Sickle Cell Disease

Today’s morning report centred around a patient thought to have Sickle Cell Disease admitted with a pain crisis.  She turned out to have sickle cell trait instead.  She was also found to be significantly polycythemic.

There were multiple learning points in the case presented:

·      Sickle cell disease is the result of a genetic abnormality in the beta-globin gene.  This leads to formation of Hemoglobin S which, when in the deoxygenated state, can lead to polymerization of the hemoglobin molecules and sickling of the RBCs.  The reason this is important is that it leads to vaso-occlusion and hemolysis, which have a number of the deleterious effects of SCD.  Patients with sickle cell trait have only one defective gene copy and typically do not get symptoms. We measure the percentage of hemoglobin S with a hemoglobin electrophoresis.

·      The majority of GIM admissions for SCD patients will be due to a vaso-occlusive pain crisis.  There are a number of other potential consequences to sickle cell disease:

o   Chronic hemolysis can lead to utilization and deficiency of nutrients such as iron and folate.  Furthermore, SCD patients are heavily dependent on a high state of reticulocytosis given their reduced RBC lifespain – acute splenic sequestration of RBCs or infection with parvovirus B19 can lead to an aplastic crisis in these patients.

o   SCD patients are at risk for lung disease including fibrotic diseases and pulmonary hypertension, partially from NO scavenging by cell-free hemoglobin.  Virtually all patients with SCD are functionally asplenic as well, and asplenia in and of itself can result in pulmonary hypertension.

o   From that standpoint, encapsulated organisms like S. pneumonia, H. influenzae, Neisseria spp, and Capnocytophagia as well as Babesia are significantly riskier for these patients.  SCD patients are also at increased risk of infection with gram negative organisms like Salmonella spp.

o   Other vaso-occlusive events can occur including myocardial infarctions, cerebrovascular infarctions, bone infarctions and avascular necrosis, as well as priapism in male patients.

·      Acute chest crisis, which is generally a medical emergency characterized by chest pain, hypoxemia, and infiltrates on the chest x-ray, involves treatment by red cell exchange or transfusion.

·      Treatment of a sickle pain crisis has a number of modalities:

o   Hydration/volume repletion – this should be considered if the patient is hypovolemic.  This will help dilute the RBC mass and increase flow in distal areas of sluggish flow where sickling is occurring the most.

o   Pain control – this usually requires opioid analgesics, but a significant portion of the pain is inflammatory so NSAIDS are also of benefit.

o   Prevention of atelectasis – these patients should all receive incentive spirometry and should be encouraged to ambulate as much as possible.

o   If febrile, obtain cultures and look for a source.  In children, empiric antibiotics are usually given.

o   Obtain a chest X-ray if there are symptoms compatible with acute chest syndrome.

·      We also spoke about Polycythemia given this person’s relatively high hemoglobin.  This can generally be grouped into primary or secondary polycythemia.  Primary occurs as a result of constitutive production of RBCs despite a lack of need.  Secondary polycythemia does not impose the same thrombotic risks as primary, and is due to other factors such as chronic hypoxemia, profound volume contraction, etc.  Useful tests can be JAK-2 mutation testing, and examining the level of erythropoietin.  Peculiar symptoms that patients with myeloproliferative disorders such as PRV and essential thrombocytosis get are erythromelalgia (painful reddening of the hands) and aquagenic pruritis (histamine release secondary to hot water).  All patients with PRV should be on ASA unless contraindicated, but hydroxyurea is added for patients with a high risk of thrombotic events, or in those who have had events.

Further Reading:

Bunn, H. F. (1997). Pathogenesis and treatment of sickle cell disease. New England Journal of Medicine, 337(11), 762-769.

Heeney, M. M., Hoppe, C. C., Abboud, M. R., Inusa, B., Kanter, J., Ogutu, B., ... & Zamoryakhin, D. (2015). A multinational trial of prasugrel for sickle cell vaso-occlusive events. New England Journal of Medicine.

Platt, O. S. (2008). Hydroxyurea for the treatment of sickle cell anemia. New England Journal of Medicine, 358(13), 1362-1369.

Image Credit: www.sicklecellga.org