroke.2 These manifestations are accompanied by inflamma- tory processes which may influence the status of some hemato- logical parameters and other biological markers in SCD patients. Patients with SCD have an increased risk of cerebrovascular accident, which is a leading cause of death in both children and adults.3 The reported age-adjusted incidence of stroke in SCD is 0.61–0.76 per 100 patient-years during the first 20 years of life.4 The incidence of the ischemic variant, which constitutes 54% of all cerebrovascular accidents (CVAs), is highest during the first decade of life and after the age of 30 years.5 Between the ages of 20 and 30 years, ischemic CVA is replaced by hemorrhagic CVA.5 The prevalence of stroke in patients with SCD in a multi-centre study in Nigeria was 12.4%,6 thus affirming that the occurrence of stroke as a complication of SCD is common among Nigerian patients. SCA is associated with the activation of the coagulation system from childhood leading to hypercoagulability, which in turn has been reported to play a role in the development of vasculopathy.7 Therefore, it is speculated that stroke and abnor- mal transcranial Doppler (TCD) velocity may be linked to derangements in clotting factors, such as von Willebrand Factor (vWF) and Factor VIII (FVIII), in children with SCD. vWF has been shown to play an important role in throm- bus formation at the site of vascular damage, and an increased level of vWF is a marker of endothelial activation and Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). Plasmatology Volume 16: 1–8 © The Author(s) 2022 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/26348535221130289