Sickle cell disease (SCD) is a genetically inherited autosomal recessive disorder caused by a missense mutation in the β-globin gene, resulting in substitution of valine for glutamic acid and the production of abnormal hemoglobin S (HbS) (1, 2). Under deoxygenation, HbS polymerizes distorting red blood cells into rigid “sickle” shapes that occlude microvasculature, trigger vaso-occlusive crises (VOCs), and eventually results in chronic hemolysis, ischemia-reperfusion injury, and multi-organ damage over time (1, 2). These pathophysiologic effects contribute to lifelong morbidity and premature mortality.

Globally, SCD remains a major burden, particularly in Sub-Saharan Africa, India, and the Middle East, where prevalence is highest (3, 4). In Saudi Arabia, SCD is endemic in several provinces with notable heterogeneity. In some regions, carrier rates (sickle cell trait) range from 2 to 27% and in high-burden areas the disease prevalence is up to ∼2.6% (3, 4). Moreover, according to systematic evaluations, the prevalence of SCD in some regions of Saudi Arabia is between 2 and 4%; recent research on the quality of life for Saudi patients (ASH) emphasizes this burden even more (5). Additionally, the Eastern and Southwestern provinces exhibit the greatest SCD burden, partly driven by high rates of consanguineous marriage and population founder effects (4–6).

Despite improved survival and advances in disease-modifying therapies, the health system impact of SCD in Saudi Arabia remains substantial. High ED utilization reflects both the severity and unpredictability of vaso-occlusive pain and gaps in outpatient support infrastructure. Patients frequently depend on hospital-based resources, particularly emergency departments (EDs), for acute care of VOCs and related complications (7–9). Furthermore, patients are encouraged to use emergency department (ED) services as entry points for care in resource-constrained settings, due to factors such as limited access to hematology specialists, geographic disparities in care, insufficient outpatient clinics, overcrowded tertiary hospitals, and obstacles in referral routes. These systemic limitations may increase avoidable ED visits, elevating expenses and placing a burden on acute care resources (10–12).

In SCD, pain is the hallmark and most frequent trigger for ED presentation. Effective analgesia, almost universally, involving opioids must balance urgency of symptom relief with concerns about tolerance, hyperalgesia, and the risk of misuse (13, 14). A recent study confirms that opioids remain the treatment of choice for VOC-associated pain, but prescribing practices differ widely across centers, and adherence to pain management protocols is inconsistent (13). The American Society of Hematology and other guideline bodies emphasize early, protocolled analgesia, but real-world deviations are common. However, disparities in clinician knowledge, local policy constraints, biases toward patients with SCD, and variable application of monitoring strategies complicate opioid management (15).

Moreover, the burden of comorbidity in SCD patients who accumulate organ damage, renal dysfunction, pulmonary hypertension, stroke, and endocrine disturbances modulates pain experiences and health service use (16). As patients age, the cumulative burden of chronic complications may increase frequency and severity of VOCs, thereby escalating ED dependency (16). Conversely, lower ED visitation in socioeconomically marginalized or uninsured groups may reflect care access barriers rather than lower disease burden. These patterns complicate inferences about ED utilization and warrant context-specific study (17).

While prior investigations have linked ED use in SCD to factors such as age, gender, insurance status, comorbidities, and disease phenotype, most are single-center or regionally confined, limiting generalizability; only few have leveraged multicenter electronic health record (EHR) datasets to integrate patient-level risk factors with system-level modifiers in Saudi Arabia or the broader Gulf region (7, 9, 11). A deeper understanding of these determinants can guide interventions like stratified pain protocols, improved outpatient follow-up capabilities, telehealth support, or resource redistribution to reduce preventable ED burden and improve patient-centered outcomes.

Therefore, to fill this knowledge gap, our study uses multicenter EHR data to assess temporal trends and predictors of ED utilization among patients with SCD across multiple NGHA tertiary centers in Saudi Arabia between 2016 and 2021. By clarifying these relationships, our findings may support refined pain management protocols, optimize outpatient care networks, and reduce avoidable ED reliance, thereby lowering costs and improving quality of life for SCD patients in Saudi Arabia.

In this multicenter retrospective cohort of 691 patients with sickle cell disease (SCD) across five NGHA tertiary hospitals in Saudi Arabia (2016–2021), we observed a marked and sustained increase in emergency department (ED) utilization, with mean annual visits rising by 76.3%. The escalation was most pronounced among younger adults and men, revealing widening demographic disparities in acute-care dependence. Importantly, the mean ED visit rate reached the high-utilization threshold in 2021, indicating a critical shift wherein the “average” SCD patient now meets criteria previously reserved for super-utilizers. This finding signals a growing strain on emergency services and highlights the urgency for targeted outpatient and community-based interventions. These findings reflect the combined effects of disease progression, system-level limitations in chronic-care access, and evolving service utilization patterns during a period of rapid health-system transformation.

Data was extracted directly from the institutional electronic health record (EHR) system, minimizing the likelihood of manual data-entry errors and ensuring complete longitudinal capture of emergency department (ED) encounters. Year-to-year variation in ED utilization was therefore interpreted as reflecting true changes in healthcare use rather than data inaccuracies. Such variability is expected in sickle cell disease (SCD) populations due to the episodic nature of vaso-occlusive events, seasonal and environmental influences, fluctuations in outpatient care access, and system-level factors, including changes in patient eligibility policies. Observed spikes in utilization, including during the COVID-19 pandemic period (2020–2021), were considered consistent with known shifts toward emergency-based care during disruptions to routine services. Accordingly, analyses focused on overall temporal trends rather than year-specific fluctuations.

The temporal increase in ED visits parallels reports from international and regional cohorts. In a U.S. registry analysis (2013–2019), only 1.8% of patients were classified as “super-high” users (≥ 33 visits/year), yet they accounted for more than half of total visits, underscoring how a small subset drives system burden (23). Regional research from Saudi Arabia similarly highlights reliance on emergency services among patients with SCD. In a cross-sectional study conducted at King Fahad Hospital, 64.3% of patients reported three or more ED visits within a 6 month period, with a median of four visits, underscoring not only frequent acute presentations but also the potential impact of pain crises and general health status on utilization (24), while another study identified male gender and educational attainment as independent predictors of higher use (9). Our multicenter design extends this evidence by demonstrating longitudinal growth in utilization and by revealing that gender and age effects persisted after adjustment for comorbidities and site.

Moreover, multiple factors may explain the upward trajectory. First, improved survival has expanded the adult NGHA SCD population in Saudi Arabia, allowing accumulation of chronic organ damage renal impairment, pulmonary hypertension, and avascular necrosis that precipitate recurrent pain crises (7, 25, 26). Second, health-system accessibility has simultaneously increased universal coverage through the Ministry of National Guard Health Affairs and enhanced ED capacity have reduced barriers to presentation, potentially encouraging ED-centered management of acute pain (27–29). Third, the COVID-19 pandemic (2020–2021) disrupted routine outpatient care and transfusion follow-ups, shifting disease control toward emergency pathways (30, 31). The convergence of improved survival, easier access, and pandemic-related disruption likely accelerated ED reliance during the latter study years.

Furthermore, male patients had higher adjusted ED visit rates than females. This contrasts with earlier Western reports in which women exhibited slightly greater healthcare use, attributed to estrogen-related modulation of nitric-oxide bioavailability and heightened pain sensitivity (32). Relatively older studies, however, mirror our findings as it showed poorer health-related quality of life among Saudi men with SCD, suggesting more severe end-organ disease (24, 33, 34). Lower fetal-hemoglobin levels, higher prevalence of nephropathy and leg ulcers in men, and gender norms that discourage early presentation until crises become severe are examples of biological and social factors that may coexist (35). Additionally, the steepest growth among young adults further implicates transition-of-care challenges when patients move from pediatric to adult hematology services a well-recognized vulnerability for recurrent ED visits. Hence, biological factors, differences in disease phenotype, sociocultural expectations regarding health seeking behavior, and occupational or lifestyle exposures may all play a role in these gender based patterns. Therefore, further research is recommended to better characterize the mechanisms underlying these differences and their implications for tailored interventions.

Although asthma (9.3%) was the most common comorbidity, none significantly predicted ED frequency after adjustment. Prior studies have linked asthma to more frequent vaso-occlusive crises via hypoxia-induced inflammation (36), yet the modest prevalence and potential underdiagnosis in our dataset may have attenuated this effect. On the other hand, medication analyses confirmed near-universal opioid administration (96.5%), consistent with ASH 2020 guidelines recommending rapid opioid initiation for vaso-occlusive pain (37). The low rate of extended-day opioid prescribing (6.5%) suggests adherence to short course protocols and growing awareness of dependency risks. Nevertheless, variation in adjunct therapy use (benzodiazepines 42.4% and neuropathic agents 43.3%) points to heterogeneity in multimodal pain management across NGHA centers. Therefore, standardizing these protocols could improve analgesic adequacy and reduce return visits (38).

Regional heterogeneity likely reflects differences in disease prevalence, resource distribution, and health literacy profiles. The Eastern and Southwestern provinces historical SCD clusters host higher case densities and greater acute care demand (39). Variations in specialist availability, outpatient follow-up models, and telemedicine coverage could explain the differences across sites. Moreover, the observed heterogeneity in ED utilization are possibly explained by structural and organizational variation across NGHA hospitals, rather than differences in disease burden alone. Within the NGHA system, hospitals differ substantially in bed capacity, emergency department size, subspecialty availability, and referral areas. These system-level differences influence not only patient flow and referral patterns, but also thresholds for ED presentation and admission. While variation in coding practices cannot be entirely excluded, NGHA hospitals operate under standardized clinical, administrative, and coding frameworks, reducing the likelihood that coding alone accounts for the observed heterogeneity. Hence, establishing integrated SCD comprehensive care networks with shared registries and online consultation may help redistribute care away from emergency departments (40). Moreover, social determinants of health, including insurance status, socioeconomic background, and health seeking behaviors may further explain regional disparities (41–43). Therefore, understanding these influences is essential for developing targeted, region specific interventions to reduce ED burden and improve equity in care delivery.

Rising ED utilization among patients with SCD signals urgent need for proactive, patient-centered care models that extend beyond episodic acute management. Frequent ED visits, hospital admissions, transfusions, and care for complications significantly contribute to the direct healthcare costs associated with SCD, imposing considerable pressure on tertiary services and national health resources (44).

Standardized national ED pain protocols, multidisciplinary outpatient clinics, and structured transition programs for adolescents could mitigate recurrent crises. These interventions align with the Saudi Vision 2030 Health Sector Transformation Program (HSTP), which prioritizes integrated, preventive, and value-based care model aimed at improving population health while containing costs and enhancing healthcare system performance (44–47). Saudi Vision 2030’s HSPT emphasizes restructuring the health system into an efficient, effective, and integrated system that enhances access, improves health outcomes, and increases quality while optimizing resource utilization (44–47). Moreover, from a cost and resource utilization perspective, Vision 2030 strategies emphasize preventive care, outpatient management models, and enhanced primary care to reduce the burden on the health system (44–47).

Digital registries, remote monitoring, telemedicine, and coordinated chronic disease bundles demonstrate Vision 2030 tools that are capable of improving SCD outcomes while reducing ED dependency (48, 49). Therefore, embedding SCD management within these frameworks can enhance equity by ensuring consistent access to comprehensive care across regions; optimize resource allocation by reducing high-cost emergency utilization; and lessen tertiary care congestion by strengthening ambulatory and preventive services.

Our data showed that the emergency department utilization among patients with sickle cell disease in the NGHA hospitals in Saudi Arabia increased substantially between 2016 and 2021, particularly among younger adults and men. These findings highlight persistent gaps in outpatient and preventive care and emphasize the need for standardized pain management and coordinated chronic care services within the evolving national health system.

Excess ED use can be reduced through short-stay observation units and multidisciplinary care models that improve continuity and coordination of care (50). Adapting these evidence-based strategies within the Saudi healthcare system may reduce recurrent ED dependence, improve patient outcomes, and enhance the efficiency of healthcare resource utilization.

This study has limitations due to its retrospective EHR design. A key limitation of the available data is that opioid prescriptions cannot be reliably linked to specific emergency department visits or clinical indications. As such, we are unable to determine whether opioids were prescribed in response to acute pain crises during ED encounters, as part of inpatient management, or within other clinical contexts. Given this limitation, opioid use in our study should not be interpreted as a proxy for disease severity, care quality, or as a causal contributor to recurrent ED visits. Moreover, data were confined to National Guard hospitals, therefore, encounters at non-network facilities were uncaptured. Additionally, another major limitation, is the unavailability of disease-specific clinical and VOCs ED utilization predictors such as pain severity scales, sickle cell genotype, hydroxyurea adherence, transfusion history, chronic pain syndromes, and socioeconomic indicators; which may have limited the explanatory depth. Moreover, although consistent ICD-10 definitions were used, misclassification bias may have been caused by diagnostic coding differences between locations. Therefore, the reported associations should be interpreted as system-level and population-level patterns rather than fully adjusted estimates of individual disease severity. Importantly, our analytic approach was designed to characterize healthcare utilization patterns within an integrated health system rather than to model biological disease severity. However, despite these constraints, multicenter coverage and analytic adjustment for site clustering strengthen internal validity and national relevance.

Prospective multicenter studies integrating genotype data, pain phenotyping, psychosocial metrics, and adherence monitoring are needed to identify modifiable drivers of recurrent ED use. Evaluating outcomes before and after Vision 2030-aligned reforms, such as tele-hematology clinics or opioid treatment programs will clarify which strategies most effectively improve quality of life and reduce acute-care burden.