Sickle cell crisis case file

Sickle cell crisis case file

Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS

Case 41

A 30-year-old woman with a history of sickle cell disease presents to the emergency department (ED) complaining of chest pain for 2 days. She states that the pain is right sided, worse with inspiration, and is more severe than her usual “crisis pain.” She has subjective fevers, mild shortness of breath, and a productive cough. She denies vomiting, hemoptysis, or lower extremity swelling. Her last pain crisis was 3 months ago. She usually takes acetaminophen and hydrocodone for pain control during her crises, however, neither have been able to provide sufficient relief during this episode. On physical examination, her temperature is 38.3 °C (101°F), blood pressure is 126/65 mm Hg, heart rate is 98 beats per minute, respiratory rate is 22 breaths per minute, and oxygen saturation is 94% on room air. Lung examination reveals crackles in the right lower lung field. She does not have any jugular venous distension, calf tenderness, or lower extremity edema.

⯈ What is the most concerning issue regarding this patient?

⯈ What is the initial management?

ANSWER TO CASE: 41

Sickle Cell Crisis

Summary: This is a 30-year-old woman with a history of sickle cell disease who presents with chest pain, shortness of breath, and cough. She is febrile, tachypneic, and hypoxic.

• Most concerning issue: Acute chest syndrome.
• Initial management: Supplemental oxygen, IV hydration, analgesia, and antibiotics.

ANALYSIS

Objectives

1. Recognize the clinical signs and symptoms of sickle cell crisis and its associated complications.
2. Understand the diagnosis and treatment of acute chest syndrome.
3. Understand the treatment of pain crises in patients with sickle cell disease.

Considerations

Sickle cell disease is common, affecting approximately 1 in every 400 African Americans and 1 in 16,000 Asian Americans. It can affect almost any organ system and has a wide variety of clinical presentations. Acute chest syndrome is the leading cause of death and second leading cause of hospitalization among patients with sickle cell disease. Acute chest syndrome can present primarily or develop after a sickle cell patient is hospitalized for a vasoocclusive crisis. The clinician’s priorities are to differentiate the mild from the life-threatening crises and to treat them.

The patient in this case, a 30-year-old woman with known sickle cell disease, has acute onset of chest pain, cough, fever, and subtle findings on the pulmonary examination. Her oxygen saturation is 94% on room air, which is concerning, and should be followed up with an arterial blood gas. Pulmonary embolism, pneumonia, and acute chest syndrome should be considered as possible diagnoses, as individual or concomitant conditions. The chest radiograph can be helpful. Acute chest syndrome is a constellation of symptoms that includes chest pain and tachypnea. It can result from infectious or noninfectious (eg, pulmonary infarct) causes. It usually presents with some combination of chest pain, fever, hypoxia, and a new pulmonary infiltrate on chest radiography. Often, acute chest syndrome and pneumonia cannot be distinguished initially. Therefore, it is prudent to treat these patients with antibiotics, obtain a Gram stain and culture of the sputum, and admit them to the hospital. The treatment for acute chest syndrome is supportive and includes oxygen, intravenous fluid hydration, and analgesia. All patients with sickle cell disease who present to the ED require close follow-up with a hematologist.

DEFINITIONS

ACUTE CHEST SYNDROME: The presence of a new lobar or segmental infiltrate on chest radiography in the presence of fever, respiratory symptoms, and/or

chest pain in patient with sickle cell disease.

VASOOCLUSIVE CRISIS: Painful episodes resulting from intravascular sickling causing obstruction of blood flow in the microcirculation leading to tissue ischemia and microinfarction.

SPLENIC SEQUESTRATION: Occurs when red cells become trapped in the spleen, resulting in a rapidly enlarging spleen, a sudden drop in hemoglobin, and the potential for shock.

APLASTIC CRISIS: A transient cessation of erythropoiesis resulting in the acute onset of anemia and reticulocytopenia. The most common cause of aplastic crisis appears to be infection, specifically parvovirus.

Approach To:

Sickle Cell Crisis

CLINICAL APPROACH

Sickle cell disease is caused by abnormal hemoglobin production. In humans, hemoglobin is composed of two alpha and two beta chains. However, in sickle cell disease, hemoglobin S (HbS) results when a valine is substituted for glutamine in the sixth position of the beta chain. Under hypoxic or acidotic conditions, this abnormal hemoglobin polymerizes and sickles, resulting in sludging in the microcirculation. In turn, this causes tissue hypoxia, ischemia, acidosis, and more sickling.

The gene for HbS is autosomal recessive. Patients who are heterozygous (sickle cell trait) are generally asymptomatic except under extreme stress (eg, severe dehydration, temperature, or pressure change), but do tend to be more susceptible than the general population to urinary tract infections. Those who have sickle cell disease (homozygous), in contrast, are highly susceptible to vasoocclusion and pain crises.

Potential triggers for sickle cell crises are numerous. Some common triggers include infections (bacterial and viral), dehydration, exposure to cold temperatures, low oxygen environments such as airplane travel or smoke-filled rooms, and trauma. It should be recognized, however, that spontaneous, unexplained crises are common. Because these patients are functionally asplenic after early childhood, they are also at significant risk for bacterial infections, especially by encapsulated organisms such as Salmonella typhi, Haemophilus influenza type B, Streptoccoccus pneumoniae, Neisseria meningitides, and Group B streptococci. In fact, the highest rate of mortality occurs in children between the ages of 1 and 3 years as a consequence of sepsis.

COMMON COMPLICATIONS

Sickle cell crisis can affect multiple organ systems (see Table 41–1). During the assessment of patients with sickle cell disease, the history should focus on identifying any precipitating causes and complications. Pain that is different from previous pain crises may be an indicator of a potentially life-threatening event. A rapid assessment of the vital signs and a careful physical examination are important, because severe complications in sickle cell crisis often present with nonspecific manifestations. The clinician’s concern should be heightened if the patient has a fever, severe abdominal pain, respiratory or neurological symptoms, joint swelling, priapism, or pain that is not relieved by usual measures.

Vasoocclusive Crisis

Acute vasoocclusive events (VOEs) or “painful crisis” are the most common complications of sickle cell disease (SCD) and the most frequent cause of ED visits in this patient population. Polymerization of the sickle cell hemoglobin causes the red blood cells to become rigid and sticky and formed into shapes that sometimes have the appearance of a sickle, hence the name. These sickled cells subsequently will cause obstruction of the microvasculature. It is probable that a multitude of factors contribute to VOEs, including red cell function, blood viscosity, adherence of sickled cells to endothelium, and environmental factors. Patients may live in a homeostatic balance with circulating sickle cells, but a seemingly minor event such as a viral illness, dehydration, trauma, or exercise may tip this balance resulting in a full-blown VOE.

Dactylitis, or hand-foot syndrome, may be the first clinical manifestation of SCD. Infarctions in the metacarpals result in episodes of pain and swelling involving the hands and feet. Infants and toddlers with dactylitis may become irritable, refuse to walk, or cry when touched or held. As children with SCD get older, pain shifts to the arms, legs, back, and pelvis, whereas adolescents may also complain of involvement of the chest and abdomen. These vasoocclusive episodes usually last from 3 to 9 days, but it is not atypical for those patients with longer episodes to continue to have patterns where their episodes remain prolonged.

Infection

Infection is the major cause of mortality in SCD. Virtually all patients with SCD are asplenic, predisposing them to overwhelming infections from encapsulated microorganisms. In addition to sepsis, patients are susceptible to other infections such as pneumonia, meningitis, and osteomyelitis. Although prophylactic penicillin and vaccines for pneumococci and Haemophilus influenzae type B have reduced the incidence of sepsis in this patient population, pneumococcal sepsis remains a significant cause of death in children with SCD. Adults are less vulnerable because their immune systems have matured to allow for type-specific antibody production; however, fever must be taken very seriously in all patients with SCD.

Acute Chest Syndrome

Acute chest syndrome (ACS) is the presence of a new lobar or segmental pulmonary infiltrate in the presence of fever, respiratory symptoms, or chest pain. Various causes may contribute to ACS including infection, pulmonary infarction

Abbreviations: CT = Computed tomography; IV = intravenous; V/Q ventilation = perfusion; PRBC = packed red blood cell.

aSupportive care includes hydration and analgesia.

due to vasoocclusion, and fat emboli from marrow infarction. Chest pain from vasoocclusion may cause splinting and hypoventilation, leading to the development of ACS in a patient who initially presents with a painful episode. Infectious organisms associated with ACS include S Pneumoniae in younger children and Mycoplasma or Chlamydia in adolescents. Acute chest syndrome carries a high risk of progression to respiratory failure and should be considered in all SCD patients with respiratory signs or symptoms.

All patients with ACS should be admitted to the hospital. The finding of an infiltrate on chest radiograph is diagnostically significant, but it should be recognized that it is common for the initial radiograph to be normal. Laboratory evaluation should include a CBC, reticulocyte count, blood and sputum cultures, and type and screen. A baseline arterial blood gas (ABG) measurement should be obtained, followed by serial ABG measurements to evaluate for worsening A-a gradient. In patients with ACS and hypoxemia (PaO2 = 70 to 80 mm Hg, O2 saturation of 92%- 95%), supplemental oxygen should be administered via nasal cannula at a rate of 2 liters per minute. Exchange (or conventional) transfusion should be initiated in patients with hypoxia or a drop in hemoglobin >2 g below baseline. All patients should receive empiric antibiotics that cover typical and atypical microorganisms, (most commonly with a macrolide and third generation cephalosporin). Analgesia for chest pain should be provided but managed carefully to prevent hypoventilation. Regular use of an incentive spirometer has shown to significantly reduce the frequency of subsequent episodes of chest pain. Intravenous fluids given to patients with ACS should not exceed 1.5 times maintenance in order to prevent volume overload.

Stroke (Cerebrovascular Accidents)

Patients with SCD are at greatly increased risk for both ischemic and hemorrhagic stroke. Most strokes in children are ischemic events, usually involving large arteries, whereas hemorrhagic strokes are more common in adults. Common presenting signs and symptoms include hemiparesis, aphasia, dysphasia, cranial nerve palsies, seizure, or coma. A noncontrast enhanced CT scan should be obtained as soon as possible, followed by MRI and MRA with diffusion weighted imaging. The treatment for ischemic stroke in children is exchange transfusion, as conventional therapies (tissue plasminogen activator and antiplatelet agents) are not indicated. Ischemic strokes in adults with SCD are thought to be more likely due to common ischemic stroke mechanisms; therefore conventional therapies are recommended.

Splenic Sequestration

Acute splenic sequestration is the most common cause of acute exacerbation of anemia in patients with SCD. This occurs when red cells become trapped in the spleen, resulting in a sudden drop in hemoglobin and the potential for shock. It typically occurs between the ages of 3 months to 5 years. Patients typically present with sudden weakness, pallor, tachycardia, or abdominal fullness. The mortality of this condition is high, and death can occur within a matter of hours without aggressive management. All patients should be transfused with packed red blood cells emergently. Splenectomy may be necessary in children with recurrent splenic sequestration.

Aplastic Crisis

Patients with SCD are susceptible to transient red cell aplasia (TRCA). The majority of TRCA are caused by Parvovirus B19 infection. The virus is directly cytotoxic to erythroid precursors, which can cause transient suppression of erythropoiesis and reticulocytopenia. This will present as significant anemia after an illness without signs of hemolysis, usually 5 days postexposure and continuing 7 to10 days. Intravenous immunoglobulin (IVIG) infusion is the standard treatment once the diagnosis is made.

Priapism

Priapism, a prolonged painful erection of the penis, is a well-recognized complication of SCD that can result in fibrosis and impotence. Approximately 50% of patients with SCD reported having at least one episode of priapism before 21 years of age. In addition to pain management, effective strategies for immediate and sustained detumescence consist of aspiration of blood from the corpora cavernosa followed by irrigation of the corpora cavernosa with dilute epinephrine. In all cases, early urologic consultation should be obtained.

Treatment

It is important to note that pain is often the primary presenting complaint of all sickle cell–associated crises. It is thought that pain is caused by ischemia secondary to sickling. This causes sludging and local acidosis, which in turn engenders more sickling and the pain worsens.

Unfortunately, recent evidence shows that patients with sickle cell disease are regularly undertreated for their pain. This is likely due to sociocultural factors as well as the challenges of navigating the subjectivity of pain. Adequately treating pain is a vital component in the treatment of sickle cell patients who present to the emergency department.

The mainstay of treatment for a pain crisis is supportive care: supplemental oxygen, hydration, and analgesia. Due to the chronicity of these pain crises, and the long-standing pain that results from sickle cell complications (eg, avascular necrosis), adequate analgesia plays a pivotal role in patient care. Patients with moderate to severe pain typically require intravenous opiates. In patients with poor vascular access secondary to chronic intravenous line placement, subcutaneous and intramuscular administration is a suitable alternative. Oral opiates are used for patients in less severe pain. Although there are no definitive studies that show which opioid is superior in treating a pain crisis, morphine sulfate or hydromorphone are commonly used as first-line agents. Hydromorphone is a good option for patients who cannot tolerate the side effects of morphine (eg, nausea and pruritus). Meperidine, a commonly prescribed opioid, should be avoided due to its increased risk of causing seizures and serotonin syndrome. Adjunctive therapy with nonsteroidals, particularly ketorolac, should be considered. However, long-term use of these medications increases the risk of renal failure and peptic ulcer disease. Dosing of analgesics should be individualized for each patient and should be titrated to pain relief. Many patients will know which medication, dose, and frequency of administration are most beneficial to them. Many sickle cell patients with recurrent pain crises and other complications are started on hydroxyurea, a myelosuppressive agent shown to reduce these crises.

COMPREHENSION QUESTIONS

41.1 A 3-year-old girl is brought into the ED by her mother for being pale and irritable. The girl is known to have sickle cell disease. Which of the following tests would help to differentiate an aplastic crisis from a vasoocclusive crisis?

A. Reticulocyte count

B. Bone marrow biopsy

C. Peripheral smear

D. Hemoglobin level

E. Haptoglobin level

41.2 A 2-year-old boy with sickle cell disease is being seen by his pediatrician. Which of the following would make the most impact on mortality risk?

A. Screening urine culture

B. Bone radiograph to assess for osteomyelitis

C. Pneumococcal vaccination

D. Chest radiograph to assess for acute chest syndrome

E. Bone marrow biopsy to assess anemia

41.3 A 12-year-old girl is brought into the ED at the direction of her pediatrician. The patient’s mother informs you that the patient has sickle cell disease. Which of the following findings would be most concerning to you?

A. Fever

B. Pain that is typical of past crises

C. Mild abdominal pain

D. Hematuria

E. Strabismus

41.4 Which of the following is most accurate concerning acute chest syndrome?

A. It is an uncommon complication of sickle cell disease.

B. It can be caused by pulmonary infection or infarct.

C. It can be ruled out with a normal chest x-ray.

D. Antibiotics should not be given until the patient is proven to have an

infection.

ANSWERS

41.1 A. The reticulocyte count is low in aplastic crisis, but elevated or normal with a vaso-occlusive crisis. A bone marrow biopsy is invasive and causes a delay in diagnosis. Neither a smear nor a haptoglobin level would differentiate between the two diagnoses. A hemoglobin level may not show a difference in the acute setting.

41.2 C. Pneumococcal sepsis is the leading cause of death in children aged 1 to 3 years. Thus, pneumococcal vaccine is critical in its prevention.

41.3 A. The clinician should be worried if the patient has a fever, severe abdominal pain, respiratory or neurological symptoms, joint swelling, pain that is not relieved by usual measures, or priapism. The other signs and symptoms here require additional workup, but are not harbingers of the same level of morbidity as a fever.

41.4 B. Acute chest syndrome is caused by pulmonary infection or infarct. It is a common complication of sickle cell disease that is difficult to confirm simply by a chest radiograph. Because it is difficult to differentiate it from infectious pneumonia, patients are empirically started on antibiotics.

CLINICAL PEARLS

⯈ Sickle cell disease can manifest in any organ system and has a variety of clinical presentations ranging from mild to life-threatening.

⯈ Because patients with sickle cell disease are functionally asplenic after early childhood, they are at risk for infection by encapsulated organisms (eg, Haemophilus influenzae, Streptococcus pneumoniae), and therefore must be immunized with the appropriate vaccines.

⯈ Acute chest syndrome is the leading cause of premature death in patients with sickle cell disease. Having a low threshold of suspicion in patients presenting with respiratory complaints, abnormal oxygen saturation, or findings on lung examination, is critical.

⯈ Treatment of acute chest syndrome involves supplemental oxygen, hydration, analgesia, empiric antibiotics, and possibly exchange transfusion.

⯈ Splenic sequestration has a very high mortality. Patients present with an abrupt drop in hemoglobin and the potential for shock, requiring emergent transfusion and spleenectomy.

⯈ Aplastic crisis occurs from a transient suppression of erythropoiesis. It is characterized by significant anemia accompanied by a low reticulocyte count. It is most commonly caused by parvovirus B19.

⯈ Patients in pain crises require prompt attention and treatment of their pain. Intravenous opiates, such as morphine or hydromorphone, are the mainstay of pain management in the ED.

References

DeBaun MR, Vichinsky E. Sickle cell disease. In: Nelson Textbook of Pediatrics. 18th ed. New York, NY: Saunders; 2007:2026-2031. 

Givens M, Rutherford C, Joshi G, et al. Impact of an emergency department pain management protocol on the pattern of visits by patients with sickle cell disease. J Emerg Med. 2007;32:239-243. 

Glassberg J. Current guidelines for sickle cell disease: management of acute complications. Emergency Medicine Practice Guidelines Update. 2009;1(3):1-3. 

McCreight A, Wickiser J. Sickle Cell Disease. In: Strange GR, Ahrens WR, Schfermeyer R, Wiebe R, eds. Pediatric Emergency Medicine. 3rd ed; 2009:Chapter 100. 

Zempsky W. Evaluation and treatment of sickle cell pain in the emergency department: paths to a better future. Clin Pediatr Emerg Med. 2010;11:265-273.

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