Sickle Cell Disease

Sickle cell disease (SCD) is a common admission to hospital in the city of Toronto. We have a multicultural population in the city and subspecialty clinics at the University Health Network. These patient suffer from multisystem disease as a result of chronic vaso-occlussion, infections and anemia, often requiring hospitalization for analgesia. However, there is a spectrum of disease activity, and not all forms are equivalent. Different forms of sickle cell disease are based on the specific mutations in the beta globin gene, which can result in varying combinations of alleles Some include:

HbSS - typical form of SCD

HbSC - C genotype is as a different point mutation at the same amino acid residue

HbSthal - patients with one S genotype and beta-thallasemia trait on the other chromosome

These three are the most common forms, but others do exist including:

Hb Lepore disease

HbE

HbD

These different mutations result in varying disease penetrance. Some patients will have disease very similar to that of typical SCD. Its important to recognize differences in genotype as the frequency of certain sydrome may vary. For example, HbSC is a milder form of disease and hence may present with sequestration crisis later in life (adult years), as opposed to HbSS disease where this occurs solely as a child. Patients with HbSC disease tend to have milder symptoms, developing the same complications but later in life.

Presentations of sickle cell disease are many and can include vaso-occlusive crisis, chest crisis, aplastic crisis and sequestration crisis. Patient present with pain, usually located to bone/muscle in VOC, and chest pain/dyspnea in patients with chest crisis. Triggers for VOC are things that impact the oxygen dissociation curve, which results in deoxygenation of Hgb, polymerization and sickling of red blood cells. This include:

Hypothermia, acidosis, hyoxemia, dehydration, and infection to name the common ones.

Treatment is usually supportive, with investigations targeted towards identifying an infection. Fluids, analgesia, oxygen therapy and antibiotics as needed. Transfusions are reserved for only those who truly require it. Usually a cut-off of 50 is targeted, though discussion with the patients hematologist and blood bank should be had.

An acute chest crisis is a dreaded complication of SCD and a previous blog entry has discussed the entity. See this link for details: Acute Chest Crisis.

The long term management usually involves hydroxyurea, which results in increasing HgF levels which improve oxygen carrying capacity and decrease the percentage of HbSS. This medication is usually inititated when patients experience frequent crises ( 3 or more per year), chest crisis, or severe VOC. It was found to have a survival benefit in these patients (see NEJM link).

Hydroxyurea and SCD