Sickle Cell Disease (SCD) Workup: Approach Considerations, Baseline Blood Study Abnormalities, Suggested Routine Clinical Laboratory Evaluations

Sections

Workup

Approach Considerations

Screening for hemoglobin S (HbS) at birth is currently mandatory in the United States. This method of case finding allows institution of early treatment and control.

Prenatal diagnosis is also available. The laboratory procedures employed in prenatal testing are sensitive and rapid. Prenatal testing must be accompanied with genetic and psychological counseling. Chorionic villus sampling can be performed at 8-12 weeks' gestation to obtain DNA. This low-risk procedure is safe. DNA from amniotic fluid cells can be examined at 16 weeks' gestation. Investigational attempts are ongoing to isolate fetal cells from maternal blood for DNA assay.

Children with sickle cell disease (SCD) frequently have abnormal pulmonary function test (PFT) results. PFTs should be performed regularly in children with a history of recurrent acute chest episodes or low oxygen saturation. Because lung function declines with age, it is important to identify those who require close monitoring and treatment.

Newer techniques for noninvasive assessment of the brain have also been used to identify children with asymptomatic brain disease. Transcranial near-infrared spectroscopy or cerebral oximetry is increasingly being used as a screening tool for low cerebral venous oxygen saturation in children with sickle cell disease.

Measurement of blood flow velocity by transcranial Doppler ultrasound (TCD) has proved a good predictor of stroke risk. Although overall, children with SCD have a stroke risk of 1% per year, those with high cerebral blood flow velocities (time-averaged mean velocity >200 cm/s) have stroke rates of greater than 10% a year. TCD surveillance remains the gold standard for stroke risk prediction in children with TCD; annual TCD screening from 2 to 16 years of age has been recommended.^[44]

Consider lumbar puncture to exclude meningitis if there is altered mental status, meningeal signs, or fever. When focal neurologic signs are present or intracranial hemorrhage is suspected, consider CT prior to lumbar puncture. Consider lumbar puncture if a subarachnoid hemorrhage is suspected and head CT is unrevealing.

Meningitis in children with SCD requires early recognition; aggressive diagnostic evaluation including CBC count, urinalysis, chest radiographs, and blood cultures; prompt administration of intravenous antibiotics active against S pneumoniae; and close observation.

Children younger than 12 months with a temperature of higher than 39°C who appear toxic, with an infiltrate on chest radiograph and an elevated WBC count, should be admitted to the hospital. Consider only outpatient treatment if no high-risk features appear on history, physical examination, or laboratory evaluation; if the child is older than 12 months; and if outpatient follow-up care can be ensured.

According to the 2003 BCSH guidelines, a full blood count is required for all patients who are admitted to the hospital, with other investigations performed as necessitated by the clinical situation. Intravenous fluids are not routinely indicated, but should be given if the patient is unable to drink, has diarrhea or is vomiting. Nasogastric fluids are an appropriate alternative to IV fluids.^[45]

In acute chest syndrome, arterial blood oxygen saturation commonly falls to a greater degree than that seen in simple pneumonia of the same magnitude. Patients with acute chest syndrome often have progressive pulmonary infiltrates despite treatment with antibiotics. Infection may set off a wave of local ischemia that produces focal sickling, deoxygenation, and additional sickling.

The 2003 BCSH guidelines strongly advocate the use of incentive spirometry for patients with chest or back pain.^[45]

Newborn hemoglobinopathy screening

The introduction of newborn screening has been one of the greatest advances in the management of sickle cell disease. Currently, 50 states and the District of Columbia have mandatory universal programs for newborn screening for hemoglobin disorders. Guidelines for screening for sickle cell disease in newborns have been established.^[46]If results are positive, a repeat hemoglobin electrophoresis should be performed for confirmation.

Fetal hemoglobin is predominant in young infants. If results show only hemoglobin (Hb) F and S, the child has either sickle cell anemia or HbS–β-0 thalassemia. If results show HbF, S, and C, the child has HbSC disease. If results show HbF, S, and A, determine whether the child has received a transfusion.

If the child has not received a transfusion and S is greater than A, HbS–beta+ thalassemia is most likely the diagnosis. If A is greater than S, the child is presumed to have the sickle trait. If A and S concentrations are close, conduct a study of the parents to determine if one of them has the thalassemia trait. Repeat Hb electrophoresis on the child after several months.

Hemoglobin electrophoresis

Hemoglobin electrophoresis differentiates individuals who are homozygous for HbS from those who are heterozygous. It establishes the diagnosis of SCD by demonstrating a single band of HbS (in HbSS) or HbS with another mutant hemoglobin in compound heterozygotes.

In children with normocytic hemolytic anemia, if results of electrophoresis show only HbS with an HbF concentration of less than 30%, the diagnosis is sickle cell anemia. If HbS and HbC are present in roughly equal amounts, the diagnosis is HbSC disease.

In children with microcytic hemolytic anemia, order quantitative Hb A₂ in addition to electrophoresis. If HbS is predominant, Hb F is less than 30% and Hb A₂ is elevated, a diagnosis of HbS–beta-0 thalassemia can be inferred. If possible, perform a study of the parents. If the HbA₂ level is normal, consider the possibility of concomitant HbSS and iron deficiency. If HbS is greater than A and HbA₂ is elevated, a diagnosis of HbS–beta+ thalassemia can be inferred. If HbS and HbC are present in equal amounts, the diagnosis is HbSC disease.

A homozygous patient will have hemoglobin SS (HbSS, 80-90%), hemoglobin F (HbF, 2-20%), and hemoglobin A2 (HbA2, 2-4%). A carrier patient will have HbSS (35-40%) and hemoglobin A (HbA, 60-65%). The test is not accurate in a patient who has recently received blood transfusions.

Baseline Blood Study Abnormalities

Typical baseline abnormalities in the patient with SCD are as follows:

Hemoglobin level is 5-9 g/dL
Hematocrit is decreased to 17-29%
Total leukocyte count is elevated to 12,000-20,000 cells/mm³ (12-20 X 10⁹/L), with a predominance of neutrophils
Platelet count is increased
Erythrocyte sedimentation rate is low
The reticulocyte count is usually elevated, but it may vary depending on the extent of baseline hemolysis
Peripheral blood smears demonstrate target cells, elongated cells, and characteristic sickle erythrocytes
Presence of RBCs containing nuclear remnants (Howell-Jolly bodies) indicates that the patient is asplenic
Results of hemoglobin solubility testing are positive, but they do not distinguish between sickle cell disease and sickle cell trait

Findings on peripheral blood smears are shown in the images below.

Peripheral blood with sickled cells at 400X magnification. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

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Peripheral blood smear with sickled cells at 1000X magnification. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

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Peripheral blood smear with Howell-Jolly body, indicating functional asplenism. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

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Suggested Routine Clinical Laboratory Evaluations

Obtaining a series of baseline values on each patient to compare with those at times of acute illness is useful. The table below shows a typical schedule of routine clinical laboratory evaluations.

Table. Schedule of Laboratory Tests for Patients With Sickle Cell Disease (Open Table in a new window)

Tests	Age	Frequency
CBC count with WBC differential, reticulocyte count	3-24 mo >24 mo	every 3 mo every 6 mo
Percent Hb F	6-24 mo >24 mo	every 6 mo annually
Renal function (creatinine, BUN, urinalysis)	≥ 12 mo	annually
Hepatobiliary function (ALT, fractionated bilirubin)	≥ 12 mo	annually
Pulmonary function (transcutaneous O₂ saturation)	≥ 12 mo	every 6 mo

Laboratory Studies in the Ill Child

Standard laboratory tests cannot be used to distinguish pain crisis from the baseline condition. If laboratory tests are obtained, they should be interpreted in light of baseline values.

There is a near ubiquitous recommendation to obtain "routine" CBC and reticulocyte counts in all sickle cell patients with an acute illness, including those presenting with apparently uncomplicated painful crisis. However, a meta-analysis found that "the routine use of complete blood count and reticulocyte count in sickle cell patients presenting with painful crisis does not alter management decisions. Selective use of these tests can be based on patient age, reported symptoms, vital signs, physical examination, and clinical judgment."^[47]

Febrile children with SCD, especially those younger than 5 years, should have an aggressive investigation. The following are usually indicated:

CBC with differential and reticulocyte count
Liver function tests (LFTs)
Urinalysis
Blood cultures

Additional studies may be indicated, depending on the clinical presentation. Type and crossmatch blood in case transfusion is necessary.

On the CBC, anemia is often identified; however, a major drop in hemoglobin (ie, more than 2 g/dL) from previously recorded values indicates a hematologic crisis. Leukocytosis is expected in all patients with sickle cell anemia, but a major elevation in the WBC count (ie, >20,000/mm³) with a left shift raises suspicion for infection. Leukopenia is suggestive of parvovirus infection. The platelet count is typically elevated. If it is low, consider hypersplenism.

The reticulocyte percentage documents the briskness of the marrow response. If the reticulocyte count is normal, splenic sequestration is the probable cause. If the reticulocyte count is low, an aplastic crisis is the probable cause. If the reticulocyte count is high, hyperhemolytic crisis is the probable cause.

Additional Tests

Measurement of blood urea nitrogen (BUN), serum creatinine, and serum electrolytes can be useful. Assays of lactic dehydrogenase and haptoglobin are useful but not required. Elevated levels of lactic dehydrogenase support the diagnosis of hemolysis being released from destroyed RBCs. Decreased levels of haptoglobin confirm the presence of hemolysis.

Arterial blood gases

Arterial blood gas measurements (ABGs) may be obtained in patients who are in respiratory distress, to supplement information provided by oxygen saturation monitoring. This will reflect the severity of pulmonary crisis. Serial ABGs are necessary to follow the response in pulmonary crisis.

Urinalysis

Perform urinalysis if the patient has fever or signs of urinary tract infection (UTI). Patients with sickle cell anemia often have hematuria and isosthenuria. If signs of UTI are present, obtain a urine Gram stain and culture.

Sickling test

Because of mandated newborn screening for sickle hemoglobinopathies, the diagnosis of SCD is already established in most patients with the disease who present for emergency care. If the diagnosis of sickle cell anemia is uncertain, a sickling test will establish the presence of HbS gene. It will not, however, differentiate between individuals who are homozygous and those who are heterozygous.

Secretory phospholipase A2

Secretory phospholipase A2 (sPLA2), an enzyme that cleaves fatty acids from triglycerides, is an accurate marker for identifying present or incipient acute chest syndrome in young patients with sickle cell pain crisis . Its serum concentration increases before acute chest syndrome becomes clinically apparent, peaks at the clinical onset of acute chest syndrome, and declines during its resolution.

Radiography

Chest radiography should be performed in patients with respiratory symptoms. Radiographic findings may initially be normal in patients with acute chest syndrome, however.

Plain radiography of the extremities is useful in evaluating subacute and chronic infarction and in assessing the number and severity of prior episodes of infarction. Plain radiographs are also excellent for evaluating deformities and other complications of bone infarction. Osteonecrosis is visible on plain images only in the later stages after the affected bone is substantially damaged.

In early dactylitis, plain radiographs will show only soft tissue swelling. Periosteal new-bone formation can be seen on radiographs 7-10 days later. Additionally, medullary expansion, cortical thinning, trabecular resorption, and resultant focal lucency may be seen 2-3 weeks after the onset of symptoms, but these findings usually resolve within weeks.

Radiography is not as sensitive as other studies for osteomyelitis in the first 1-2 weeks. However, plain images subsequently show cortical destruction, periosteal new bone, and (with time) sinus tracts and sequestra.

See Skeletal Sickle Cell Anemia for more information on imaging studies in SCD.

Magnetic Resonance Imaging

MRI can demonstrate avascular necrosis of the femoral and humeral heads and may distinguish between osteomyelitis and bony infarction in patients with bone pain. MRI is the best method for detecting early signs of osteonecrosis in patients with SCD and for identifying episodes of osteomyelitis.

MRI allows the early detection of changes in bone marrow due to acute and chronic bone marrow infarction, marrow hyperplasia, osteomyelitis, and osteonecrosis. Bone sequestra, sinus tracts, and subperiosteal abscesses are also clearly identified when present.

As with plain radiography, the sine qua non of diagnosing osteomyelitis on MRI is the identification of cortical destruction, for which MRI is exquisitely sensitive. MRI has a specificity of 98% and a sensitivity of 85-97% for identifying bone marrow infarcts.

Children with sickle cell disease who have "silent" cerebral infarcts revealed with MRI have a higher rate of abnormal neuropsychometric (NPM) findings and a higher risk of overt strokes. Stroke prevention strategies based on abnormal MRI results have not been tested, but children with abnormal MRI or NPM findings may be evaluated more frequently and carefully and considered for therapeutic measures.

According to the 2014 American Heart Association/American Stroke Association (AHA/ASA) primary stroke prevention guidelines, MRI and MRA findings for identifying children with SCD for primary stroke prevention have not been established. As such, these tests are not recommended in lieu of TCD for this purpose.^[44]

Computed Tomography

Although CT is not an initial study in most patients, CT may be useful to demonstrate subtle regions of osteonecrosis not apparent on plain radiographs in patients who are unable to have an MRI.^[4]

CT scanning is performed to exclude renal medullary carcinoma in patients presenting with hematuria. CT is not the test of choice for evaluation of acute osteomyelitis.

Nuclear Medicine Scans

Nuclear medicine scanning can be used to detect early osteonecrosis. This modality also plays a role in detecting osteomyelitis.

Technetium-99m (^99m Tc) bone scanning can be used to detect early stages of osteonecrosis, and it is not as costly as MRI. Tc-99m bone-marrow scans demonstrate areas of decreased activity in marrow infarction.^[48]

Indium-111 (¹¹¹In) white blood cell (WBC) scanning is useful for diagnosing osteomyelitis, which appears as an area of increased activity within bone. However, areas of marrow proliferation, which are common in patients with SCD, would also demonstrate increased activity on¹¹¹ In WBC scans.

The combination of a bone scan and a bone marrow scan has been used to differentiate acute osteomyelitis from bone infarcts in patient with SCD, since the clinical presentation of these 2 conditions may be very similar. Acute osteomyelitis produces increased activity on the bone scan with normal activity on the bone-marrow scan, while bone infarction produces decreased activity on the bone-marrow scan with corresponding abnormal uptake on the bone scan.

Transcranial Doppler Ultrasonography

Transcranial Doppler ultrasonography (TCD) can identify children with SCD who are at high risk for stroke by documenting abnormally high blood flow velocity in the large arteries of the circle of Willis—the middle cerebral or internal carotid arteries. Velocity, which is usually increased by severe anemia, becomes elevated in a focal manner when stenosis reduces the arterial diameter. (MRI, with or without angiography, and NPM studies have also been used to detect these abnormalities.)

The upper limit of normal flow velocity varies with the method used. Values are lower for duplex Doppler (180 cm/s) than for non–duplex Doppler (200 cm/s).

Children with HbSS or HbS–β-0 thalassemia should be considered candidates for TCD screening. TCD screening should begin at age 2 years and continue to age 16 years.^{[44, 49]}TCD is repeated annually if TCD results are normal or every 4 months if TCD results are marginal. Abnormal results should prompt a repeat TCD within 2-4 weeks.

According to the AHA/ASA primary prevention guidelines, while there is no established optimal screening interval, it is reasonable for younger children and those with borderline abnormal TCD velocities to be screened more often to detect incidence of high-risk TCD indications for intervention.^[44]

The Stroke Prevention in Sickle Cell Anemia (STOP) trial demonstrated that a transfusion program in patients with abnormal TCD results normalizes the TCD results and reduces the risk of strokes.^[50]A subsequent trial (STOPII) showed that when transfusions are discontinued, an unacceptably high percentage of patients show TCD reversion to high risk, and some suffer actual strokes.^[51]On the other hand, TCD results normalize over time in some patients who do not receive transfusions.

Abdominal Ultrasonography

In patients with abdominal pain, abdominal ultrasonography can be used to rule out cholecystitis, cholelithiasis, or an ectopic pregnancy and to measure spleen and liver size. Assess liver and spleen size. Abdominal ultrasonography can be used to visualize stones and to detect signs of thickening gallbladder walls or ductal inflammation, indicating possible cholecystitis. Abdominal ultrasound is useful to document spleen size and the presence of biliary stones.

Ultrasonography of the kidneys is performed to exclude other causes of postrenal or obstructive uropathy (eg, nephrolithiasis) and may demonstrate papillary necrosis.

Echocardiography

Echocardiography is used to identify patients with pulmonary hypertension based on tricuspid regurgitant jet velocity. Patients with sickle cell disease may have an array of abnormalities of systolic and diastolic function. Adults should be tested for evidence of pulmonary hypertension with Doppler echocardiography. Cardiac echocardiography should be performed for patients with dyspnea.

Left ventricular diastolic dysfunction (LVDD) is commonly reported in SCD patients and is linked to premature death. Echocardiography is the most widely used method to evaluate LV diastolic function, but the majority of patients with SCD-associated cardiomyopathy have high-output left heart failure, and the evaluation of diastolic function is more challenging in this setting.^[52]

The diagnosis of high-output heart failure, especially when it is at an early stage, could be missed by echocardiography and/or right heart catheterization performed with the patient at rest. However, early-stage high-output heart failure can be identified on invasive low-level exercise testing that shows exercise-induced elevation of LV filling pressure despite a normal resting value. Consequently, Hammoudi et al recommend considering low-level invasive exercise testing in SCD patients with inconclusive measurements at rest when there is clinical suspicion of heart failure (specifically, symptoms with exercise and no history of congestion, or use of diuretics).^[52]

Treatment & Management

Pecker LH, Lanzkron S. Sickle Cell Disease. Ann Intern Med. 2021 Jan. 174 (1):ITC1-ITC16. [QxMD MEDLINE Link].
Sedrak A, Kondamudi NP. Sickle Cell Disease. 2023 Jan. [QxMD MEDLINE Link]. [Full Text].
Shatat IF, Jakson SM, Blue AE, Johnson MA, Orak JK, Kalpatthi R. Masked hypertension is prevalent in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study. Pediatr Nephrol. 2013 Jan. 28(1):115-20. [QxMD MEDLINE Link].
Linguraru MG, Orandi BJ, Van Uitert RL, Mukherjee N, Summers RM, Gladwin MT, et al. CT and image processing non-invasive indicators of sickle cell secondary pulmonary hypertension. Conf Proc IEEE Eng Med Biol Soc. 2008. 2008:859-62. [QxMD MEDLINE Link]. [Full Text].
Olujohungbe A, Howard J. The clinical care of adult patients with sickle cell disease. Br J Hosp Med (Lond). 2008 Nov. 69(11):616-9. [QxMD MEDLINE Link].
Johnson L, Carmona-Bayonas A, Tick L. Management of pain due to sickle cell disease. J Pain Palliat Care Pharmacother. 2008. 22(1):51-4. [QxMD MEDLINE Link].
De D. Acute nursing care and management of patients with sickle cell. Br J Nurs. 2008 Jul 10-23. 17(13):818-23. [QxMD MEDLINE Link].
Teixeira RS, Terse-Ramos R, Ferreira TA, Machado VR, Perdiz MI, Lyra IM, et al. Associations between endothelial dysfunction and clinical and laboratory parameters in children and adolescents with sickle cell anemia. PLoS One. 2017. 12 (9):e0184076. [QxMD MEDLINE Link]. [Full Text].
Manwani D, Frenette PS. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. Blood. 2013 Dec 5. 122 (24):3892-8. [QxMD MEDLINE Link]. [Full Text].
Zen Q, Batchvarova M, Twyman CA, Eyler CE, Qiu H, De Castro LM, et al. B-CAM/LU expression and the role of B-CAM/LU activation in binding of low- and high-density red cells to laminin in sickle cell disease. Am J Hematol. 2004 Feb. 75(2):63-72. [QxMD MEDLINE Link].
Ford AL, Ragan DK, Fellah S, Binkley MM, Fields ME, Guilliams KP, et al. Silent infarcts in sickle cell anemia occur in the borderzone region and are associated with low cerebral blood flow. Blood. 2018 Jul 30. [QxMD MEDLINE Link].
Stotesbury H, Kirkham FJ, Kölbel M, Balfour P, Clayden JD, Sahota S, et al. White matter integrity and processing speed in sickle cell anemia. Neurology. 2018 Jun 5. 90 (23):e2042-e2050. [QxMD MEDLINE Link]. [Full Text].
Merlet AN, Chatel B, Hourdé C, Ravelojaona M, Bendahan D, Féasson L, et al. How Sickle Cell Disease Impairs Skeletal Muscle Function: Implications in Daily Life. Med Sci Sports Exerc. 2018 Aug 8. [QxMD MEDLINE Link].
Silva PO, Ferreira AS, Lima CMA, Guimarães FS, Lopes AJ. Balance control is impaired in adults with sickle cell anaemia. Somatosens Mot Res. 2018 Jul 16. 1-10. [QxMD MEDLINE Link].
Morris CR. Asthma management: reinventing the wheel in sickle cell disease. Am J Hematol. 2009 Apr. 84(4):234-41. [QxMD MEDLINE Link].
National Institutes of Health. Introduction to Genes and Disease: Anemia, Sickle Cell. National Center for Biotechnology Information. Available at http://www.ncbi.nlm.nih.gov/books/NBK22238/. Accessed: December 12, 2023.
Centers for Disease Control and Prevention. Sickle Cell Disease: Health Care Professionals: Data & Statistics. Centers for Disease Control and Prevention. Department of Health and Human Services. Available at http://www.cdc.gov/ncbddd/sicklecell/data.html. July 6, 2023; Accessed: December 12, 2023.
Naik RP, Derebail VK. The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait. Expert Rev Hematol. 2017 Dec. 10 (12):1087-1094. [QxMD MEDLINE Link]. [Full Text].
Derebail VK, Nachman PH, Key NS, Ansede H, Falk RJ, Kshirsagar AV. High prevalence of sickle cell trait in African Americans with ESRD. J Am Soc Nephrol. 2010 Mar. 21 (3):413-7. [QxMD MEDLINE Link]. [Full Text].
Ataga KI, Saraf SL, Derebail VK. The nephropathy of sickle cell trait and sickle cell disease. Nat Rev Nephrol. 2022 Jun. 18 (6):361-377. [QxMD MEDLINE Link]. [Full Text].
Nissenson AR, Port FK. Outcome of end-stage renal disease in patients with rare causes of renal failure. I. Inherited and metabolic disorders. Q J Med. 1989 Nov. 73(271):1055-62. [QxMD MEDLINE Link].
Saborio P, Scheinman JI. Disease of the month - Sickle cell nephropathy. J Amm Soc Nephrol. 1999. 10:187.
Miller ST, Sleeper LA, Pegelow CH, Enos LE, Wang WC, Weiner SJ, et al. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. 2000 Jan 13. 342(2):83-9. [QxMD MEDLINE Link].
Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9. 330(23):1639-44. [QxMD MEDLINE Link].
Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood. 2004 Jun 1. 103(11):4023-7. [QxMD MEDLINE Link]. [Full Text].
Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004 Feb 26. 350(9):886-95. [QxMD MEDLINE Link].
Parent F, Bachir D, Inamo J, et al. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011 Jul 7. 365(1):44-53. [QxMD MEDLINE Link].
Wright SW, Zeldin MH, Wrenn K, Miller O. Screening for sickle-cell trait in the emergency department. J Gen Intern Med. 1994 Aug. 9(8):421-4. [QxMD MEDLINE Link].
Materials & Multimedia on Sickle Cell Disease. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/ncbddd/sicklecell/materials/index.html. July 6, 2023; Accessed: December 12, 2023.
Chiang EY, Frenette PS. Sickle cell vaso-occlusion. Hematol Oncol Clin North Am. 2005 Oct. 19(5):771-84, v. [QxMD MEDLINE Link].
Rhodes M, Akohoue SA, Shankar SM, Fleming I, Qi An A, Yu C, et al. Growth patterns in children with sickle cell anemia during puberty. Pediatr Blood Cancer. 2009 Oct. 53(4):635-41. [QxMD MEDLINE Link]. [Full Text].
Telfer P, Coen P, Chakravorty S, Wilkey O, Evans J, Newell H, et al. Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London. Haematologica. 2007 Jul. 92(7):905-12. [QxMD MEDLINE Link].
Nicholson GT, Hsu DT, Colan SD, et al. Coronary artery dilation in sickle cell disease. J Pediatr. 2011 Nov. 159(5):789-794.e1-2. [QxMD MEDLINE Link].
Dahoui HA, Hayek MN, Nietert PJ, et al. Pulmonary hypertension in children and young adults with sickle cell disease: evidence for familial clustering. Pediatr Blood Cancer. 2010. 54(3):398-402.
Onyekwere OC, Campbell A, Teshome M, Onyeagoro S, Sylvan C, Akintilo A, et al. Pulmonary hypertension in children and adolescents with sickle cell disease. Pediatr Cardiol. 2008 Mar. 29(2):309-12. [QxMD MEDLINE Link].
Parent F, Bachir D, Inamo J, et al. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011 Jul 7. 365(1):44-53. [QxMD MEDLINE Link].
Akinsola FB, Kehinde MO. Ocular findings in sickle cell disease patients in Lagos. Niger Postgrad Med J. 2004 Sep. 11 (3):203-6. [QxMD MEDLINE Link].
Hingorani M, Bentley CR, Jackson H, Betancourt F, Arya R, Aclimandos WA, et al. Retinopathy in haemoglobin C trait. Eye (Lond). 1996. 10 ( Pt 3):338-42. [QxMD MEDLINE Link].
Sokol JA, Baron E, Lantos G, Kazim M. Orbital compression syndrome in sickle cell disease. Ophthalmic Plast Reconstr Surg. 2008 May-Jun. 24 (3):181-4. [QxMD MEDLINE Link].
Wisotsky BJ, Tesser PM, Schultz JS. Trabecular meshwork hemorrhage in a patient with sickle cell trait. Arch Ophthalmol. 1995 Mar. 113 (3):381. [QxMD MEDLINE Link].
Goldbaum MH, Jampol LM, Goldberg MF. The disc sign in sickling hemoglobinopathies. Arch Ophthalmol. 1978 Sep. 96 (9):1597-600. [QxMD MEDLINE Link].
Babalola OE, Wambebe CO. When should children and young adults with sickle cell disease be referred for eye assessment?. Afr J Med Med Sci. 2001 Dec. 30 (4):261-3. [QxMD MEDLINE Link].
Gill HS, Lam WC. A screening strategy for the detection of sickle cell retinopathy in pediatric patients. Can J Ophthalmol. 2008 Apr. 43 (2):188-91. [QxMD MEDLINE Link].
[Guideline] Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Dec. 45 (12):3754-832. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Centre for Clinical Practice at NICE (UK). Guidelines for the management of the acute painful crisis in sickle cell disease. Br J Haematol. 2012 Jun. 120(5):744-52. [QxMD MEDLINE Link]. [Full Text].
[Guideline] US Preventive Services Task Force. Screening for sickle cell disease in newborns: U.S. Preventive Services Task Force recommendation statement. Agency for Healthcare Research and Quality (AHRQ). Sep 2007. [Full Text].
Bernard AW, Venkat A, Lyons MS. Best evidence topic report. Full blood count and reticulocyte count in painful sickle crisis. Emerg Med J. 2006 Apr. 23(4):302-3. [QxMD MEDLINE Link]. [Full Text].
Cerci SS, Suslu H, Cerci C, Yildiz M, Ozbek FM, Balci TA, et al. Different findings in Tc-99m MDP bone scintigraphy of patients with sickle cell disease: report of three cases. Ann Nucl Med. 2007 Jul. 21(5):311-4. [QxMD MEDLINE Link].
[Guideline] Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014. National Heart, Lung and Blood Institute. Available at https://www.nhlbi.nih.gov/sites/default/files/media/docs/Evd-Bsd_SickleCellDis_Rep2014.pdf. September 8, 2014; Accessed: December 12, 2023.
Lee MT, Piomelli S, Granger S, Miller ST, Harkness S, Brambilla DJ, et al. Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood. 2006 Aug 1. 108(3):847-52. [QxMD MEDLINE Link]. [Full Text].
Adams RJ, Brambilla D. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005 Dec 29. 353(26):2769-78. [QxMD MEDLINE Link]. [Full Text].
Hammoudi N, Lionnet F, Redheuil A, Montalescot G. Cardiovascular manifestations of sickle cell disease. Eur Heart J. 2020 Apr 1. 41 (13):1365-1373. [QxMD MEDLINE Link].
[Guideline] Brawley OW, Cornelius LJ, Edwards LR, Gamble VN, Green BL, Inturrisi C, et al. National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med. 2008 Jun 17. 148(12):932-8. [QxMD MEDLINE Link]. [Full Text].
Payne J, Aban I, Hilliard LM, Madison J, Bemrich-Stolz C, Howard TH, et al. Impact of early analgesia on hospitalization outcomes for sickle cell pain crisis. Pediatr Blood Cancer. 2018 Aug 27. e27420. [QxMD MEDLINE Link].
Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10. 312(10):1033-48. [QxMD MEDLINE Link].
FDA approves new treatment for sickle cell disease. U.S. Food & Drug Administration. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm566084.htm. July 7, 2017; Accessed: December 12, 2023.
Niihara Y, et al; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med. 2018 Jul 19. 379 (3):226-235. [QxMD MEDLINE Link].
Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, et al. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2. 376 (5):429-439. [QxMD MEDLINE Link]. [Full Text].
Kutlar A, Kanter J, Liles DK, Alvarez OA, Cançado RD, Friedrisch JR, et al. Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis. Am J Hematol. 2019 Jan. 94 (1):55-61. [QxMD MEDLINE Link].
Vichinsky E, Hoppe CC, Ataga KI, et al and the, HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8. 381 (6):509-519. [QxMD MEDLINE Link].
Gluckman E, Cappelli B, Bernaudin F, et al, behalf of Eurocord, the Pediatric Working Party of the European Society for Blood and Marrow Transplantation, et al. Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood. 2017 Mar 16. 129 (11):1548-1556. [QxMD MEDLINE Link]. [Full Text].
Curtis SA, Shah NC. Gene therapy in sickle cell disease: Possible utility and impact. Cleve Clin J Med. 2020 Jan. 87 (1):28-29. [QxMD MEDLINE Link]. [Full Text].
McGann PT, Ware RE. Hydroxyurea therapy for sickle cell anemia. Expert Opin Drug Saf. 2015 Sep 14. 1-10. [QxMD MEDLINE Link].
Heeney MM, Ware RE. Hydroxyurea for children with sickle cell disease. Pediatr Clin North Am. 2008 Apr. 55(2):483-501, x. [QxMD MEDLINE Link].
Strouse JJ, Lanzkron S, Beach MC, Haywood C, Park H, Witkop C, et al. Hydroxyurea for sickle cell disease: a systematic review for efficacy and toxicity in children. Pediatrics. 2008 Dec. 122(6):1332-42. [QxMD MEDLINE Link].
Hankins JS, McCarville MB, Rankine-Mullings A, Reid ME, Lobo CL, et al. Prevention of conversion to abnormal TCD with hydroxyurea in sickle cell anemia: A phase III international randomized clinical trial. Am J Hematol. 2015 Sep 28. [QxMD MEDLINE Link].
Siklos (hydroxyurea) Prescribing Information [package insert]. Bryn Mawr, Pennsylvania: Medunik USA, Inc. 12/2017. Available at [Full Text].
Hilliard LM, Kulkarni V, Sen B, Caldwell C, Bemrich-Stolz C, Howard TH, et al. Red blood cell transfusion therapy for sickle cell patients with frequent painful events. Pediatr Blood Cancer. 2018 Aug 27. e27423. [QxMD MEDLINE Link].
Firth PG, Head CA. Sickle cell disease and anesthesia. Anesthesiology. 2004 Sep. 101(3):766-85. [QxMD MEDLINE Link].
Cappellini MD, Piga A. Current status in iron chelation in hemoglobinopathies. Curr Mol Med. 2008 Nov. 8(7):663-74. [QxMD MEDLINE Link].
Rienhoff HY Jr, Viprakasit V, Tay L, et al. A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload. Haematologica. 2011 Apr. 96(4):521-5. [QxMD MEDLINE Link]. [Full Text].
Das BB, Sobczyk W, Bertolone S, Raj A. Cardiopulmonary stress testing in children with sickle cell disease who are on long-term erythrocytapheresis. J Pediatr Hematol Oncol. 2008 May. 30(5):373-7. [QxMD MEDLINE Link].
Leen JS, Ratnakaram R, Del Priore LV, Bhagat N, Zarbin MA. Anterior segment ischemia after vitrectomy in sickle cell disease. Retina. 2002 Apr. 22 (2):216-9. [QxMD MEDLINE Link].
Karim A, Laghmari M, Dahreddine M, Guedira K, Ibrahimy W, Essakali N, et al. [Hyphema with secondary hemorrhage: think about sickle cell disease]. J Fr Ophtalmol. 2004 Apr. 27 (4):397-400. [QxMD MEDLINE Link].
Nasrullah A, Kerr NC. Sickle cell trait as a risk factor for secondary hemorrhage in children with traumatic hyphema. Am J Ophthalmol. 1997 Jun. 123 (6):783-90. [QxMD MEDLINE Link].
Rogovik AL, Li Y, Kirby MA, Friedman JN, Goldman RD. Admission and length of stay due to painful vasoocclusive crisis in children. Am J Emerg Med. 2009 Sep. 27(7):797-801. [QxMD MEDLINE Link].
Wang WC, Ware RE, Miller ST, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14. 377(9778):1663-72. [QxMD MEDLINE Link].
Gladwin MT, Kato GJ, Weiner D, et al. Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA. 2011 Mar 2. 305(9):893-902. [QxMD MEDLINE Link].
[Guideline] Howard J, Hart N, Roberts-Harewood M, Cummins M, Awogbade M, Davis B, et al. Guideline on the management of acute chest syndrome in sickle cell disease. Br J Haematol. 2015 May. 169 (4):492-505. [QxMD MEDLINE Link]. [Full Text].
Styles L, Wager CG, Labotka RJ, Smith-Whitley K, Thompson AA, Lane PA, et al. Refining the value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE). Br J Haematol. 2012 Jun. 157 (5):627-36. [QxMD MEDLINE Link]. [Full Text].
Ogunlesi F, Heeney MM, Koumbourlis AC. Systemic corticosteroids in acute chest syndrome: friend or foe?. Paediatr Respir Rev. 2014 Mar. 15 (1):24-7. [QxMD MEDLINE Link].
[Guideline] Brandow AM, Carroll CP, Creary S, Edwards-Elliott R, Glassberg J, Hurley RW, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020 Jun 23. 4 (12):2656-2701. [QxMD MEDLINE Link]. [Full Text].
Goodwin EF, Partain PI, Lebensburger JD, Fineberg NS, Howard TH. Elective cholecystectomy reduces morbidity of cholelithiasis in pediatric sickle cell disease. Pediatr Blood Cancer. 2016 Sep 19. [QxMD MEDLINE Link].
Rogers ZR. Priapism in sickle cell disease. Hematol Oncol Clin North Am. 2005 Oct. 19(5):917-28, viii. [QxMD MEDLINE Link].
Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Long-term oral phosphodiesterase 5 inhibitor therapy alleviates recurrent priapism. Urology. 2006 May. 67(5):1043-8. [QxMD MEDLINE Link].
Burnett AL, Anele UA, Trueheart IN, Strouse JJ, Casella JF. Randomized controlled trial of sildenafil for preventing recurrent ischemic priapism in sickle cell disease. Am J Med. 2014 Jul. 127 (7):664-8. [QxMD MEDLINE Link]. [Full Text].
Chinegwundoh FI, Smith S, Anie KA. Treatments for priapism in boys and men with sickle cell disease. Cochrane Database Syst Rev. 2020 Apr 6. 4:CD004198. [QxMD MEDLINE Link].
[Guideline] Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Jan. 42(1):227-76. [QxMD MEDLINE Link]. [Full Text].
Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998 Jul 2. 339(1):5-11. [QxMD MEDLINE Link].
DeBaun MR, Gordon M, McKinstry RC,et al. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014 Aug 21. 371(8):699-710. [QxMD MEDLINE Link].
[Guideline] Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011 Feb. 42(2):517-84. [QxMD MEDLINE Link]. [Full Text].
Freed J, Talano J, Small T, Ricci A, Cairo MS. Allogeneic cellular and autologous stem cell therapy for sickle cell disease: 'whom, when and how'. Bone Marrow Transplant. 2012 Dec. 47 (12):1489-98. [QxMD MEDLINE Link]. [Full Text].
Ware RE, Helms RW, SWiTCH Investigators. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH). Blood. 2012 Apr 26. 119 (17):3925-32. [QxMD MEDLINE Link].
Ware RE, Davis BR, Schultz WH, Brown RC, Aygun B, et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016 Feb 13. 387 (10019):661-70. [QxMD MEDLINE Link].
Frangoul H, Locatelli F, Sharma A, Bhatia M, et al. Exagamglogene Autotemcel for Severe Sickle Cell Disease. Blood. 2023. 142(Supple 1):1052. [Full Text].
Orkin SH, Bauer DE. Emerging Genetic Therapy for Sickle Cell Disease. Annu Rev Med. 2018 Oct 24. [QxMD MEDLINE Link].
Ribeil JA, Hacein-Bey-Abina S, Payen E, et al. Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med. 2017 Mar 2. 376 (9):848-855. [QxMD MEDLINE Link]. [Full Text].
Esrick EB, Lehmann LE, Biffi A, et al. Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease. N Engl J Med. 2021 Jan 21. 384 (3):205-215. [QxMD MEDLINE Link].
Kanter J, Thompson AA, Kwiatkowski JL, et al. Efficacy, safety, and health-related quality of life (HRQOL) in patients with sickle cell disease (SCD) who have received lovotibeglogene autotemcel (lovo-cel) gener therapy: Up to 60 months of followup (1051). Presented at the 65th Annual Meeting & Exposition of the American Society of Hematology. 2023 Dec 11. San Diego, CA. [Full Text].
Kanter J, Walters MC, Krishnamurti L, Mapara MY, Kwiatkowski JL, Rifkin-Zenenberg S, et al. Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease. N Engl J Med. 2022 Feb 17. 386 (7):617-628. [QxMD MEDLINE Link]. [Full Text].
Kanter J, Thompson AA, Pierciey FJ Jr, Hsieh M, Uchida N, Leboulch P, et al. Lovo-cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB-206 study. Am J Hematol. 2023 Jan. 98 (1):11-22. [QxMD MEDLINE Link]. [Full Text].
Walters MC, De Castro LM, Sullivan KM, Krishnamurti L, Kamani N, Bredeson C, et al. Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease. Biol Blood Marrow Transplant. 2016 Feb. 22 (2):207-211. [QxMD MEDLINE Link]. [Full Text].
Tanhehco YC, Bhatia M. Hematopoietic stem cell transplantation and cellular therapy in sickle cell disease: where are we now?. Curr Opin Hematol. 2019 Nov. 26 (6):448-452. [QxMD MEDLINE Link].
Krishnamurti L, Neuberg DS, Sullivan KM, et al. Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. Am J Hematol. 2019 Apr. 94 (4):446-454. [QxMD MEDLINE Link]. [Full Text].
Kar BC. Splenectomy in sickle cell disease. J Assoc Physicians India. 1999 Sep. 47(9):890-3. [QxMD MEDLINE Link].
Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1997 Apr 4. 46:1-24. [QxMD MEDLINE Link].
Kazancioglu R, Sever MS, Yüksel-Onel D, Eraksoy H, Yildiz A, Celik AV, et al. Immunization of renal transplant recipients with pneumococcal polysaccharide vaccine. Clin Transplant. 2000 Feb. 14(1):61-5. [QxMD MEDLINE Link].
Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. 2009 Jul 31. 58:1-52. [QxMD MEDLINE Link].
[Guideline] Liem RI, Lanzkron S, D Coates T, DeCastro L, Desai AA, Ataga KI, et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease. Blood Adv. 2019 Dec 10. 3 (23):3867-3897. [QxMD MEDLINE Link]. [Full Text].
[Guideline] DeBaun MR, Jordan LC, King AA, Schatz J, Vichinsky E, Fox CK, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020 Apr 28. 4 (8):1554-1588. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Chou ST, Alsawas M, Fasano RM, Field JJ, Hendrickson JE, Howard J, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020 Jan 28. 4 (2):327-355. [QxMD MEDLINE Link]. [Full Text].
Kanter J, Liem RI, Bernaudin F, Bolaños-Meade J, Fitzhugh CD, Hankins JS, et al. American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation. Blood Adv. 2021 Sep 28. 5 (18):3668-3689. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Molecular and cellular changes of hemoglobin S.
Skeletal sickle cell anemia. H vertebrae. Lateral view of the spine shows angular depression of the central portion of each upper and lower endplate.
Peripheral blood with sickled cells at 400X magnification. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Peripheral blood smear with sickled cells at 1000X magnification. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Peripheral blood smear with Howell-Jolly body, indicating functional asplenism. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Effects of therapy with hydroxyurea.
Skeletal sickle cell anemia. Bone-within-bone appearance. Following multiple infarctions of the long bones, sclerosis may assume the appearance of a bone within a bone, reflecting the old cortex within the new cortex.
A 12-year-old boy with HgbSS disease presents to the pediatric emergency department after his mother tried to wake him for school this morning and noted altered mental status, left-sided gaze paralysis with his head tilted to the left, and flaccid paralysis of the right arm and leg. A CT scan of the brain was obtained immediately.
Embolic stroke of the left middle cerebral artery. SCD is the most common cause of stroke in children and one of the most devastating complications of SCD. Clinically overt strokes are typically due to embolism of the intracranial internal carotid artery and proximal middle cerebral artery (MCA), while "silent strokes" more typically occur in the smaller lacunar and penetrating arteries. As RBCs undergo sickling and hemolysis within the cerebral circulation, they adhere to the vascular endothelium and promote a hypercoaguable state and fuel thromboembolism formation. Treatment options include prophylactic therapy with hydroxyurea to promote HgbF concentrations and monitoring via transcranial Doppler to evaluate MCA blood flow velocity. Children found to have high velocities are at increased risk for stroke and commonly receive RBC transfusions to decrease the concentration of HgbS.
The spleen enlarges during the first year of life in SCD, as it becomes congested with trapped slow-flowing sickled cells within the splenic sinuses and reticuloendothelial system. The histology image shown demonstrates splenic congestion from sequestered sickled RBCs (arrows). Microvascular occlusions produce chronic tissue hypoxia and microinfarctions. Over time, fibrosis induces autosplenectomy. With functional asplenia, patients are particularly susceptible to infection by the encapsulated organisms Streptococcus pneumoniae and Haemophilus influenzae. Vaccination and prophylactic daily penicillin throughout childhood are mainstays of treatment to prevent sepsis and meningitis
Splenic sequestration is an important cause of morbidity that occurs when sudden splenic pooling of blood within the reticuloendothelial system causes an acute drop in circulatory volume and shock-like symptoms (hypotension, tachycardia) with a rigid distended abdomen. It is an acute emergency and can be fatal in 1-2 hours secondary to circulatory hypovolemia. Treatment is with volume resuscitation and blood transfusion. The CT image shown demonstrates splenomegaly with a mass-like process (arrows) from splenic sequestration.
Patients with SCD are also at increased risk of developing pulmonary arterial hypertension (PAH). The etiology is most likely multifactorial but likely related to increased cardiac output secondary to underlying chronic anemia. Impedance to the elevated blood flow will cause further dilation and increase in pulmonary pressures. Postsickling changes including interstitial fibrosis secondary to vaso-occlusive crisis of ACS and hypoperfusion with resultant hypoxia of the pulmonary vascular beds are both proposed offenders inciting further dilation and elevation of pulmonary pressures. A pulmonary arteriogram depicting the markedly dilated vascular supply of the lungs seen in PAH is shown.
Proliferative sickle cell retinopathy. Sickle cell retinopathy is believed to be vaso-occlusion of peripheral arterioles of the retina leading to retinal hypoxia, ischemia, and infarction. New vessels then form at the junction of the vascular and avascular areas of retina. This neovascularization of retinal tissue and resultant traction of fibrovascularization places patients at risk for vitreous hemorrhage (arrows) and retinal detachment. Another common ocular manifestation is hyphema. Anterior chamber bleeding occurs spontaneously, but sickled erythrocytes obstruct the trabecular meshwork leading to significant elevations of intraocular pressure. Patients are particularly susceptible to glaucomatous optic nerve damage from even mildly elevated intraocular pressures. Pressures greater than 36 mm Hg for 24 hours are an indication for surgical drainage in both SCD and sickle cell trait, regardless of the size of hyphema. Image courtesy of the National Eye Institute, National Institutes of Health (NEI/NIH).
A 19-year-old man with known HgbSS disease presents because his girlfriend reports his eyes are yellow. He has no complaints. Physical exam is notable for mild abdominal pain, but is otherwise within normal limits. What imaging test is warranted for this work-up? The image shown is of a male child with similar symptoms. Image courtesy of Wikimedia Commons.
Right upper quadrant ultrasoundChronic hemolysis of sickled cells in HgbSS disease and high heme turnover yields hyperbilirubinemia and is associated with increased formation of bile stones. Stone formation occurs as substances in bile reach concentrations that approach the limits of their solubility. As saturation levels are reached, crystals precipitate, become trapped in mucus, and produce sludge (shown). Over time, the crystals aggregate and form stones. Occlusion of the biliary tree by sludge and/or stones produces clinical disease, typically right upper quadrant pain. The scleral icterus seen in the image of the previous slide is most likely secondary to the elevated circulating levels of bilirubin as a result of an acute hemolytic event (such as an acute vaso-occlusive crisis).
Renal papillary necrosisThe microvascular beds of the renal parenchyma are susceptible to sickling and vaso-occlusive crisis because of their inherent low-oxygen and high-osmolarity state. Depending on the location of occlusion, symptoms vary from a decreased ability to concentrate urine (yielding nocturia and polyuria), a disruption of exchange mechanisms (yielding hyperkalemia) or hematuria, which further damages renal tubules. In renal papillary necrosis, repeated vascular occlusion infarcts the renal medullary pyramids and papillae. This causes sloughing of papillae, which obstructs the urinary tract. Treatment options include hydration, high-dose antibiotics for resulting pyelonephritis, and possible percutaneous nephrostomy tube or invasive retrieval of sloughed papillae in acute urinary obstruction. The intravenous pyelogram demonstrates the "egg-in-a-cup" appearance of sloughed renal papillae (arrows) secondary to renal papillary necrosis.
Skeletal sickle cell anemia. Hand-foot syndrome. Soft tissue swelling with periosteal new-bone formation and a moth-eaten lytic process at the proximal aspect of the fourth phalanx.
Skeletal sickle cell anemia. Advanced dactylitis. Lytic processes are present at the first and fifth metacarpals, along with periostitis, which is most prominent in the third metacarpal.
Skeletal sickle cell anemia. Expanded medullary cavity. The diploic space is markedly widened due to marrow hyperplasia. Trabeculae are oriented perpendicular to the inner table, giving a hair-on-end appearance.
Skeletal sickle cell anemia. Detailed view of the expanded medullary cavity in the same patient as in the previous image.
Skeletal sickle cell anemia. Osteonecrosis. Image shows flattening of the femoral heads with a mixture of sclerosis and lucency characteristic of osteonecrosis.
Skeletal sickle cell anemia. Osteonecrosis. Detail of the right hip.
Skeletal sickle cell anemia. Osteonecrosis. Detail of the left hip.
Skeletal sickle cell anemia. Bone infarct. Image shows patchy sclerosis of the humeral head and shaft representing multiple prior bone infarcts.
Skeletal sickle cell anemia. Chronic infarcts and secondary osteoarthritis. Image shows advanced changes of irregular sclerosis and lucency on both sides of the knee joint reflecting numerous prior infarcts. The joint surfaces are irregular and the cartilages are narrowed due to secondary osteoarthritis.
Skeletal sickle cell anemia. Osteonecrosis. Coronal T1-weighted MRI shows a slightly flattened femoral head with a serpentine margin of low signal intensity around an area of ischemic marrow with signal intensity similar to that of fat.
Skeletal sickle cell anemia. Osteonecrosis in the same patient as in the previous image. Coronal T2-weighted MRI shows a serpentine area of low signal intensity and additional focal areas of abnormal low signal intensity in the femoral head; these findings reflect collapse of bone and sclerosis.
Skeletal sickle cell anemia. Osteomyelitis. CT scan in a soft tissue window demonstrates a large abscess in the left thigh encircling the femur, with hypoattenuating pus surrounded by a rim of vivid enhancement.
Skeletal sickle cell anemia. Osteomyelitis and bone-within-bone. Bone-window CT scan in the same patient as in the previous image shows a bone-within-bone appearance (concentric rings of cortical bone) in the right femur. On the left, a sinus tract (cloaca) traverses the lateral aspect of the femoral cortex, and a small, shardlike sequestrum is present deep to the sinus tract.
Skeletal sickle cell anemia. Bone scan of bone infarct shows an area of increased uptake in the distal femoral metaphysis corresponding to the infarct demonstrated on the previous plain radiograph.

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Author

Joseph E Maakaron, MD Research Fellow, Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Coauthor(s)

Ali T Taher, MD, PhD, FRCP Professor of Medicine, Associate Chair of Research, Department of Internal Medicine, Division of Hematology/Oncology, Director of Research, NK Basile Cancer Center, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Specialty Editor Board

Jeanne Yu, PharmD

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Mark Ventocilla, OD, FAAO Chief Executive Officer, Elder Eye Care Group, PLC; Chief Executive Officer, Mark Ventocilla, OD, Inc; President, California Eye Wear, Oakwood Optical

Mark Ventocilla, OD, FAAO is a member of the following medical societies: American Academy of Optometry, American Optometric Association

Disclosure: Nothing to disclose.

Acknowledgements

Roy Alson, MD, PhD, FACEP, FAAEM Associate Professor, Department of Emergency Medicine, Wake Forest University School of Medicine; Medical Director, Forsyth County EMS; Deputy Medical Advisor, North Carolina Office of EMS; Associate Medical Director, North Carolina Baptist AirCare

Roy Alson, MD, PhD, FACEP, FAAEM is a member of the following medical societies: Air Medical Physician Association, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians, North Carolina Medical Society, Society for Academic Emergency Medicine, and World Association for Disaster and Emergency Medicine