Hydroxyurea in the sickle cell disease modern era.

INTRODUCTION: Sickle cell disease is an inherited disorder characterized by hemoglobin S polymerization leading to vaso-occlusion and hemolytic anemia. These result in a variety of pathological events, causing both acute and chronic complications. Millions around the world are affected by sickle cell disease with predominance in sub-Saharan Africa. Hydroxyurea was the first drug approved for use in sickle cell disease to reduce the occurrence of painful crises and blood transfusions in patients with frequent, moderate to severe painful crises. AREAS COVERED: With the development of new therapeutics, the role of hydroxyurea is evolving. This narrative review aims to provide clinical data, safety information, and supplementary evidence for the role of hydroxyurea in the current era of sickle cell disease. A comprehensive literature search of databases, including PubMed and Cochrane Library, was conducted from 1963 to 2024. EXPERT OPINION: Even though new medications have been approved for sickle cell disease, hydroxyurea remains the gold standard. Hydroxyurea is not only a disease modifier but it has additional clinical benefits, it is affordable, and its longevity has prompted expanded research in areas such as underutilization and pharmacogenomics. As the treatment landscape evolves, hydroxyurea's long-standing record of efficacy and safety continues to support its role as a key agent in disease management.

Esophageal and Ileal Ulcers Caused by Hydroxycarbamide: A Case Report and Literature Review.

Hydroxycarbamide, an antimetabolic agent used to treat myeloproliferative disorders, causes side effects, including myelosuppression, skin ulcers, and oral mucositis. Gastrointestinal ulcers are uncommon, and esophageal ulcers have not been previously reported. We present the case of a 74-year-old woman who developed esophageal and ileal ulcers after hydroxycarbamide treatment. Our case and previous reports suggest that hydroxycarbamide can cause ulcers throughout the gastrointestinal tract, which can improve rapidly after discontinuing medication. When new signs and symptoms occur, drug-induced etiologies should be considered as a potential cause. Timely diagnostic treatment with discontinuation of medication is crucial in such cases.

Provider prescription of hydroxyurea in youth and adults with sickle cell disease: A review of prescription barriers and facilitators.

Sickle cell disease (SCD) is an inherited red blood cell disorder associated with frequent painful events and organ damage. Hydroxyurea (HU) is the recommended evidence-based treatment of SCD. However, among patients eligible for HU, prescription rates are low. Utilizing a scoping review approach, we summarized and synthesized relevant findings regarding provider barriers and facilitators to the prescription of HU in youth and adults with SCD and provided suggestions for future implementation strategies to improve prescription rates. Relevant databases were searched using specified search terms. Articles reporting provider barriers and/or facilitators to prescribing HU were included. A total of 10 studies met the inclusion criteria. Common barriers to the prescription of HU identified by providers included: doubts around patients' adherence to HU and their engaging in required testing, concerns about side effects, lack of knowledge, cost and patient concerns about side effects. Facilitators to the prescription of HU included beliefs in the effectiveness of HU, provider demographics and knowledge. Findings suggest significant provider biases exist, particularly in the form of negative perceptions towards patients' ability to adhere to taking HU and engaging in the required follow-up. Improving provider knowledge and attitudes towards HU and SCD may help improve low prescription rates.

Hydroxyurea attenuates hepatic stellate cell proliferation in vitro and liver fibrogenesis in vivo.

Liver fibrosis results from excessive proliferation of, and collagen production by hepatic stellate cells (HSCs) that is caused by chronic liver injury. No drugs are available to cure liver fibrosis. Hydroxyurea is an anti-proliferative drug that is used in benign and malignant disorders. Here, we studied the effect of hydroxyurea on primary HSCs and its anti-fibrotic effect in the CCl4 mouse model of liver fibrosis. Primary rat HSCs were cultured in the absence or presence of hydroxyurea (0.1-1.0 mmol/L). CCl4 or vehicle was administered to C57BL/6/J mice for 4 weeks, with or without hydroxyurea (100 mg/kg/day) co-treatment. We used real-time cell proliferation analysis, Oil Red O (lipid droplet) staining, immunohistochemistry, Acridine Orange staining (apoptosis), Sytox green staining (necrosis), RT-qPCR, ELISA, and Western Blotting for analysis. Hydroxyurea dose-dependently suppressed lipid droplet-loss and mRNA levels of Col1α1 and Acta2 in transdifferentiating HSCs. In fully-activated HSCs, hydroxyurea dose-dependently attenuated PCNA protein levels and BrdU incorporation, but did not reverse Col1α1 and Acta2 mRNA expression. Hydroxyurea did not induce apoptosis or necrosis in HSCs or hepatocytes. Hydroxyurea suppressed accumulation of desmin-positive HSCs and hepatic collagen deposition after CCl4 treatment. CCl4 -induced regenerative hepatocyte proliferation, Col1α1 and Acta2 mRNA expression and α-SMA protein levels were not affected. This study demonstrates that hydroxyurea inhibits HSC proliferation in vitro and attenuates early development of liver fibrosis in vivo, while preserving hepatocyte regeneration after toxic insults by CCl4. Thus, hydroxyurea may have therapeutic value against liver fibrosis.

Multiple cardiac surgical procedures in a case of an octogenarian with essential thrombocythemia.

BACKGROUND: Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by an elevation of platelet counts with a tendency for thrombosis and hemorrhage. The perioperative management of cardiovascular surgery of an ET patient is complicated. There is limited literature on the perioperative management of patients with ET undergoing cardiovascular surgery, particularly those requiring multiple procedures. CASE PRESENTATION: An 85-year-old woman with a history of essential thrombocythemia (ET), which resulted in an abnormally high platelet count, was diagnosed with aortic valve stenosis, ischemic heart disease and paroxysmal atrial fibrillation. She underwent aortic valve replacement, coronary artery bypass grafting, and pulmonary vein isolation. The postoperative course was uneventful, nor hemorrhage and thrombosis. CONCLUSIONS: We represent a case of perioperative management and successful treatment of three combined cardiac surgery for an octogenarian ET patient who is the oldest case ever reported.

Managing women of childbearing age with chronic myeloid leukemia: safety and treatment considerations.

INTRODUCTION: TKIs are paradigmatic in CML management and offer patients the prospect of a normal life expectancy. As a consequence, the focus of both the clinician and patient has shifted to considerations of quality of life, including the ability to parent children. Unfortunately, TKIs are teratogenic so that alternative treatment options may be required during pregnancy to adequately control disease and minimize risk. AREAS COVERED: In this review, we summarize and provide an overview of the literature on the management of CML in women of childbearing age. We discuss the various treatment options as well as their advantages, disadvantages, and safety considerations. We discuss CML in the context of: 1) planned pregnancies with CML; 2) unplanned pregnancies with CML; 3) CML diagnosed during pregnancy. EXPERT OPINION: Confidence in managing pregnancy and CML continues to grow. In the majority of cases, with careful planning and counseling, no treatment is required and disease control can be safely regained after pregnancy ends. For those who require treatment, various options are available and there is growing evidence to suggest that some TKIs may be safe in the later stages of pregnancy.

Impact of adherence to hydroxyurea on health outcomes among patients with sickle cell disease.

Although new pharmaceutical therapy options have recently become available, hydroxyurea is still the most commonly used and affordable treatment option for sickle cell disease (SCD). This study aimed to update the evidence on hydroxyurea adherence and its association with clinical and economic outcomes among individuals with SCD. This retrospective study used Texas Medicaid claims data from 09/2011-08/2016. Individuals were included if they had ≥1 inpatient or ≥2 outpatient SCD diagnoses, had ≥1 hydroxyurea prescription, were 2-63 years of age, and were continuously enrolled in Texas Medicaid between 6 months before and 1 year after the first hydroxyurea prescription fill date (index date). Hydroxyurea adherence (Medication Possession Ratio; MPR), vaso-occlusive crisis (VOC)-related outcomes, healthcare utilization and expenditures (SCD-related and all-cause) during the 1 year following the index date were measured. Bivariate and multivariable analyses were used to address the study objectives. Among 1035 included individuals (age: 18.8 ± 12.5 years, female: 52.1%), 20.9% were adherent to hydroxyurea (defined as MPR≥0.8). After adjustment for demographic and clinical characteristics, compared to being non-adherent, adhering to hydroxyurea was significantly associated with: a lower risk (Odds Ratio [OR] = 0.480, p = .0007) and hazard rate (Hazard Ratio [HR] = 0.748, p = .0005) of a VOC event, fewer VOC events (Incidence Rate Ratio [IRR] = 0.767, p = .0009), fewer VOC-related hospital days (IRR = 0.593, p = .0003), fewer all-cause and SCD-related hospitalizations (IRR = 0.712, p = .0008; IRR = 0.707, p = .0008, respectively) and emergency department visits (IRR = 0.768, p = .0037; IRR = 0.746, p = .0041, respectively), and lower SCD-related total healthcare expenditures (IRR = 0.796, p = .0266). Efforts to increase adherence to hydroxyurea could improve clinical and economic outcomes among individuals with SCD.

Skin cancer in essential thrombocythaemia and polycythaemia vera patients treated with hydroxycarbamide.

Hydroxycarbamide (HC) is used as a cytoreductive treatment in myeloproliferative neoplasms (MPN). Observational studies have raised the possibility that HC contributes to the development of secondary malignancies, including skin tumours in MPN patients. In this retrospective observational study, we report a single-centre experience of 324 HC-treated MPN patients with long-term follow-up, compared to 47 MPN patients not on HC. Thirty-three patients (10.2%) (HC) versus one patient (2.1%) (no HC) developed skin tumours during follow-up (Hazard ratios [HR] 5.70, 95% confidence intervals 0.66-48.09, p = 0.112). However, male gender, age at MPN diagnosis, type of MPN (polycythaemia rubra vera) and previous history of skin cancer were prognostic variables associated with development of skin cancer.

Impact of the COVID-19 Pandemic on the Implementation of Mobile Health to Improve the Uptake of Hydroxyurea in Patients With Sickle Cell Disease: Mixed Methods Study.

BACKGROUND: Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on the implementation of an mHealth behavioral intervention for improving hydroxyurea adherence among patients with SCD. METHODS: The first 2 sites initiated enrollment 3 months prior to the start of the pandemic (November 2019 to March 2020). During implementation, site A clinics shut down for 2 months and site B clinics shut down for 9 months. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to evaluate the implementation and effectiveness of the intervention. mHealth implementation was assessed based on patients' daily app use. Adherence to hydroxyurea was calculated as the proportion of days covered (PDC) from prescription records over the first 12 and 24 weeks after implementation. A linear model examined the relationship between app usage and PDC change, adjusting for baseline PDC, lockdown duration, and site. We conducted semistructured interviews with patients, health care providers, administrators, and research staff to identify factors associated with mHealth implementation and effectiveness. We used a mixed methods approach to investigate the convergence of qualitative and quantitative findings. RESULTS: The percentage of patients accessing the app decreased after March 15, 2020 from 86% (n=55) to 70% (n=45). The overall mean PDC increase from baseline to week 12 was 4.5% (P=.32) and to week 24 was 1.5% (P=.70). The mean PDC change was greater at site A (12 weeks: 20.9%; P=.003; 24 weeks: 16.7%; P=.01) than site B (12 weeks: -8.2%; P=.14; 24 weeks: -10.3%; P=.02). After adjustment, PDC change was 13.8% greater in those with increased app use after March 15, 2020. Interview findings indicated that site B's closure during COVID-19 had a greater impact, but almost all patients reported that the InCharge Health app helped support more consistent medication use. CONCLUSIONS: We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may "insulate" the implementation of interventions to increase medication adherence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080167; https://clinicaltrials.gov/ct2/show/NCT04080167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/16319.

A Microbiota-Dependent Response to Anticancer Treatment in an In Vitro Human Microbiota Model: A Pilot Study With Hydroxycarbamide and Daunorubicin.

Background: Anticancer drug efficacy is linked to the gut microbiota's composition, and there is a dire need to better understand these interactions for personalized medicine. In vitro microbiota models are promising tools for studies requiring controlled and repeatable conditions. We evaluated the impact of two anticancer drugs on human feces in the MiniBioReactor Array (MBRA) in vitro microbiota system. Methods: The MBRA is a single-stage continuous-flow culture model, hosted in an anaerobic chamber. We evaluated the effect of a 5-day treatment with hydroxycarbamide or daunorubicine on the fecal bacterial communities of two healthy donors. 16S microbiome profiling allowed analysis of microbial richness, diversity, and taxonomic changes. Results: In this host-free setting, anticancer drugs diversely affect gut microbiota composition. Daunorubicin was associated with significant changes in alpha- and beta-diversity as well as in the ratio of Firmicutes/Bacteroidetes in a donor-dependent manner. The impact of hydroxycarbamide on microbiota composition was not significant. Conclusion: We demonstrated, for the first time, the impact of anticancer drugs on human microbiota composition, in a donor- and molecule-dependent manner in an in vitro human microbiota model. We confirm the importance of personalized studies to better predict drug-associated-dysbiosis in vivo, linked to the host's response to treatment.

Cytoreductive treatment and association with platelet function and maturity in patients with essential thrombocythaemia.

Patients with essential thrombocythaemia (ET) have an increased risk of thromboembolic events, which may differ according to different cytoreductive drugs. We investigated the effect of cytoreductive treatment on platelet function and turnover in ET patients. Blood samples were obtained at 1 and 24 h after aspirin intake. Platelet function was evaluated by platelet aggregation and flow cytometry. Platelet turnover was assessed by immature platelet count, immature platelet fraction (IPF) and mean platelet volume (MPV). A total of 47 ET patients were included and grouped into 21 patients not receiving cytoreductive treatment, 15 patients receiving hydroxycarbamide and 11 patients receiving pegylated interferon alpha (peg-IFN). Patients receiving peg-IFN had significantly higher IPF and MPV than the other ET groups. Patients not receiving cytoreductive treatment had significantly higher platelet aggregation 24 h after aspirin intake than the other ET groups (p-values from 0.03 to 0.0002). Patients receiving hydroxycarbamide had significantly higher expression of platelet granule makers, P-selectin and CD63, than patients receiving peg-IFN (p-values ≤0.003). Cytoreduction provides more consistent platelet inhibition compared with no cytoreductive treatment. Moreover, peg-IFN provides superior inhibition of platelet activation markers than hydroxycarbamide, which in part may explain differences in risk of thromboembolic events in ET patients.

Transfusional Approach in Multi-Ethnic Sickle Cell Patients: Real-World Practice Data From a Multicenter Survey in Italy.

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03397017.

Higher hydroxyurea adherence among young adults with sickle cell disease compared to children and adolescents.

BACKGROUND: Sickle cell disease (SCD) results in severe complications, such as anaemia and pain episodes. Hydroxyurea (HU) is efficacious in SCD, yet adherence remains low. OBJECTIVE: To assess the relationship of HU adherence to health care utilization and patients' characteristics. METHODS: This is a 5-year retrospective chart review. Patients' demographics and medical history were collected from the electronic medical record (EMR). HU adherence was evaluated using foetal haemoglobin "HbF%", mean corpuscular volume "MCV", and absolute neutrophil count "ANC". Age groups included children (<12 years), adolescents (12-17 years), and young adults (≥18 years). RESULTS: A total of 113 SCD patients on HU were included (median age 14 years, IQR 10-20; 50% female; 88% HbSS). Young adults had significantly higher HU adherence compared to adolescents and children, including higher median HbF% (24.2 vs. 12.4 vs. 8.6, p = .003), MCV (fl) (106.4 vs. 96.2 vs. 95.4, p = .01) and lower ANC (103/ml) (3.25 vs. 4.9 vs. 4.2, p = .01), respectively. Patients with chronic pain had lower HU adherence (HbF% 15.3 vs. 10.7, p = .04; ANC 3.6 vs. 6.3, p = .002; MCV 102.3 vs. 93.1, p = .1). Patients with higher HbF or MCV and lower ANC had significantly less frequent emergency room visits (rs=-0.26, p = .01; rs=-0.23, p = .01; rs=0.24, p = .01) and hospitalizations (rs=-0.27, p = .01; rs=-0.31, p = .01; rs=0.21, p = .02) as well as shorter length of stays (rs=-0.27, p = .0045; rs=-.34, p = 0.004; rs=0.23, p = .02), respectively. Similar trends in HU adherence and health care utilization were seen in subgroup analysis of only HbSS patients. There was no significant association of HU adherence to patients' sex, socio-economic status, distance from hospital, and HU duration. CONCLUSIONS: Young adults with SCD had significantly higher HU adherence compared to children and adolescents. Patients with lower HU adherence and/or chronic pain had increased health care utilization. Future studies examining barriers to adherence and evaluating interventions to optimize HU adherence in SCD are warranted.KEY MESSAGESYoung adults with SCD had significantly higher HU adherence, as reflected in their laboratory markers, compared to children and adolescents.Patients with higher HU adherence and/or those without chronic pain had lower or less frequent health care utilization.No significant association of HU adherence to patients' sex, socio-economic status and distance from hospital.

Cost analysis of acute care resource utilization among individuals with sickle cell disease in a middle-income country.

BACKGROUND: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized hematology center in Brazil. METHODS: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period. RESULTS: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSß0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSß0-thalassemia were admitted more often (79% versus 21%, p < 0.0001), and their admission costs were higher ($1677.18 versus $1224.47/visit, p = 0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs. Costs of ED visits not resulting in admissions were lower among HbSS/HbSß0-thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR <65% ($98.16/visit versus $182.46/visit, p = 0.0007). No difference in admission costs were observed relative to hydroxyurea use. DISCUSSION: In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSß0-thalassemia but is dependent on adherence level.

Evaluating the implementation of a multi-level mHealth study to improve hydroxyurea utilization in sickle cell disease.

Background: Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the intervention implementation. In this report, we describe engagement with stakeholders, planning of the implementation process, and final analytical plan to evaluate the implementation outcomes. Methods: During 19 meetings, a 16-member multidisciplinary SCDIC implementation team created, conceived, and implemented a project that utilized Intervention Mapping to guide designing an intervention and its evaluation plan. The process included five steps: (1) needs assessment of low hydroxyurea utilization, (2) conceptual framework development, (3) intervention design process, (4) selection of models and frameworks, and (5) designing evaluation of the intervention implementation. Results: Behavioral theories guided the needs assessment and the design of the multi-level mHealth intervention. In designing the evaluation approach, we combined two implementation frameworks to best account for the contextual complexity at the organizational, provider, and patient levels: (1) the Consolidated Framework for Implementation Research (CFIR) that details barriers and facilitators to implementing the mHealth intervention at multiple levels (users, organization, intervention characteristics, broader community), and (2) the Technology Acceptance Model (TAM), a conceptual model specific for explaining the intent to use new information technology (including mHealth). The Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) framework was used to measure the outcomes. Discussion: Our research project can serve as a case study of a potential approach to combining different models/frameworks to help organize and plan the evaluation of interventions to increase medication adherence. The description of our process may serve as a blueprint for future studies developing and testing new strategies to foster evidence-based treatments for individuals living with SCD.

Alpha haemoglobin-stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment.

Alpha haemoglobin-stabilising protein (AHSP) is a key chaperone synthesised in red blood cell (RBC) precursors. Many studies have reported AHSP as a potential biomarker of various diseases. AHSP gene expression has been studied in detail, but little is known about AHSP protein levels in RBCs. We investigated the AHSP concentration of RBC lysates from control subjects (n = 10) and patients with sickle cell anaemia (SCA) with (n = 10) and without (n = 12) hydroxycarbamide (HC) treatment, to evaluate the clinical relevance of AHSP in SCA. We developed a sandwich enzyme-linked immunosorbent assay method, with which we were able, for the first time, to determine the mean AHSP concentration in control RBC lysates (0·82 µg/ml). The AHSP concentration (2·23 µg/ml) was significantly higher in untreated patients with the SS genotype than in controls. The AHSP concentration decreased significantly on HC treatment (1·50 µg/ml) but remained significantly higher than that in controls. A strong positive correlation was observed between the AHSP concentration and the α-haemoglobin pool with the three groups of subjects pooled into a single group. Our present findings indicate that AHSP concentration can be considered a candidate biomarker for monitoring HC responses in patients with SCA and suggest a role for AHSP in various RBC diseases.

Oxygen gradient ektacytometry does not predict pain in children with sickle cell anaemia.

The loss of red blood cell (RBC) deformability in sickle cell anaemia (SCA) is considered the primary factor responsible for episodes of acute pain and downstream progressive organ dysfunction. Oxygen gradient ektacytometry (Oxygenscan) is a recently commercialised functional assay that aims to describe the deformability of RBCs in SCA at differing oxygen tensions. So far, the Oxygenscan has been evaluated only by a small number of research groups and the validity and clinical value of Oxygenscan-derived biomarkers have not yet been fully established. In this study we examined RBC deformability measured with the Oxygenscan in 91 children with SCA at King's College Hospital in London. We found a significant correlation between Oxygenscan-derived biomarkers and well-recognised modifiers of disease severity in SCA: haemoglobin F and co-inherited α-thalassaemia. We failed, however, to find any independent predictive value of the Oxygenscan in the clinical outcome measure of pain, as well as other important parameters such as hydroxycarbamide treatment. Although the Oxygenscan remains an intriguing tool for basic research, our results question whether it provides any additional information in predicting the clinical course in children with SCA, beyond measuring known markers of disease severity.