SICKLE CELL DISEASE

It is an autosomal recessive red blood cell disorder. The manifestations of the disease are primarily related to chronic RBC hemolysis and vaso-occlusive events. Hb is a tetramer composed of 2 alpha globulins and 2 beta type globulins

Alpha chain

2 copies on Ch 16
Expressed from birth throughout life

Beta chain

1 copy on Ch 11
Beta type globulin changes at approximately 6 months

HbS = substitution of valine for glutamic acid as the sixth amino acid of the beta globin chain. Hemoglobin tetramer (alpha2/beta S2) that is poorly soluble when deoxygenated. Deoxygenation or hypoxic states results in the HbS aligning with other HbS molecules. Results in RBC distortion into crescent or sickle shape. Marked decrease in red cell deformability. Results in small vessel vaso-occlusions and chronic hemolytic anemia. SC Disease = homozygosity hemoglobin S (HbS), SC Trait = heterozygous for HbS + HbA (Clinically silent) SC Combined heterozygosity = HbS + different ß-globin mutation (eg. ß thalasemia)

Populations At Risk: Central African descent, Latin America, India, Middle East, Mediterranean
US: 8-10% of African Americans HbS carriers
0.15% of African Americans born with SCD.

Survival:
Overall survival reduced, but recent improvement with institution of comprehensive care
Today, 50% of patients survive beyond 50yo

Causes of Death:
1-3yo: Infection is the leading cause of death
10-20yo: Strokes, Acute chest syndrome, Aplastic crisis, Splenic Sequestration crisis

Acute painful episodes, Multiorgan failure, Psychosocial issues, Altered Growth and development, Infections, Bacteremia, Meningitis, Bacterial pneumonia, Osteomyelitis, Cerebrovascular events, Bone complications, Infarction and necrosis, Marrow infarction, Sequestration Crisis, Cardiac complications, Myocardial infarction, Cholelithiasis, Aplastic Crisis, Chronic liver disease, Priapism, Renal complications, Pulmonary complications, Retinopathy

A painful vaso-occlusive crisis is the most frequent clinical symptom of sickle cell disease.

In infants, painful symmetrical swelling of the hands and feet (dactylitis or hand-foot syndrome) caused by infarctions of the small bones may be the initial manifestation of sickle cell anemia.
Most bony vaso-occlusive events occur primarily in the bone marrow cavity. Most are multifocal and associated with mild tenderness and localized edema.
As the child matures, the painful episodes usually affect the joints, especially the hips and knees and those of the chest wall and back. Document the frequency, the precipitants, and the similarity of painful episodes on each visit to exclude more serious causes, such as infection.

Abdominal pain often occurs as excruciating pain with diffuse tenderness, distension, and muscular rigidity of the abdominal wall.

The pain often is caused by small infarcts of the mesentery and viscera, usually without peritoneal signs.
A thorough history, obtained from the patient or the parents, is crucial because their recognition of the nature of the pain helps in distinguishing vaso-occlusive pain from that of other etiologies, such as cholecystitis, perforated viscus, or appendicitis

Sequestration crisis is a distinct form of acute hypersplenism unique to infants and young children.

Vascular occlusion occurs in the splenic sinusoids, resulting in large volumes of blood trapped in the substance of the spleen.
If these events occur gradually, the patient may present with progressive pallor, fatigue, left-sided abdominal pain, and increasing splenomegaly.
This event may occur before or after autoinfarction of the spleen transpires. If splenic sequestration occurs more abruptly, patients may present in extremis, manifesting severe hypovolemic shock.

Promptly evaluate older patients who complain of chest pain, cough, dyspnea, or tachypnea to exclude acute chest syndrome.

The acute febrile pneumonic process is associated with new infiltrates on chest radiographs. Chest pain may precede the radiographic findings, or they may occur with the onset of pain. Although initial chest radiographs may be normal, subsequent radiographs reveal an infiltrate, which may rapidly extend to involve 1 or more lobes and the pleura.
The etiology may be infectious (eg, pneumonia), vaso-occlusive, or both. This syndrome often results in hypoxia and, occasionally, death.

If vascular occlusion occurs in large or small cerebral vessels, a neurologic event may occur.
Patients may have gait disturbances, hemipareses, paresthesias, aphasias, altered consciousness, or seizures.
MRI findings or high flow on transcranial Doppler sonography of silent lesions are associated with a high risk of stroke
Infants and children are susceptible to aplastic anemia crisis.

During episodes of crisis, the degree of anemia worsens, and jaundice decreases due to a profound reticulocytopenia, resulting in no erythrocyte precursors in the bone marrow.
The patient appears acutely ill, tachycardic, and pale, yet nonicteric.
Occasionally, patients recover in several days.
The symptoms are usually due to an infection by the parvovirus B19 prototype.

Infection is a major cause of morbidity and mortality in patients with SCD.
Affected children are vulnerable to life-threatening infection as early as four months of age because of splenic dysfunction and the inability of the spleen to filter microorganisms from the blood stream.
Splenic dysfunction is followed eventually by splenic infarction, usually by two to four years of age.
In the absence of normal splenic function the patient is susceptible to overwhelming infection by encapsulated organisms, especially Streptococcus pneumoniae and Haemophilus influenzae.
Particularly susceptible to Salmonella infections
Dysfunctional IgG and IgM antibody responses, defects in alternative pathway fixation of complement, and opsonophagocytic dysfunction may also play a role in the predisposition to invasive infection

Lab Investigations and Results:

CBC:↓ RBC, ↑ MCV, ↑ retics, ↑ WBC, N- ↑ plts
↑ Bilirubin
↑ lactate dehydrogenase
↓ serum haptoglobin
Hb electrophoresis