The Journal of Emergency Medicine, Vol. 51, No. 4, pp. 370–381, 2016
! 2016 Elsevier Inc. All rights reserved.
0736-4679/$ - see front matter
EMERGENCY MEDICINE MANAGEMENT OF SICKLE CELL DISEASE
COMPLICATIONS: AN EVIDENCE-BASED UPDATE
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
prevalent in persons of African, Mediterranean, Indian,
and Middle Eastern descent (1–3). The sickle cell
mutation is inherited in an autosomal recessive fashion;
homozygotes exhibit sickle cell disease (SCD or HbSS)
and heterozygotes exhibit sickle cell trait (SCT).
Assuming that they have not inherited a second
abnormal hemoglobin (Hb) chain, individuals with SCT
are commonly asymptomatic and possess a normal
lifespan, while those with SCD are predisposed to
severe infections, complications associated with
repetitive capillary obstruction, painful vaso-occlusive
crises, and multi-system organ damage (1,2).
Complications of SCD occur secondary to the sickle
cell mutation: a sixth codon substitution of the B-globin
chain, replacing hydrophobic valine with hydrophilic
glutamic acid, thereby causing sickling of the Hb
molecule under de-oxygenated conditions. The congregation of these sickled cells results in microvascular
sludging and vascular obstruction, leading to the acute
As SCD is a component of American newborn
screening, the discovery of undiagnosed SCD in the
emergency department (ED) is relatively uncommon.
More frequently, patients with known SCD present to
the ED for evaluation secondary to sequelae of the disease
after the fourth month of life (decline in fetal hemoglobin
Emergency physicians are adept at managing
multiple disease processes; however, given the range of
, Abstract—Background: Sickle cell disease (SCD) affects
approximately 100,000 individuals in the United States. Due
to alterations in the structural conformation of hemoglobin
molecules under deoxygenated conditions, patients with SCD
are predisposed to numerous sequelae, many of which require
acute intervention. Objective: Our aim was to provide emergency physicians with an evidence-based update regarding
the diagnosis and management of SCD complications.
Discussion: SCD patients experience significant morbidity
and mortality secondary to cerebrovascular accident, acute
chest syndrome, acute vaso-occlusive pain crises, SCD-related
multi-organ failure, cholecystitis, acute intrahepatic cholestasis, acute sickle hepatic crisis, acute hepatic sequestration,
priapism, and renal disease. Emergency physicians must recognize acute manifestations of SCD in order to deliver timely
management and determine patient disposition. Conclusions:
A comprehensive review of the emergency department
management of acute SCD complications is provided. Comprehensive understanding of these aspects of SCD can assist physicians in expediting patient evaluation and treatment, thus
decreasing the morbidity and mortality associated with this
hemoglobinopathy. ! 2016 Elsevier Inc. All rights reserved.
, Keywords—sickle cell disease; acute chest; acute pain
crisis; cerebrovascular accident; transfusion
Sickle cell disease (SCD) affects nearly 100,000
individuals in the United States, and approximately
2 million Americans carry the sickle cell trait. SCD is
RECEIVED: 21 January 2016; FINAL SUBMISSION RECEIVED: 12 May 2016;
ACCEPTED: 17 May 2016
Emergency Medicine Management of Sickle Cell Disease
pathophysiologic manifestations of SCD, encounters
with these patients often prove challenging. This review
seeks to provide emergency physicians with an improved
understanding of SCD complications and an evidencebased approach to their management.
MANAGING ACUTE COMPLICATIONS OF SCD:
VASO-OCCLUSIVE CRISES AND SEQUELAE OF
Cerebrovascular accident: Ischemic stroke and intracranial hemorrhage. Cerebrovascular accident (CVA),
including ischemic stroke and subsequent intracranial
hemorrhage due to hemorrhagic conversion of the
ischemic stroke, is a major complication of SCD. Patients
presenting to the ED for assessment will display
symptoms that vary according to the anatomic location
of the infarct or hemorrhage. Small infarcts in the adult
and pediatric populations are relatively common and
involve the basal ganglia and deep white matter within
the anterior circulation (4). Risk factors for CVA in
patients with SCD include low Hb, history of acute chest
syndrome (ACS), and history of hypertension (4). The
pathophysiology regarding anemia and a history of
ACS as CVA risk factors is poorly understood. SCD
experts hypothesize severe anemia as precipitating
increased cerebral blood flow and increased cerebral
flow velocity, thereby predisposing SCD patients (the
majority experiencing chronic anemia) to cerebrovascular damage. Scientists also postulate the temporal
association between ACS and CVAs as resulting from
repetitive episodes of hypoxia in the setting of ACS.
This hypoxia likely causes additional damage to cerebral
vessels, previously injured by microvascular insults (5).
In the assessment of adult and pediatric patients
presenting with symptoms concerning for acute intracranial pathology, neuroimaging is key. Initial evaluation of
the adult patient commonly includes non-contrast head
computed tomography (CT), subsequently followed by
CT angiography or magnetic resonance angiography
(MRA) during the inpatient course.
Goals for the acute treatment of ischemic stroke in the
adult SCD patient include limiting injury due to the CVA
and establishing secondary prevention through the
optimization of cerebral perfusion (maintenance of
euglycemia and normothermia and avoidance of hypoxia)
(6). Caution is advised when considering the administration of thrombolytics to adult SCD patients experiencing
an acute ischemic CVA. Increased rates of intracranial
hemorrhage have been reported in this patient population
(6). Similar to adult patients without a medical history of
SCD, antiplatelet and statin therapy should be considered
after an ischemic CVA (6). In addition to the strategies
mentioned for secondary CVA prevention, experts
also recommend regular transfusions to maintain Hb
S < 30%; however, data supporting this intervention
was collected in young adults with SCD having
experienced their first CVA during childhood (hence its
employment in the pediatric population, as discussed
In contrast to adults, magnetic resonance imaging
(MRI) with diffusion-weighted imaging and MRA of
the head and neck should be performed in pediatric
patients with suspected acute ischemic stroke, as a
non-contrast head CT will miss early signs of ischemic
infarct (5). All pediatric patients diagnosed with an
ischemic stroke thought secondary to SCD should receive
intravenous (IV) fluids and undergo exchange transfusion
to achieve an Hb S level of < 30% (5). This procedure
should be performed in consultation with a hematologist.
If an exchange transfusion cannot be arranged, a simple
transfusion should be performed (5). A maximum Hb of
13 g/dL status post transfusion is the recommended
target, as pediatric children with SCD may be at risk
for recurrent ischemia secondary to increased blood
viscosity (5). Currently, thrombolysis is not recommended in pediatric SCD patients presenting with ischemic
CVAs (5). One key point that the emergency physician
must consider when evaluating the pediatric SCD patient
is that hemorrhagic transformation occurs in 30% of
children with arterial ischemic and is frequently
To date, there are no published studies regarding the
management of hemorrhagic CVA in adult or pediatric
SCD patients (6). Previously recognized efficacious
treatments for acute intracranial hemorrhage in the
general adult and pediatric population include reversal
of anticoagulation, treatment in an intensive care unit
(ICU), treatment of seizures with antiepileptic agents,
and appropriate management of blood pressure (BP) (6).
While BP management in acute CVA is well addressed
in adult emergency medicine literature, the management
of pediatric hypertension in the setting of CVA is not as
well studied. Hypertension in children, defined as
BP > 95th percentile for age, within the first 72 h after
ischemic stroke is associated with an increased risk of
death (8). In the pediatric population, a BP goal of the
50–95th percentile for age and height, with permissive
hypertension up to 20% > 95th percentile, should be
targeted (6). Pediatric experts recommend use of
labetolol or an angiotensin-converting enzyme inhibitor
to lower BP by 25%, though renal function should be
Of note, seizures are common after pediatric neurologic injury (10). Patients with persistent lethargy or
altered mental status should be evaluated with electroencephalography for subclinical seizure activity (7).
E. Simon et al.
Table 1. Differentiating Acute Chest Syndrome and Acute Pain Crisis
Acute Chest Syndrome
Chest x-ray study
Pulmonary Acute Pain Crisis
Chest pain, fever, shortness of breath, hypoxia
New infiltrate (pediatric: middle or upper lobe; adult: lower lobe)
Antibiotics: community-acquired pneumonia vs. health
care–associated pneumonia (history-dependent);
Acute respiratory distress syndrome
Chest pain, fever, shortness of breath
No acute cardiopulmonary findings
Pain controlled without hypoxia: home
Unable to attain pain relief: admission
Atelectasis and subsequent pneumonia
due to splinting and low tidal volumes
ICU = intensive care unit.
In the setting of SCD, an investigation of alternative
causes of CVA cannot be overlooked. Etiologies include
infection, cardiac embolism, and cavernous venous sinus
Imaging, to include MRI and MRA of the head and
neck, may be essential in narrowing the differential
ACS.ACS, the most common reason for ICU admission in
the SCD patient population, is a leading cause of
morbidity and mortality (case fatality rate of 10%) (11).
The classic triad of ACS includes fever, hypoxia, and a
new pulmonary infiltrate on chest x-ray study. The
presence of any one of these signs or symptoms should
raise clinical suspicion in the setting of SCD. When
evaluating a patient for ACS, a chest x-ray study should
be obtained to identify the presence of a new infiltrate,
a complete blood count (CBC) should be sent to assess
anemia, and continuous oxygenation monitoring should
be performed to detect hypoxia.
While the pathogenesis of ACS has yet to be determined, infection secondary to Mycoplasma pneumoniae
frequently represents the underlying etiology in the
pediatric population (12). In adult sickle cell patients,
Chlamydophila pneumonia is the most commonly
encountered pathogen (13). Additional non-infectious
etiologies of ACS include fat emboli (released as a result
of bony infarct from vaso-occlusion) and pulmonary
emboli (disseminated post microvascular pulmonary
Differentiating ACS and pulmonary acute pain crisis
(APC) (which will be discussed) is difficult, as these
SCD complications often present with fever, shortness
of breath, chest pain, and leukocytosis (1,2,14). Any
respiratory symptoms associated with chest pain and
hypoxia should raise suspicion for ACS. A new
infiltrate on chest x-ray study is diagnostic of ACS, as
opposed to APC. Unfortunately, the chest x-ray study
may be normal early in ACS (2,14). When evaluating
chest x-ray studies, note that children are more likely to
display upper or middle lobe disease, as opposed to
adults, who frequently display lower lung disease with
an infiltrate and associated pleural effusion (14). See
Table 1 for a review of ACS vs. pulmonary symptoms
ACS can rapidly progress to acute respiratory distress
syndrome due to pulmonary sequestration or infarct.
Given this fact, patients with signs or symptoms
consistent with ACS should be managed in an intensive
care setting. Long-term complications of ACS include
pulmonary fibrosis, pulmonary hypertension, and cor
pulmonale. Acute right ventricular failure is a
complication of ACS and if suspected, ultrasound (US)
should be utilized to assess right ventricular contractility
and size (14).
Evidence-based guidelines and expert panels are
shown in Table 2 for the management and treatment of
APC. Vaso-occlusive pain crises may manifest in a
number of locations, including the pulmonary system,
central nervous system, skeletal system (arthralgias/
dactylitis), and gastrointestinal system (abdominal
pain). In the setting of these crises, patients commonly
present with fever and leukocytosis (12). Although fever
and leukocytosis are not specific indicators of infection, it
is wise to evaluate for an infectious etiology in the sickle
cell patient population, as these individuals are highly
susceptible to pathogens (addressed within at a later
SCD patients are prone to several complications that
must be considered during the evaluation of patients
presenting with pain crisis. These complications range
from the sequelae of hemoglobinopathy to renal
pathology (both later addressed) to the infectious
etiologies mentioned. Inquiries regarding prior pain
crises, differences between current and previous
episodes, the presence of fever, transfusion history,
medications, baseline Hb level, and a thorough physical
examination can assist in determining diagnoses. Any
atypical pain pattern not consistent with previous
episodes requires further evaluation.
In addition to an assessment for conditions requiring
acute interventions, it is important to note that the
Emergency Medicine Management of Sickle Cell Disease
Table 2. Management and Treatment of Acute Pain Crisis (3,15)
ACS patients should be hospitalized for pain control and SpO2 monitoring
ACS patients should receive antibiotics (parenteral cephalosporin or oral macrolide therapy)
ACS patients should receive supplemental O2 to maintain SpO2 > 95%
Patients with ACS should receive a blood transfusion to improve O2 carrying capacity
if Hb is > 1 g/dL below baseline (if baseline is > 9 g/dL, may not be required;
ACS with rapid progression (SpO2 < 90% despite O2 therapy, respiratory distress, progressive
pulmonary infiltrates, decline in Hb despite simple transfusion) requires urgent exchange
ACS = acute chest syndrome; APC = acute pain crisis; Hb = hemoglobin.
management of pain crises includes the provision of early
analgesia—an area in which emergency physicians
commonly under-prescribe (2,3). Evidence-based
guidelines regarding management and treatment of pain
crises are demonstrated in Table 3.
Opioid analgesics are the current mainstay of APC
therapy. Morphine, fentanyl, and hydromorphone are
commonly utilized in the ED treatment of acute pain
crisis (15–23). Caution is recommended in the
utilization of meperidine (normeperidine, the active
metabolite of meperidine, undergoes renal excretion
and is associated with an increased incidence of
seizures in the setting of renal dysfunction; a finding
common in occlusive crisis) (3,12,15).
Varying algorithms for the management of APC
are detailed by multiple guidelines and organizations
(16–22). Provided as an example, the National Heart,
Lung, and Blood Institute (NHLBI) algorithm is
depicted in the Figure 1. This example was chosen by
the authors given its value in demonstrating an
all-encompassing approach to patient analgesia: the
inclusion of patient perception of pain, a mention of
detailed recommendations regarding initial opioid
dosing, the provision of direction regarding adjuncts to
pain control, and an emphasis on repeated patient
assessment in determining disposition.
As all of the APC guidelines note, further studies are
required to evaluate the adequacy of varying opioid
analgesics regimens in controlling APC pain, to
determine the efficacy of delivery routes and dosing
intervals, and to develop consensus statements regarding
the provision of patient analgesia in APCs (16–22). If
possible, organizations should work toward the
development of APC patient-management protocols, as
case studies have demonstrated decreased time to the
delivery of patient analgesia, improvement in overall
patient pain control, decreased frequency of ED visits,
fewer total hospital days, and increased utilization
of primary provider services status post algorithm
As depicted in Figure 1, pain-control adjuvants
detailed by the NHLBI include sedatives, anxiolytics,
and antihistamines. While employed to augment the
analgesic effect of opioids by managing associated
symptoms, such as anxiety, and to prevent mast cell
degranulation induced by opioid administration,
controlled studies of these treatments in SCD are lacking,
and per the NHLBI, guidelines for their use are derived
from employment in other pain states (16).
Similar to other algorithms and treatment guidelines,
the NHLBI recommends that all patients who do not
achieve adequate pain relief be admitted to the hospital
for further therapy (16). Patients with an anticipated
discharge to home should be prescribed an oral
pain-control regimen with potency comparable to the
IV pain regimen, which provided pain relief during the
hospital course (16–22).
For APC patients requiring admission, patientcontrolled pain management strategies deserve
consideration by the emergency physician. Despite the
need for further research, case reports and limited case
studies have demonstrated shorter time to pain control,
Table 3. Management and Treatment of Acute Pain Crisis (3,14)
Initiate analgesia within 30 min of triage; provide multi-modal
(opioid and adjunct) analgesia
Employ individualized prescribing and pain-monitoring protocols
Give nonsteroidal anti-inflammatory drugs as adjuvant pain therapy
Level of Recommendation
Quality of Evidence
E. Simon et al.
Figure 1. National Heart, Lung, and Blood institute algorithm for the management of acute pain crisis (16). SCD = sickle cell
Emergency Medicine Management of Sickle Cell Disease
Figure 1. (Continued).
improved pain relief and, in some cases, earlier time to
hospital discharge among patients receiving patientcontrolled pain management (26,27).
In addition to pain control, literature addressing APC
treatment commonly advises the initiation of oxygen
supplementation and fluid resuscitation. However, recent
guidelines question these classic treatments. To date,
oxygen has demonstrated no benefit in SCD pain crises,
and new research suggests it may actually result in
myelosuppression and an increased need for transfusion
(14). Current expert guidelines recommend that if
saturations remain > 92%, no supplemental oxygen is
recommended (14). Although IV fluids are frequently
provided in the setting of APC, it is now commonly
recognized that excessive hydration can contribute to
atelectasis, hyperchloremic metabolic acidosis (if normal
saline is utilized), and pulmonary edema. If the patient is
overtly dehydrated and hypovolemic, IV fluids are
warranted. Otherwise, maintenance of euvolemia is
Although this review centers on the management of
acute SCD complications, hydroxycarbamide (also
known as hydroxyurea [HU]) therapy warrants
mention. HU is the most common intervention utilized
in the long-term management of SCD for the prevention of vaso-occlusive events (28). HU has been
demonstrated to increase fetal Hb levels, subsequently
preventing the polymerization of Hb S under deoxygenated conditions (17,28,29). As demonstrated by
the Multi-Center Study of Hydroxyurea in Sickle Cell
Anemia and the Pediatric Hydroxyurea Phase 3 Clinical Trial (BABY HUG), the administration of HU
significantly decreases the incidence of adult and pediatric vaso-occlusive crisis, APC, and rates of hospitalization secondary to SCD complications (17,28,29). If
not previously initiated, HU therapy should be
considered in consultation with a hematologist for all
patients presenting to the ED with SCD
SCD-related multi-organ failure. This severe, lifethreatening complication of SCD is characterized by
sudden vaso-occlusion with organ failure, specifically
affecting the lungs, liver, and kidneys. Patients may
present with fever, tachypnea, and, in severe cases,
hemodynamic compromise (14). Careful assessment of
the pulmonary and renal systems, including advanced
imaging, is advised. Laboratory studies commonly reveal
elevated lactate dehydrogenase, anemia, thrombocytopenia, and an acute kidney injury or acute renal failure.
Chest x-ray study is often notable for multi-lobar
infiltrates. Patients with SCD-related multi-organ failure
require ICU admission in addition to specialty
hematology or nephrology, or both, consultation (14).
E. Simon et al.
Exchange transfusion is often warranted in association
with hematology consultation (14).
Sequelae of Hemoglobinopathy
Right upper quadrant abdominal pain. Abdominal
complications are common in SCD, especially
complications causing pain in the right upper quadrant
(RUQ). For SCD patients with RUQ pain, the challenge
for the emergency physician is to ascertain the underlying
etiology: cholelithiasis, cholecystitis, acute intrahepatic
cholestasis (AIC), acute sickle hepatic crisis, or acute
hepatic sequestration (AHS) (1). In the evaluation of
RUQ pathology, initial studies including CBC, liver
function tests, coagulation panel (prothrombin time/
activated partial thromboplastin time/international
normalized ratio [PT/aPTT/INR]), and imaging with
ultrasound (US) or CT are essential.
Hemolysis precipitates the formation of pigmented
gallstones in up to 70% of patients, increasing the
risk of symptomatic cholelithiasis and cholecystitis in
AIC is a result of sickled red blood cells (RBCs)
occluding hepatic sinusoids, causing vascular stasis and
local hypoxia. As Kupffer cells (hepatic macrophages)
phagocytose sickled erythrocytes, canaliculi occlude
with bile (30). Patient presentation ranges from isolated
hyperbilirubinemia with preserved hepatic function
(PT/aPTT/INR within normal limits) to RUQ pain,
transaminitis, and extreme elevations of bilirubin and
alkaline phosphatase. In the latter case, renal failure,
thrombocytopenia, and severely prolonged coagulation
times often develop (31). If severe acute intrahepatic
cholestasis is suspected, early consultation with
hematology for exchange transfusion is indicated.
Acute sickle hepatic crisis affects 10% of patients
admitted for abdominal pain crises (31). Acute sickle
hepatic crisis simulates acute cholecystitis with RUQ
pain, fever, leukocytosis, and variable increases in serum
transaminases and bilirubin levels; however, unlike
cholecystitis, hepatomegaly occurs (31). Treatment is
supportive with pain control and consultation for possible
AHS occurs secondary to obstruction of sinusoidal
flow by masses of sickled erythrocytes and can be a
complication of acute sickle hepatic crisis (15,30). In
addition to RUQ pain, fever, jaundice, and
hepatomegaly, an acute drop in Hb and hematocrit
with reticulocytosis occurs (31). Consultation with
hematology is recommended. This too can be an
indication for simple or exchange transfusion (1,32).
It is important to note that the laboratory studies of a
patient with SCD cannot be interpreted in a vacuum.
In SCD patients, chronic liver disease often occurs
secondary to hemosiderosis (transfusions) and silent
HIDA = hepatobiliary; PT/aPTT/INR = prothrombin time/activated partial thromboplastin time/international normalized ratio; RUQ = right upper quadrant; TTP = tenderness to palpation;
US = ultrasound.
RUQ pain, mid-epigastric pain, nausea,
indigestion, emesis, fever, jaundice
Acute hepatic sequestration
Fever, RUQ TTP,
RUQ pain, mid-epigastric pain, nausea,
indigestion, emesis, fever
Acute sickle hepatic crisis
Fever, RUQ TTP,
Acute decrease in hemoglobin and
hematocrit with elevated reticulocyte
count, and hyperbilirubinemia
Pain control, consultation for admission
and possible transfusion (in
consultation with a hematologist)
Inpatient monitoring with exchange
transfusion (in consultation with a
Inpatient monitoring for isolated
hyperbilirubinemia vs. admission and
exchange transfusion (in consultation
with a hematologist) in severe cases
RUQ pain, mid-epigastric pain, nausea,
Fever, RUQ TTP
Laboratory studies within normal limits
RUQ US demonstrating gallstones or
Leukocytosis, transaminitis, coagulation
studies within normal limits
RUQ US demonstrating pericholecystic
fluid, common bile duct dilatation, or
gallbladder wall thickening
Variable: isolated hyperbilirubinemia
without transaminitis, to severe
transaminitis, acute renal failure,
thrombocytopenia and coagulation
Variable transaminitis and
RUQ pain, mid-epigastric pain,
postprandial nausea, indigestion,
RUQ pain, mid-epigastric pain, nausea,
indigestion, emesis, fever
Common Patient Presentation
Sickle cell nephropathy/infarcts. The kidney is one of the
most commonly affected organs in SCD (34). Ischemic
damage caused by RBC sickling in the vasa recta
predisposes patients to a number of glomerulopathies
resulting in renal dysfunction (29). Infarct of the renal
medulla secondary to vaso-occlusion can present with
flank pain and costovertebral angle tenderness (34).
Alternatively, papillary necrosis can result in gross or
microscopic hematuria (2). Because renal dysfunction
can be a manifestation of infarction of the renal
medulla or papillary necrosis, admission for IV fluid
Table 4. Summary of Right Upper Quadrant Pathology (1,2,31,32)
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
levels (>2 g/dL) associated with splenomegaly,
reticulocytosis, and signs of intravascular volume
depletion (12). Patients may present with abdominal
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).
Emergency management of splenic sequestration is
aimed at restoring circulating blood volume through IV
fluid resuscitation or blood transfusion (11–13). As
splenic sequestration has a high rate of recurrence, all
cases should be managed in conjunction with a
hematologist, as patients may be considered for
splenectomy (1,12). After 3–5 years of age, the risk of
splenic sequestration decreases dramatically, owing to
splenic auto-infarction (12,13).
Imaging of the RUQ. Abdominal US is the primary
modality for evaluation of RUQ pathology in sickle cell
patients. US may reveal gallstones, common bile duct
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
pain is limited. In one study, CT provided a diagnosis
that affected management in 17 of 30 patients (33).
Hepatic infarction, hepatic abscess, iron overload, and
retained common bile duct stones post cholecystectomy
were among the notable findings (33). Clinical judgment
should be employed when assessing the need for CT.
Table 4 offers a summary of RUQ pathology.
microvascular occlusions (30). Obtaining a history
regarding frequency of transfusions and baseline hepatic
function is invaluable in assessing chronic vs. acute
Antibiotics, surgical resection
HIDA scan vs. elective cholecystectomy
Emergency Medicine Management of Sickle Cell Disease
E. Simon et al.
administration and serial renal function examination is
advised. Definitive diagnosis of these etiologies can be
obtained with CT scan (CT with IV contrast vs. CT IV
pyelogram) (2,35). Careful assessment of baseline renal
function panel is required, as the pattern and rate of
change of serum creatinine is more helpful than the
absolute level (34). Ultimately, 30% of patients with
SCD develop chronic kidney disease, with approximately
12% of patients developing end-stage renal disease
Figure 2. Aspiration/injection site (36).
Priapism. Priapism occurs in up to 30% of males with
SCD (34). Ischemic priapism (low-flow or venoocclusive priapism) is the most common form of priapism
encountered in the SCD population, representing > 60%
of cases in children and > 25% of cases in adults
presenting for treatment (36). Patients experiencing
ischemic priapism often present with rigid, painful
corpora cavernosa. As this condition is associated with
decreased or absent cavernosal blood flow, emergent
intervention is required to prevent irreversible corporal
damage and subsequent erectile dysfunction (37).
If questions arise regarding the etiology of the
priapism, blood gas testing is a reliable diagnostic
method of distinguishing ischemic from non-ischemic
priapism in the ED. Blood aspirated from the corpus
cavernosum in patients with ischemic priapism is
oxygen-deplete and, therefore, dark, while blood from
the corpus cavernosum in patients with non-ischemic
priapism is normally oxygenated and therefore bright
red (38). Cavernosal blood gases in males with ischemic
priapism typically have a PO2 of < 30 mm Hg, a PCO2 of
> 60 mm Hg, and a pH < 7.25 (38).
Treatment of ischemic priapism in the male adult and
male pediatric population includes needle aspiration of
blood from the corpora cavernosa, followed by
intercavernosal injection of sympathomimetic (1-mL
aliquots [up to 3 mL] of 100–500 mg/mL phenylephrine)
(2,22). Figure 2 provides a reference of relevant anatomy.
Assuming a clock face is placed with the 12 o’clock
position centrally located to the dorsal vein, it is advised
that aspiration and injection occur at the 3 o’clock and 9
o’clock positions to avoid injury to the dorsal vein, deep
dorsal nerve, and urethra (38). Measures to treat SCD
(hydration and exchange transfusions) may be utilized
but should not delay aspiration and phenylephrine
Infection. Given the lifelong risk of increased infection,
any fever in a patient with SCD necessitates evaluation.
Common etiologies of fever in an SCD patient include
APC, bacteremia, osteomyelitis, or infection causing
ACS (39). Evaluation of adult and pediatric SCD
patients should include a thorough history and physical
examination. In addition to obtaining a urine culture for
children reporting urinary symptoms, pediatric SCD
experts recommend that a blood culture be obtained
when leukocyte count is > 20 ! 109/L with a high
proportion of bands (39). Current literature does not
advocate for this testing in adult patients, as clinical judgment should govern their evaluation.
Bacterial infections are a common cause of mortality
in SCD (39). Increased susceptibility to bacterial
infection is often the result of impaired splenic function.
Due to chronic splenic infarction, 14% of SCD patients
are functionally asplenic by 6 months of age, which
reaches 94% by 5 years of age (2). In addition, a number
of sickle cell patients are asplenic secondary to
therapeutic splenectomy, the treatment for recurrent
sequestration crises (2).
Bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae type b, non-typhi
Salmonella species, Mycoplasma, Chlamydophila
pneumonia, and Yersinia enterocolitis, commonly
occur in sickle cell patients (39). Before widespread
S. pneumoniae and H. influenzae type b vaccination,
pediatric patients with SCD had a 400-fold increased
risk of S. pneumoniae sepsis and a 2- to 4-fold increased
risk of H. influenzae sepsis compared with age-matched
children without SCD (39).
In terms of viral disease affecting SCD patients,
hepatitis C and B (discussed in the Transfusion
Complications section), parvovirus B19 (addressed under
the Aplastic Crisis section), and influenza are notable.
One study, performed by Bundy et al., demonstrated a
hospitalization rate of pediatric SCD patients with influenza as 56 times that of their non-SCD counterparts
(40). While yet a hypothesis, this variation is attributed
to the pre-disposition of SCD patients with influenza
toward development of secondary bacterial pneumonia,
ACS, or APC; therefore, addressing this viral illness is
paramount (40). Current Centers for Disease Control
and Prevention (CDC) Guidelines advocate the provision
of oseltamivir to all SCD patients (>2 weeks of age)
presenting within 48 h of the onset of flu-like symptoms,
in order to decrease the severity and shorten the duration
Emergency Medicine Management of Sickle Cell Disease
of illness (41). It is also advised that oseltamivir
chemoprophylaxis be given to all patients, aged
3 months or older, having a known exposure to persons
with confirmed influenza infections (American
Academy of Pediatrics recommendation; oseltamivir is
Food and Drug Administration–approved for use in
patients > 1 year of age) (41).
In order to prevent serious infection among SCD
patients, the following measures have also been
recommended by the CDC:
1. Prophylactic penicillin V for patients aged 2 months
to 5 years to prevent serious bacterial infection (1).
2. Pneumococcal vaccine at 2 months of age to reduce
the risk of pneumococcal infection (1).
3. Influenza vaccination at 6 months and annually
4. Meningococcal vaccination for children with
splenic dysfunction at 2 years of age (1).
Although commonly addressed by primary care
managers, it serves the emergency physician to make inquiries regarding penicillin prophylaxis and vaccination
status during encounters with SCD patients, as this information will aid in the development of differential diagnoses (42).
Aplastic crisis. Aplastic crisis in SCD is commonly
secondary to parvovirus B19 infection, but can occur
with any infectious agent. Patients may present with
pallor and tachycardia due to a transient failure of
erythropoiesis (2). A prodrome of upper respiratory
symptoms is often followed by an acute, severe drop in
Hb. In severe cases, patients present with hemodynamic
instability and a decreased reticulocyte count.
Fortunately, the decline in reticulocyte count is generally
brief, resolving in a matter of days (1,2).
ED care of aplastic crisis is supportive and depends on
the degree of anemia and cardiovascular compromise
(10). If the reticulocyte count is < 1–2% with no signs
of spontaneous recovery, simple transfusions are
administered to raise the Hb to approximately > 9 g/dL
and the hematocrit to 30% (11,43). SCD patients with
aplastic crisis should be admitted to the ICU with
droplet precautions (11).
Transfusion indications. The goal of transfusion is to
increase oxygen-carrying capacity, but this is not
straightforward in SCD. Patients with SCD experience
chronic anemia, but compensatory mechanisms,
including increased cardiac output, improve oxygen
delivery. Simple transfusions are utilized for severe
anemia causing physiologic compromise, or a sudden
decrease in Hb levels in the setting of acute splenic
or hepatic sequestration crisis (12). Exchange
transfusions are needed in the setting of suspected or
confirmed CVA, treatment-resistant acute chest or
acute lung disease, multi-organ failure, preparation for
general anesthesia, and priapism unresponsive to other
Transfusion complications. Transfusing RBCs to patients
with SCD can be precarious, as increasing RBC mass
increases blood viscosity, thereby exacerbating sickling
(12). In addition to increased blood viscosity, the
complication of multi-transfusion hepatopathy is also
well studied in the sickle cell population. Individuals
receiving repetitive transfusions may experience hepatic
iron overload, subsequently requiring chelation therapy
(37). Blood-borne infections including chronic hepatitis
B, hepatitis C, and cytomegalovirus are also commonly
encountered in the highly transfused sickle cell
population; however, studies reporting the prevalence of
these infections (supported by confirmative genotyping
and polymerase chain reaction) are limited (37). The risks
and benefits of a simple vs. exchange transfusion
should always be determined in consultation with a
SCD is a chronic hemoglobinopathy with significant
morbidity and mortality due to its sequelae. Complications include ACS, CVA, vaso-occlusive pain crises,
SCD-related multi-organ failure, cholecystitis, AIC,
acute sickle hepatic crisis, AHS, acute renal disease,
and priapism. Emergency physicians must recognize
these acute manifestations, provide early pain
management and resuscitation, and expeditiously
determine patient disposition.
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Elsevier; 2010. Available at: https://www.clinicalkey.com/
#!/content/medical_topic/21-s2.0-1014713. Accessed December
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Ma OJ, Yealy DM, Mecker GD, Cline DM, eds. Tintinalli’s
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evidence-based report by expert panel members. JAMA 2014;312:
4. Roach S, Golomb M, Adams R, et al. Management of stroke in
infants and children. American Heart Association: scientific
statement. Stroke 2008;39:2644–91.
5. Ohene-Frempong K, Weiner S, Sleeper L, et al. Cerebrovascular
accidents in sickle cell disease: rates and risk factors. Blood
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code: early management of the child with stroke. J Pediatr 2015;
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Room. 2015. Available at: http://ccpem.com/index.php?option=com_
easyblog&view=entry&id=499&Itemid=101. Accessed December
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15. Afenyi-Annan A, Ballas S, Hassell K, et al. Managing acute
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guidelines/sc_mngt.pdf. Accessed December 01, 2015.
17. Lovett P, Sule H, Lopez B. Sickle cell disease in the emergency
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clinical care of adults with sickle cell disease in the UK. 2008.
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Sat 5:49 PM a 5
I EHS 468 Syllabus - Spring 2018.pdf
Compare QRS, S...
EHS 468 Syllabus... X
Length 3-4 paragraphs.
Reference, and article or
URL given. Technical
formalism are used
Somewhat too long or
short. Reference or
Small number of errors
in terminology or
Much too long or short.
No reference or article
Chosen point identified Chosen point identified, No point identified, or
and clearly explained. but explanation not explanation very
Factually correct as fully clear. Minor unclear. Major errors in
report of chosen aspect errors in report of
report of authors'
of article. Explains
meaning. Relies on
Understanding chosen point; goes
quotations or superficial
of article beyond merely paraphrased in student's paraphrase; little
paraphrasing or quoting. own words, but very evidence of
Class knowledge used close to original. Minor understanding. Major
problems from not
related to class
Goes beyond summary; Shows understanding of Critical discussion
relevant issues, but missing, or shows
connects to other data or contributes no
ideas. Tight focus on substantial original misunderstanding of
main point. Report is points. Focus is
article. No clear focus.
somewhat loose. Some Structure of discussion
thinking; paragraphs and overall organization, but
has no clear
discussion is focused,
relationships between organization. Examples
coherent. Examples, ideas not always clear. used, but not connected
data used appropriately. Crucial examples, data to discussion.
not always given.
Clear articulate writing Edits needed. Proof Turns in something
used. One or two minor reading will help you. Not college level work
edits needed to be a Read aloud to yourself at all. Get help at the
perfect paper! Keep up and or ask others to read writing center.
the great work
it out loud to you.
thoughts on the article
in a clear manner.
Discusses what you
learned from reading
the article or ideas you
might use in the future.
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thoughts, but did not your own thoughts or
elaborate. No mention ideas about what is
of learning from reading discussed in the article.
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