However, although most pain experienced by SCD patients

is likely due to vaso-occlusion, there are also other mechanisms of pain that are poorly understood. A schema for the differential diagnosis of SCD-related pain as well as systematic approach to the treatment of SCD-related pain are presented in Fig. 4[40]. In addition, there is a paucity of specialised resources available for patients aged > 18 years seeking treatment for SCD-related pain. For patients presenting with acute VOE, rapid and aggressive treatment is needed. Traditional treatments include opioids, non-steroidal anti-inflammatory drugs, and hydration [40]. Hydroxyurea (discussed below), although not helpful for acute relief, can decrease the learn more number of painful episodes when taken chronically. Relaxation techniques, warmth, massage, and psychological pain management (e.g. cognitive behavioural therapy) should be considered. It is essential to examine all patients presenting with VOE for signs of infection [41], ACS, pulmonary embolism, splenic or hepatic sequestration,

cholecystitis, stroke, or other underlying etiologies. Many high-risk complications may also present as VOE, and thus careful evaluation of patients with pain is critical. One study of SCD patients aged > 21 years demonstrated that more than 50% of patients who died in the hospital were admitted with the diagnosis of seemingly uncomplicated VOE [42]. Transfusion therapy is not recommended for patients with isolated acetylcholine pain crisis because of the see more significant

risk of iron overload in patients who receive more than 20 lifetime blood transfusions, as well as the propensity for allo-antibody formation. Hydroxyurea (HU) is currently the only established preventative pharmacologic treatment for both paediatric and adult patients with recurrent VOEs [43] and [44]. The mechanism of action is partly a result of the increased production of foetal haemoglobin, as well as decreased production of leukocytes and reticulocytes that may contribute to vaso-occlusion [43] and [44]. The Multi-Centre Study of Hydroxyurea in Sickle Cell Anaemia (MSH) confirmed its efficacy in adults with SCD by reducing the number of acute VOEs and hospitalisations [45]. There are also significant cumulative data from several multicentre, randomised, placebo-controlled studies in paediatric patients that demonstrate the safety and efficacy of HU in children [46], [47], [48] and [49]. Paediatric patients maintained on the maximum tolerated dose of HU over several years showed significant reductions in VOEs, hospitalisations, end-organ damage, chronic hypoxemia, and stroke without significant neutropenia, growth reduction, documented carcinogenesis, or end-organ damage. HU is grossly under-utilised in high-resource countries, likely in part because of a lack of physicians comfortable with prescribing the medication, as well as the current recommendations for periodic laboratory testing.