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• W4281832415 abstract "A 28-year-old man presented to the emergency department with right shoulder pain that radiated to the right arm as well as pain of the right hip and lower back. His medical history is significant for sickle cell disease (SCD) with the HbSS genotype (homozygous for the S globin). He had a hemorrhagic stroke in the setting of venous sinus thrombosis 2 years earlier with no persisting neurologic deficits as well as osteonecrosis of bilateral hips and right knee requiring right total hip arthroplasty and right total knee arthroplasty. His pain started 3 days earlier after he exerted himself performing yard work and had progressively worsened. He described the pain as sharp, throbbing, and 10/10 in severity. The pain did not improve with acetaminophen or oxycodone. He also reported shortness of breath, which had resolved. He did not have fever, chills, chest pain, cough, abdominal pain, diarrhea, or recent trauma. Home medications included apixaban, l-glutamine, hydroxyurea, and folic acid. He had not missed any doses of his medications. He required 2 admissions in the past year for sickle cell pain crisis. Vital signs demonstrated an oral temperature of 37.7°C, blood pressure of 122/82 mm Hg, heart rate of 99 beats/min, respiratory rate of 19 breaths/min, and oxygen saturation of 94% on room air. Physical examination found tenderness to palpation of the right shoulder, right arm, and right hip with limited range of motion secondary to pain. There was no ecchymosis, erythema, or warmth of the shoulder or hip joints. Peripheral pulses were normal. Lungs were clear to auscultation bilaterally. Laboratory evaluation revealed the following (reference ranges provided parenthetically): hemoglobin, 9.0 g/dL (13.5 to 17.5 g/dL); hematocrit, 26.7% (38.3% to 48.6%); platelet count, 267 × 109/L (135 to 317 × 109/L); white blood cell count, 13.2 × 109/L (3.4 to 9.6 × 109/L); neutrophils, 10.29 × 109/L (1.56 to 6.45 × 109/L); lymphocytes, 1.51 × 109/L (0.95 to 3.07 × 109/L); monocytes, 1.09 × 109/L (0.26 to 0.81 × 109/L); eosinophils, 0.03 × 109/L (0.03 to 0.48 × 109/L); basophils, 0.06 × 109/L (0.01 to 0.08 × 109/L); sodium, 134 mmol/L (135 to 145 mmol/L); potassium, 4.1 mmol/L (3.6 to 5.2 mmol/L); bicarbonate, 25 mEq/L (22 to 29 mEq/L); blood urea nitrogen, 11 mg/dL (8 to 24 mg/dL); creatinine, 0.85 mg/dL (0.74 to 1.35 mg/dL); calcium, 9.8 mg/dL (8.8 to 10.2 mg/dL); glucose, 85 mg/dL (70 to 140 mg/dL); and procalcitonin, 0.17 ng/mL (≤0.15 ng/mL). Absolute reticulocyte count was 198 × 109/L (30.4 to 110.9 × 109/L) with a reticulocyte index of 3.1%. His baseline hemoglobin level ranged from 9 to 10 g/dL. Hemoglobin S percentage was 81.5%, which was increased from 69.8% at time of diagnosis. Radiographic examination of the right shoulder showed stable changes of the proximal humerus, suggesting chronic avascular necrosis (Figure). Radiographic examination of the hips and pelvis showed stable right total hip arthroplasty with well-seated components without evidence of loosening. In addition, there was unchanged sequela of left femoral head osteonecrosis. Chest film showed no focal consolidation, pleural effusion, or pneumothorax. Electrocardiographic findings were unremarkable, with no notable ischemic changes. High-sensitivity troponin level was normal.1.Which of the following is the most likely diagnosis?a.Acute avascular necrosisb.Acute coronary syndromec.Opioid-induced hyperalgesiad.Osteomyelitise.Vaso-occlusive crisis (VOC) On evaluation of a patient with SCD and acute pain, it is important to rule out common orthopedic complications of SCD, such as avascular necrosis.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar Radiography is the initial study of choice when avascular necrosis is suspected clinically. In this case, radiographs of the hips and right shoulder were obtained, which showed evidence of chronic avascular necrosis unchanged from prior films. Whereas this is likely to be a cause of chronic pain for our patient, it would not explain his acute pain. Acute coronary syndrome can be manifested as atypical chest pain or pain of the shoulder or arm. This was appropriately ruled out with a normal electrocardiogram and high-sensitivity troponin level. Opioid-induced hyperalgesia is a type of neuropathic pain that can occur with long-term opioid use.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar In addition to hyperalgesia (increased pain in response to a stimulus that should provoke pain), patients may also experience allodynia (pain in response to a stimulus that usually does not provoke pain) with escalating opioid dosages. This diagnosis is unlikely as the patient has not taken opioids long term for pain. Impaired immune function and functional asplenia place patients with SCD at risk for development of osteomyelitis.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar However, in the absence of fever, localized erythema, or swelling, this diagnosis is less likely. Our patient did have a mildly elevated white blood cell count on presentation. Leukocytosis can be seen in sickle cell patients without an infection. Vaso-occlusive crisis is the most likely diagnosis. Patients typically present with a sudden onset and throbbing and sharp pain involving the lower back, joints, or extremities.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar There is often a prodromal phase of 1 or 2 days with symptoms of numbness, paresthesia, or aches in the associated area.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar The patient was subsequently admitted to the hospital for management of VOC.2.What initial treatment should be given for this patient’s condition?a.Exchange transfusionb.Intravenous fluidsc.Nonsteroidal anti-inflammatory drugs (NSAIDs)d.Opioidse.Simple transfusion Exchange transfusion is not indicated for VOC alone; however, exchange transfusion is used in the setting of acute ischemic stroke, severe acute chest syndrome (ACS), multiorgan failure, acute sickle hepatopathy, and severe sepsis.2Howard J. Sickle cell disease: when and how to transfuse.Hematology Am Soc Hematol Educ Program. 2016; 2016: 625-631Crossref PubMed Scopus (62) Google Scholar There is a role for hydration with intravenous fluids if there is clinical evidence of dehydration to restore the patient to a euvolemic state.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar,3Brandow A.M. Carroll C.P. Creary S. et al.American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain.Blood Adv. 2020; 4: 2656-2701Crossref PubMed Scopus (51) Google Scholar Whereas hydration with intravenous fluids can be a useful adjunctive therapy, it should not preclude adequate pain management. American Society of Hematology guidelines for management of acute pain related to SCD issue a conditional recommendation for 5 to 7 days of NSAIDs in addition to opioids.3Brandow A.M. Carroll C.P. Creary S. et al.American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain.Blood Adv. 2020; 4: 2656-2701Crossref PubMed Scopus (51) Google Scholar It is important to consider potential harms of NSAID use, such as renal, vascular, and gastrointestinal toxic effects. Our patient takes apixaban for history of venous sinus thrombosis, and NSAIDs would increase bleeding risk. Thus, NSAIDs would not be appropriate or the first management option. The cornerstone of therapy for VOC is rapid (preferably within 30 minutes) and effective analgesia with opioid medications.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar An individualized approach based on baseline opioid therapy and prior effective therapy is recommended.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar,3Brandow A.M. Carroll C.P. Creary S. et al.American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain.Blood Adv. 2020; 4: 2656-2701Crossref PubMed Scopus (51) Google Scholar Intranasal and subcutaneous routes of administration should also be considered to prevent delay in administration of analgesia.3Brandow A.M. Carroll C.P. Creary S. et al.American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain.Blood Adv. 2020; 4: 2656-2701Crossref PubMed Scopus (51) Google Scholar Simple transfusion is indicated in the case of symptomatic anemia in SCD but not for isolated vaso-occlusive pain.2Howard J. Sickle cell disease: when and how to transfuse.Hematology Am Soc Hematol Educ Program. 2016; 2016: 625-631Crossref PubMed Scopus (62) Google Scholar Iron overload and increased risk of red blood cell (RBC) alloimmunization may result from frequent blood transfusions.2Howard J. Sickle cell disease: when and how to transfuse.Hematology Am Soc Hematol Educ Program. 2016; 2016: 625-631Crossref PubMed Scopus (62) Google Scholar,4Fasano R.M. Booth G.S. Miles M. et al.Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease.Br J Haematol. 2015; 168: 291-300Crossref PubMed Scopus (150) Google Scholar He received treatment with a morphine patient-controlled analgesia pump. Subsequently, the morphine patient-controlled analgesia pump was transitioned to oral oxycodone as needed when his pain was better controlled. The following day, a fever developed, with temperature of 38.1°C. He also noted shortness of breath and pleuritic chest pain. Oxygen saturation on room air was 96%. Blood culture specimens were obtained. Electrocardiography revealed sinus tachycardia with a heart rate of 105 beats/min and no ST-segment changes.3.Which of the following is the next most appropriate diagnostic evaluation?a.Arterial blood gasb.Bronchoalveolar lavagec.Computed tomography pulmonary angiography (CTPA)d.D-dimere.Troponin With development of fever, shortness of breath, and pleuritic chest pain, there was clinical concern for ACS. Acute chest syndrome often develops after onset of severe pain and is defined as an acute illness characterized by fever or respiratory symptoms, with a new pulmonary infiltrate on chest imaging.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar Other signs and symptoms of ACS may include hypoxia, chest pain, skeletal pain, and hemoptysis.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar Arterial blood gas analysis is useful for confirming hypoxia but is not usually necessary in adult patients with oxygen saturation above 94% on room air, such as in our case. Bronchoalveolar lavage would not be done before confirming a pulmonary infiltrate and is typically needed only if patients are not responding to standard therapy. The appropriate next step is CTPA because chest imaging is needed to confirm the diagnosis of ACS. Whereas ACS can be diagnosed with chest radiography, CTPA can be useful in excluding pulmonary embolism and is recommended if there is a high clinical suspicion of pulmonary embolism.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar D-dimer testing is not helpful in SCD because levels are typically elevated.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar With an electrocardiogram showing no ischemic changes, acute coronary syndrome is unlikely, and troponin should be ordered only if other work-up is unrevealing. Our patient’s CTPA study found consolidative air space disease in the right lower lobe with no evidence of pulmonary embolism.4.What is the next most appropriate step in management of this patient’s condition?a.Exchange transfusionb.Bronchodilator therapyc.Corticosteroidsd.Antibiotic therapye.Inhaled nitric oxide A pulmonary infiltrate was identified along with symptoms of chest pain and shortness of breath, which meets criteria of ACS. Exchange transfusion is warranted for severe clinical features, such as worsening hypoxia, increased respiratory rate, thrombocytopenia, or multilobar disease on chest imaging.2Howard J. Sickle cell disease: when and how to transfuse.Hematology Am Soc Hematol Educ Program. 2016; 2016: 625-631Crossref PubMed Scopus (62) Google Scholar The decision to initiate exchange transfusion should be made only after consultation with a hematologist. Our patient had disease localized to 1 lobe and no significant hypoxia or oxygen requirements; therefore, exchange transfusion was deferred with careful monitoring of evidence of clinical deterioration. Simple transfusion is recommended to be administered early in the hypoxic or symptomatic patient to increase hemoglobin level to greater than 10 g/dL, and failure to improve after simple transfusion is another indication for exchange transfusion.2Howard J. Sickle cell disease: when and how to transfuse.Hematology Am Soc Hematol Educ Program. 2016; 2016: 625-631Crossref PubMed Scopus (62) Google Scholar Bronchodilators should be used only if patients have a history of asthma or evidence of bronchospasm.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar Corticosteroids are indicated only in the case of acute asthma exacerbation, and there is a risk of rebound sickling with corticosteroid use.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar Because clinicians can usually not distinguish causes of ACS, patients must be treated empirically for pneumonia, including coverage of atypical organisms such as Mycoplasma and Chalmydophila.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar Whereas case reports have found benefit with inhaled nitric oxide therapy, there are no randomized controlled trials to support its routine use for ACS.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar Our patient was prescribed moxifloxacin, a respiratory fluoroquinolone with pseudomonal coverage that can be used for hospital-acquired pneumonia. He also received 1 simple transfusion. During the next 48 hours, he showed improvement in symptoms, including resolution of fever, chest pain, and shortness of breath. On hospital day 4, he was discharged home, with follow-up in the hematology clinic arranged.5.Which of the following medications should be given to prevent recurrence of VOC?a.Crizanlizumabb.Aspirinc.Montelukastd.Rivaroxabane.Simvastatin Crizanlizumab is a humanized monoclonal antibody that inhibits P-selectin.6Ataga K.I. Kutlar A. Kanter J. et al.Crizanlizumab for the prevention of pain crises in sickle cell disease.N Engl J Med. 2017; 376: 429-439Crossref PubMed Scopus (339) Google Scholar The SUSTAIN trial reported that crizanlizumab is associated with significantly lower frequency of pain crises and similar incidence of serious adverse effects in patients with SCD compared with placebo,6Ataga K.I. Kutlar A. Kanter J. et al.Crizanlizumab for the prevention of pain crises in sickle cell disease.N Engl J Med. 2017; 376: 429-439Crossref PubMed Scopus (339) Google Scholar leading to its approval by the Food and Drug Administration (FDA) in 2019. Studies have investigated aspirin and montelukast for management of SCD, and neither drug was found to decrease the frequency or severity of VOC.7Greenberg J. Ohene-Frempong K. Halus J. Way C. Schwartz E. Trial of low doses of aspirin as prophylaxis in sickle cell disease.J Pediatr. 1983; 102: 781-784Abstract Full Text PDF PubMed Scopus (76) Google Scholar,8Field J.J. Kassim A. Brandow A. et al.Phase 2 trial of montelukast for prevention of pain in sickle cell disease.Blood Adv. 2020; 4: 1159-1165Crossref Scopus (1) Google Scholar Anticoagulants like rivaroxaban have a role in managing some complications of SCD, such as thrombotic events; however, there is no evidence to suggest that rivaroxaban prevents VOC. In addition, the patient was already taking apixaban for history of sinus venous thrombosis. Simvastatin is hypothesized to benefit SCD because of its ability to decrease inflammation and to improve endothelial function.9Hoppe C. Jacob E. Styles L. Kuypers F. Larkin S. Vichinsky E. Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial.Br J Haematol. 2017; 177: 620-629Crossref PubMed Scopus (35) Google Scholar A small pilot study with 19 individuals reported reduction in sickle cell–related pain in patients treated with simvastatin for 3 months.9Hoppe C. Jacob E. Styles L. Kuypers F. Larkin S. Vichinsky E. Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial.Br J Haematol. 2017; 177: 620-629Crossref PubMed Scopus (35) Google Scholar Larger, randomized controlled trials are needed to further evaluate the efficacy of simvastatin in reducing VOC and hospitalizations in SCD. He returned to the hematology clinic after his hospitalization and was subsequently prescribed monthly intravenous infusions of crizanlizumab. Three months later, he has not required hospitalization for any complication of SCD including VOC. Sickle cell disease, the most common hemoglobinopathy, is due to a mutation in the β-globin gene, producing hemoglobin S (HbS). This altered hemoglobin protein is more likely to polymerize in the deoxygenated state, causing reduced deformability and thus “sickling” of RBCs.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar,10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Clinical manifestations of SCD are heterogeneous, depending on the specific genotype. Our patient had HbSS disease, which typically is manifested with severe features of multiorgan involvement. Infections, severe anemia, and VOC are acute complications of SCD that require prompt diagnosis and treatment. It is important to identify potential triggers of VOC, such as dehydration, hypoxia, significant physical or emotional stress, temperature extremes, infection, and select comorbidities.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar Our patient was a 28-year-old man who presented with VOC, which may have been triggered by his physically exerting himself while performing yardwork. It is also possible that a respiratory infection may have triggered VOC, leading to indiscernible consolidations on chest imaging. He initially had diffuse joint pain but quickly developed systemic symptoms concerning for ACS. This rapid progression of multiorgan involvement is explained by the underlying mechanisms of VOC. The polymerized sickled RBCs from HbSS disease adhere to vascular endothelium and induce chronic inflammation through chemokines. This chronic inflammation promotes microvascular occlusion, large-vessel intimal hyperplasia, thrombosis, bone marrow fat embolization, and ultimately tissue ischemia.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar Acute chest syndrome can develop when pulmonary tissue and vasculature are involved. Manifestations of ACS can include pulmonary infections, fat embolism, and infarction. The sequelae of ACS can induce a V/Q mismatch, leading to respiratory distress and persistent hypoxia.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar A mild form of ACS was suspected in our patient because of radiographic evidence of a pulmonary infiltrate, fever, and pleuritic chest pain. Our patient was not found to have significant hypoxia and did not require supplemental oxygen. Acute chest syndrome represents a spectrum of disease, ranging from a mild respiratory illness to respiratory failure, with severe hypoxia associated with a higher transfusion requirement and increased mortality.5Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. BCSH CommitteeGuideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (84) Google Scholar Because the clinical features of pneumonia also meet the criteria for ACS, treatment of coexisting entities was of utmost importance. In general, the management of SCD involves treating symptomatic anemia and preventing complications of SCD, such as VOC. Hydroxyurea was the first drug approved by the FDA for treatment of homozygous SCD.10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Hydroxyurea works by increasing fetal hemoglobin production and decreasing intracellular HbS polymerization.10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Adults with SCD treated with hydroxyurea have fewer episodes of VOC and ACS, require fewer blood transfusions, and have longer overall survival.10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar l-Glutamine, an amino acid precursor for nicotinamide adenine dinucleotide, is another therapy for SCD approved by the FDA. Glutamine and glutathione levels are depleted in erythrocytes in patients with SCD, which is believed to be due to increased oxidation in sickle RBCs and higher l-glutamine consumption.10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar l-Glutamine has been reported to decrease hospitalizations and frequency of VOC and ACS in patients with SCD.1Darbari D.S. Sheehan V.A. Ballas S.K. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management.Eur J Haematol. 2020; 105: 237-246Crossref Scopus (30) Google Scholar,10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Crizanlizumab, a humanized monoclonal antibody, works by inhibiting P-selectin. P-selectin is responsible for initiating the process of leukocyte adhesion to the endothelium, which is known to contribute to abnormal blood flow in patients with SCD.6Ataga K.I. Kutlar A. Kanter J. et al.Crizanlizumab for the prevention of pain crises in sickle cell disease.N Engl J Med. 2017; 376: 429-439Crossref PubMed Scopus (339) Google Scholar The SUSTAIN trial compared crizanlizumab with placebo in 198 patients with SCD, reporting a lower rate of VOC in the high-dose crizanlizumab group (1.08 per year) compared with placebo (2.91 per year).6Ataga K.I. Kutlar A. Kanter J. et al.Crizanlizumab for the prevention of pain crises in sickle cell disease.N Engl J Med. 2017; 376: 429-439Crossref PubMed Scopus (339) Google Scholar Adverse effects of crizanlizumab include nausea, vomiting, arthralgias, pruritus, and chest pain.6Ataga K.I. Kutlar A. Kanter J. et al.Crizanlizumab for the prevention of pain crises in sickle cell disease.N Engl J Med. 2017; 376: 429-439Crossref PubMed Scopus (339) Google Scholar Voxelotor was the most recent drug to gain FDA approval in the treatment of SCD. Voxelotor is an oral agent that works by inhibiting sickled hemoglobin polymerization. The HOPE trial reported significant improvements in hemoglobin concentrations and reductions in hemolysis markers with voxelotor compared with placebo.11Howard J. Ataga K.I. Brown R.C. et al.Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Haematol. 2021; 8: e323-e333Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Future studies are needed to determine the impact of this drug on hospitalizations and mortality in SCD. Allogeneic hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for SCD that works by replacing the patient’s hematopoietic stem cells with a donor’s cells, allowing normal RBC production.10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar In patients with severe complications of SCD, such as stroke, recurrent episodes of VOC, ACS, recurrent priapism, osteonecrosis, or transfusion-associated alloimmunization, HSCT should be considered.10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar The limited availability of suitable donors along with the risk of complications after transplant, such as infection, graft failure, and graft-vs-host disease, is a barrier to HSCT for most patients.10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar In 2017, a 13-year-old boy with HbSS disease became the first person to be successfully treated with gene therapy.10Kapoor S. Little J.A. Pecker L.H. Advances in the treatment of sickle cell disease.Mayo Clin Proc. 2018; 93: 1810-1824Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Gene therapy, a rapidly evolving field, uses genetically modified autologous stem cells, eliminating the requirement for a donor.12Frangoul H. Altshuler D. Cappellini M.D. et al.CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia.N Engl J Med. 2021; 384: 252-260Crossref PubMed Scopus (311) Google Scholar Several clinical trials are currently underway to further study the safety and efficacy of gene therapy for SCD. Whereas newer therapies have helped to increase life expectancy and improve morbidity associated with SCD, gene therapy has the potential to soon revolutionize the management of SCD. The authors report no competing interests." @default.
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