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Individuals are diagnosed with sickle cell disease (SCD) if they have one of several genotypes that result in at least half of their hemoglobin (Hgb) being Hgb S. Sickle cell anemia (SCA) refers to the condition associated with homozygosity for the Hgb S mutation (Hgb SS). Other Hgb mutations may occur with Hgb S causing a similar but milder condition. In SCA, the presence of intracellular hemoglobin S polymerization leads to chronic hemolytic anemia, vasoocclusive crises of varying severity and frequency with cumulative organ damage and systemic manifestations that include impairment in growth and development, susceptibility to infection, and reduced quality and duration of life
Segal JB et al. Hydroxyurea for the Treatment of Sickle Cell Disease. Rockville, MD: Agency for Healthcare Research and Quality, 2008 Feb. Report No. 08-E007
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Epidemiology
Platt OS et al. N Engl J Med 1994;330:1639–1644 (3764 patients. followed to determine life expectancy)
Sickle Cell Research for Treatment and Cure. Bethesda, MD: NIH Publication No. 02-5214;2002:1–16
Dept. of Energy, Human Genome Project. www.nhlbi.nih.gov/resources/docs/scd30/scd30.pdf [accessed August 5, 2013]
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Major Sickle Hemoglobinopathies: Laboratory Features
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Acute Pain Syndrome
Most common type of pain
Unpredictably abrupt in onset
Sometimes migratory
Varies in intensity from a mild ache to a severe and debilitating pain
Acute pain may occur with chronic pain and frequent episodes of acute pain can resemble chronic pain
In adults, about one-third of episodes are associated with a preceding or concurrent infection
Factors that potentiate Hgb S polymerization may precipitate an acute painful episode. These factors include acidosis, hypoxia, and dehydration
Chronic pain
Caused by obvious pathophysiology (eg, leg ulcers, avascular necrosis, chronic osteomyelitis)
Intractable chronic pain with no obvious sign
Ballas SK. Current issues in sickle cell pain and its management. Hematology Am Soc Hematol Educ Program. 2007:97–105
Ballas SK. Semin Hematol 2001;38:307–314
Benjamin LJ et al. Guideline for the Management of Acute and Chronic Pain in Sickle-Cell Disease, APS Clinical Practice Guidelines Series, No. 1. Glenview, IL: American Pain Society; 1999:1–98
Castro O et al. Blood 1994;84:643–649
Rees DC et al. Br J Haematol 2003;120:744–752
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
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Epidemiology
In SCD, pain is the most common complaint and reason for patients to consult doctors and to be admitted to the hospital
Among patients with SCD in the United States, an acute pain episode accounts for ~90% of visits to the ER and 70% of all hospitalizations
Mean rate per year of acute pain episodes
Hgb SS (0.8)
Hgb Sβ-thalassemia (1.0)
Hgb SC (0.4)
The rate of painful crises increases over the first 3 decades of life and then declines as a consequence of the earlier mortality of adults with higher rates of pain
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Treatment
Initial management of severe acute pain in the emergency department (ED)
Arrival at ED to time +15–20 minutes after arrival
Assess for common SCD acute pain states
Determine pain type (onset, duration, frequency)
(1) Pain is atypical for SCD: Determine related symptoms (look for infections, complication, other comorbidities and precipitating factors). Next, assess pain, treat, and conduct work-up to determine etiology
(2) Pain is typical for SCD: See next step
Determine pain characteristics (intensity, location, and quality based on self-report)
(1) Assess self-reported pain with an instrument such as a visual analog scale (VAS), Wong-Baker Faces Pain Rating Scale, or a simple verbal descriptor scale (0–10 scale; 0 = none, 10 = worst imaginable)
Obtain treatment history (home meds, acute pain, hospital care, meds in past 24 hours, out-of-home meds)
Examine pertinent physical factors
Summarize assessment of profile and select treatment (based on characteristics of episode, prior treatment history, and physical findings)
(1) Not on chronic opioid therapy: Start IV loading dose of short-acting opioid (eg, morphine or hydromorphone; see Table 61-1 for opioid dosages)
(2) On chronic opioid therapy: Select medication and loading dose based on overall assessment and prior treatment history. Patient and family often know what medications and dosage have been effective in the past. Next, start IV loading dose of short-acting opioid. Administer SC if insufficient venous access
(3) Begin IV hydration (see Acute Pain Syndrome, Notes Section)
Time +15–30 minutes after ED arrival
Add combination therapy as indicated (eg, antiinflammatory and or antihistamine to improve response to therapy). See Acute Pain Syndrome Notes
Assess degree of pain relief every 15–30 minutes; use a pain relief scale to assess response (eg, 0 = none, 1 = little; 2 = moderate; 3 = good; 4 = complete)
Time +30 minutes to +2–8 hours after ED arrival
Assess pain relief every 15–30 minutes. If no pain relief achieved, administer one-quarter to one-half of initial loading dose of opioid to relief (see Table 61-1) with coanalgesic (see Acute Pain Syndrome, Notes Section, number 4)
Admit to hospital if complications, treatment ineffective, or oral therapy cannot be maintained
Discharge in absence of above admission criteria on oral analgesics to maintain adequate pain relief and refer to managing clinician
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Major barriers to effective pain management
(a) Clinicians' limited knowledge of SCD; (b) inadequate assessment of pain; (c) bias against opioid use; (d) inadequate understanding about opioid tolerance, physical dependence, and addiction; (e) unwarranted fear of addiction among patients and families
Tolerance, physical dependence, addiction
(a) Tolerance: A physiologic response to opioid administration, the first sign of which is decreased duration of medication action. Larger doses or shorter intervals may be needed to achieve the same analgesic effect; (b) physical dependence: a physiologic response to opioid administration that requires no treatment unless withdrawal symptoms occur or are anticipated; (c) addiction: a psychological dependence with genetic, psychological, and social roots. Consultation with appropriate specialists in substance abuse is recommended. Estimates of the risk of addiction with opioid therapy in SCD appears to parallel that observed in the community at-large (Solomon LR. Blood 2008;111: 997–1003); (d) pseudoaddiction: is the seeking of additional medication because of undertreatment of pain
Hydration. (a) There is theoretical and empirical evidence that rehydration with a hypotonic solution (5% dextrose injection [D5W] or 5% dextrose/0.2% sodium chloride injection [D5W/1⁄4NS]), unless contraindicated (eg, brain injury, severe hyponatremia, etc.), is preferable. Such therapy has been shown to swell red cells, reduce the MCHC and thereby reduce the rate and extent of intracellular Hgb S polymerization. (Rosa M et al. A study of induced hyponatremia in the prevention and treatment of sickle-cell crisis. N Engl J Med 1980;303:1138–1143.) (b) The Management of Sickle Cell Disease Guidelines (2002) recommends the use of 5% dextrose with 0.45% sodium chloride injection (D5W1/2NS) plus 20 mEq KCl/L adjusted for serum chemistry results given at a rate not exceeding 1.5 times maintenance (including volume for drug infusions)
Hypovolemia should be corrected prior to the administration of ketorolac and NSAIDs should be used with caution in patients with CHF, dehydration, hypovolemia, or any other condition that may compromise renal blood flow and increase the risk of developing renal toxicity. Ketorolac should be used with caution in patients with impaired hepatic function or a history of liver disease
Ketorolac is contraindicated in patients with: (1) active peptic ulcer disease (PUD); (2) recent GI bleeding or perforation; (3) a history of PUD or GI bleeding; (4) advanced renal impairment or at risk for renal failure caused by volume depletion; (5) previously demonstrated hypersensitivity to ketorolac, other NSAIDs, or aspirin, or patients currently receiving aspirin or NSAIDs; and (6) suspected or confirmed cerebrovascular bleed, hemorrhagic diathesis, or incomplete hemostasis. Ketorolac should not be used in nursing mothers
Antiinflammatory medications, for example: Ketorolac
Multiple-dose treatment; adults < 65 years old: Ketorolac 30 mg; administer intravenously over at least 15 seconds or slowly by deep intramuscular injection every 6 hours (maximum daily dose = 120 mg)
≥65 Years old, weight <50 kg, or renally impaired patients (see manufacturer's warnings): Ketorolac 15 mg; administer intravenously over at least 15 seconds or by slow deep intramuscular injection every 6 hours (maximum daily parenteral dose = 60 mg)
Ketorolac (transition from IV/IM to oral)
< 65 Years old: Ketorolac 20 mg; administer orally initially, followed by 10 mg every 4–6 hours (maximum dose not to exceed 40 mg/24 hours)
≥65 Years old, weight < 50 kg, or renally impaired patients (see manufacturer's warnings): Ketorolac 10 mg; administer orally every 4–6 hours (maximum dose not to exceed 40 mg/24 hours)
Note: In adults, the maximum combined duration of ketorolac use (parenteral and oral) is limited to 5 days. The use of an H2-blocker has been recommended to reduce GI side effects
(See Perlin E et al. Am J Hematol 1994;46:43–47)
Chronic hemolysis. Routine supportive treatment should include folic acid 1 mg/day administered orally (Pearson HA, Cobb WT. J Lab Clin Med 1964;64:913–921)
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Moderate pain relief, acceptable toxicities: Begin opioid analgesics on an around-the-clock (ATC) schedule (see Tables 61-1 and 61-2)
Moderate pain relief, toxicities not acceptable: Add combination therapy to include antiinflammatory medications; for example, ibuprofen 400–600 mg; administer orally every 6 hours (consider adding an H2-blocker to reduce risk of GI side effects)
Moderate pain relief not achieved: Continue to adjust therapy by increasing the dose until pain is relieved. Increase dose in increments of 25–50% of the opioid analgesic loading dose
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Acute Chest Syndrome
Multicenter Acute Chest Syndrome Study (MACSS) definition: A pulmonary infiltrate consistent with consolidation, plus at least 1 of the following:
Chest pain
Fever >38.5°C (>101.3°F)
Tachypnea
Wheezing
Cough
Associated conditions:
Pulmonary infarction (30%)
Pulmonary fat embolization (16%)
Infection (33%) including chlamydia (13%), mycoplasma (12%), viruses (12%), and bacterial isolates (8%) which included Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae
Ballas SK. Semin Hematol 2001;38:307–314
Bellet PS et al. N Engl J Med 1995;333:699–703
Charache A et al. N Engl J Med 1995;332:1317–1322
Emre U et al. J Pediatr 1993;123:272–275
Lacy CF et al., eds. Albuterol. In: Drug Information Handbook 2011. 20th ed. Hudson, OH: Lexi-Comp; 2011:49–51
Rosse WF et al. New views of sickle cell disease pathophysiology and treatment. Hematology Am Soc Hematol Educ Program 2000:2–17
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
Vichinsky EP et al. N Engl J Med 2000; 342:1855–1865
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Epidemiology
Second most common cause of hospitalization in SCD
Most common complication of surgery and anesthesia
Incidence (per 100 patient-years):
Hgb SS overall (12.8)
Hgb SS ages 2–4 years (25.3)
Hgb SS adults (8.8)
Hgb Sβ-thalassemia (9.4)
Hgb SC (5.2)
Hgb Sβ+ thalassemia (3.9)
In-hospital mortality:
9% for adults
<2% for children
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Treatment
Carefully monitor oxygenation, hydration, and acid–base balance. Obtain daily weight, input/output, CBC, and appropriate serum chemistry panels. Measure baseline and pre-/posttransfusion Hgb S concentration. Follow CXR until stabilization is documented
Therapy:
Oxygen, by nasal cannula at a rate of 2 L/min or greater if needed to maintain a PaO2 of 70–80 mm Hg (or oxygen saturation of ≥90%)
Hydration with 5% dextrose injection (D5W) or 5% dextrose/0.2% sodium chloride injection (D5W/1⁄4NS) at a rate not to exceed 1.5 times maintenance (volume to include any drug infusions); also refer to Acute Pain Syndrome, Notes Section
Bronchodilator therapy for adults exacerbation of asthma (acute, severe):
Albuterol nebulizer solution (5 mg/mL), administer 2.5–5 mg by nebulizer every 20 minutes up to 3 doses, followed by 2.5–10 mg every 1–4 hours as needed or 10–15 mg/hour by continuous nebulization. (For adults with bronchospasm, albuterol nebulizer solution [5 mg/mL], administer 2.5 mg 3–4 times daily as needed)
Albuterol metered-dose inhaler (90 mcg/puff), administer 4–8 puffs every 20 minutes for up to 4 hours, then every 1–4 hours as needed. (For adults with bronchospasm, 2 puffs every 4–6 hours for quick relief)
Institute opioids or other analgesic therapy to prevent hypoventilation (see the Acute Pain Syndrome section)
Incentive spirometry protocol to prevent hypoventilation in patients able to perform it
Transfuse packed RBCs to achieve a Hgb S concentration <30–40%, or to a stable Hgb of 8–9 g/dL (see the section Red Blood Cell Transfusion)
Indications:
Poor respiratory function
PaO2 <70 mm Hg on room air
A decline in PaO2 >10% from baseline in a patient with chronic hypoxia
Note: Exchange transfusion should be undertaken in patients with a high baseline Hgb in whom transfusion of RBCs is recommended (eg, goal to reduce the Hct to <30%), signs of increasing infiltrate on CXR, if the arterial PO2 cannot be maintained above 70 Torr or if the patient is experiencing dyspnea or tachypnea (also see the section Red Blood Cell Transfusion)
Antibiotics should be given to febrile or severely ill patients. This should include:
A third-generation cephalosporin:
Ceftriaxone 1000 mg (maximum, 2000 mg); administer intravenously in 50–100 mL 5% dextrose injection (D5W) over 30 minutes every 24 hours, and
A broad-spectrum macrolide or fluoroquinolone antibiotic:
Azithromycin 500 mg; administer intravenously in 250–500 mL D5W over 60 minutes every 24 hours, or
Ciprofloxacin 400 mg; administer intravenously in 200 mL D5W over 60 minutes every 12 hours
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Notes
Assess baseline oxygenation and continue to monitor ABGs as needed. The A-a gradient appears to be the best predictor of clinical severity
Limit hydration. Avoid fluid overload
Incentive spirometry is encouraged since it reduces the risk of ACS by 88% in patients hospitalized with thoracic bone ischemia/infarction
In 2010, a Cochrane Collaboration study was performed to assess the benefits and risks associated with the use of bronchodilators in sickle cell disease patients with acute chest syndrome. This study found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. The authors' conclusions stated "if bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated." Recommendations were proposed for well-designed, adequately powered randomized controlled trials to assess the risk and benefits of this treatment in patients with SSD acute chest syndrome. (Knight-Madden JM, Hambleton IR. Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease (review). Cochrane Database Syst Rev 2010 Jul 11;CD003733. Available at: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003733.pub2/abstract [accessed August 5, 2013])
Goal of transfusion therapy is to prevent progression of acute chest syndrome (ACS) to acute respiratory failure. Transfusions may not be required if the decline in A-a gradient is due to chest wall splinting that corrects with adequate analgesic therapy and incentive spirometry
Infection is a contributing factor as cause of death in 56% of ACS patients. Organisms include Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, legionella, Staphylococcus aureus, cytomegalovirus, and chlamydia as well as atypical microorganisms (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae)
In ACS patients it is often difficult to exclude a bacterial superinfection from a lung infarct
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Acute Cholecystitis
Gilbert DN et al., eds. Gallbladder (cholecystitis). In: The Sanford Guide To Antimicrobial Therapy 2011, 41st ed. Speeryville, VA: Antimicrobial Therapy, Inc.; 2011:15
Nzeh DA et al. Pediatr Radiol 1989;19:290–292
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
Walker TM et al. J Pediatr 2000;135:80–85
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Epidemiology
Cholelithiasis occurs as early as 2–4 years of age; incidence progressively increases with age; ≈30% of 18-year-old patients have cholelithiasis
Acute attacks of cholecystitis are difficult to differentiate from hepatic crisis. Biliary scintigraphy may be helpful in differentiating acute cholecystitis from sickle hepatic crisis but is not always diagnostic (D'Alonzo WA Jr, Heyman S. Pediatr Radiol 1985;15:395–398)
The natural history of asymptomatic cholelithiasis is unknown; however, up to 30% of patients may develop symptoms or complications within 3 years. The prevalence of cholelithiasis appears to be lower in patients co-inheriting α-or β-thalassemia
Patients with sickle cell trait have no increased risk of developing pigment stones
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Treatment
The treatment of acute cholecystitis is similar to that of the general population
Therapy:
Hydration (as clinically indicated) with 5% dextrose injection (D5W) or 5% dextrose/0.2% sodium chloride injection (D5W/1⁄4NS) at a rate not to exceed 1.5 times maintenance (volume to include any drug infusions). Also, refer to Acute Pain Syndrome, Notes Section
Institute opioids or other analgesic therapy as appropriate based on clinical symptoms with superimposed vasoocclusive crises (see the section Acute Pain Syndrome)
Antimicrobial therapy including
Piperacillin sodium 3000 mg + tazobactam sodium 375 mg; administer intravenously in 50–150 mL D5W or 0.9% sodium chloride injection (0.9% NS) over 20–30 minutes every 6 hours, or
Imipenem 500 mg/cilastatin 500 mg; administer intravenously in 50–100 mL D5W or 0.9% NS over 20–60 minutes every 6 hours (if life-threatening)
Elective cholecystectomy is recommended several weeks after an acute episode subsides, given the greater operative risks during an episode of acute cholecystitis in SCD
Note:
Although cholecystectomy in asymptomatic patients is controversial, an aggressive surgical approach has the benefit of reducing the risk of complications arising from cholecystitis and eliminating the gallbladder as a confounding diagnosis in RUQ pain (eg, sickle cell hepatic crises)
Laparoscopic cholecystectomy on an elective basis in a well-prepared patient has been reported to be the standard surgical approach to symptomatic patients but does not reduce the risk of sickle cell-related complications as compared with open cholecystectomy
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Acute Hepatic Sequestration (Right Upper Quadrant Syndrome)
Characterized by:
RUQ pain simulating acute cholecystitis
Fever
Jaundice
Elevations in hepatic transaminases
Marked elevations in serum bilirubin/alkaline phosphatase
Progressive hepatomegaly
Note: The rapid decrease in transaminases with treatment differentiates hepatic crisis from the slower decline characteristic of acute viral hepatitis
Halton CS. Hepatic sequestration in sickle cell disease. BMJ 1985;290(6740):744
Rosse WF et al. New views of sickle cell disease: pathophysiology and treatment. Hematology Am Soc Hematol Educ Program. 2000:2–17
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
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Epidemiology
A rarely recognized complication of vaso-occlusive crisis in SCD
Prevalence in SCD is not well described
Approximately 10% of Hgb SS patients develop a transient and less-severe form of intrahepatic cholestasis that is usually self-limited
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Treatment
Carefully monitor oxygenation, hydration, and acid–base balance. Obtain daily weight, input/output, CBC, and appropriate serum chemistry panels. Measure baseline and pre-/posttransfusion Hgb S concentration
Hydration with 5% dextrose injection (D5W) or 5% dextrose/0.2% sodium chloride injection (D5W/1⁄4NS) at a rate not to exceed 1.5 times maintenance (volume to include any drug infusions)
Note: In the event of hypervolemia, the administration of diuretic therapy may be required. Also, refer to Acute Pain Syndrome, Notes Section
Oxygen by nasal cannula at a rate of 2 L/min or greater, if needed to maintain a PaO2 of 70–80 mm Hg
Institute opioids or other analgesic therapy based on clinical symptoms (see the section Acute Pain Syndrome)
Transfuse packed RBCs to maintain Hgb close to baseline and Hgb S <30%
Note:
Exchange transfusion is the preferred method of transfusion although simple transfusion may be considered
Fatal hyperviscosity syndrome may result from simple transfusion as an episode of hepatic sequestration resolves. A spontaneous and rapid increase in the serum hemoglobin from sequestered RBCs ("reverse sequestration") accounts for this clinical finding. Patients should be carefully monitored in the recovery phase of acute hepatic sequestration for an acutely rising Hgb that could place the patient at risk for hyperviscosity. If suspected, promptly institute exchange transfusion with a goal of reducing the Hct to <30% (also see the section Acute Splenic Sequestration: Hyperviscosity)
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Notes
Differential diagnosis of RUQ syndrome in a patient with a sickle cell disease who presents with RUQ pain and abnormal LFTs includes: Acute cholecystitis, intrahepatic cholestasis, acute viral hepatitis, biloma, focal nodular hyperplasia in children, fungal ball, hepatic artery stenosis, hepatic infarct/abscess, hepatic vein thrombosis, mesenteric/colonic ischemia, pancreatitis, periappendiceal abscess, pericolonic abscess, pulmonary infarct/abscess, renal vein thrombosis
Patients should be taught to regularly monitor their liver size (and spleen size, especially in younger children and in adults coinheriting α-thalassemia who are at risk for acute splenic sequestration) in an effort to identify acute hepatic sequestration in its early stages
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Acute Splenic Sequestration
Acutely enlarging spleen
Decrease in steady state Hgb concentration by at least 2 g/dL and evidence of increased erythropoiesis (eg, marked elevations in the reticulocyte count or nucleated RBCs)
In more severe episodes, hypovolemic shock may complicate precipitous drops in Hgb with marked splenic enlargement
Glader BE. Anemia. In: Embury SH et al., eds. Sickle Cell Disease: Basic Principles and Clinical Practice. New York, NY: Raven Press; 1994:545–554
Rosse WF et al. New views of sickle cell disease: pathophysiology and treatment. Hematology Am Soc Hematol Educ Program. 2000:2–17
Solanki DL et al. Am J Med 1986;80:985–990
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
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Epidemiology
Majority of cases occur in children with Hgb SS before 2 years of age with almost all by age 6 years
Attacks may be associated with or preceded by bacterial or viral infections
Acute chest syndrome has been reported to complicate acute splenic syndrome in 20% of cases
Occurs less frequently in Hgb SC and Hgb S β+-thalassemia disease, but may occur beyond childhood because of persistent splenomegaly
Occurrence in adults is rare, but may occur with persistent splenic function in patients with concurrent α-thalassemia
A mortality rate of 12% has been reported with first attacks in SCD-SS (Hgb SS)
Recurrent episodes may occur in 50% with a mortality rate of 20%
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Treatment
Acute management:
Carefully monitor oxygenation, hydration, and acid–base balance. Obtain daily weight, input/output, CBC, and appropriate serum chemistry panels. Measure baseline and pre-/posttransfusion Hgb S concentration
Immediate treatment:
Oxygen by nasal cannula at a rate of 2 L/min or higher, if needed to maintain a PaO2 of 70–80 mm Hg or oxygen saturation ≥90%
Hydration with 5% dextrose injection (D5W) or 5% dextrose/0.2% sodium chloride injection (D5W/1⁄4NS) at a rate not to exceed 1.5 times maintenance (volume to include any drug infusions). Also, refer to Acute Pain Syndrome, Notes Section
Transfuse packed RBCs by simple transfusion to maintain the baseline Hgb level
Following transfusion therapy and correction of hypovolemia, remobilization of sequestered RBCs may result in a Hgb increase greater than that predicted on the basis of the volume of administered RBCs. Because this can lead to hypervolemia, careful monitoring is indicated and use of diuretic therapy may be required
If hyperviscosity is contributing an important role in the pathogenesis of an acute complication of SCD, exchange transfusion using a mechanical device directed at reducing the hyperviscosity should be performed. The goal of this therapy would be to reduce the Hct to <30%
Chronic management:
Following an acute episode, subsequent management is influenced by the high recurrence rate of this syndrome
Chronic transfusions are recommended in children <2 years of age following a severe episode to keep Hgb SS levels <30% until splenectomy can be considered after 2 years of age
Splenectomy is recommended in patients who experience a life-threatening episode of acute splenic sequestration shortly after being placed on a chronic transfusion program. A splenectomy can also be considered in patients with chronic hypersplenism
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Priapism
Sustained, painful, and unwanted erection resulting from vasoocclusive obstruction of penile venous drainage. Priapism has been classified as:
Mantadakis E et al. Blood 2000;95:78–82
Rackoff WR et al. J Pediatr 1992;120:882–885
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
Winter CC. J Urol 1978;119:227–228
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Epidemiology
Mean age of onset: 12 years
By age 20 years, 89% of males will have experienced 1 or more episodes
Precipitating factors include:
Complications include fibrosis of the penis and impotence
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Treatment
Outpatient management:
Encourage oral fluid intake
Administer oral analgesics
Attempt to urinate as soon as priapism develops and encourage frequent urination
Instituting medication and conservative therapy within 4–6 hours of the onset of symptoms can usually lead to reduction of erection
In-patient management:
Carefully monitor oxygenation, hydration, and acid–base balance. Obtain daily weight, input/output, CBC, and appropriate serum chemistry panels, and baseline coagulation profile. Measure baseline and pre-/posttransfusion Hgb S concentration
Hydration with 5% dextrose injection (D5W) or 5% dextrose/0.2% sodium chloride injection (D5W/1⁄4NS) at a rate not to exceed 1.5 times maintenance (volume to include any drug infusions). See Acute Pain Syndrome, Notes Section
Oxygen by nasal cannula at a rate of 2 L/min or greater if needed to maintain a PaO2 of 70–80 mm Hg or oxygen saturation ≥90%
Institute opioids or other analgesic therapy as appropriate (see the section Acute Pain Syndrome)
An urologist can perform penile aspiration if more conservative measures fail to achieve detumescence within 1 hour. Use a 23-gauge needle to aspirate blood from the corpus cavernosum followed by irrigation with a 1:1,000,000 solution of epinephrine in 0.9%sodium chloride injection
Note: This is performed within 4–6 hours of onset and under conscious sedation and local analgesia. Successful in 15 young males on 37 of 39 occasions (Mantadakis E et al. Blood 2000;95:78–82)
Transfusion of packed RBCs is considered if penile aspiration with irrigation fails to achieve detumescence. Administer packed RBCs to reduce Hgb S to <30%
Note: It is unclear if simple transfusion is equivalent to exchange transfusion
Management of recurrent priapism:
Chronic simple transfusion programs have been utilized to maintain the Hgb S <30%
Note: Limit this approach to 6–12 months with frequent assessments
Penile shunting (Winter procedure) creates a shunt between the glans penis and the distal corpora with a Tru-Cut biopsy needle. This permits penile blood to drain from the distended corpora cavernosa into the uninvolved corpus spongiosa
Note: Complications of priapism and its treatment:
Bleeding from the holes placed in the penis as part of the penile aspiration or shunting procedures
Infection, skin necrosis, damage, or strictures of the urethra, fistulas, and impotence
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Transient Red Cell Aplasia (TRCA)
Characterized by a temporary suppression of erythropoiesis. Presenting manifestations may include:
Preceding febrile illness
Headache
Fatigue
Dyspnea
More severe anemia than usual
Reticulocytopenia✫ (eg, <1%)
Anand A et al. N Engl J Med 1987;316:183–186
Bell LM et al. N Engl J Med 1989;321:485–491
Gilbert DN et al., eds. Parvo B19 virus (erythrovirus B19). In: The Sanford Guide to Antimicrobial Therapy 2011, 41st ed. Speeryville, VA: Antimicrobial Therapy; 2011:156
Kurtzman G et al. N Engl J Med 1989;321:519–523
Ohene-Frempong K, Steinberg MH. Clinical aspects of sickle cell anemia in adults and children. In: Steinberg MH et al., eds. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. New York, NY: Cambridge University Press; 2001:611–670
Serjeant GR et al. Lancet 1993;341:1237–1240
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
Young NS, Brown KE. N Engl J Med 2004;350:586–597
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Epidemiology
In regions not endemic for malaria, 70–100% of episodes are caused by human parvovirus B19
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Treatment
Transfuse packed RBCs to maintain Hgb close to baseline if ≥25% decrease in Hgb from baseline with declining or absent reticulocyte levels and symptomatic anemia
Transfuse small volumes cautiously to avoid hypervolemia and complications arising from an abrupt increase in serum viscosity
Notes:
Although TRCA is usually self-limited with resolution over a period of 2–3 weeks, transfusion support may be required to maintain the RBC mass and blood volume during this time period
If patients are beginning to show evidence of RBC production as determined by reticulocyte count, transfusion support may not be required
During the earliest phases of acute illness, obtain anti-B19 parvovirus IgM and IgG levels. If initial titers are negative, repeat in 1 week to assess for recent infection manifested by a rise in IgM levels
Obtaining B19 parvovirus PCR (polymerase chain reaction) may be better for documenting acute infection
If there is failure to spontaneously resolve the B19 infection, discontinuing immunosuppressive therapy (if applicable) or instituting antiretroviral therapy in patients with HIV infection (if applicable) may terminate the underlying B19 viremia
In patients with persistent chronic B19 viremia and anemia requiring ongoing transfusion support, intravenous immunoglobulin containing viral neutralizing antibody may lead to a prompt decline in serum viral B19 viral DNA and accompanying reticulocytosis and increased Hgb production
Immune globulin intravenous (human) 400 mg/kg per day, intravenously, daily for 5 consecutive days, days 1–5 (total dosage/5-day course = 2000 mg/kg) or 1000 mg/kg IV for 3 consecutive days
Occasional responses to a single 400–mg/kg dose have been reported
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Notes
Siblings and close contacts with SCD should be monitored for the development of aplastic crises
Complications reported to arise from TRCA in small series or single centers include bone marrow necrosis with pancytopenia, stroke, acute chest syndrome, splenic or hepatic sequestration, and glomerulonephritis
Most adults have acquired immunity to B19 parvovirus; however, susceptible individuals exposed to patients with active B19 parvovirus infection are at risk of contracting erythema infectiosum. Isolation precautions for pregnant staff are necessary
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Stroke and CNS Disease
Cerebrovascular accidents (CVAs), transient ischemic attacks (TIAs), subarachnoid, intraparenchymal, and intraventricular hemorrhage
Broderick JP et al. Stroke 1999;30:905–915
Lansberg MG et al. Chest 2012;141(2_Suppl): e601S–e636S. doi:10.1378/chest.11–2302
Malinow MR et al. Circulation 1999;99:178–182
Mayberg MR et al. Stroke 1994;25:231–232
Ohene-Frempong K et al. Blood 1998;91:288–294
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002:83–94
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Notes
Without controlled trials in adults with SCD documenting the worth of transcranial Doppler (TCD) in reducing the risk of brain infarction, prevention should be based on standard recommendations applicable to adults without SCD
In adults with SCD, the role of chronic transfusion in the prevention and treatment of stroke is unclear. However, chronic transfusion with the target of reducing Hgb S to less than 30% of total hemoglobin, as used in children, is an option. Moreover, the duration of time after which transfusion can be safely stopped has not been defined though some have suggested that transfusion may be safely withdrawn in older patients who have been extensively treated (Rana S et al. J Pediatr 1997;131:757–760). Management of iron overload must be managed with chelation
In the event of intracranial hemorrhage complicating SCD in adults, consultation with a neurological specialty team is also indicated with stabilization in a neurological intensive care unit. A careful evaluation to rule out meningitis, sepsis, hypoxia, drug intoxication, or other metabolic arrangements is required (recommendations from children with SCD). A noncontrast cranial CT should be performed as soon as possible. The work-up and management should be approached based on the location of the blood on CT scan (eg, SAH, intraparenchymal hemorrhage, intraventricular hemorrhage). Initial management should include: IV normotonic fluids to avoid dehydration; a rapid search for coagulopathy (eg, PT, aPTT); complete blood count, comprehensive metabolic profile, Hgb S level; discontinuation of any medication with hemorrhagic risk and correction of any coagulopathy. A neurosurgical consultation should be obtained to advise for additional diagnostic studies and management as needed to identify aneurysms, arteriovenous malformations or hematoma that may require surgical intervention. The effect of transfusion on the course and outcome of intracranial hemorrhage complicating SCD is not know; however, reducing the Hgb S to <30% of total Hgb is recommended
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Treatment
Compared with children, there is little information on the treatment and prevention of stroke in adults with SCD. Treatment and prevention recommendations for adults with SCD are therefore based primarily on current recommendations in adults without SCD. It is recommended that physicians with experience and skill in stroke management and interpretation of CT scans supervise treatment
General guidelines:
Oxygen by nasal cannula at a rate of 2 L/min or greater if needed to maintain a PaO2 of 70–80 mm Hg for oxygen saturation of ≥90%
Assess the patient for cause of pain and complications. Conduct a rapid pain assessment with a simple self-reported pain scale. Institute opioids or other analgesic therapy as appropriate (see Acute Pain Syndrome)
Hydration (if required based on clinical evaluation to avoid dehydration) with normotonic fluids: eg, 5% dextrose solution (D5W)/normal saline (NS)
TIAS and CVAs:
Consult the Feburary 2012:141 (2 Suppl) Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Physicians Evidence-Based Clinical Guidelines section on Antithrombotic and Thrombolytic Therapy for Ischemic Stroke. Specifics on inclusion/exclusion criteria for recombinant tissue plasminogen activator (r-TPA) as well as additional antithrombotic management recommendations for ischemic stroke/TIA and guidance in patients with a history of symptomatic primary intracerebral hemorrhage are expertly presented in this guideline
Subarachnoid Hemorrhage (SAH):
Transfuse packed RBCs to reduce Hgb S to <30%
Note: The effect of RBC transfusion on altering the course or outcome of SAH is unknown
Nimodipine (calcium channel antagonist) is indicated in adults with SAH from ruptured berry aneurysms to counteract delayed arterial vasospasm
Dosage: administer 60 mg orally every 4 hours for 21 days (one hour before or two hours after a meal; avoid grapefruit juice). Nimodipine may increase the blood pressure lowering effect of concomitantly administered antihypertensives and blood pressure should be carefully monitored; dose adjustment of the blood pressure lowering drug(s) may be necessary. Nursing mothers are advised not to breast feed their babies when taking nimodipine. Dosage should be reduced to one 30 mg capsule every 4 hours with close monitoring of blood pressure in patients with "severely disturbed liver function" (eg, liver cirrhosis). Strong inhibitors of CYP3A4 should not be administered concomitantly with nimodipine
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]. (See chapter 13 on stroke and CNS disease in adults)
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Work-up for Adults with TIA or Ischemic Stroke
CBC/diff; EKG; transthoracic echocardiogram with consideration given to TEE, especially in young patients; aPTT; PT; and a brain study to include MRI, DWI, and MRA, and/or TCD, and carotid duplex US or CT angiography to determine the status of the intracranial and extracranial vessels. Blood tests for protein C and S deficiency, homocysteine elevation, and anticardiolipin antibodies may be appropriate. Health care providers should consider etiologies seen in young patients with stroke without SCD: eg, CNS infection, illicit drug use and arterial dissection
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Epidemiology
Cerebrovascular accidents (CVAs) are a leading cause of death in children and adults
Age-adjusted prevalence for CVAs:
Among Hgb SS patients first CVAs were:
In all SCD patients recurrent CVAs occur in 16% of survivors of first-time CVAs
Overall, the mortality rate for hemorrhagic CVA was 24–26% for Hgb SS patients

Adapted from The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
Notes:
r-tPA should not be given unless emergent care and appropriate treatment facilities available
Antiplatelet agents are usually recommended for TIA in TIA's without SCD, but there are few data on the efficacy in SCD
If antiplatelet therapy is administered in patients with acute ischemic stroke or TIA (after intracranial hemorrhage has been excluded), aspirin therapy at a dosage of 160–325 mg should be administered orally within 48 hours after symptom onset and reduced after 1–2 weeks to secondary prevention dosing (75–100 mg/day orally). Benefits: (1) fewer deaths: 9 per 1000; (2) good functional outcome at 30 days after ischemic stroke: 7 per 1000; (3) reduction in recurrent strokes: 7 per 1000. Risks: (1) nonfatal major extracranial bleeding events: 4 per 1000; (2) symptomatic intracranial hemorrhages: 2 per 1000
Aspirin therapy for acute ischemic stroke or TIA should not be given for the first 24 hours after administration of r-tPA
According to established guidelines, alteplase (t-PA) is indicated when:
The patient is at least 18 years old
The patient's NIH Stroke Scale score is ≥4 (ischemic stroke in any circulation with a clinically significant deficit)
Alteplase can begin within 3 hours after symptom onset
Cranial CT shows no evidence of hemorrhage
It is not clear whether alteplase is appropriate for patients with SCD and hyperacute ischemic stroke; no experience with its use has been reported. However, there is no clear justification to exclude SCD patients. Caution is advised if severe stroke (<7% risk of symptomatic brain hemorrhage with an absolute risk of fatal ICH of 3.5% with IV r-tPA initiated within 3 hours in patients with acute ischemic stroke)
The 9th ed ACCP Guidelines on Antithrombotic and Thrombolytic Therapy for Ischemic Stroke (See reference by Lansberg MG et al. Chest 2012;141(2_Suppl): e601S–e636S. doi:10.1378/chest.11-2302) also recommends r-tPA use "in patients with acute ischemic stroke in whom treatment can be initiated within 4.5 hours but not within 3 hours of symptom onset"
Thrombolytic therapy cannot be recommended if:
Evidence of intracranial hemorrhage (ICH) on pretreatment evaluation
Suspicion of subarachnoid hemorrhage (SAH) on pretreatment evaluation
Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma or previous stroke
History of ICH
Minor neurological deficit
Rapidly improving symptoms
Uncontrolled hypertension at the time of treatment (eg, >185 mm Hg systolic or >110 mm Hg diastolic)
Seizure at the onset of stroke
Active internal bleeding
Intracranial neoplasm, arteriovenous malformation, or aneurysm
Known bleeding diathesis, including but not limited to: Current use of oral anticoagulants (eg, warfarin sodium) or an INR >1.7 or a PT >15 seconds
Administration of heparin within 48 hours preceding the onset of stroke and have an elevated aPTT at presentation
Platelet count <100,000/mm3
Blood glucose of <50 mg/dL or >400 mg/dL
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Chronic Pain Syndrome: Acute Osteomyelitis and Acute Septic Arthritis
Almeida A, Roberts I. Br J Haematol 2005;129:482–490
Gilbert DN et al., eds. Bone: osteomyelitis. In: The Sanford Guide to Antimicrobial Therapy 2011. 41st ed. Speeryville, VA: Antimicrobial Therapy; 2011:4
Glader BE. Anemia. In: Embury SH et al., eds. Sickle Cell Disease: Basic Principles and Clinical Practice. New York, NY: Raven Press; 1994:545–554
Keeley K, Buchanan GR. J Pediatr 1982;101:170–175
Rao S et al. J Pediatr 1985;107:685–688
Sickle cell disease: Clinical and epidemiologic aspects. In: Bunn HF, Forget BG, eds. Hemoglobin: Molecular, Genetic and Clinical Aspects. Philadelphia, PA: WB Saunders; 1986:502–564
Solanki DL et al. Am J Med 1986;80:985–990
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
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Epidemiology
United States and most of the world:
Salmonella sp. are the most common causative organisms of osteomyelitis in Hgb SS patients (~60% or higher); Staphylococcus aureus is second most common, followed by Gram-negative enteric bacilli
Some regions of the world:
Gram-negative organisms, such as Klebsiella sp. may predominate
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Treatment
Assess the patient for cause of pain and complications. Rapid pain assessment with simple self-reported pain scale
Hydration (as appropriate to the patient's clinical evaluation) with 5% dextrose injection or 0.9% sodium chloride injection at a rate not to exceed 1.5 times maintenance (volume to include any drug infusions); Also, refer to Acute Pain Syndrome, Notes Section
Institute opioid therapy or other analgesics as appropriate (see the section Acute Pain Syndrome)
Institute appropriate antibiotics (see below)
Adults with Acute Osteomyelitis
Empiric parenteral antibiotics that cover Salmonella sp., Staphylococcus aureus, and other Gram-negative organisms until culture results are available, for example:
Vancomycin 1000 mg; administer intravenously over 1 hour every 12 hours, with
Ciprofloxacin 400 mg; administer intravenously over 1 hour every 12 hours, or
Levofloxacin 750 mg; administer intravenously over 90 minutes every 24 hours
Note:
Collect blood and bone cultures before empiric therapy
If blood culture is negative, need culture of bone; culture of sinus tract not predictive of bone culture
Definitive treatment is chosen according to in vitro susceptibility and continued for up to 6 weeks, depending on the nature and extent of the infection
For the patient with suspected vertebral osteomyelitis ± epidural abscess, obtain MRI early to look for epidural abscess
The doses identified are for adults with clinically severe (often life-threatening) infections and assume normal renal function and not severe hepatic dysfunction
Adults with Acute Monoarticular Septic Arthritis (Not at Risk for Sexually Transmitted Disease)
Empiric parenteral antibiotics (after collection of blood and joint fluid) that covers Salmonella sp., Staphylococcus aureus, and other Gram (−) organisms until culture results are available (see empiric antimicrobial coverage in section on Acute Osteomyelitis)
Note: Consider surgical drainage of the joint with the evacuation of exudates and breaking up joint loculations to reduce the risk of persistent infection and articular cartilage destruction
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Notes
Osteomyelitis in SCD must be differentiated from acute bone infarction. Plain radiography and radionuclide bone imaging are of little or no use in differential diagnosis. However, radionuclide marrow imaging may be useful in depicting diminished uptake in infarction and normal uptake in infection
Despite progress made with various imaging techniques, a definitive diagnosis of osteomyelitis in SCD depends more upon clinical assessment and positive blood or bone cultures obtained by aspiration or biopsy
Consult institutional antimicrobial susceptibility profiles to guide selection of fluoroquinolone (in particular)
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Systemic Fat Embolization
Characterized by embolization of necrotic marrow and fat in the setting of massive bone marrow infarction. Respiratory insufficiency and multiorgan failure from systemic emboli may occur with clinical signs dependent upon the organ involved and degree of involvement
Castro O. Hematol Oncol Clin North Am 1996;10:1289–1303
Milner PF, Brown M. Blood 1982;60:1411–1419
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
Vichinsky EP et al. N Engl J Med 2000;342:1855–1865
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Epidemiology
A well-documented complication in the setting of acute chest syndrome
Responsible for symptoms in 8.8% of patients with acute chest syndrome
Systemic fat embolization can occur concurrently with an infectious agent
Risk factors:
Hgb SC
Pregnancy
Prior corticosteroid treatment
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Treatment
A high index of suspicion is required. All ACS patients are considered to be at risk. Treatment should not await proof of diagnosis
Oxygen by nasal cannula at a rate of 2 L/min, or greater if needed to maintain a PaO2 of 70–80 mm Hg or oxygen saturation ≥90%. If needed, initiate critical care supportive measures to manage respiratory insufficiency
Assess the patient for cause of pain and complications. Conduct a rapid pain assessment with a simple self-reported pain scale. Institute opioids therapy or other analgesics based upon an individual patient's clinical evaluation (see the section Acute Pain Syndrome)
Hydration with 5% dextrose injection or 5% dextrose/0.2% sodium chloride injection at a rate not to exceed 1.5 times maintenance (volume to include any drug infusions). Also, refer to Acute Pain Syndrome, Notes Section
Transfuse packed RBCs to reduce Hgb S to <30%
Note: Case reports suggest that exchange transfusion may prevent some deterioration (see sections on Acute Chest Syndrome and Red Blood Cell Transfusion)
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Notes
Clinical symptoms may include severe bone pain, fever, hypoxia, azotemia, liver damage, altered mental status or coma, progressive anemia and thrombocytopenia, and disseminated intravascular coagulation
Findings that prove systemic fat embolization: Fat droplets within retinal vessels or in biopsies of petechiae
Indirect evidence of systemic fat embolization: Positive fat stains in bronchial macrophages, lung microvesicle cells, or venous blood buffy coat
In the setting of acute chest syndrome patients with systemic fat embolization have a lower oxygen saturation at presentation, are more likely to have upper lobe infiltrates during hospitalization, and have a higher incidence of vasoocclusive events in comparison with patients with pulmonary infarction or infection
Systemic fat embolization may precipitate or coexist with acute chest pain syndrome (see treatment section for Acute Chest Syndrome)
Vichinsky EP et al. N Engl J Med 2000;342:1855–1865
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Acute Multiorgan Failure Syndrome
Sudden onset of severe dysfunction of 2 or more major organ systems during an acute painful vasoocclusive episode. This syndrome may occur without an apparent predisposing event other than high baseline hemoglobin
Initial presentation:
Fever
Nonfocal encephalopathy
Evidence of rhabdomyolysis
Rapid decrease in Hgb and platelet count
Organ-specific manifestations:
Renal: hematuria or acute renal failure
Liver: acute hepatic necrosis or hepatic sequestration syndrome
Lung: pulmonary infiltrates, hypoxia
Bone marrow: generalized necrosis with fat emboli
Pancreas: pancreatitis
Notes:
For associated acute chest syndrome, see the section Acute Chest Syndrome
The use of granulocyte colony-stimulating factor has been associated with sickle cell crisis and multiorgan failure in 3 patients with sickle cell syndrome (2 patients after stem-cell mobilization with 1 death; 1 patient with stage II breast cancer treated with CMF chemotherapy + G-CSF)
Abboud M et al. Lancet 1998;351:959
Adler BK et al. Blood 2001;97:3313–3314
Bakanay SM et al. Blood 2005;105:545–547
Hassell KL et al. Am J Med 1994;96:155–162
Rosse WF et al. New views of sickle cell disease: pathophysiology and treatment. Hematology Am Soc Hematol Educ Program. 2000:2–17
The Management of Sickle Cell Disease, 4th ed. NIH Publication No. 02-2117. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; 2002. www.nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf [accessed August 5, 2013]
Wei A, Grigg A. Blood 2001;97:3998–3999
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Epidemiology
This syndrome is most commonly reported in Hgb S β-thalassemia but may occur in patients with classical Hgb SS disease with a high hematocrit
Second only to acute chest syndrome as the cause of sickle cell–related mortality
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Treatment
Carefully monitor oxygenation, hydration, and acid–base balance. Obtain daily weight, input/output, CBC, and appropriate serum chemistry panels. Measure baseline and pre-/post-transfusion Hgb S concentration. Follow CXR until stabilization is documented
Oxygen by nasal cannula at a rate of 2 L/min, or greater if needed to maintain a PaO2 of 70–80 mm Hg. Mechanical ventilation as appropriate to the clinical condition
Hydration with 5% dextrose injection or 5% dextrose/0.2% sodium chloride injection at a rate not to exceed 1.5 times maintenance (volume to include any drug infusions) with careful assessment of hydration status and fluid requirements in the setting of concomitant acute renal failure
Assess the patient for cause of pain and complications. Rapid pain assessment with simple self-reported pain scale if possible based on the underlying mental status. Institute opioids therapy or other analgesics as appropriate (see the section Acute Pain Syndrome)
Perform aggressive transfusion to reduce Hgb S to <30%:
Simple transfusion (Packed RBCs) if Hgb <7 g/dL and no evidence of hyperviscosity, or
Exchange transfusion using a mechanical device, if Hgb >7 g/dL or hyperviscosity is playing a role in the pathogenesis of the acute complication of SCD
Note: Prompt initiation of transfusion therapy or exchange transfusion has the potential of reversing this syndrome
Critical care support is directed at the affected underlying organ systems
If narcosis is suspected:
Try Naloxone 0.4 mg (1 mL) in 9 mL 0.9% sodium chloride injection to produce a concentration = 0.04 mg/mL, administer 0.5 mL (0.02 mg) by intravenous injection every 2 minutes, or
Naloxone 0.4–2 mg/dose; administer intravenously, subcutaneously, or intramuscularly; may repeat every 2–3 minutes as needed to a maximum dose of 10 mg
Empiric antibiotics, pending culture results
Antibiotics should be given to febrile or severely ill patients. These include (normal renal function):
A third-generation cephalosporin:
Ceftriaxone 1000 mg (maximum 2000 mg); administer intravenously in 50–100 mL D5W over 30 minutes every 24 hours, and
A broad-spectrum macrolide or fluoroquinolone antibiotic:
Azithromycin 500 mg; administer intravenously over 60 minutes every 24 hours, or
Ciprofloxacin 400 mg; administer intravenously over 60 minutes every 12 hours
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Notes
There are no reported prospective trials in the management of multiorgan failure syndrome complicating SCD. Treatment approaches are based upon clinical observations and expert opinion
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