eMedicine Specialties > Pediatrics: General Medicine > Hematology
Sickle Cell Anemia: Treatment & Medication
Updated: Jul 9, 2009
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Treatment
Medical Care
The following are treatment considerations in patients with sickle cell disease:
- Anemia
- No scientific evidence shows that patients develop folate deficiency; however, folic acid (1 mg/d) is commonly prescribed for adults to prevent development of megaloblastic anemia due to increased folate requirements caused by hemolysis.
- For anemic crisis with splenic sequestration, give early red cell transfusions because the process can rapidly progress to shock. Do not allow hemoglobin (Hb) levels to rise to more than 10 g/dL, since the spleen may disgorge trapped cells, which can create a relative polycythemia and increased blood viscosity. Children who experience a single sequestration event frequently have recurrences. Surgical splenectomy or a short-term transfusion regimen has been suggested for this complication.
- Transfusion is required in an aplastic crisis if the anemia is symptomatic (eg, dyspnea, signs of hypovolemia). Because aplastic crises are self-limited, transfusion may be avoided if the child is stable and can be adequately observed. If hospitalization is required, use precautions to prevent transmission of parvoviral infection to patients who are immunosuppressed or caretakers who are pregnant.
- Infection
- Penicillin prophylaxis significantly reduces the incidence of S pneumoniae infection and may decrease the mortality rate. Begin at age 2-4 months with 125 mg bid; at 3 years, increase the dose to 250 mg bid. As with all long-term medication regimens, compliance is a serious problem; therefore, remind parents of the importance at each visit.
- Protein-conjugated pneumococcal vaccines (PCVs) that effectively protect children against invasive infections are now extensively used. The 7-serotype PCV (PCV7) in combination with penicillin prophylaxis and PPV23 booster vaccination offers the best hope for improved prevention against S pneumoniae infection. In a recent study, more than two thirds of S pneumoniae isolates stereotyped were PCV7 serotypes and included most penicillin-nonsusceptible strains. Most nonvaccine-serotype isolates were penicillin-sensitive.
- Acute chest syndrome (ACS)
- Obtain appropriate cultures, but treat expectantly for Streptococcus pneumoniae and Mycoplasma pneumoniae.
- Administer oxygen if saturation is less than 94%.
- If that level cannot be maintained at a fraction of inspired oxygen (FiO2) of 0.4, provide simple transfusion (avoid raising hematocrit to more than 36%). If no improvement is seen, reduce the HbS level to 30% with erythrocytapheresis or exchange transfusion.
- The process can rapidly progress to respiratory failure. Ventilatory assistance may be required.
- Some patients have repeated severe acute chest syndrome. Chronic transfusion reduces the recurrence and hydroxyurea reduces by about half, the rate of acute chest syndrome.
- Pain
- Inform parents and children that recurring pain is expected. Assist them in developing an approach that allows continued normal activities even with pain. Instruct parents and family members to provide sympathy, but with encouragement and support designed to help the child accept pain, not submit to it. Parents and family members are encouraged to provide local measures and over-the-counter drugs for mild pain. Physicians suggest keeping on hand a small supply of a mild narcotic analgesic for pain that does not respond to lesser measures.
- Pain that does not respond to the above measures almost always requires hospitalization. Avoid providing 1-2 doses of parenteral narcotics in the emergency department, since moderately severe sickle cell pain is expected to persist for several days. For pain severe enough to require hospitalization, treat with morphine or other major narcotic analgesics in doses sufficient to provide a reasonable degree of relief. Continuous infused morphine is most effective. Choose dosage to provide reasonable pain relief with precautions to avoid oversedation and respiratory depression. A starting dose of morphine (0.05-0.01 mg/kg/h) is suggested following a bolus dose to provide a reasonable degree of pain relief. Adjust according to patient response. Patient-controlled analgesia with self-administered bolus morphine and low-dose continuous intravenous (IV) infusion is effective and well accepted by patients.
- Fentanyl and nalbuphine have also been used as continuous IV infusion. Ketorolac can be given along with opioid analgesics and typically reduces the opioid dose required to achieve the desired effect.
- Dependence seldom occurs because the duration of sickle pain is brief (5-7 d). Addiction, described as narcotic-seeking behavior, is rarely encountered. It can result if a patient uses narcotics for euphoriant or stimulant effects rather than analgesia. Narcotic addiction in people with sickle cell disease is no more common than in the general population and may be minimized with a carefully designed analgesic regimen.
- Stroke
- Unless long-term transfusion therapy is provided, 70-90% of children who experience a single stroke have subsequent events.
- The ultimate goal of transfusion is to maintain the HbS level at less than 30%.
- Do not raise the total hemoglobin level to more than 10-12 g/dL when the HbS level is more than 30% because the resulting high viscosity can cause progression or additional areas of infarction.
- Cholecystitis
- If patients present with right upper quadrant abdominal pain, evaluate the gall bladder with ultrasonography.
- Provide appropriate medical and supportive care for cholecystitis if stones are visualized, if gall bladder walls are thickening, or upon signs of ductal inflammation.
- Arrange for elective cholecystectomy when inflammation resolves.
- Avascular necrosis of femoral or humeral head
- Decrease weight bearing of an affected lower extremity using crutches and touchdown gait.
- Femoral head core decompression is under investigation to determine if use in the early stages of the process may prevent progression.
- Potent nonsteroidal anti-inflammatory drugs (NSAIDs) are necessary when chronic changes are present.
- Hip replacement may be required after full linear growth is achieved.
- Priapism
- At the onset of priapism, patients should be advised to drink extra fluids, use oral analgesics, and attempt to urinate. A nightly dose of pseudoephedrine (30 mg orally [PO]) may prevent priapism in some cases. For episodes that last more than 2 hours, patients should go to the emergency department to receive intravenous hydration and parenteral analgesia. According to one protocol, if detumescence does not occur within 1 hour after arrival in the emergency department, penile aspiration followed by irrigation of the corpora with a 1:1,000,000 solution of epinephrine in saline is initiated. (The procedure should be performed within 4-6 h of priapism onset.)
- The concomitant use of automated red cell exchange transfusions to reduce the HbS level to less than 30% may also be considered, especially if early intervention with irrigation fails.
- Should the condition recur despite aspiration and local instillation of vaso-active drugs, consider shunting. In this procedure, known as the Winter procedure, a shunt is created between the glans penis and the distal corpora cavernosa; this allows blood from the distended corpora cavernosa to drain into the uninvolved corpus spongiosa. A larger shunt may be created if this is not successful.
- Complications of priapism and treatment include bleeding from the holes placed in the penis as part of the aspiration or shunting procedures, infections, skin necrosis, damage or strictures of the urethra, fistulas, and impotence. If impotence persists for 12 months, the patient may wish to consider implantation of a semirigid penile prosthesis.
- New approaches to prevent recurrent priapism include use of phosphodiesterase type 5 inhibitors like sildenafil.
Surgical Care
Preoperative transfusion is generally recommended for all surgeries requiring general anesthesia. Simple transfusion to a hematocrit of about 30 has shown to be effective in preventing postoperative complications as exchange transfusion. Nevertheless complications still occur, including acute chest syndrome.
Studies have shown a marked reduction in catheter-associated complications compared to prior studies. Implantable ports are now increasingly used in sickle cell patients who need long-term erythrocytapheresis.
- Transfusion and chelation
- Alloimmunization is a common problem that arises from the differences in certain minor red cell antigens found in the predominantly black patient population and the mostly white blood donors. Matching for C, E, Kell, JKB (Kidd), and Fya (Duffy) antigens can significantly reduce alloimmunization.
- Intraoperative and postoperative complications may result from hypoxia, dehydration, or hypothermia that occurs during or after a surgical procedure. They may be minimized or avoided if transfusions are given before the procedure.
- Although one study demonstrated no overall difference in the complication rate among subjects who received either preoperative exchange or simple transfusion, it provided little guidance for what type of transfusion would be best in individual situations.
- In general, raising the hemoglobin concentration to a level of more than 10 g/dL but less than 12 g/dL provides the patient with approximately 20-30% hemoglobin A. The presence of this fraction of normal hemoglobin may provide some protection from complications.
- Many anesthesiologists require a hemoglobin concentration of more than 10 g/dL prior to the procedure.
- More complex procedures or longer duration of anesthesia times are more likely to lead to acute chest syndrome or other complications. Providing preoperative transfusion may decrease the risk.
- The approach is less certain for patients whose baseline hemoglobin level is more than 10 g/dL. If complexity of the surgical procedure or duration and risk of anesthesia is considerable, exchange transfusion or erythrocytapheresis can reduce the HbS concentration to 30%, while keeping the total hemoglobin level at less than 12 g/dL.
- In patients undergoing retinal surgery, the HbS concentration or combined concentration of HbS and C needs to be reduced to less than 30% (increase the hemoglobin A concentration to 70%).
- Individualize all other situations based on the complexity of the procedure and underlying medical condition.
- With continued transfusion, iron overload inevitably develops and can result in heart and liver failure and multiple other complications. Serum ferritin is an inaccurate means of estimating the iron burden; liver iron evaluation, or perhaps MRI, are more accurate means of determining tissue iron concentration and the response to chelation.
- Three agents are available for iron chelation: desferrioxamine, deferasirox, and deferiprone (orphan drug in the United States).
- Desferrioxamine is an efficient chelator but its need to be given parenterally by prolonged infusion and nearly every day has limited its effectiveness in many patients.5 Deferasirox has a similar capacity to chelate iron as desferrioxamine and is administered PO. Renal toxicity might be a limiting factor in its use. Deferiprone does not seem to be as effective as the other two agents but is available PO, selectively removes cardiac iron, and might be most effective when used with desferrioxamine or deferasirox.
- Erythrocytapheresis
- Erythrocytapheresis is an automated red cell exchange procedure that removes blood that contains HbS from the patient while simultaneously replacing that same volume with packed red cells free of HbS.6 Transfusion usually consists of sickle-negative, leuco-reduced, and phenotypically matched blood for red cell antigens C, E, K, Fy, and Jkb.
- The procedure is performed on a blood cell processor (pheresis machine) with a continuous-flow system that maintains an isovolemic condition. Red cells are removed and simultaneously replaced first with normal saline followed by transfused packed RBCs along with the patient's plasma. The net RBC mass/kg is calculated for each procedure based on the measured hematocrit of the transfused and removed blood and the total RBC volume transfused.
- Erythrocytapheresis thus has the advantage of controlling iron accumulation in patients with sickle cell disease who undergo long-term transfusion, and the ability to achieve adequate Hb and HbS concentrations without exceeding the normal concentration. This precision is achieved because the computer in the pheresis machine is able to use various physiologic parameters before transfusion such as height, weight, and Hb level to compute the expected amount of packed RBCs required to obtain a specific posttransfusion hemoglobin level. Further, erythrocytapheresis requires the least amount of time when compared to using similar blood volumes on patients receiving simple blood transfusions.
- Although erythrocytapheresis is more expensive than simple transfusion, if the cost of chelation and organ damage due to iron overload is considered, erythrocytapheresis without chelation costs less than simple transfusion programs. Central venous access devices can safely be used for long-term erythrocytapheresis in patients with sickle cell disease with a low rate of complications.
- Stem cell transplantation
- Although sickle cell disease can be resolved with allogeneic marrow transplantation, the current application of stem cell transplantation (SCT) is complex. Results indicate an event-free survival rate of approximately 84% and a mortality rate of less than 6%.
- The risk-benefit ratio has led to the establishment of certain guidelines. Two restrictions limit SCT applicability to approximately 5% of children who qualify through hematologic diagnosis. Donors must be human leukocyte antigen (HLA) compatible and full siblings (those with sickle trait are acceptable), and candidates should be limited to patients younger than 16 years with HbSS or HbS–β-0 thalassemia who have evidence of disease severity demonstrated by the following:
- Stroke
- Recurrent acute chest syndrome
- Recurrent severe crisis pain (>2 episodes/y for several years)
- Recurrent priapism
- Impaired neuropsychological function with evidence of cerebral infarction
- Sickle cell nephropathy
- Bilateral proliferative retinopathy and major visual impairment in at least one eye
- Osteonecrosis of multiple joints
- Red cell alloimmunization with more than 2 antibodies during long-term transfusion therapy
Diet
- An age-appropriate, well-balanced diet is suggested. No special requirements are indicated.
Activity
- Encourage children to participate in physical activities. Because of anemia, they have less stamina than their hematologically healthy playmates. Advise supervising adults of this limitation, particularly teachers and coaches who may require children to run designated distances.
- Arrange for children to have ready access to liquids and a place to rest and cool off.
Medication
Analgesics
Pain is the hallmark of sickle cell disease. Although frequency and severity widely vary, most patients have interval symptoms. Once pain has begun, no therapy reverses the process. Analgesics may provide a reasonable degree of comfort. Although certain dosing guidelines are available, the amount of drug given should be titrated to the degree of pain experienced.
Acetaminophen (Tylenol, Tempra)
A mild, nonnarcotic analgesic available OTC that is generally used for mild pain.
Adult
325-650 mg PO q4-6h; not to exceed 4 g/d
Pediatric
10-15 mg/kg PO q4-6h; not to exceed 2.6 g/d
Possible reduced analgesic effects with rifampin; conversely, possible increased hepatotoxicity with barbiturates, carbamazepine, hydantoins, and isoniazid
Documented hypersensitivity; G-6-PD deficiency
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hepatotoxicity possible with prolonged high doses or overdose; contained in many OTC products and combined use with these products may result in cumulative doses exceeding recommended maximum dose
Avoid overdose or excessive use; family must also be provided with more potent analgesics to use for more severe pain in order to avoid overuse of acetaminophen and resultant hepatotoxicity
Acetaminophen with codeine (Tylenol-3)
A mild narcotic analgesic. Provide the family with a small supply for use when pain severity is greater than what can be managed with acetaminophen alone. Counsel parents to use only for severe pain, not as the first medication for each symptom.
Adult
30-60 mg/dose PO (based on codeine component) q4-6h
Pediatric
1 mg/kg (based on codeine component) PO q4-6h
Use combination of acetaminophen and codeine that allows an appropriate codeine dose without providing excessive amount of acetaminophen
Possible reduced analgesic effects with rifampin; conversely, possible increased hepatotoxicity with barbiturates, carbamazepine, hydantoins, and isoniazid; possible interaction with antihistamines or other mild sedatives
Toxicity of codeine increases with CNS depressants, tricyclic antidepressants, MAOIs, neuromuscular blockers, CNS depressants, phenothiazines, and opioid analgesics
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Toxicity from overdose or overuse of acetaminophen, codeine, or both; caution parents that if prescribed dose is not effective, children should be brought to medical attention
Morphine (Duramorph)
A strong opiate analgesic for treatment of severe pain. Although many have concerns about its addictive potential and dangers associated with excessive doses, no reasonable alternative is available to manage the severe pain encountered.
Adult
0.8-10 mg/h IV continuous infusion, with patient-controlled bolus as needed
Pediatric
0.01-0.02 mg/kg/h IV continuous infusion, with patient-controlled bolus as needed
Possible potentiation of above-mentioned adverse effects with use of other sedative, CNS depressants, or antihistamines
Documented hypersensitivity; respiratory depression; altered level of consciousness
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Titrate dose to meet level of pain; careful, frequent evaluations are necessary to ensure decrease in dose as pain severity lessens
Caution in hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate
Fentanyl (Sublimaze)
A synthetic opioid analgesic, which is primarily a mu receptor agonist. Fentanyl is 50-100 times more potent than morphine. It has short duration of action (as long as 1-2 h) and minimal cardiovascular effects, such as hypotension. Respiratory depression is uncommon, but this effect lasts longer than its analgesic effect. Frequently used as patient-controlled analgesia for relief of pain. Unlike morphine, histamine release is not commonly seen with fentanyl.
Adult
25-50 mcg IV bolus q1-2h prn; beginning continuous IV basal rate 25 mcg/h, with incremental dose escalation as required
Pediatric
0.5-1 mcg/kg IV bolus q2-4h prn; continuous IV basal rate 0.5 mcg/kg/h initially, with incremental dose escalation as required
Cytochrome P450 isoenzyme CYP 3A3/4 substrate; CNS depressants, alcohol, phenothiazines, MAOIs, tricyclic antidepressants may potentiate adverse effects of fentanyl; other medications inhibiting or inducing the CYP 3A3/4 enzymes may change the effects of fentanyl
Documented hypersensitivity; hypotension or potentially compromised airway; paralytic ileus
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Physical and psychological dependence may occur with prolonged use; caution with decreased respiratory reserve and compromised respiratory function, cardiac bradyarrhythmias, decreased respiratory reserve and compromised respiratory function; may impair mental and/or physical ability required to perform hazardous tasks; biliary tract disease, including acute pancreatitis (spasm of the sphincter of Oddi may occur)
Ketorolac (Toradol)
Potent NSAID available for parenteral administration. Indicated for management <5 d of moderately severe acute pain that requires analgesia at opioid level. Inhibits prostaglandin synthesis by decreasing activity of cyclooxygenase, and decreasing formation of prostaglandin precursors. Can be given along with opioid analgesics and typically reduces the opioid dose required to achieve the desired effect.
Adult
30 mg IV/IM q6h; not to exceed 120 mg/d IV/IM; switch to PO therapy (ketorolac or other)
PO dosing is indicated only as continuation to IV/IM: 20 mg PO initially, then 10 mg PO q6h; not to exceed 40 mg/d
Do not administer (by any route) for more than 5 d
Pediatric
<2 years: Not established
2-16 years: Not established. However, AAP recommends 10 mg PO q6h or 0.5-1 mg/kg/dose IV/IM q6h; not to exceed 60 mg/d
>16 years: Administer as in adults
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; closely monitor PT (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding; not for epidural or intrathecal use; therapy should not exceed 5 d, all routes combined; PO ketorolac is only indicated as continuation of IV/IM therapy
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke; risk may increase with duration of use and in patients at risk for cardiovascular disease; increased risk of serious GI adverse events (eg, bleeding, ulceration, perforation of stomach or intestines) that can occur at any time and without warning; higher risk in elderly or debilitated patients; caution with asthma, elderly, dehydration, history of coagulation defects, preexisting anemia, GI ulceration, bleeding or perforation, liver dysfunction, renal disease, hypertension, fluid retention, or CHF
Nalbuphine (Nubain)
Opioid agonist/antagonist. Stimulates kappa opioid receptor in the CNS, which causes inhibition of ascending pain pathways. An antagonist at the opioid mu receptors, it is useful for moderate-to-severe pain in sickle cell disease.
Adult
10 mg IV q3-6h; not to exceed 20 mg/dose and 160 mg/d
Pediatric
Not established; limited data suggest 0.1 mg/kg IV q3-6h (for larger children, recommend maximum initial dose of 5 mg before escalating to larger dose)
CNS depressants, alcohol, phenothiazine, tricyclic antidepressants may potentiate adverse effects; coadministration with cimetidine may increase toxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Precipitates narcotic withdrawal in patients receiving opioids long term, likely due to the antagonistic effect from competitive inhibition at the opiate mu receptor; can elicit respiratory depression; caution with coma, head injury, intracranial lesion, or increased intracranial pressure, acute asthma or COPD, hepatic or renal dysfunction, or in patients undergoing biliary tract surgery; spasm of the sphincter of Oddi may occur; caution in patients with myocardial infarction who have nausea or vomiting
Anti-sickling agents
Considerable effort is being expended to identify agents whose ultimate effect interferes with the sickling process and prevents the many complications of sickle cell disease.
Hydroxyurea (Hydrea)
Although numerous agents are being investigated, this is the only agent shown to decrease incidence and severity of pain. Mechanism of action is thought to be the induction of fetal hemoglobin production. The beneficial effects demonstrated may be due to other effects of the drug.
Adult
20 mg/kg/d PO initially; titrate upward by 5 mg/kg/d q12wk to maximal acceptable toxicity, usually considered to be a leukocyte count above 4000/µL
Pediatric
Administer as in adults
Similar dose usage in investigational trials for children as used in adults; consider close supervision of pediatric hematologist knowledgeable in treatment of sickle cell disease
Coadministration with fluorouracil can increase neurotoxicity; may interfere with immune response to live virus vaccine (MMR) and reduce efficacy
Documented hypersensitivity; signs of bone marrow, liver, or renal disease or failure; prospective patients must avoid pregnancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Until a stable dose is established, obtain leukocyte counts q2wk; monitor renal and liver toxicity monthly; not yet approved for use in children with sickle cell disease; studies in progress to evaluate safety and efficacy; concerns of possible teratogenicity; concerns that it may be leukemogenic, although evidence is limited to reports of use in treatment of adult preleukemic disorders
Antibiotics
Antibiotic prophylaxis reduces the incidence of infection and may have positive effects on mortality.
Penicillin VK (Beepen-VK, Pen. Vee K, Veetids)
Inhibits the biosynthesis of cell wall mucopeptide.
Adult
250-500 mg PO bid/qid
Pediatric
<2 months: Not established
2 months to 3 years: 125 mg PO bid
>3 years: 250 mg PO bid
Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal function
Ceftriaxone (Rocephin)
Third-generation cephalosporin antibiotic. Most common antibiotic used in the management of fever in patients with sickle cell disease in the acute care/ED setting. Widely distributed throughout the body, including gallbladder, lungs, bone, bile, and CSF (diffuses into the CSF at higher concentrations when the meninges are inflames).
Adult
1-2 g IV/IM q12-24h; not to exceed 4 g/d
Pediatric
75 mg/kg IV/IM q24h or if meningitis suspected 50 mg/kg IV/IM bid
High-dose probenecid (decreases elimination half-life of ceftriaxone); coadministration with aminoglycosides, furosemide, ethacrynic acid may increase risk of nephrotoxicity
Documented hypersensitivity; hyperbilirubinemic neonates, particularly those who are premature since may displace bilirubin from albumin binding sites, increasing the risk of kernicterus
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Use with caution in patients with gallbladder, biliary tract, liver, or pancreatic disease or in patients with history of colitis or penicillin hypersensitivity
Cefuroxime (Zinacef)
Second-generation cephalosporin antibiotic. Drug of choice for community-acquired pneumonia in sickle cell disease.
Adult
1.5-3 g IV q8h; depending on type and severity of infection
Pediatric
>3 months: up to 80 mg/kg/dose IV q8h; not to exceed 3 g/dose depending on type and severity of infection
Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patients receiving potent diuretics such as loop diuretics or aminoglycosides; coadministration with aminoglycosides increases nephrotoxic potential; decreased immunologic response to typhoid vaccine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Reduce dose with renal impairment; caution in patients with history of colitis or penicillin hypersensitivity; caution in phenylketonurics as cefuroxime suspension contains phenylalanine
Azithromycin (Zithromax)
Macrolide antibiotic. Useful for treatment of
community-acquired pneumonia in sickle cell disease as an adjunct to a cephalosporin antibiotic to cover Chlamydia or Mycoplasma infections.
Adult
500 mg IV qd for at least 2 d, followed by 500 mg PO qd to complete a 7-10 d course of therapy
Pediatric
>6 months: 10 mg/kg IV/PO on day 1, followed by 5 mg/kg on days 2-5
Cytochrome P450 isoenzyme CYP3A3/4 substrate; mild CYP 3A/4 isoenzyme inhibitor; may increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine; caution with amiodarone, bromocriptine, carbamazepine, digoxin, dihydroergotamine, disopyramide, ergonovine, ergotamine, erythromycin, fentanyl, hexobarbital, methylergonovine, methysergide, nelfinavir, phenytoin, pimozide, rifabutin, tacrolimus, theophylline, triazolam, and warfarin; aluminum-containing and magnesium-containing medications decrease azithromycin peak levels
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients; may cause photosensitivity reactions
Phosphodiesterase type 5 inhibitors
These agents are used to treat pulmonary hypertension associated with sickle cell disease. Phosphodiesterase type 5 (PDE5) inhibitors are also used to prevent priapism associated with sickle cell disease.
Sildenafil (Revatio)
Promotes selective smooth muscle relaxation in lung vasculature, possibly by inhibiting PDE5. This results in subsequent reduction of blood pressure in pulmonary arteries and increase in cardiac output.
Adult
20 mg PO tid
Pediatric
Not established
Potentiates vasodilatory effect of NO, resulting in potentially fatal drop in blood pressure; coadministration with ketoconazole, erythromycin, or cimetidine increases plasma sildenafil concentrations; coadministration with rifampin decreases plasma levels of sildenafil; coadministration with bosentan increases bosentan levels by 50% and reduces sildenafil levels by 63%
Documented hypersensitivity, concurrent or intermittent use of organic nitrates in any form
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects include headaches (16%), flushing (10%), upset stomach (7%), nasal congestion (4%), and a blue haze at the periphery of vision (3%); adverse effects occur more often in men taking the 100-mg dose; serious adverse effects occur in patients with severe heart disease and those who are taking nitrates; rates of MI were 1.7 and 1.4 per 100 man-years for sildenafil and placebo groups
Endothelin receptor antagonist
These agents are used for pulmonary hypertension associated with sickle cell disease.
Bosentan (Tracleer)
Improves pulmonary arterial hemodynamics by competitively binding to ET-1 receptors endothelin-A and endothelin-B in pulmonary vascular endothelium and pulmonary vascular smooth muscle. This leads to a significant increase in CI associated with a significant reduction in PAP, PVR, and mean RAP.
Adult
Starting dose: 62.5 mg PO bid for 4 wk, followed by 125 mg PO bid indefinitely
Pediatric
Not established; 62.5 mg PO bid recommended if <40 kg or >12 y; not to exceed 125 mg/d
Toxicity may increase when administered concomitantly with inhibitors of isoenzymes CYP450 2C9 and CYP450 3A4 (eg, ketoconazole, erythromycin, fluoxetine, sertraline, amiodarone, cyclosporine A); induces isoenzymes CYP450 2C9 and CYP450 3A4, causing decrease in plasma concentrations of drugs metabolized by these enzymes
Documented hypersensitivity; coadministration with cyclosporin A or glyburide
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May cause a dose-related decrease in hemoglobin and hematocrit; hemoglobin levels should be monitored after 1 and 3 mo of treatment and then q3mo; overall mean decrease in hemoglobin concentration is 0.9 g/dL (change to end of treatment); most of this decrease of hemoglobin concentration is detected in first few weeks of treatment, and hemoglobin levels stabilize by 4-12 wk of treatment
Iron chelators
Iron overload is a consequence of the numerous transfusions required and may lead to complications such as heart or liver failure. Iron chelators help maintain hemoglobin levels within the desired range.
Deferoxamine mesylate (Desferal mesylate)
Promotes renal and hepatic excretion in urine and bile in feces. Gives urine a red discoloration. Readily chelates iron from ferritin and hemosiderin but not from transferrin. Does not affect iron in the cytochromes or hemoglobin. Most effective when provided to the circulation continuously by infusion. Helps prevent damage to the liver and bone marrow from iron deposition.
Adult
20-40 mg/kg/d SC infused over 8-12 h via an infusion pump
Pediatric
Administer as in adults
Concomitant administration with prochlorperazine can cause a transient loss of consciousness
Documented hypersensitivity; severe renal disease and anuria (dose reduction after the loading dose should be considered in these circumstances)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Tachycardia, hypotension, and shock may occur in patients receiving long-term therapy and could add to the cardiovascular collapse due to iron toxicity; GI side effects of the drug include abdominal discomfort, nausea, vomiting, and diarrhea, which may add to the symptoms of acute iron toxicity; flushing and fever are reported
Deferasirox (Exjade tablets)
PO iron chelation agent that is demonstrated to reduce the liver iron concentration in adults and children who receive repeated RBC transfusions. Binds iron with high affinity in a 2:1 ratio.
Adult
Initial: 20 mg/kg PO qd on empty stomach 30 min ac; calculate dose to nearest whole tab.
Maintenance: Adjust the dose by 5-mg/kg/d to 10-mg/kg/d increments q3-6mo according to the serum ferritin level trends; not to exceed 30 mg/kg/d
Note: Dissolve the tablets completely in water, orange juice, or apple juice; then immediately drink the suspension; resuspend any remaining residue in a small volume of liquid and swallow.
Pediatric
<2 years: Not established
>2 years: Administer as in adults
Data are limited; do not take with aluminum-containing antacids
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Common adverse effects include diarrhea, nausea, abdominal pain, headache, pyrexia, cough, and rash; may increase the serum creatinine and hepatic enzyme levels; decrease the dose with a persistent elevation of serum creatinine level; may cause auditory and visual disturbances; slight decreases in serum copper and zinc levels may occur; dissolve the tabs completely in water, orange juice, or apple juice, and drink the resulting susp immediately (do not swallow the tablet whole, do not chew or crush); measure the serum ferritin levels monthly, and adjust the dose every 3-6 mo based on the serum ferritin level trends
Deferiprone (Ferriprox)
1,2 dimethyl-3-hydroxypyridine-4-one is a member of a family of hydroxypyridine-4-one (HPO) chelators that requires 3 molecules to fully bind iron (III), each molecule providing 2 coordination sites (bidentate chelation). Designated as an orphan drug in the United States.
Adult
50-75 mg/kg/d PO divided bid/qid; typical daily dose ranges between 3-6 g
Pediatric
Data limited; 37-75 mg/kg/d PO divided bid/qid was administered in 20 children (mean age 10.6 y) with thalassemia
Data are limited; none reported
Documented hypersensitivity; severe liver impairment; existing neutropenia or agranulocytosis
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor CBC count and liver function tests; may cause neutropenia and agranulocytosis (0.6%), arthropathy, abnormal liver function test results and liver fibrosis, nausea, and zinc deficiency; discontinue if persistent arthropathy occurs
More on Sickle Cell Anemia |
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 Treatment & Medication: Sickle Cell Anemia |
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Further Reading
Keywords
sickle cell anemia, sickle cell disease, crescent cell anemia, sickle-shaped erythrocytes, crescent-shaped erythrocytes, sickle cell crisis, ACS, acute chest syndrome, SCD, hemoglobin S, HbS, homozygotic HbSS, aplastic crisis, fifth disease, hemolytic anemia, Streptococcus pneumoniae, osteomyelitis, meningitis, acute chest syndrome, pulmonary infarction, respiratory distress, bone marrow infection, hand-foot syndrome, hypoxemia, dehydration, stroke, convulsion, priapism, bone marrow transplantation, hemorrhagic stroke, moya moya, cholecystitis, cholelithiasis, bile duct obstruction, unwanted erection, treatment, diagnosis
