Sickle cell disease (SCD) is an autosomal–recessive genetic illness that is caused by a mutation that replaces the sixth amino acid with valine resulting in the generation of irregular sickle–shaped erythrocyte that disrupt blood flow in small vessels [1, 2]. This vaso–occlusion leads to distal tissue ischemia, chronic hemolytic anemia, microvascular thrombosis, ischemic pain, tissue infarction, and poor quality of life . Frequent sickling and continuing hemolytic anemia could lead to chronic organ damage and parenchymal injury and eventually result in substantial morbidity and early mortality [1, 2]. Although the phenotypic expression of SCD is well- known, environmental factors, such as infections, cold weather and air quality, genetic predisposition, and fetal hemoglobin levels have been shown to impact the manifestations of the disease . In 2010, the number of newborns who have been diagnosed with SCD was estimated to be 305,800 globally, and is projected to increase by one–third to 404,200 patients in 2050 resulting in a total number of 14,242,000 newly diagnosed patients between 2010 and 2050 . In Saudi Arabia, the prevalence of SCD varies significantly between different regions mainly due to the variable rates of consanguineous marriages . The highest reported prevalence of SCD is in the Eastern region with a prevalence rate of 145 patients per 10,000 people, followed by the Southern region and Western region with prevalence rates of 24 patients per 10,000 people and 12 patients per 10,000 people, respectively,with two major phenotypes (e.g., the mild and severe phenotypes) [2, 6]. The mild phenotype is present among patients with the Arab/Indian haplotype and is characterized by elevated Hb F levels, whereas the Benin haplotype is more severe, and is most prevalent in the Western region .
Vaso–occlusion pain episodes are the hallmark of SCD accountable for acute systemic painful vaso–occlusive crisis (VOC) . VOCs are unpredictable and often require immediate emergency care and hospitalization . On the other hand, the chronic pain that accompanies SCD in many cases is not a mere continuation of VOC, but can be due to multiple reasons, such as, central sensitization, neuropathic pain, and avascular necrosis of bone at various joints (e.g., shoulders, hips, and ankles) . Therefore, the quality of life of SCD patients is greatly impaired due to the recurrent painful episodes, organ failures, neurocognitive deficits, and early mortality . According to an online questionnaire–based study that explored the impact of VOCs on health–related quality of life (HRQoL) among a sample of 303 adults with SCD in the United States, patients with frequent VOCs (e.g., ≥4 episodes) reported worse emotional and social functioning domains’ scores of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) . In Saudi Arabia, the HRQoL of 629 adult SCD patients was assessed in two tertiary care hospitals in the Eastern and Southern regions using the Medical Outcomes 36-Item Short-Form Health Survey (SF–36) questionnaire and found that patients who were presented with fever, swelling, skin redness, and received blood transfusions had worse SF–36 domains’ scores .
There are several therapeutic agents that have been approved for the management of SCD, such as hydroxyurea, L-glutamine, crizanlizumab, and voxelotor . Hydroxyurea (HU) is one of the oldest prescription drugs for the management of SCD that was approved by the United States Food and Drug Administration (USFDA) in 1998 and was until recently the only available therapy to ameliorate SCD severity . HU has shown to decrease the rates of acute chest syndrome, acute pain episodes, hospitalization, and red blood cell (RBC) transfusions in both adults and children with SCD [14, 15].
In Saudi Arabia, the painful VOCs episodes among SCD patients are mostly managed by HU besides opioid (e.g., codeine, hydrocodone/paracetamol, hydrocodone/ibuprofen, oxycodone, morphine, hydromorphone, oxymorphone, methadone, diamorphine and fentanyl) and non–opioid analgesics (e.g., paracetamol, celecoxib, naproxen, ibuprofen, and ketorolac) . However, the impact of HU on the rates of VOCs among SCD patients has only been examined in few studies and mostly among pediatric SCD patients despite the relatively high prevalence of SCD among certain communities in Saudi Arabia [17, 18]. Therefore, the aim of this study was to examine the impact of HU on the rates of VOCs and its impact on important hematological markers, such as Hgb, HCT, and PLT Ct among SCD patients in a large tertiary care referral center in Saudi Arabia.