Simon 2016
Simon 2016
Simon 2016
370–381, 2016
Ó 2016 Elsevier Inc. All rights reserved.
0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2016.05.042
Clinical
Review
Erica Simon, DO, MHA,* Brit Long, MD,* and Alex Koyfman, MD†
*Department of Emergency Medicine, San Antonio Military Medical Center, Fort Sam Houston, Texas and †Department of Emergency
Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas
Reprint Address: Brit Long, MD, 506 Dakota Street, Apartment 1, San Antonio, TX 78203
, Abstract—Background: Sickle cell disease (SCD) affects prevalent in persons of African, Mediterranean, Indian,
approximately 100,000 individuals in the United States. Due and Middle Eastern descent (1–3). The sickle cell
to alterations in the structural conformation of hemoglobin mutation is inherited in an autosomal recessive fashion;
molecules under deoxygenated conditions, patients with SCD homozygotes exhibit sickle cell disease (SCD or HbSS)
are predisposed to numerous sequelae, many of which require
and heterozygotes exhibit sickle cell trait (SCT).
acute intervention. Objective: Our aim was to provide emer-
Assuming that they have not inherited a second
gency physicians with an evidence-based update regarding
the diagnosis and management of SCD complications. abnormal hemoglobin (Hb) chain, individuals with SCT
Discussion: SCD patients experience significant morbidity are commonly asymptomatic and possess a normal
and mortality secondary to cerebrovascular accident, acute lifespan, while those with SCD are predisposed to
chest syndrome, acute vaso-occlusive pain crises, SCD-related severe infections, complications associated with
multi-organ failure, cholecystitis, acute intrahepatic chole- repetitive capillary obstruction, painful vaso-occlusive
stasis, acute sickle hepatic crisis, acute hepatic sequestration, crises, and multi-system organ damage (1,2).
priapism, and renal disease. Emergency physicians must recog- Complications of SCD occur secondary to the sickle
nize acute manifestations of SCD in order to deliver timely cell mutation: a sixth codon substitution of the B-globin
management and determine patient disposition. Conclusions: chain, replacing hydrophobic valine with hydrophilic
A comprehensive review of the emergency department
glutamic acid, thereby causing sickling of the Hb
management of acute SCD complications is provided. Compre-
molecule under de-oxygenated conditions. The congre-
hensive understanding of these aspects of SCD can assist physi-
cians in expediting patient evaluation and treatment, thus gation of these sickled cells results in microvascular
decreasing the morbidity and mortality associated with this sludging and vascular obstruction, leading to the acute
hemoglobinopathy. Ó 2016 Elsevier Inc. All rights reserved. manifestations (1,2).
As SCD is a component of American newborn
, Keywords—sickle cell disease; acute chest; acute pain screening, the discovery of undiagnosed SCD in the
crisis; cerebrovascular accident; transfusion emergency department (ED) is relatively uncommon.
More frequently, patients with known SCD present to
INTRODUCTION the ED for evaluation secondary to sequelae of the disease
after the fourth month of life (decline in fetal hemoglobin
Sickle cell disease (SCD) affects nearly 100,000 concentration) (3).
individuals in the United States, and approximately Emergency physicians are adept at managing
2 million Americans carry the sickle cell trait. SCD is multiple disease processes; however, given the range of
370
Emergency Medicine Management of Sickle Cell Disease 371
pathophysiologic manifestations of SCD, encounters mentioned for secondary CVA prevention, experts
with these patients often prove challenging. This review also recommend regular transfusions to maintain Hb
seeks to provide emergency physicians with an improved S < 30%; however, data supporting this intervention
understanding of SCD complications and an evidence- was collected in young adults with SCD having
based approach to their management. experienced their first CVA during childhood (hence its
employment in the pediatric population, as discussed
MANAGING ACUTE COMPLICATIONS OF SCD: later) (6).
VASO-OCCLUSIVE CRISES AND SEQUELAE OF In contrast to adults, magnetic resonance imaging
HEMOGLOBINOPATHY (MRI) with diffusion-weighted imaging and MRA of
the head and neck should be performed in pediatric
Vaso-Occlusive Crises
patients with suspected acute ischemic stroke, as a
Cerebrovascular accident: Ischemic stroke and intracra- non-contrast head CT will miss early signs of ischemic
nial hemorrhage. Cerebrovascular accident (CVA), infarct (5). All pediatric patients diagnosed with an
including ischemic stroke and subsequent intracranial ischemic stroke thought secondary to SCD should receive
hemorrhage due to hemorrhagic conversion of the intravenous (IV) fluids and undergo exchange transfusion
ischemic stroke, is a major complication of SCD. Patients to achieve an Hb S level of < 30% (5). This procedure
presenting to the ED for assessment will display should be performed in consultation with a hematologist.
symptoms that vary according to the anatomic location If an exchange transfusion cannot be arranged, a simple
of the infarct or hemorrhage. Small infarcts in the adult transfusion should be performed (5). A maximum Hb of
and pediatric populations are relatively common and 13 g/dL status post transfusion is the recommended
involve the basal ganglia and deep white matter within target, as pediatric children with SCD may be at risk
the anterior circulation (4). Risk factors for CVA in for recurrent ischemia secondary to increased blood
patients with SCD include low Hb, history of acute chest viscosity (5). Currently, thrombolysis is not recommen-
syndrome (ACS), and history of hypertension (4). The ded in pediatric SCD patients presenting with ischemic
pathophysiology regarding anemia and a history of CVAs (5). One key point that the emergency physician
ACS as CVA risk factors is poorly understood. SCD must consider when evaluating the pediatric SCD patient
experts hypothesize severe anemia as precipitating is that hemorrhagic transformation occurs in 30% of
increased cerebral blood flow and increased cerebral children with arterial ischemic and is frequently
flow velocity, thereby predisposing SCD patients (the asymptomatic (7).
majority experiencing chronic anemia) to cerebrovascu- To date, there are no published studies regarding the
lar damage. Scientists also postulate the temporal management of hemorrhagic CVA in adult or pediatric
association between ACS and CVAs as resulting from SCD patients (6). Previously recognized efficacious
repetitive episodes of hypoxia in the setting of ACS. treatments for acute intracranial hemorrhage in the
This hypoxia likely causes additional damage to cerebral general adult and pediatric population include reversal
vessels, previously injured by microvascular insults (5). of anticoagulation, treatment in an intensive care unit
In the assessment of adult and pediatric patients (ICU), treatment of seizures with antiepileptic agents,
presenting with symptoms concerning for acute intracra- and appropriate management of blood pressure (BP) (6).
nial pathology, neuroimaging is key. Initial evaluation of While BP management in acute CVA is well addressed
the adult patient commonly includes non-contrast head in adult emergency medicine literature, the management
computed tomography (CT), subsequently followed by of pediatric hypertension in the setting of CVA is not as
CT angiography or magnetic resonance angiography well studied. Hypertension in children, defined as
(MRA) during the inpatient course. BP > 95th percentile for age, within the first 72 h after
Goals for the acute treatment of ischemic stroke in the ischemic stroke is associated with an increased risk of
adult SCD patient include limiting injury due to the CVA death (8). In the pediatric population, a BP goal of the
and establishing secondary prevention through the 50–95th percentile for age and height, with permissive
optimization of cerebral perfusion (maintenance of hypertension up to 20% > 95th percentile, should be
euglycemia and normothermia and avoidance of hypoxia) targeted (6). Pediatric experts recommend use of
(6). Caution is advised when considering the administra- labetolol or an angiotensin-converting enzyme inhibitor
tion of thrombolytics to adult SCD patients experiencing to lower BP by 25%, though renal function should be
an acute ischemic CVA. Increased rates of intracranial considered (6,9).
hemorrhage have been reported in this patient population Of note, seizures are common after pediatric neuro-
(6). Similar to adult patients without a medical history of logic injury (10). Patients with persistent lethargy or
SCD, antiplatelet and statin therapy should be considered altered mental status should be evaluated with electro-
after an ischemic CVA (6). In addition to the strategies encephalography for subclinical seizure activity (7).
372 E. Simon et al.
Clinical presentation Chest pain, fever, shortness of breath, hypoxia Chest pain, fever, shortness of breath
Laboratory studies Leukocytosis Leukocytosis
Chest x-ray study New infiltrate (pediatric: middle or upper lobe; adult: lower lobe) No acute cardiopulmonary findings
Treatment Antibiotics: community-acquired pneumonia vs. health Pain controlled without hypoxia: home
care–associated pneumonia (history-dependent); Unable to attain pain relief: admission
ICU admission
Feared complication Acute respiratory distress syndrome Atelectasis and subsequent pneumonia
due to splinting and low tidal volumes
In the setting of SCD, an investigation of alternative an infiltrate and associated pleural effusion (14). See
causes of CVA cannot be overlooked. Etiologies include Table 1 for a review of ACS vs. pulmonary symptoms
infection, cardiac embolism, and cavernous venous sinus of APC.
thrombosis (7). ACS can rapidly progress to acute respiratory distress
Imaging, to include MRI and MRA of the head and syndrome due to pulmonary sequestration or infarct.
neck, may be essential in narrowing the differential Given this fact, patients with signs or symptoms
diagnosis (7). consistent with ACS should be managed in an intensive
care setting. Long-term complications of ACS include
ACS.ACS, the most common reason for ICU admission in pulmonary fibrosis, pulmonary hypertension, and cor
the SCD patient population, is a leading cause of pulmonale. Acute right ventricular failure is a
morbidity and mortality (case fatality rate of 10%) (11). complication of ACS and if suspected, ultrasound (US)
The classic triad of ACS includes fever, hypoxia, and a should be utilized to assess right ventricular contractility
new pulmonary infiltrate on chest x-ray study. The and size (14).
presence of any one of these signs or symptoms should Evidence-based guidelines and expert panels are
raise clinical suspicion in the setting of SCD. When shown in Table 2 for the management and treatment of
evaluating a patient for ACS, a chest x-ray study should ACS.
be obtained to identify the presence of a new infiltrate,
a complete blood count (CBC) should be sent to assess APC. Vaso-occlusive pain crises may manifest in a
anemia, and continuous oxygenation monitoring should number of locations, including the pulmonary system,
be performed to detect hypoxia. central nervous system, skeletal system (arthralgias/
While the pathogenesis of ACS has yet to be deter- dactylitis), and gastrointestinal system (abdominal
mined, infection secondary to Mycoplasma pneumoniae pain). In the setting of these crises, patients commonly
frequently represents the underlying etiology in the present with fever and leukocytosis (12). Although fever
pediatric population (12). In adult sickle cell patients, and leukocytosis are not specific indicators of infection, it
Chlamydophila pneumonia is the most commonly is wise to evaluate for an infectious etiology in the sickle
encountered pathogen (13). Additional non-infectious cell patient population, as these individuals are highly
etiologies of ACS include fat emboli (released as a result susceptible to pathogens (addressed within at a later
of bony infarct from vaso-occlusion) and pulmonary juncture) (11).
emboli (disseminated post microvascular pulmonary SCD patients are prone to several complications that
infarction) (13). must be considered during the evaluation of patients
Differentiating ACS and pulmonary acute pain crisis presenting with pain crisis. These complications range
(APC) (which will be discussed) is difficult, as these from the sequelae of hemoglobinopathy to renal
SCD complications often present with fever, shortness pathology (both later addressed) to the infectious
of breath, chest pain, and leukocytosis (1,2,14). Any etiologies mentioned. Inquiries regarding prior pain
respiratory symptoms associated with chest pain and crises, differences between current and previous
hypoxia should raise suspicion for ACS. A new episodes, the presence of fever, transfusion history,
infiltrate on chest x-ray study is diagnostic of ACS, as medications, baseline Hb level, and a thorough physical
opposed to APC. Unfortunately, the chest x-ray study examination can assist in determining diagnoses. Any
may be normal early in ACS (2,14). When evaluating atypical pain pattern not consistent with previous
chest x-ray studies, note that children are more likely to episodes requires further evaluation.
display upper or middle lobe disease, as opposed to In addition to an assessment for conditions requiring
adults, who frequently display lower lung disease with acute interventions, it is important to note that the
Emergency Medicine Management of Sickle Cell Disease 373
Level of Quality of
Recommendation Recommendation Evidence
ACS patients should be hospitalized for pain control and SpO2 monitoring Consensus Panel expertise
ACS patients should receive antibiotics (parenteral cephalosporin or oral macrolide therapy) Strong Low quality
ACS patients should receive supplemental O2 to maintain SpO2 > 95% Strong Low quality
Patients with ACS should receive a blood transfusion to improve O2 carrying capacity Weak Low quality
if Hb is > 1 g/dL below baseline (if baseline is > 9 g/dL, may not be required;
consult hematology)
ACS with rapid progression (SpO2 < 90% despite O2 therapy, respiratory distress, progressive Strong Low quality
pulmonary infiltrates, decline in Hb despite simple transfusion) requires urgent exchange
transfusion
Consult hematology
management of pain crises includes the provision of early the provision of patient analgesia in APCs (16–22). If
analgesia—an area in which emergency physicians possible, organizations should work toward the
commonly under-prescribe (2,3). Evidence-based development of APC patient-management protocols, as
guidelines regarding management and treatment of pain case studies have demonstrated decreased time to the
crises are demonstrated in Table 3. delivery of patient analgesia, improvement in overall
Opioid analgesics are the current mainstay of APC patient pain control, decreased frequency of ED visits,
therapy. Morphine, fentanyl, and hydromorphone are fewer total hospital days, and increased utilization
commonly utilized in the ED treatment of acute pain of primary provider services status post algorithm
crisis (15–23). Caution is recommended in the employment (23–25).
utilization of meperidine (normeperidine, the active As depicted in Figure 1, pain-control adjuvants
metabolite of meperidine, undergoes renal excretion detailed by the NHLBI include sedatives, anxiolytics,
and is associated with an increased incidence of and antihistamines. While employed to augment the
seizures in the setting of renal dysfunction; a finding analgesic effect of opioids by managing associated
common in occlusive crisis) (3,12,15). symptoms, such as anxiety, and to prevent mast cell
Varying algorithms for the management of APC degranulation induced by opioid administration,
are detailed by multiple guidelines and organizations controlled studies of these treatments in SCD are lacking,
(16–22). Provided as an example, the National Heart, and per the NHLBI, guidelines for their use are derived
Lung, and Blood Institute (NHLBI) algorithm is from employment in other pain states (16).
depicted in the Figure 1. This example was chosen by Similar to other algorithms and treatment guidelines,
the authors given its value in demonstrating an the NHLBI recommends that all patients who do not
all-encompassing approach to patient analgesia: the achieve adequate pain relief be admitted to the hospital
inclusion of patient perception of pain, a mention of for further therapy (16). Patients with an anticipated
detailed recommendations regarding initial opioid discharge to home should be prescribed an oral
dosing, the provision of direction regarding adjuncts to pain-control regimen with potency comparable to the
pain control, and an emphasis on repeated patient IV pain regimen, which provided pain relief during the
assessment in determining disposition. hospital course (16–22).
As all of the APC guidelines note, further studies are For APC patients requiring admission, patient-
required to evaluate the adequacy of varying opioid controlled pain management strategies deserve
analgesics regimens in controlling APC pain, to consideration by the emergency physician. Despite the
determine the efficacy of delivery routes and dosing need for further research, case reports and limited case
intervals, and to develop consensus statements regarding studies have demonstrated shorter time to pain control,
Initiate analgesia within 30 min of triage; provide multi-modal Consensus Panel expertise
(opioid and adjunct) analgesia
Employ individualized prescribing and pain-monitoring protocols Consensus Panel expertise
Give nonsteroidal anti-inflammatory drugs as adjuvant pain therapy Moderate Low quality
374 E. Simon et al.
Figure 1. National Heart, Lung, and Blood institute algorithm for the management of acute pain crisis (16). SCD = sickle cell
disease.
Emergency Medicine Management of Sickle Cell Disease 375
Figure 1. (Continued).
376 E. Simon et al.
improved pain relief and, in some cases, earlier time to Exchange transfusion is often warranted in association
hospital discharge among patients receiving patient- with hematology consultation (14).
controlled pain management (26,27).
Sequelae of Hemoglobinopathy
In addition to pain control, literature addressing APC
treatment commonly advises the initiation of oxygen Right upper quadrant abdominal pain. Abdominal
supplementation and fluid resuscitation. However, recent complications are common in SCD, especially
guidelines question these classic treatments. To date, complications causing pain in the right upper quadrant
oxygen has demonstrated no benefit in SCD pain crises, (RUQ). For SCD patients with RUQ pain, the challenge
and new research suggests it may actually result in for the emergency physician is to ascertain the underlying
myelosuppression and an increased need for transfusion etiology: cholelithiasis, cholecystitis, acute intrahepatic
(14). Current expert guidelines recommend that if cholestasis (AIC), acute sickle hepatic crisis, or acute
saturations remain > 92%, no supplemental oxygen is hepatic sequestration (AHS) (1). In the evaluation of
recommended (14). Although IV fluids are frequently RUQ pathology, initial studies including CBC, liver
provided in the setting of APC, it is now commonly function tests, coagulation panel (prothrombin time/
recognized that excessive hydration can contribute to activated partial thromboplastin time/international
atelectasis, hyperchloremic metabolic acidosis (if normal normalized ratio [PT/aPTT/INR]), and imaging with
saline is utilized), and pulmonary edema. If the patient is ultrasound (US) or CT are essential.
overtly dehydrated and hypovolemic, IV fluids are Hemolysis precipitates the formation of pigmented
warranted. Otherwise, maintenance of euvolemia is gallstones in up to 70% of patients, increasing the
encouraged (14). risk of symptomatic cholelithiasis and cholecystitis in
Although this review centers on the management of SCD (2).
acute SCD complications, hydroxycarbamide (also AIC is a result of sickled red blood cells (RBCs)
known as hydroxyurea [HU]) therapy warrants occluding hepatic sinusoids, causing vascular stasis and
mention. HU is the most common intervention utilized local hypoxia. As Kupffer cells (hepatic macrophages)
in the long-term management of SCD for the preven- phagocytose sickled erythrocytes, canaliculi occlude
tion of vaso-occlusive events (28). HU has been with bile (30). Patient presentation ranges from isolated
demonstrated to increase fetal Hb levels, subsequently hyperbilirubinemia with preserved hepatic function
preventing the polymerization of Hb S under deoxy- (PT/aPTT/INR within normal limits) to RUQ pain,
genated conditions (17,28,29). As demonstrated by transaminitis, and extreme elevations of bilirubin and
the Multi-Center Study of Hydroxyurea in Sickle Cell alkaline phosphatase. In the latter case, renal failure,
Anemia and the Pediatric Hydroxyurea Phase 3 Clin- thrombocytopenia, and severely prolonged coagulation
ical Trial (BABY HUG), the administration of HU times often develop (31). If severe acute intrahepatic
significantly decreases the incidence of adult and pedi- cholestasis is suspected, early consultation with
atric vaso-occlusive crisis, APC, and rates of hospital- hematology for exchange transfusion is indicated.
ization secondary to SCD complications (17,28,29). If Acute sickle hepatic crisis affects 10% of patients
not previously initiated, HU therapy should be admitted for abdominal pain crises (31). Acute sickle
considered in consultation with a hematologist for all hepatic crisis simulates acute cholecystitis with RUQ
patients presenting to the ED with SCD pain, fever, leukocytosis, and variable increases in serum
complications (27). transaminases and bilirubin levels; however, unlike
cholecystitis, hepatomegaly occurs (31). Treatment is
SCD-related multi-organ failure. This severe, life- supportive with pain control and consultation for possible
threatening complication of SCD is characterized by transfusion (1,31).
sudden vaso-occlusion with organ failure, specifically AHS occurs secondary to obstruction of sinusoidal
affecting the lungs, liver, and kidneys. Patients may flow by masses of sickled erythrocytes and can be a
present with fever, tachypnea, and, in severe cases, complication of acute sickle hepatic crisis (15,30). In
hemodynamic compromise (14). Careful assessment of addition to RUQ pain, fever, jaundice, and
the pulmonary and renal systems, including advanced hepatomegaly, an acute drop in Hb and hematocrit
imaging, is advised. Laboratory studies commonly reveal with reticulocytosis occurs (31). Consultation with
elevated lactate dehydrogenase, anemia, thrombocyto- hematology is recommended. This too can be an
penia, and an acute kidney injury or acute renal failure. indication for simple or exchange transfusion (1,32).
Chest x-ray study is often notable for multi-lobar It is important to note that the laboratory studies of a
infiltrates. Patients with SCD-related multi-organ failure patient with SCD cannot be interpreted in a vacuum.
require ICU admission in addition to specialty In SCD patients, chronic liver disease often occurs
hematology or nephrology, or both, consultation (14). secondary to hemosiderosis (transfusions) and silent
Emergency Medicine Management of Sickle Cell Disease 377
HIDA = hepatobiliary; PT/aPTT/INR = prothrombin time/activated partial thromboplastin time/international normalized ratio; RUQ = right upper quadrant; TTP = tenderness to palpation;
HIDA scan vs. elective cholecystectomy
hematologist)
pathology, pericholecystic fluid, and increased
echogenicity of the gallbladder and pancreas secondary
to iron deposition (a known complication of recurrent
transfusions) (33). Data regarding the utilization of CT
in the evaluation of sickle cell patients with abdominal
hyperbilirubinemia
Table 4 offers a summary of RUQ pathology.
biliary sludge
Splenic sequestration. Splenic sequestration typically
occurs in children 10–27 months of age, but it may be
seen as early as 2 months of age (11,12). Pooling
of RBCs in splenic sinusoids results in
splenic sequestration, with an acute decline in Hb
Examination Findings
hepatomegaly
Fever, RUQ TTP
RUQ TTP
pain, pallor, tachycardia, and hypotension. Sequestration
can rapidly progress to shock and death. Decreases in Hb
levels > 4 g/dL are associated with 35% mortality in the
pediatric population (11,12).
RUQ pain, mid-epigastric pain, nausea,
US = ultrasound.
of illness (41). It is also advised that oseltamivir decrease in Hb levels in the setting of acute splenic
chemoprophylaxis be given to all patients, aged or hepatic sequestration crisis (12). Exchange
3 months or older, having a known exposure to persons transfusions are needed in the setting of suspected or
with confirmed influenza infections (American confirmed CVA, treatment-resistant acute chest or
Academy of Pediatrics recommendation; oseltamivir is acute lung disease, multi-organ failure, preparation for
Food and Drug Administration–approved for use in general anesthesia, and priapism unresponsive to other
patients > 1 year of age) (41). treatment (12).
In order to prevent serious infection among SCD
patients, the following measures have also been Transfusion complications. Transfusing RBCs to patients
recommended by the CDC: with SCD can be precarious, as increasing RBC mass
increases blood viscosity, thereby exacerbating sickling
1. Prophylactic penicillin V for patients aged 2 months
(12). In addition to increased blood viscosity, the
to 5 years to prevent serious bacterial infection (1).
complication of multi-transfusion hepatopathy is also
2. Pneumococcal vaccine at 2 months of age to reduce
well studied in the sickle cell population. Individuals
the risk of pneumococcal infection (1).
receiving repetitive transfusions may experience hepatic
3. Influenza vaccination at 6 months and annually
iron overload, subsequently requiring chelation therapy
thereafter (1).
(37). Blood-borne infections including chronic hepatitis
4. Meningococcal vaccination for children with
B, hepatitis C, and cytomegalovirus are also commonly
splenic dysfunction at 2 years of age (1).
encountered in the highly transfused sickle cell
Although commonly addressed by primary care population; however, studies reporting the prevalence of
managers, it serves the emergency physician to make in- these infections (supported by confirmative genotyping
quiries regarding penicillin prophylaxis and vaccination and polymerase chain reaction) are limited (37). The risks
status during encounters with SCD patients, as this infor- and benefits of a simple vs. exchange transfusion
mation will aid in the development of differential diagno- should always be determined in consultation with a
ses (42). specialist (12).
4. Roach S, Golomb M, Adams R, et al. Management of stroke in the use of opioids in adult patients. Br J Haematol 2014;
infants and children. American Heart Association: scientific 166:157–64.
statement. Stroke 2008;39:2644–91. 23. Tanabe P, Hafner J, Martinovich Z, Artz N. Adult emergency
5. Ohene-Frempong K, Weiner S, Sleeper L, et al. Cerebrovascular department patients with sickle cell pain crisis: results from a
accidents in sickle cell disease: rates and risk factors. Blood quality improvement learning collaborative model to improve
1998;91:288–94. analgesic management. Acad Emerg Med 2012;19:430–8.
6. Strouse J, Lanzkron S, Urrutia V. The epidemiology, evaluation and 24. Kavanagh P, Sprinz P, Wolfgang T, et al. Improving the
treatment of stroke in adults with sickle cell disease. Expert Rev management of vaso-occlusive episodes in the pediatric emergency
Hematol 2011;4:597–606. department. Pediatrics 2015;136:e1016–25.
7. Elbers J, Wainwright M, Amlie-Lefond C. The pediatric stroke 25. Givens M, Rutherford C, Joshi G, Delaney K. Impact of an
code: early management of the child with stroke. J Pediatr 2015; emergency department pain management protocol on the visits by
167:19–244. patients with sickle cell disease. J Emerg Med 2007;32:239–43.
8. Beslow LA, Smith SE, Vossough A, et al. Hemorrhagic 26. van Beers EJ, van Tuijn CF, Nieuwkerk PT, et al. Patient-controlled
transformation of childhood arterial ischemic stroke. Stroke 2011; analgesia versus continuous infusion of morphine during
42:941–6. vaso-occlusive crisis in sickle cell disease, a randomized controlled
9. Brush LN, Monagle PT, Mackay MT, Gordon AL. Hypertension at trial. Am J Hematol 2007;82:955–60.
time of diagnosis and long-term outcome after childhood ischemic 27. Gonzalez ER, Bahal N, Hansen LA, et al. Intermittent injection vs
stroke. Neurology 2013;80:1225–30. patient-controlled analgesia for sickle cell crisis pain. Comparison
10. Abend NS, Gutierrez-Colina AM, Topjian AA, et al. Nonconvulsive in patients in the emergency department. Arch Intern Med 1991;
seizures are common in critically ill children. Neurology 2011;76: 151:1373–8.
1071–7. 28. Wang W. Minireview: prognostic factors and the response to
11. Eskenazi AE, Bertstein MC, Gordon JB. Hematologic disorders in hydroxyurea treatment in sickle cell disease. Exp Biol Med 2016;
the pediatric intensive care unit. In: Rogers MC, ed. Textbook of 241:730–6.
Pediatric Intensive Care. 3rd ed. Baltimore, MD: Lippincott 29. Thornburg C, Files B, Luo Z, et al. Impact of hydroxyuria on
Williams & Wilkins; 1997:1395–431. clinical events in the BABY HUG trial. Blood 2012;20:4304–10.
12. Jenkins T. Sickle cell anemia in the pediatric intensive care unit: 30. Norris W. Acute hepatic sequestration in sickle cell disease. J Natl
novel approaches for managing life-threatening complications. Med Assoc 2004;96:1235–9.
AACN Clin Issues 2002;13:154–68. 31. Ebert E, Nagar M, Hagspiel K. Gastrointestinal and hepatic
13. Sickle cell in the ICU. Critical Care Perspectives in the Emergency complications of sickle cell disease. Clin Gastroenterol Hepatol
Room. 2015. Available at: http://ccpem.com/index.php?option=com_ 2010;8:483–9.
easyblog&view=entry&id=499&Itemid=101. Accessed December 32. Johnson C, Omata M, Tong M, et al. Liver involvement in sickle cell
01, 2015. disease. Medicine (Baltimore) 1985;64:349–56.
14. Cecchini J, Fartoukh M. Sickle cell disease in the ICU. Curr Opin 33. Banerjee S, Owen C, Chopra S. Sickle cell hepatopathy. Hepatology
Crit Care 2015;21:569–75. 2001;33:1021–8.
15. Afenyi-Annan A, Ballas S, Hassell K, et al. Managing acute 34. Gebreselassie S, Simmons M, Montague D. Genitourinary manifes-
complications of sickle cell disease. In: Evidence-Based tations of sickle cell disease. Cleve Clin J Med 2015;82:679–83.
Management of Sickle Cell Disease. Bethesda, MD: National Heart, 35. De Gracia-Nieto A, Samper A, Rojas-Cruz C, et al. Genitourinary
Lung, and Blood Institute; 2014:31–54. manifestations of sickle cell disease. Arch Esp Urol 2011;64:597.
16. National Institutes of Health. National Heart, Lung, and Blood 36. Bruno D, Wigfall D, Zimmerman S, et al. Genitourinary
Institute Division of Blood Diseases and Resources. The complications of sickle cell disease. J Urol 2001;166:803.
management of sickle cell disease. Bethesda, MD: NIH publication 37. Olujohungbe A, Burnett A. How I manage priapism due to sickle
02–2117; 2002. Available at: https://www.nhlbi.nih.gov/files/docs/ cell disease. Br J Haematol 2013;160:754.
guidelines/sc_mngt.pdf. Accessed December 01, 2015. 38. Montague D, Jarow J, Broderick G, et al. American Urological
17. Lovett P, Sule H, Lopez B. Sickle cell disease in the emergency Association guideline on the management of priapism. J Urol
department. Emerg Med Clin North Am 2014;32:629–47. 2003;170(4 Pt 1):1318–24.
18. Rees D, Olujohungbe A, Parker N, Stephens A, Telfer P, Wright J. 39. Sobota A, Sabharwal V, Fonebi G, Steinberg M. How we prevent
Guidelines for the management of the acute painful crisis in sickle and manage infection in sickle cell disease. Br J Haematol 2015;
cell disease. Br J Haematol 2003;20:744–52. 170:757–67.
19. Olujohungbe A, Bennett L, Chapman C, et al. Standards for the 40. Bundy D, Strouse J, Casella J, Miller M. Burden of influenza-related
clinical care of adults with sickle cell disease in the UK. 2008. hospitalization among children with sickle cell disease. Pediatrics
Available at: http://sct.screening.nhs.uk/getdata.php?id=10991. Ac- 2010;125:234–43.
cessed December 01, 2015. 41. Centers for Disease Control and Prevention. Influenza. Influenza
20. NHS Sickle Cell and Thalassaemia Screening Programmes. Sickle antiviral medications: summary for clinicians. 2016. Available at:
cell disease in childhood: standards and guidelines for clinical care. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.
Published 2010. Available at: http://sct.screening.nhs.uk. Accessed htm. Accessed December 01, 2015.
December 01, 2015. 42. Savlov D, Beck C, DeGroot J, Odame I, Friedman J. Predictors of
21. National Institute for Health and Care Excellence (NICE). Sickle bacteremia among children with sickle cell disease presenting
cell acute painful episode: Management of an acute painful with fever. J Pediatr Hematol Oncol 2014;36:384–8.
sickle cell episode in hospital. NICE Clinical Guideline 143. 43. Rogers ZR, Nickerson BG. Life-threatening complications in sickle
http://guidance.nice.org.uk/CG143. Accessed December 01, 2015. cell disease. In: In: Levin DL, Morriss FC, eds. Essentials of
22. Telfer P, Bahal N, Lo A, Challands J. Management of the Pediatric Intensive Care. 2nd ed., Vol. II. New York: Churchill
acute painful crisis in sickle cell disease—a re-evaluation of Livingstone, Quality Medical Publishing; 1997:483–7.
Emergency Medicine Management of Sickle Cell Disease 381
ARTICLE SUMMARY
1. Why is this topic important?
Sickle cell disease (SCD) affects approximately
100,000 individuals in the United States and is due to
structural abnormalities in hemoglobin. Patients with
SCD are predisposed to numerous sequelae, many of
which require acute intervention.
2. What does this review attempt to show?
This review provides an evidence-based update in the
diagnosis and management of SCD complications.
3. What are the key findings?
SCD patients experience significant morbidity and
mortality secondary to cerebrovascular accident, acute
chest syndrome, vaso-occlusive pain crises, SCD-related
multi-organ failure, cholecystitis, acute intrahepatic
cholestasis, acute sickle hepatic crisis, acute hepatic
sequestration, priapism, and renal disease. Common treat-
ments, such as provision of intravenous fluids and supple-
mental oxygen, are not supported in current literature
outside of the setting of hypovolemia and hypoxemia.
Many of the acute complications of SCD require blood-
product transfusion or exchange transfusion in association
with specialist consult. Early diagnosis and management
of these conditions can improve outcomes.
4. How is patient care impacted?
This discussion and review of SCD complications ap-
proaches key pearls and pitfalls in the diagnosis and man-
agement of SCD complications, while citing evidence-
based recommendations.