The Journal of Emergency Medicine, Vol. 51, No. 4, pp.

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

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

, 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

RECEIVED: 21 January 2016; FINAL SUBMISSION RECEIVED: 12 May 2016;

ACCEPTED: 17 May 2016

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.

Table 1. Differentiating Acute Chest Syndrome and Acute Pain Crisis

Acute Chest Syndrome Pulmonary Acute Pain Crisis

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

ICU = intensive care unit.

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

Table 2. Management and Treatment of Acute Pain Crisis (3,15)

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

ACS = acute chest syndrome; APC = acute pain crisis; Hb = hemoglobin.

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,

Table 3. Management and Treatment of Acute Pain Crisis (3,14)

Recommendation Level of Recommendation Quality of Evidence

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

microvascular occlusions (30). Obtaining a history

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

exchange transfusion (in consultation

hyperbilirubinemia vs. admission and

Pain control, consultation for admission

with a hematologist) in severe cases
regarding frequency of transfusions and baseline hepatic

transfusion (in consultation with a

consultation with a hematologist)
Inpatient monitoring with exchange
function is invaluable in assessing chronic vs. acute

Inpatient monitoring for isolated

pathology (1,2).

and possible transfusion (in

Antibiotics, surgical resection
Treatment
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

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

Leukocytosis, transaminitis, coagulation

pain is limited. In one study, CT provided a diagnosis

hematocrit with elevated reticulocyte

RUQ US demonstrating pericholecystic
Laboratory studies within normal limits

thrombocytopenia and coagulation

RUQ US demonstrating gallstones or

fluid, common bile duct dilatation, or

that affected management in 17 of 30 patients (33).

Variable: isolated hyperbilirubinemia

transaminitis, acute renal failure,

Acute decrease in hemoglobin and

Laboratory Studies/Imaging

without transaminitis, to severe

Hepatic infarction, hepatic abscess, iron overload, and

count, and hyperbilirubinemia

abnormalities (PT/aPTT/INR)
studies within normal limits
retained common bile duct stones post cholecystectomy

gallbladder wall thickening

were among the notable findings (33). Clinical judgment

Variable transaminitis and

should be employed when assessing the need for CT.

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

levels (>2 g/dL) associated with splenomegaly,

Fever, RUQ TTP,

Fever, RUQ TTP,

hepatomegaly

hepatomegaly
Fever, RUQ TTP

reticulocytosis, and signs of intravascular volume

depletion (12). Patients may present with abdominal
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,

RUQ pain, mid-epigastric pain, nausea,

RUQ pain, mid-epigastric pain, nausea,

RUQ pain, mid-epigastric pain, nausea,

Emergency management of splenic sequestration is
Table 4. Summary of Right Upper Quadrant Pathology (1,2,31,32)

indigestion, emesis, fever, jaundice

postprandial nausea, indigestion,

aimed at restoring circulating blood volume through IV

Common Patient Presentation

fluid resuscitation or blood transfusion (11–13). As

RUQ pain, mid-epigastric pain,

splenic sequestration has a high rate of recurrence, all

indigestion, emesis, fever

indigestion, emesis, fever

cases should be managed in conjunction with a

hematologist, as patients may be considered for
indigestion, emesis

splenectomy (1,12). After 3–5 years of age, the risk of

splenic sequestration decreases dramatically, owing to
splenic auto-infarction (12,13).
emesis

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
Acute hepatic sequestration
Symptomatic cholelithiasis

Acute sickle hepatic crisis

predisposes patients to a number of glomerulopathies

Disease Process

resulting in renal dysfunction (29). Infarct of the renal

medulla secondary to vaso-occlusion can present with
Acute intrahepatic

US = ultrasound.

flank pain and costovertebral angle tenderness (34).

cholestasis
Cholecystitis

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
378 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
(32,36).
Figure 2. Aspiration/injection site (36).
Priapism. Priapism occurs in up to 30% of males with
SCD (34). Ischemic priapism (low-flow or veno- examination. In addition to obtaining a urine culture for
occlusive priapism) is the most common form of priapism children reporting urinary symptoms, pediatric SCD
encountered in the SCD population, representing > 60% experts recommend that a blood culture be obtained
of cases in children and > 25% of cases in adults when leukocyte count is > 20  109/L with a high
presenting for treatment (36). Patients experiencing proportion of bands (39). Current literature does not
ischemic priapism often present with rigid, painful advocate for this testing in adult patients, as clinical judg-
corpora cavernosa. As this condition is associated with ment should govern their evaluation.
decreased or absent cavernosal blood flow, emergent Bacterial infections are a common cause of mortality
intervention is required to prevent irreversible corporal in SCD (39). Increased susceptibility to bacterial
damage and subsequent erectile dysfunction (37). infection is often the result of impaired splenic function.
If questions arise regarding the etiology of the Due to chronic splenic infarction, 14% of SCD patients
priapism, blood gas testing is a reliable diagnostic are functionally asplenic by 6 months of age, which
method of distinguishing ischemic from non-ischemic reaches 94% by 5 years of age (2). In addition, a number
priapism in the ED. Blood aspirated from the corpus of sickle cell patients are asplenic secondary to
cavernosum in patients with ischemic priapism is therapeutic splenectomy, the treatment for recurrent
oxygen-deplete and, therefore, dark, while blood from sequestration crises (2).
the corpus cavernosum in patients with non-ischemic Bacterial pathogens, including Streptococcus pneumo-
priapism is normally oxygenated and therefore bright niae, Haemophilus influenzae type b, non-typhi
red (38). Cavernosal blood gases in males with ischemic Salmonella species, Mycoplasma, Chlamydophila
priapism typically have a PO2 of < 30 mm Hg, a PCO2 of pneumonia, and Yersinia enterocolitis, commonly
> 60 mm Hg, and a pH < 7.25 (38). occur in sickle cell patients (39). Before widespread
Treatment of ischemic priapism in the male adult and S. pneumoniae and H. influenzae type b vaccination,
male pediatric population includes needle aspiration of pediatric patients with SCD had a 400-fold increased
blood from the corpora cavernosa, followed by risk of S. pneumoniae sepsis and a 2- to 4-fold increased
intercavernosal injection of sympathomimetic (1-mL risk of H. influenzae sepsis compared with age-matched
aliquots [up to 3 mL] of 100–500 mg/mL phenylephrine) children without SCD (39).
(2,22). Figure 2 provides a reference of relevant anatomy. In terms of viral disease affecting SCD patients,
Assuming a clock face is placed with the 12 o’clock hepatitis C and B (discussed in the Transfusion
position centrally located to the dorsal vein, it is advised Complications section), parvovirus B19 (addressed under
that aspiration and injection occur at the 3 o’clock and 9 the Aplastic Crisis section), and influenza are notable.
o’clock positions to avoid injury to the dorsal vein, deep One study, performed by Bundy et al., demonstrated a
dorsal nerve, and urethra (38). Measures to treat SCD hospitalization rate of pediatric SCD patients with influ-
(hydration and exchange transfusions) may be utilized enza as 56 times that of their non-SCD counterparts
but should not delay aspiration and phenylephrine (40). While yet a hypothesis, this variation is attributed
administration (32,26). to the pre-disposition of SCD patients with influenza
toward development of secondary bacterial pneumonia,
Infection. Given the lifelong risk of increased infection, ACS, or APC; therefore, addressing this viral illness is
any fever in a patient with SCD necessitates evaluation. paramount (40). Current Centers for Disease Control
Common etiologies of fever in an SCD patient include and Prevention (CDC) Guidelines advocate the provision
APC, bacteremia, osteomyelitis, or infection causing of oseltamivir to all SCD patients (>2 weeks of age)
ACS (39). Evaluation of adult and pediatric SCD presenting within 48 h of the onset of flu-like symptoms,
patients should include a thorough history and physical in order to decrease the severity and shorten the duration
Emergency Medicine Management of Sickle Cell Disease 379

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).

Aplastic crisis. Aplastic crisis in SCD is commonly CONCLUSIONS

secondary to parvovirus B19 infection, but can occur
with any infectious agent. Patients may present with SCD is a chronic hemoglobinopathy with significant
pallor and tachycardia due to a transient failure of morbidity and mortality due to its sequelae. Complica-
erythropoiesis (2). A prodrome of upper respiratory tions include ACS, CVA, vaso-occlusive pain crises,
symptoms is often followed by an acute, severe drop in SCD-related multi-organ failure, cholecystitis, AIC,
Hb. In severe cases, patients present with hemodynamic acute sickle hepatic crisis, AHS, acute renal disease,
instability and a decreased reticulocyte count. and priapism. Emergency physicians must recognize
Fortunately, the decline in reticulocyte count is generally these acute manifestations, provide early pain
brief, resolving in a matter of days (1,2). management and resuscitation, and expeditiously
ED care of aplastic crisis is supportive and depends on determine patient disposition.
the degree of anemia and cardiovascular compromise
(10). If the reticulocyte count is < 1–2% with no signs
of spontaneous recovery, simple transfusions are
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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.