A hypercoagulable state, chronic inflammation, and increased risk of venous thrombosis and stroke are prominent features in patients with sickle cell disease (SCD). Coagulation factor XII (FXII) triggers activation of the contact system that is known to be involved in both thrombosis and inflammation, but not in physiological hemostasis. Therefore, we investigated whether FXII contributes to the prothrombotic and inflammatory complications associated with SCD. We found that when compared with healthy controls, patients with SCD exhibit increased circulating biomarkers of FXII activation that are associated with increased activation of the contact pathway. We also found that FXII, but not tissue factor, contributes to enhanced thrombin generation and systemic inflammation observed in sickle cell mice challenged with tumor necrosis factor α. In addition, FXII inhibition significantly reduced experimental venous thrombosis, congestion, and microvascular stasis in a mouse model of SCD. Moreover, inhibition of FXII attenuated brain damage and reduced neutrophil adhesion to the brain vasculature of sickle cell mice after ischemia/reperfusion induced by transient middle cerebral artery occlusion. Finally, we found higher FXII, urokinase plasminogen activator receptor, and αMβ2 integrin expression in neutrophils of patients with SCD compared with healthy controls. Our data indicate that targeting FXII effectively reduces experimental thromboinflammation and vascular complications in a mouse model of SCD, suggesting that FXII inhibition may provide a safe approach for interference with inflammation, thrombotic complications, and vaso-occlusion in patients with SCD.

A rise in hospital‐acquired venous thromboembolism (HA‐VTE) in children has led to increased awareness regarding VTE prophylaxis and risk assessment. Despite no consensus exists regarding these practices in pediatrics. To describe common practices in VTE prophylaxis, VTE risk assessment models, and anticoagulation dosing strategies in pediatric hospitals that are members of the Children's Hospital Acquired Thrombosis (CHAT) Consortium. An electronic survey of 44 questions evaluating practices surrounding pediatric HA‐VTE risk assessment and prevention was distributed between August 9, 2021, and August 30, 2021, to the primary investigators from the 32 institutions within the CHAT Consortium. The survey response rate was 100% (n = 32). In total, 85% (n = 27) of the institutions assess HA‐VTE, but only 63% (n = 20) have formal hospital guidelines. Within the institutions with formal guidelines, 100% (n = 20) include acute systemic inflammation or infection and presence of a central venous catheter (CVC) as risk factors for VTE. Pharmacologic prophylaxis is prescribed at 87% (28) of institutions, with enoxaparin being the most frequent (96%, n = 27). Variability in responses persisted regarding risk factors, risk assessment, thromboprophylaxis, dosing of prophylactic anticoagulation or anticoagulant drug monitoring. A majority of providers were comfortable providing thromboprophylaxis across all age groups. In addition, the global coronavirus disease 2019 increased the providers' use of prophylactic anticoagulation 78% (n = 25). Practices among institutions are variable in regard to use of HA‐VTE prophylaxis, risk assessment, or guideline implementation, highlighting the need for further research and a validated risk assessment model through groups like the CHAT Consortium.

Mobile health (mHealth) applications have been utilized in chronic diseases to improve medication adherence, though factors driving engagement remain understudied. We previously demonstrated the benefits of mHealth app utilization in increasing adherence to hydroxyurea. In the “Integration of mHealth into Sickle Cell Disease (SCD) Care to Increase Hydroxyurea Utilization” (meSH) study, greater engagement with the InCharge Health app increased the percentage of days covered (PDC) for hydroxyurea. However, factors influencing app engagement were not investigated. This study aimed to identify patient-level factors associated with mHealth engagement during and post-study among adolescents and adults with SCD. All meSH participants were included. The InCharge Health app use was measured for 24 weeks (study period) and 12 weeks (post-study period). Baseline demographics and validated measures of self-efficacy, financial hardship, and pain severity, impact, and frequency were evaluated as predictors of app engagement during the study period and post-study using linear models. Complete app use data were obtained from 284 of 293 participants, including 150 (52.8%) females and 240 (84.8%) who were HbSS/HbSβ0-thalassemia with a median age of 27 years. During the study period, 232 (81.7%) used InCharge Health at least once (median use excluding zeros: 26 days; IQR: 7–72 days). During the post-study period, 132 (46.5%) participants used the app at least once (median use excluding zeros: 16 days; IQR: 3–44 days). During the study period, the HbSS genotype, age > 25 years, higher education, higher self-efficacy score, and lower pain severity were associated with greater app engagement. Only age (p = 0.0032) and financial hardship (p = 0.0125) were significant in a multivariable model after backward elimination. During the post-study period, older age (p = 0.035), lower pain severity (p = 0.021) and lower frequency of pain (p = 0.033) predicted mHealth engagement. All three remained significant in a multivariable model after backward elimination. Older age, lower financial hardship, lower pain severity, and greater self-efficacy were associated with increased engagement with a mHealth intervention for improving medication adherence among people living with SCD. This research can shift future app development from focusing on factors that drive patient interaction with mHealth targeting modifiable factors influencing app engagement. The trial was registered with ClinicalTrials.gov. Registration Identifier: NCT04080167. Registration date: November 11, 2019.

Red blood cell transfusions can lead to iron overload (IO) in sickle cell disease (SCD). We aimed to determine the relationship between SCD patients with IO and SCD comorbidities. Iron chelation regimen for IO in SCD patients was also studied. A cohort of 245 SCD adult patients receiving care at the Medical University of South Carolina (MUSC) was studied. Information was obtained from medical records. Statistical analysis was performed to examine correlations and odds ratios with 95% confidence intervals. We identified 85 (34.7%) participants who met IO criteria. The results showed a significant as-sociation of IO with stroke (OR= 14.67, p= 0.0001), pulmonary hypertension (OR= 4.75, p= 0.0006), acute chest syndrome (OR= 2.46, p= 0.003), and deep vein thrombosis (OR= 1.84, p= 0.04). There was a strong correlation bet-ween liver iron concentration (LIC) and ferritin levels (r= 0.5148, p<0.0001). Liver enzymes correlated well with LIC and ferritin levels. Eighty-six percent of participants (74/85) were on chelation therapy, but only 19% of them achieved a good response to the treatment. One-third of SCD individuals developed IO, associated with several comorbidities. Comprehensive measures must include periodic determinations of LIC and ferritin, followed by appropriate chelation therapy to prevent organ damage.