EM:RAP COMMENTARY
Sickle Cell Crisis and You: A How-to Guide
Ryan Raam, MD*; Haney Mallemat, MD; Paul Jhun, MD; Mel Herbert, MD
*Corresponding Author. E-mail: ryanraam@gmail.com, Twitter: @raamrodEM.
0196-0644/$-see front matter
Copyright © 2016 by the American College of Emergency Physicians.
http://dx.doi.org/10.1016/j.annemergmed.2016.04.016
SEE RELATED ARTICLE, P. e21.
[Ann Emerg Med. 2016;67:787-790.]
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EM:RAP or its authors.
ANNALS CASE
A 19-year-old man with sickle cell anemia presented to the
emergency department (ED) with a 1-day history of severe
bilateral arm pain and swelling. Vitals signs showed
a blood pressure of 117/82 mm Hg, a pulse rate of 76
beats/min, and an oral temperature of 36.8
C (98.2
F).
Physical examination was remarkable for tense swelling,
warmth, and tenderness to palpation of both triceps muscles.
Laboratory tests showed an elevated creatine kinase level
of 20,734 IU/L. Point-of-care ultrasonography of the triceps
showed diffuse muscle thickening with loss of the normal
fascicular architecture compared with the unaffected biceps.
Diagnosis: sickle cell–induced myonecrosis.1
MY, OH, MY.MYONECROSIS!
Myonecrosis is a pretty rare complication of sickle cell
disease (SCD).2 In fact, there are mostly case reports in the
literature! But there is a host of other more common, can’t-
miss complications that can develop as a result of these
crescent-shaped deformities of our circulating minilife-givers.
Keeping all these straight can sometimes be overwhelming, so
we’ll run through some of the critical complications of SCD
and how to have a sensible approach to these patients.
APPROACH TO SCD FOR DUMMIES
Over the years, there have been several guidelines about the
management of acute SCD crises,3-5 some of which include
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treatment algorithms. But when it comes to a basic diagnostic
approach to the sickle cell patient in the ED, we just hear
crickets chirping in the midst of awkward silence. Sure, you
might have a set of shiny tools, but if you can’t even figure out
where to use them, they’re pretty useless. So here’s a simple
algorithm (Figure) that can help you keep things straight
when all cognitive systems fail (it goes without saying that
every patient encounter should be individualized).
The important branch point of this algorithm centers
around the point-of-care hemoglobin level, if your facility
has the capability. At the heart of SCD is a combination of
vaso-occlusion and hemolysis resulting in any number of
secondary complications (because of the valine substitute at
position.zzz.). Despite this, in uncomplicated sickle cell
presentations, a full rainbow set of tubes is not usually
needed.6-8 The approach to SCD in the ED relies on a
thorough history and physical examination. Before we get
ahead of ourselves, though, let’s break down the different
pathways of this algorithm; it’s so easy you can even do it
on your drive home post–night shift.
SEQUESTRATION AND HEMOLYSIS: A PROBLEM
OF CONSUMPTION
If the hemoglobin of a sickle cell patient is outside the
range of error (a decrease of more than 2 g/dL from his or
her baseline)5, more evaluation is usually warranted to
figure out why. The next most important laboratory test to
determine why the hemoglobin level decreased is the
reticulocyte count, which gives you a snapshot of how well
the bone marrow is replenishing the depleted peripheral
RBCs. If the retic count is appropriately high (ie, the bone
marrow factory is firing on all cylinders to meet market
demands), then the worsening anemia is primarily a
problem of peripheral consumption of the RBCs. The
differential in this case is either sequestration (in the liver or
spleen) or hemolytic crisis.
When the Spleen Becomes a Sponge
Question: What’s worse than a crashing sickle cell
patient? Answer: a crashing pediatric sickle cell patient.
Annals of Emergency Medicine 787
EM:RAP Commentary
Figure. Algorithmic approach to sickle cell crisis.
Splenic sequestration usually occurs in children, peaking
at aged 1 to 4 years8,9 (although it can occur in adults
as well).10 These patients are usually very ill appearing,
presenting in extremis and shock owing to their spleens
having greedily hoarded a large amount of peripheral
RBCs. Tip-offs to diagnosis, in addition to an acute
decrease in hemoglobin level, are clinical: circulatory shock
and a very large spleen on ultrasonography or examination.
Aggressively treat these patients with fluid resuscitation
until you can get the more definitive blood transfusion
started, with a goal hemoglobin level between 6 and 8 g/dL.
Just to make things even more complicated, the spleen
will often release a large amount of peripheral RBCs
after transfusion, causing you to overshoot your goal
hemoglobin level. This puts the patient at risk of
hyperviscosity and subsequent strokes. One recommended
transfusion approach is to transfuse the equivalent
milliliters per kilogram of blood as the observed
hemoglobin concentration in grams per deciliter. For
example, if the hemoglobin is 5 g/dL, then transfuse 5 mL/kg
at a time.11 Hepatic sequestration presents in the same way
as splenic sequestration (except with an enlarged liver) and
is managed similarly.one less thing to think about!
When Red Cells Explode, Measure the Guts
So how do you differentiate a hemolytic crisis from
splenic sequestration if both are characterized by a decrease
in hemoglobin level and an elevated reticulocyte count?
The answer lies in the indirect bilirubin, aspartate and
alanine transaminases, and lactate dehydrogenase. When
RBCs are destroyed in an acute hemolytic crisis, an increase
in lactate dehydrogenase, bilirubin, and aspartate and
alanine transaminase levels occurs. This won’t be the case
in a sequestration crisis. Hemolytic crises are usually self-
limited, but patients might need a blood transfusion if they
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Raam et al
have severe anemia. And as a word of precaution, don’t
forget the “county handshake” (rectal examination) for
patients with an acute decrease in hemoglobin level. Sickle
cell patients are prone to gastrointestinal bleeding events
the same as everyone else; they just don’t tolerate it as well
because of their baseline anemia.
APLASTIC CRISIS: A PROBLEM OF PRODUCTION
On the other hand, if the reticulocyte count is low
(usually <2%), this suggests that the blood factory
workers in the bone marrow aren’t working hard enough
to meet the peripheral demands of the chronic hemolysis
that characterizes SCD. Somewhere out there, Upton
Sinclair is rolling in his grave. But really, it’s not the bone
marrow’s fault. Up to 80% of the time, an aplastic crisis in
sickle cell patients is caused by parvovirus B19 infection.12
Infection usually lasts approximately 7 to 10 days and is
self-limited. In addition to transfusing these patients for
symptomatic anemia and thrombocytopenia, don’t forget
to put them in isolation so pregnant patients don’t
develop fetal hydrops.13
ACUTE CHEST SYNDROME: THE OTHER ACS
If all is good in the land of enchanted hemoglobins, your
job is to ensure that the patient doesn’t have acute chest
syndrome (ACS). To be clear, when we mention “ACS” in
this section, we’re not talking about acute coronary
syndrome (although technically you could have both ACS
and ACS at the same time; how horrible would that be?).
So what is this other ACS that we speak of? ACS is defined
as some combination of fever, chest pain, hypoxia,
respiratory symptoms (cough, wheezing, rales, or
tachypnea), and a new pulmonary infiltrate on chest
radiograph.5,7,8 Up to 80% of patients will have isolated
Volume 67, no. 6 : June 2016
Raam et al
fever, cough, or rales on examination.14,15 ACS is the
leading cause of death in patients with SCD, so don’t
dillydally with this diagnosis.5 Approximately half of ACS
cases don’t have a known cause, but about one third of the
time, it’s from infection. All of these patients need a
cephalosporin and macrolide to cover for typical and
atypical organisms.14 Other therapies that have proven to
be helpful in preventing further pulmonary complications
include incentive spirometry and bronchodilators.3,16 If the
patient is hypoxic, go ahead and slap on (gently!) some
supplemental oxygen.
What happens if the patient has persistent hypoxemia or
multiorgan failure despite your cocktail of antibiotics,
incentive spirometry, and supportive measures? Other
disease processes may be causing the episode of ACS,
including fat embolism or pulmonary infarction.14 These
patients might benefit from either exchange transfusion (if
your facility has this) or simple transfusion.17 They can also
get pulmonary hypertension and diastolic dysfunction, so
keep the “usual” causes of chest pain and dyspnea in your
differential after you’ve excluded ACS—the sickle
ACS.oh, you know what we mean.
A CRISIS OF EPIC PROPORTIONS
Ah, and last but certainly not least, is the most
commonly encountered presentation of SCD in the ED:
vaso-occlusive pain crisis, which accounts for more than
80% of inpatient admissions for crises.18,19 It typically
presents as back or extremity pain, but can also rear its head
(pun intended) in other parts of the body, presenting as
headache and abdominal or chest pain. But before you go
diagnosing every SCD patient within earshot of a simple
pain crisis, it’s your duty to rule out other potential
musculoskeletal catastrophes: septic arthritis, osteomyelitis,
and avascular necrosis. SCD patients are pretty good at
knowing their typical pain crises, so if they explain that this
time “something is different,” pay attention!8,13 In general,
evaluation of patients with these conditions is similar to
that of other patients.
When treating SCD patients for a pain crisis, the name of
the game is hit ’em hard and hit ’em fast. Guidelines are
emphatic that appropriate treatment include aggressive
intravenous narcotics that are redosed every 15 to 30 minutes,
and there is no “maximum” dose of analgesia.3,5,7,8,13
Morphine (0.1 mg/kg) and hydromorphone (0.015 mg/kg)
are generally recommended. If your department has a
standardized SCD pain management protocol, or if the patient
has a special pain contract, go ahead and follow it. Although
there’s no “one size fits all,” protocols have been shown to be
pretty effective.20,21 Because all SCD patients have baseline
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EM:RAP Commentary
renal insufficiency (even if their serum creatinine level is
normal!), be careful with nonsteroidal anti-inflammatory
drugs and meperidine. Seizure-inducing meperidine
metabolitesþrenal insufficiency¼a bad time for everyone
involved.3,5,7,8,13 For pain crisis patients who are
admitted, remember to order the incentive spirometry.
It’s been shown to help prevent ACS from their pain-
induced splinting and opioid-induced respiratory
suppression.5
Intravenous Fluids, Oxygen, Drug-Seeking Myths
Despite your irresistible urge to order supplemental
oxygen and a normal saline solution bolus for every SCD
pain patient who walks through your door, stop and think
about what you’re doing. Supplemental oxygen should be
reserved for patients who are truly hypoxic (pulse oximetry
less than 95%).3,5,7,8,13 Also, a bolus of intravenous fluids
to “just tank them up” is now considered poor form.
Intravenous fluids should be given only to patients who are
hypovolemic or need to be resuscitated.3,5,7,8,13 In fact, one
study showed that administering intravenous fluid boluses
might actually precipitate ACS!15 But if you’re going to
administer intravenous fluids, keep it to D5 0.45% normal
saline solution at 1 to 1.5 times the maintenance
rate.3,5,7,8,13
Finally, 2 words on sickle cell patients and faking their
pain: they’re not! As a rule, SCD patients are not
hypertensive or tachycardic even though they’re having a
pain crisis.22-24 And less than 5% of SCD patients are
found to be drug seeking.13 So pretty please, with a cherry
on top, treat these patients with a healthy dose of empathy
and that sweet, sweet “D.”
BACK TO THE CASE
The patient was admitted for monitoring and supportive
care, including intravenous fluids and pain control. He had
an uneventful hospital course and after a few days was
discharged home.
Author affiliations: From the Department of Emergency Medicine,
University of Southern California, Los Angeles, CA (Raam, Herbert);
the Department of Emergency Medicine, University of Maryland
School of Medicine, Baltimore, MD (Mallemat); and the
Department of Emergency Medicine, University of California–San
Francisco, San Francisco, CA (Jhun).
Funding and support: By Annals policy, all authors are required to
disclose any and all commercial, financial, and other relationships
in any way related to the subject of this article as per ICMJE conflict
of interest guidelines (see www.icmje.org).The authors have stated
that no such relationships exist and provided the following details:
Dr. Raam reports other from EM:RAP, outside of the submitted
Annals of Emergency Medicine 789
EM:RAP Commentary
work. Dr. Jhun reports other from Hippo Education, Inc., outside of
the submitted work. Dr. Herbert reports other from EM:RAP and
Hippo Education, Inc., outside of the submitted work.
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