Your analysis?

An inside joke entitles today's post from morning report where we actually discussed a patient who presented with a "sickle cell crisis".

Sickle cell disease results from a point mutation at position 6 of chromosome 11 leading to a glutamate to valine substitution. There are 3 main forms of SCD and these are:

HbSS- typical form of SCD

HbSC- one S genotype, and one C genotype that results from a different mutation. Less severe

HbSBeta-thal- one S and one beta thal trait.

Others include HbE, HbD, Hb Lepore.

Clinical manifestations are broad in SCD and include vaso-occlusive crises (VOC) that result from sickled RBCs obstructing capillaries resulting in ischemia and necrosis. VOC include bony pain crises, and include one of the most severe complications of SCD which is an Acute Chest Syndrome (ACS). Other complications include priapism, stroke (cause of "stroke int the young"), painful leg ulcers, AVN, as well as aplastic crises, hemolytic crises, sequestration crises,and pulmonary hypertension, to name a few.

Principles of management include fluid rehydration, appropriate analgesia, antibiotics if indicated, plasma exchange for certain circumstances such as ACS

What about hydroxyurea (HU)?

HU increases HBF concentrations, and was shown in a landmark NEJM study in 1995 by Charache et. al to reduce morbidity by decreasing the number of painful crises from a median of 4.5 to 2.5 per year. Rates of ACS, blood transfusions also decreased, and time to painful crises also increased in the HU group. An observational follow up of 233 out of 299 of these patients 9 years later by Steinberg et. al from JAMA showed a mortality reduction of 40%. Lastly, one clue that might point to adherence, is that due to its effects, HU should cause an elevated MCV, and so certainly a low MCV might suggest non-adherence. 

What about infection?

Infection is another important consideration in patients with sickle cell disease. Patient with HbSS by adulthood will be functionally asplenic because of autoinfarcting their spleen. Thus one clue that perhaps a patient dose not have HbSS disease is if they have a history of splenectomy in their PMH. Patients with HbSbetathal can have associated splenomegaly. 

As a result of either no spleen, or no functioning spleen, patients will be at risk of infection with encapsulated organisms - S.pneumo, H.influenzae, N. meningitidis - and other Gram negatives such as E.Coli, Salmonella species, and Pseudomonas. As a result, patients should be vaccinated. See this CMAJ article that discusses optimal management of patients pre-splenectomy, the vaccine aspect applies to SCD patients. 

Other principles of management

Folic acid - due to chronic hemolysis and high requirements.

Medic alert bracelet

Patient education

Click here for the original 1995 NEJM article and also here for a 2008 NEJM review on HU and SCD