Setting: emergency department (ED)
CC: “I have really bad pain in my legs, back, and chest.”
VS: R: 28 breaths/minute; BP: 152/88 mm Hg; P: 110 beats/minute; T: 101.8°F
HPI: A 28-year-old man with a history of sickle cell (SS) disease arrives at the ED with recurrence of a pain crisis. This is the same as his usual crisis. He has been noncompliant with hydroxyurea. Besides pain, he has had fever. At home, it was 102°F.
PMHX:
Gallstones
Osteomyelitis
Skin ulcers
Pneumonia
Priapism episode in past
Gallstones in SS disease are from an aggregation of chronically high indirect bilirubin levels.
The mechanism of skin ulcers is not clear, but poor flow is likely.
Medications:
Folic acid
Hydroxyurea (not taking)
Oxycodone
What is the most important step at this time?
a. Perform physical examination.
b. Draw blood cultures and start antibiotics.
c. Begin intravenous (IV) fluids.
d. Restart hydroxyurea
e. Obtain old records to confirm SS in this patient.
Answer b. Draw blood cultures and start antibiotics.
Because doing the physical examination advances the clock and moves “Simulated Time,” this is a “Save-a-Life Point.” Infection in SS is easily fatal unless rapidly treated. Start antibiotics immediately. Pneumococcus, Haemophilus, Klebsiella, and Salmonella can all be growing in the blood at the time of the first temperature elevation.
Sickle Cell + Fever = Blood Cultures + Ceftriaxone NOW!
Sickle cell anemia eliminates the spleen through the process of autoinfarction.
No Spleen = Encapsulated Organisms Kill the Patient
PE:
Chest: some rales at left base; decreased excursion from splinting
Extremities: ulcer with superficial purulent material over anterior shin; scarring from old ulcers scattered on legs
Heart: 1/6 systolic murmur
Neurological: nonfocal
Genitals: normal
What causes priapism in SS disease?
a. Stasis in penis
b. Arterial insufficiency
c. Stasis and infarction of prostatic plexus of veins
d. Decreased hemoglobin concentration
Answer c. Stasis and infarction of prostatic plexus of veins
The same stasis and infarction of flow that cause chest syndrome, retinal lesions, skin lesions, and stroke, also diminishes flow out of the penis as veins pass through the prostate.
SS disease is associated with decreased nitric oxide, causing priapism, which is similar to how pulmonary hypertension develops.
The patient is very uncomfortable. Because you will be treating patients unfamiliar to you in an ED setting, you will be confronted with people you are not sure have SS crisis. Ethically, it is better to treat everyone as having a genuine event and give pain medications. The most important part of this case is to give oxygen, fluids, and antibiotics before all other considerations. Stopping the crisis and preventing septic death from an autosplenectomized adult with SS disease is the most important task.
Initial Orders:
Oxygen
Normal saline (NS) continuously
Ceftriaxone (if febrile)
Hydromorphone (Dilaudid) IV
CBC and peripheral smear
Liver function tests (LFTs)
Reticulocyte count
Chest x-ray
Electrophoresis (if patient is unknown to you)
Urinalysis (UA) and blood cultures (if not done)
Folic acid
Any patient in pain can have hypertension and tachycardia. Treat the pain first and recheck blood pressure and heart rate.
SS disease originates from a single amino acid substitution. Valine replaces glutamic acid at position 6
You move the clock forward 1 hour and check to see that the pain has improved with “Interval History.” Rechecking oxygen saturation is always a good idea because the root cause of SS crisis is an abnormal crystallization of sickle hemoglobin at low oxygen states.
Test Results:
CBC and peripheral smear: hematocrit 28%; smear: sickled cells, WBCs 18,000/μL (Figure 2-3)
LFTs: indirect bilirubin elevated 2.5 mg/dL
Reticulocyte count: 15%
Chest x-ray: left lower lobe infiltrate
UA: no WBCs
Figure 2-3. Sickle cells. Homozygous sickle cell disease. A nucleated red blood cell and neutrophil are also in the field. (Reproduced with permission from Longo DL, et al. Harrison’s Principles of Internal Medicine, 18th ed. 2012, www.accessmedicine.com.)
Why are there high levels of bilirubin and bilirubin stones in SS disease?
• Normal RBCs live 90 to 120 days.
• Sickle RBCs live only 10 to 20 days.
Everyone with SS disease has a reticulocyte count 5 to 10 times higher than normal because cells are rapidly destroyed.
SS disease is a chronic, partially compensated hemolytic anemia.
Although the chest x-ray shows an infiltrate, the patient is already on antibiotics for fever. Other antibiotic choices are levofloxacin, moxifloxacin, or adding vancomycin to the ceftriaxone. This is all to cover pneumococcus. WBC counts are routinely elevated in SS disease. This is an expected finding and is part of the chronic hyperactivity of the marrow.
Expected Abnormalities in Sickle Cell Disease
• Reticulocyte count 5% to 25%
• High indirect bilirubin level
• Elevated WBC count
Salmonella is the most common documented cause of osteomyelitis in SS disease.
Pulmonary hypertension is common in SS disease from deficient nitric oxide (NO).
You move the clock forward 1 day after the initial laboratory test results are checked and oxygen, fluids, pain medications, and antibiotics are ordered. On hospital days 2 and 3, the hematocrit levels drop from 28% to 25% to 20%.
What is the most likely cause?
a. Folic acid insufficiency
b. Parvovirus
c. Sepsis
d. Sickle cell crisis itself
Answer b. Parvovirus
Parvovirus can “freeze” the marrow in SS disease. It has a predilection for infecting those with hemoglobinopathy. Folic acid deficiency can definitely lead to a sudden stop in RBC production, so you should check to see if you remembered to order a folic acid test. Sepsis can stop marrow production but should not work this fast. You should not ascribe sudden drops in hematocrit levels to the SS crisis alone. Pain crises are not the same as hemolytic events. The etiology of pain in SS crisis is not precisely clear, but it is definitely not the same as seeing a drop in hematocrit.
Orders:
Reticulocyte count
Repeat CBC
Folic acid if not ordered
The reticulocyte count comes back as 2%. This is far too low for SS disease especially in a person on folic acid.
Orders:
Parvovirus polymerase chain reaction (PCR) for DNA
IV immunoglobulin (IVIG) if the hematocrit level continues to drop
Transfusion
The most accurate test for SS disease is hemoglobin electrophoresis.
Sickle cell trait is increased in certain countries because it stops the spread of malaria by destroying the first infected cells.
Despite giving oxygen and adding vancomycin to ceftriaxone and hydration, the patient’s chest pain and hypoxia worsen. What is the next step?
a. Change antibiotics.
b. Provide continuous positive airway pressure (CPAP).
c. Perform exchange transfusion.
Answer c. Perform exchange transfusion.
Exchange transfusion is the fastest way to terminate a pain crisis. It involves replacing the majority or the patient’s blood. This effectively eliminates the sickling. Indications for exchange transfusion are:
• Acute chest syndrome not responding (hypoxia worsens)
• Central nervous system (CNS) events or stroke
• Priapism
• Retinal infarction
Order a hematology consultation for a patient with severe sickle crisis, especially for one needing an exchange transfusion. Move the clock forward a few hours. After the transfusion, the patient’s symptoms resolve. Cultures do not grow an organism. Move the clock forward 6 to 12 hours at a time.
On hospital day 7, the patient is ready to leave. You get the message “This case will end in 5 minutes of real time.”
What are your final orders?
Folic acid test
Pneumococcal vaccine (if not previously given in last 5 years)
Hydroxyurea
Follow-up office visit in 1 week
Hydroxyurea increases levels of fetal hemoglobin.
Sickle cell disease predisposes to dehydration by impairing renal tubular concentrating ability.