Sickle Cell Disease
Introduction
Sickle cell disease is a group of inherited red blood cell disorders affecting haemoglobin synthesis. The disease is caused by a glu – val mutation of the Beta-globin gene resulting in the formation of HbS. HbS undergoes sickling when deoxygenated resulting in hemolysis, anemia and thrombosis. Clinical features manifest from ages 3-6 months as the concentration of fetal hemoglobin decreases.
Sickle Cell Crisis is an umbrella term used to refer to a number of acute conditions including vaso-occlusive crisis, that occur in those patients with underlying Sickle Cell Disease. The triggers of sickle cell crisis are not entirely understood but they are more likely to occur when there is a decrease in circulating blood volume e.g. dehydration, sepsis - when there is local vasoconstriction e.g. smoking, exposure to cold temperature - or when there is localised hypoxia e.g. after strenuous exercise.
Risk Factors:
Genetic: Sickle cell anaemia occurs in children that inherit an abnormal gene from both parents.
Ethnicity: This condition is most commonly seen in patients of Afro-Caribbean, Middle Eastern or Indian origin.
Complications of Sickle Cell Disease
Splenomegaly – may indicate sequestration crisis
Infarction: Stroke, splenic infarct, leg ulcers
Crises: Pulmonary/ Acute Chest Syndrome, mesenteric, bone/joints
Kidney Disease
Liver/Lung Disease
Erection/priapism – can be stuttering (2-4h duration and recurrent) or severe (>4h, may lead to permanent impotence)
Dactylitis (painful swelling of the joints of the hands and feet)
Clinical Features
Conditions which constitute a sickle cell crisis include;
Vaso-occlusive Crisis
Most common complication of sickle cell disease.
Arises when abnormally shaped (sickled) red blood cells clump together in blood vessels causing local ischaemia and pain.
most commonly affect the spine, joints, chest and abdomen.
can affect more than one site at time
pain is often in the same distribution in recurrent crises
Pain ranges from moderate to severe. These episodes frequently resolve within 5 to 7 days however severe cases may persist for a number of months.
Pain can also be accompanied by fever without the presence of an underlying infection. This reflects tissue necrosis.
Splenic Sequestration Crisis
Occurs mostly in children
Present with acute and painful enlargement of the spleen due to intrasplenic sequestration of sickled red cells.
May cause a sudden drop in haemoglobin levels (>2g/dL) that may result in hypovolaemia and shock
Acute Chest Syndrome
The most serious complication. Accounts for 25% of deaths.
Occurs secondary to vaso-occlusive crisis in the lungs.
Sickled red cells cause occlusions in the pulmonary vasculature resulting in localized hypoxia and further sickling
Patients can present with chest pain, cough, wheeze, tachypnea and hypoxia
Management must be prompt as patients can quickly develop respiratory failure
Aplastic Crisis
Usually triggered by parvovirus B19 directly suppressing the bone marrow
Results in a worsening of the patients’ baseline anaemia which may require transfusion
Bone marrow suppression is self-limiting and usually lasts for approximately ten days
Differential Diagnosis
Patients with a history of sickle cell disease will recognize their pain as typical in character and location. However differential diagnoses should include conditions specific to the site of the pain particularly if the pain differs from previous crises.
Any patient with signs of sepsis e.g. fever should be treated as such until the diagnosis is definitively outruled.
Clinical Investigations
Investigations should be aimed at identifying the underlying precipitant. If the patient is presenting with an exacerbation of pain that is very typical to them and is otherwise well they may not require any haematological investigations. It is important to remember that IV access and phlebotomy may be very challenging in this patient cohort, especially as they get older, due to lifelong frequent venepuncture.
Bedside
ECG - if complaining of chest pain
Urinary BHCG all - women of child bearing age
VBG - if concerned about sepsis or shock. Assess lactate and acid base balance
ABG - if concerned about respiratory failure
Laboratory
FBC- compare baseline and current Hb
Blood film – assess for target cells and schistocytes
U + E, LFT, CRP, LDH- assess for infection and evidence of end organ failure
Consider Group and hold/cross match
Appropriate microbiology samples as clinically indicated eg blood cultures, sputum
Radiology
CXR - If patient has chest pain or if concerned about resp failure.
CT Abdo - If concerend about intra- abdominal pathology or severe splenic sequestration
Management + Disposition
Initial Resuscitation
Correct hypoxia with high flow O2
If evidence of respiratory failure -> ventilatory support as required in resuscitation area
Splenic sequestration resulting in hypovolaemia and shock needs to be managed urgently
fluid of choice should be blood but NB patient may have multiple antibiodies from previous transfusions so advise should urgently be sought from haematology .
Evidence of dehydration
fluid resuscitation with bolus of IV crystalloid and reassess. Ongoing dehydration will make the sickle crisis worse so needs to be managed as a matter of urgency
Symptomatic Treatment
Figure 1: Saint James Hospital Emergency Department Protocol for management of Acute Sickle Cell Crisis
Specific Treatment
Fever empiric antibiotics as per local guidelines
Vaso-occlusive crisis
Aggressive pain management
IV fluid rehydration
Acute chest syndrome
Supportive oxygen
Adequate analgesia to avoid hypoventilation
Consider empirical antibiotics for pneumonia
Blood Transfusion
Transfusion is not typically indicated in acute sickle cell pain crisis and should not be carried out without input from haematology
Disposition
Urgent input from hematology should be sought urgently if the patient has:
Chest, abdominal or neurological symptoms
Priapism
Pain which is atypical or does not respond to usual analgesia
Most presentations require admission .
Acute Chest Syndrome in particular should be discussed early on with ICU as clinical deterioration is often rapid
References
Sprigings D, Chambers JB. 2018. Acute Medicine; A Practical Guide to the Management of Medical Emergencies. Fifth Edition. Wiley Blackwell
Yale SH, Nagib N, Guthrie T. 2000. Approach to Vaso-occlusive Crisis in Adults with Sickle Cell Disease. 61(5):1349-1356
Borhade MB, Kondamudi NP. Sickle Cell Crisis
Sickle Cell Disease: Managing Acute Painful Episodes in Hospital. 2012. National Institute of Healthcare and Clinical Excellence. Clinical Guideline CG143.
Tuohy E. St James Hospital HOPe Guidelines for Acute Chest Syndrome. 2020. Guideline SCDC-0002
This blog was written by Dr Sarah Daubras and was last updated in April 2021