Sickle Cell Disease Flashcards
What is the definition of sickle cell disease?
Group of genetic disorders that affect the structure of haemoglobin, resulting in the production of HbS.
What is the genetic mutation involved in sickle cell disease?
Point mutation in codon 6 of the beta globin gene that substitutes glutamine to valine producing beta S
What is the pathophysiology of sickle cell disease?
Genetic mutation alters the structure of Hb resulting in HbS
HbS polymerises if exposed to low oxygen levels for a prolonged period which distorts the red cell and damages its membrane
What is the difference between sickle cell trait and sickle cell anaemia?
Sickle cell trait:
One normal, one abnormal beta gene
Asymptomatic carrier state but may sickle in severe hypoxia (eg high altitude, under anaesthesia)
Blood film normal
Sickle cell anaemia:
Two abnormal beta genes
Episodes of tissue infarction due to vascular occlusion (sickle crisis)
Chronic haemolysis
Sequestration of sickled RBCs in liver and spleen
Hyposplenism
What are some clinical features of sickle cell anaemia?
Vaso-occlusive crises (acute pain in hands and feet)
Acute chest syndrome (caused by infection, fat embolism from necrotic bone marrow in vaso-occlusive crises, or pulmonary infarction due to sequestration of sickle cells
Pulmonary hypertension
Anaemia
What are some precipitants of sickle crises?
Hypoxia
Dehydration
Infection
Cold exposure
Stress/fatigue
What are some investigations for sickle cell disease?
Bloods: FBC, red cell indices, blood film
High performance liquid chromatography (HPLC) or electrophoresis: to quantify haemoglobins present
What is the management of a sickle crisis?
High flow oxygen
IV fluids and opiate analgesia
Red cell exchange transfusion in severe crisis (eg chest crisis, stroke)
Antibiotics if evidence of infection
What is the long term management of sickle cell anaemia?
Vaccinations (hyposplenism)
Folic acid supplementation
Hydroxycarbamide (increases HbF production)
Regular transfusions
New therapies (crizaniluzumab, voxelotor)
Bone marrow transplant and gene editing
