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Sickle Cell Anemia

Published on 19/07/2015 by admin

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 Splenic autoinfarction: Absent or small calcified spleen

image Massive splenic infarction: Rare complication defined as when > 50% of spleen is infarcted
image Splenic sequestration: Massive splenomegaly
image Splenic abscess: Usually due to prior infarcts
• Gallbladder: Gallstones in young patients
• Extramedullary hematopoiesis: Most commonly paravertebral soft tissue masses of homogeneous density
• Kidneys

image Papillary necrosis on CT urography
image Large kidneys in early phase of disease; gradual atrophy with development of chronic renal failure
• Bones

image Widened medullary spaces, thinning of cortex, coarsening of trabecular pattern, and osteopenia
image Osteonecrosis and multiple bone infarcts

– High T2WI MR signal in affected areas with serpiginous low T2 signal outline (double-line sign)
image H-shaped or “Lincoln log” vertebrae 

– Cortical thinning leads to endplate deformities
image Osteomyelitis
image Persistence of red (cellular) marrow in bones with low-signal marrow on T1WI

– Demand for increased production of RBCs prevents normal conversion of red to yellow marrow
• Findings of iron deposition due to repetitive transfusions

image Hyperdense liver on NECT
image Liver, spleen, and bone marrow abnormally low signal on all MR pulse sequences (particularly on T2WI)
image Involved organs demonstrate characteristic signal loss on in-phase GRE images
image
(Left) Axial NECT in a patient who presented with sickle cell anemia and severe left upper quadrant pain demonstrates a heavily calcified and heterogeneous spleen image, indicating chronic and possibly acute infarction.

image
(Right) Splenectomy specimen from the same patient illustrates a mottled spleen with capsular discoloration image that was heavily calcified on microscopy.
image
(Left) Axial NECT in a patient with homozygous sickle cell anemia demonstrates a small and heavily calcified spleen image, also known as autosplenectomy.

image
(Right) Axial CECT in a patient with sickle cell anemia demonstrates multiple wedge-shaped hypodense areas image in the spleen, representing massive splenic infarction, an uncommon complication that rarely results in the formation of a splenic abscess.

TERMINOLOGY

Abbreviations

• Sickle cell anemia (SCA)

Definitions

• Inherited hemolytic anemia arising due to abnormal hemoglobin (hemoglobin S), resulting in deformation of red blood cells and leading to microvascular occlusions and infarcts

IMAGING

General Features

• Best diagnostic clue

image Small, densely calcified spleen on CT
image Papillary necrosis on intravenous pyelogram (IVP) or CT urography
image Cholelithiasis in a young African American patient
• Size

image Spleen may be undetectable (autosplenectomy) but rarely may enlarge due to sequestration syndrome

CT Findings

• Spleen

image Splenic autoinfarction: Absent or small calcified spleen
image Massive splenic infarction

– Splenic infarcts usually small and repetitive, leading to autoinfarction
– Massive splenic infarction defined as when > 50% of spleen is infarcted
– Often no precipitating factor, but may be associated with hypoxia (high altitude or mountain climbing)
image Splenic abscess: Rare (< 1%) complication usually seen in patients with persistent splenomegaly (rather than autoinfarction) and massive infarcts
image Splenic sequestration: Often associated with massive splenomegaly

– Represents severe, life-threatening anemia with massive splenomegaly and reticulocytosis
• Gallbladder: Gallstones in young patients
• Brain: White matter infarcts
• Extramedullary hematopoiesis: May have many different manifestations, including paravertebral soft tissue masses (homogeneous soft tissue density), hepatosplenomegaly, or perinephric soft tissue “rind” encasing kidneys
• Liver: Hyperdense liver due to repeated transfusions
• Kidneys

image Papillary necrosis on CT urography (blunted, irregular calyces, “golf ball-on-tee” appearance, etc.)
image Large kidneys in early phase of disease; gradual atrophy with development of chronic renal failure
image Renal medullary carcinoma

– More common in patients with sickle cell trait than with sickle cell disease
– Very rare, highly aggressive malignancy with high mortality and early metastatic disease
– Poorly marginated, heterogeneous renal mass with infiltrative appearance (similar to transitional cell carcinoma or lymphoma)
• Bones

image Avascular necrosis and multiple bone infarcts
image H-shaped vertebrae with endplate deformities
image Osteomyelitis

MR Findings

• Persistence of red (cellular) marrow in bones with low-signal marrow on T1WI

image Demand for increased production of RBCs (due to RBC destruction and anemia) prevents normal conversion of red to yellow marrow
image Stimulation of RBC production leads to widened medullary spaces, thinning of cortex, coarsening of trabecular pattern, and osteopenia
image T1 images of skull demonstrate low-signal widening of diploic spaces due to bone marrow expansion
image Cortical thinning leads to endplate deformities of vertebral bodies
• Multiple medullary bone infarcts and avascular necrosis (especially humeral and femoral heads)

image High T2 signal in affected areas with serpiginous low T2 signal outline (double-line sign)
• Findings of iron deposition (hemosiderosis) due to repetitive blood transfusions

image Liver, spleen, and bone marrow abnormally low signal on all pulse sequences (particularly on T2WI)
image Involved organs demonstrate characteristic signal loss on in-phase GRE images (opposite of steatosis)
image Iron deposition can be quantified using MR (usually GRE sequences with multiple TEs)
• Osteomyelitis
• White matter infarcts in brain

Ultrasonographic Findings

• Heterogeneous, coarsened liver parenchyma ± hepatomegaly
• Gallstones
• Increased renal echogenicity

Radiographic Findings

• Radiography

image Chest x-ray

– Enlarged heart due to anemia
– Pulmonary opacities due to infarcts and hemorrhage, bacterial pneumonia, or acute chest syndrome
– H-shaped or “Lincoln log” vertebrae in spine
– Extramedullary hematopoiesis with paraspinal soft tissue thickening and enlargement
image Abdominal radiograph

– Small, calcified spleen
– Splenomegaly due to sequestration syndrome
image Skull radiograph

– Marrow expansion with thickened, striated appearance of skull
image Extremity radiographs

– Patchy sclerosis and lucencies due to infarcts
– Osteonecrosis (most often femoral/humeral heads)
– Bone destruction due to osteomyelitis (Salmonella)
image Hand radiographs

– Hand-foot syndrome with thick periostitis and subperiosteal new bone
• IVP

image Papillary necrosis

Imaging Recommendations

• Best imaging tool

image NECT to visualize calcified spleen
image US to visualize gallstones
image Radiographs or CT for pulmonary and spinal findings

DIFFERENTIAL DIAGNOSIS

Asplenia

• Congenital absence of spleen which is often associated with other congenital anomalies

image Endocardial cushion defects, pulmonary atresia or stenosis, transposition of great vessels

Splenectomy

• History of surgical removal of spleen

Papillary Necrosis From Other Causes

• Analgesic use (especially phenacetin), diabetes, renal vein thrombosis, renal tuberculosis, congestive heart failure, cirrhosis, hemophilia, etc.

Bone Infarcts From Other Causes

• Trauma, steroid use, lupus erythematosus, Gaucher disease, hemophilia, thalassemia, etc.

PATHOLOGY

General Features

• Etiology

image Genetically inherited disorder of hemoglobin molecule

– Homozygous sickle cell (HGSC) due to point mutation in gene coding for β-globin synthesis
– Deformation of hemoglobin molecule distorts RBCs, creating elongated shape (sickle cells)

image Hemoglobin chains polymerize when deoxygenated, resulting in distorted RBC morphology (sickling)
image Sickling leads to microvascular obstruction/occlusion in multiple organs
• Genetics

image Autosomal recessive disorder

– 1st disease found to have molecular/genetic etiology
– Most common genetic disorder in African Americans
image Sickle cell disease requires 2 sickle cell hemoglobin genes and accounts for 60-70% of cases
image Sickle trait results when patient has only 1 abnormal sickle cell gene (30-40% of cases)

– Patients with sickle cell trait typically asymptomatic with normal life expectancy, no anemia, no pain crises, and no susceptibility to infections
– Associated with ↑ risk for renal medullary carcinoma
image Some patients may have 1 copy of sickle cell hemoglobin gene and 1 copy of another abnormal hemoglobin molecule (such as β-thalassemia)

– Patients usually symptomatic, but less so compared to standard sickle cell disease
image In Africa, SCA and sickle trait have been shown to reduce susceptibility to malaria (Plasmodium falciparum)
image SCA often detected by genetic screening programs in newborns
• Associated abnormalities

image Bone infarct
image Papillary necrosis
image Splenic infarcts
image Osteomyelitis
image Cholelithiasis
image Extramedullary hematopoiesis

Staging, Grading, & Classification

• Early stage

image Acute pulmonary syndrome
• Late stage

image Renal and pulmonary failure

Gross Pathologic & Surgical Features

• Small, infarcted spleen
• Cholelithiasis may lead to acute cholecystitis
• Bone infarcts and osteomyelitis

Microscopic Features

• Liver

image Sinusoid dilatation
image Perisinusoidal fibrosis
• Kidney

image Papillary necrosis
image Hemorrhage within medulla with medullary necrosis and fibrosis
• Lung

image Acute chest syndrome with bacterial pneumonia in up to 40%
image May have fat emboli due to bony infarcts
image Pulmonary vein thrombosis
image Pleural effusions common
• Brain

image White matter infarct (often silent)
image Intraparenchymal hemorrhage
• Bone

image Acute and chronic infarcts
image Osteomyelitis
image Medullary expansion

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image Acute, painful vasoocclusive crisis (may occur several times each year)

– May be precipitated by cold weather, low oxygen levels (such as when flying), dehydration, or stress
– Can affect any part of body (bones, abdomen, etc.)
– Patients often also have chronic low-level pain
image Acute chest syndrome: Chest pain, fever, cough
image Hand-foot syndrome: Dactylitis with severe pain and swelling of hands/feet (usually children < 3 years old)
image Fatigue and poor stamina due to chronic anemia
image Lab findings: Mild to moderate anemia (hematocrit of 20-30%), reticulocytosis, elevated lactate dehydrogenase (LDH), sickled RBCs on peripheral blood smear
• Other signs/symptoms

image Strokes may be clinically silent or symptomatic
image Biliary colic and cholecystitis due to gallstones
image Pulmonary hypertension
image High-output cardiac failure due to anemia
image Osteomyelitis, stroke, biliary colic
image Renal insufficiency, pain from splenic infarct
image Vascular collapse due to sequestration syndrome

Demographics

• Age

image Usually diagnosed in newborns, but symptoms first manifest after 6 months
image Now diagnosed at birth due to mandatory screening in USA
• Epidemiology

image Endemic in African Americans

– 1:5,000 infants overall and 1:500 African American newborns in USA

Natural History & Prognosis

• Painful vasoocclusive crises present in 1/2 of SCA patients prior to 5 years of age
• Acute chest syndrome accounts for 25% of deaths

image Other causes include stroke, sepsis, and acute sequestration syndrome
image Acute sequestration syndrome

– Significant percentage of blood volume sequestered in organ (most often spleen)
– May be life threatening, resulting in vascular collapse
– Etiology unknown
• Prognosis dramatically improved with more sophisticated therapies, with median survival in USA now 40-50 years

image In adulthood, end organ failure (especially lungs and kidney) has major impact on survival

Treatment

• Pain control in acute pain crises
• Hydroxyurea can ↑ hemoglobin levels and can help patients with symptomatic anemia and pain symptoms
• Transfusions utilized in select situations, including acute severe anemia, acute chest syndrome, and acute strokes

image Iron chelation agents may be needed to treat resultant iron overload as result of multiple transfusions
• Pain control, oxygen, antibiotics, and transfusions for acute chest syndrome
• Bone marrow or stem cell transplant can be curative

DIAGNOSTIC CHECKLIST

Consider

• Consider sickle cell anemia in young African American patients when confronted with absent or small/calcified spleen, gallstones, or characteristic bone findings
• Prior splenectomy if spleen not identified

Image Interpretation Pearls

•  

image
(Left) Coronal coned-down MIP view from a CT IVP demonstrates blunting image of the right lower pole calyx with contrast extravasation image (“golf ball-on-tee” appearance) within the papilla of the right lower pole calyx, consistent with papillary necrosis.
image
(Right) Axial CECT in a young child with sickle cell trait demonstrates an aggressive, infiltrative hypodense mass image in the right kidney with adjacent lymphadenopathy image. This was found to represent a renal medullary carcinoma.
image
(Left) Coronal NECT demonstrates the characteristic H-shaped lumbar vertebra image associated with sickle cell disease. Note the presence of sclerosis in the femoral head image, compatible with avascular necrosis. This patient required a total left hip replacement 3 months later.

image
(Right) Axial T2 MR demonstrates markedly low signal of both the liver and spleen in a patient with iron deposition due to repetitive transfusions.
image
(Left) Coronal T2 FS MR demonstrates serpiginous high T2 signal image in the distal femur and proximal tibia. Affected areas show a characteristic double-line sign with adjacent hyperintense and hypointense rims around their margins, characteristic of a bone infarct.

image
(Right) Coronal CECT demonstrates multiple, bilateral paraspinal soft tissue masses image, a characteristic appearance of extramedullary hematopoiesis.
image
Coronal T1WI MR image of the right knee in a 28-year-old African American with known sickle cell disease presenting with a 3-month history of a painful, swollen right knee. Note the oval-shaped, low-signal abnormality image within the medial femoral condyle, consistent with a bone infarct.

image
Coronal T2WI MR of the right knee in the same patient demonstrates high signal within the more chronic medial condylar infarct image and an area of high signal without bony sclerosis in the lateral femoral condyle image, indicating a more acute infarct. Note the associated high-signal joint effusion image.
image
Coronal single-shot fast spin-echo MR in a patient with known sickle cell disease shows hepatomegaly, gallstones image, and the lack of recognizable splenic tissue image.
image
Coronal T1WI MR demonstrates serpiginous abnormal low T1 signal in the tibia and femur. This is a characteristic appearance of a bone infarct.
image
Axial T2* GRE MR reveals low intensity in the liver, indicative of hemosiderosis from hemolysis and transfusions. A peculiar finding in this patient with sickle cell disease is the very low intensity in the renal cortex image, which is attributed to the deposition of hemosiderin within the proximal convoluted tubules.
image
Axial NECT in a patient with known sickle cell disease, presenting with fever, hemoptysis, profound hypoxia, and an acute pulmonary syndrome shows bilateral areas of confluent ground-glass opacity image thought to be due to acute pulmonary hemorrhage from pulmonary infarcts related to sickle cell disease.

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