Sickle Cell Disease

Epidemiology

-1:13 African American Babies born with sickle cell trait

-Estimated life expectancy 20 years less than average

-Prevalent where malaria is common

Background

-Inherited autosomal recessive disorder with abnormal hemoglobin (Hgb S)

-Hgb S is unstable and polymerizes in multiple stressors causing the erythrocyte to stiffen and elongate to cause a sickle shape

Pathology

-Mutation occurs in the amino acid sequence of the Hgb beta chain (sub valine for glutamate)

-RBC sickles in low oxygen state

-Impaired flexibility of the RBC causing hemolysis and release of ATP

-ATP conversion and binding results in 2,3 biphosphoglycerate and induction of more sickling and pulmonary inflammation

-Free Hgb binds to nitrous oxide resulting in endothelial dysfunction vascular injury, and pulmonary htn

Fetal Hemoglobin

-Primary oxygen-carrying protein in fetus

-Two alpha and two gamma subunits (increased oxygen affinity to take from mother)

-Hgb F 60-80% at birth and will slowly disappear over the first year

-In SCD Hgb F persists

Signs and Symptoms of SCD in children

-Onset within the first year

-Anemia

-Fatigue

-Episodes of pain

-Frequent infections

-Delayed growth (small stature, delayed puberty, smaller hand and feet, hypermetabolic syndrome, poor nutrition)

-Vision problems

-Gall stones

-Splenomegaly

-Poor healing skin ulcer over the lower tibia

Physical Exam Findings

-Chronically ill appearing

-Jaundice

-Hepatomegaly

-Cardiomegaly

-Nonhealing wounds on lower legs

-Retinopathy

What is neonatal screening?

A test performed on newborns to identify certain genetic, metabolic, and infectious conditions.

What does a CBC show in sickle cell disease?

Very low hemoglobin (hgb), low hematocrit (hct), reactive thrombocytosis, and mild leukocytosis.

What will a smear show in sickle cell disease?

Sickle cells, reticulocytes, nucleated RBCs, Howell-Jolly bodies, and target cells.

What is the bilirubin level in sickle cell disease?

Increased bilirubin.

What is a sickle cell crisis?

Acute painful episodes due to acute vaso-occlusion from sickled RBCs, either spontaneously or provoked.

How long can a sickle cell crisis last?

It can last hours to days.

What are common sites of pain during a sickle cell crisis?

Common sites are the spine and appendicular bones.

What serious complications can arise from a sickle cell crisis?

It may cause stroke, priapism, acute chest syndrome, ischemic necrosis of bones, and renal infarction.

How do repeat episodes of sickle cell crisis affect the body?

Repeat episodes can affect the lungs, heart, and liver, with pulmonary hypertension indicating poor prognosis.

At what age does the frequency of sickle cell crises peak?

The frequency peaks at 19-39 years old.

What is the variability of sickle cell crises?

They have variable severity and frequency.

What is splenic sequestration in the context of sickle cell disease?

It refers to the clogging and enlarging of the spleen due to sickled cells.

What is Acute Chest Syndrome?

A new pulmonary infiltrate with dyspnea and hypoxia.

What is the rank of Acute Chest Syndrome in terms of complications in Sickle Cell Disease (SCD)?

It is the 2nd most common complication in SCD.

What percentage of deaths in Sickle Cell Disease (SCD) are attributed to Acute Chest Syndrome?

25% of deaths in SCD.

What is the treatment for Acute Chest Syndrome?

Antibiotic therapy, oxygen supplementation, and if severe hypoxia, consider transfusion.

Treatments in SCD Crisis

-Mild cases treated supportively with NSAIDS

-Severe cases require admission for pain control

-Fluids

-Oxygen

-Transfusion therapy in aplastic crisis, hemolysis crisis, CVA and pain crisis

SCD Management

-Refer to hematologist or sickle cell center

-Maintain vaccination schedule (pneumococcal)

-Ages 2-16 will get yearly transcranial US to rule out stroke

SCD Treatment

-Folic Acid 1 mg daily

-Hydroxyurea

-L-Glutamine

-Omega 3 fatty acid

-ACE inhbitor in underlying microalbuminuria

-Adakveo (monoclonial antibody)

-Chelating Agents (prevent iron overload)

-Bone Marrow Transplant

Hydroxyurea (Hydrea)

-Used in SCD, CML, polycythemia, thrombocytopenia

-Dose: 500 mg capsule but weight based

-Precautions: avoid live vaccines, radiation recall, hepatotoxicity, pancreatitis, peripheral neuropathy, discontinue 3 months prior to coneption, may cause fetal harm

-Side Effects: Myelosuppression, macrocytosis, secondary leukemia, skin cancer, rash, nausea and vomiting

Sickle Cell Trait

-Heterozygous hemoglobin AS

-No anemia and normal RBC

-Electrophoresis shows 40% hgb S

-Risk of rhabdo

-Risk of thrombosis

-Microscopic and gross hematuria

-Genetic counseling recommended