Sickle Cell Disorder Flashcards
Define Sickle Cell Disorder
A chronic condition characterised by sickling of red blood cells, caused by inheritance of haemoglobin S (Hb S)
What are the types of sickle cell disorder
Sickle cell anaemia = Hb SS (homozygous)
Sickle cell trait = Hb AS (heterozygous)
Sickle cell disease = Anything involving sickling: compound heterozygosity for Hb S and C and HbS and beta-thalassaemia
What is the aetiology of sickle cell disorder
Autosomal recessive inherited point mutation at codon 6 of the beta globin chain gene (glutamic acid → valine) of chromosome 11
The change from polar and soluble to non-polar and insoluble causes HbS to polymerise and form tactoids
RBC becomes distorted, dehydrated and adhered to the vascular endothelium
RBCs block vessels, damaging them and sequester in liver and spleen
Shortened lifespan (20 days) + low affinity HbA release O2 readily → EPO drive lower → anaemia
What causes the symptoms of crisis in sickle cell disease
Symptoms are due to a shortened lifespan of RBCs, leading to haemolysis + vessel occlusion
Painful Crises are Stimulated by:
- Infection
- Exertion
- Dehydration
- Hypoxia
- Psychological stress
- Acidosis
What are the risk factors of sickle cell disease
FHx or carriers
Coinheritance of Gilbert syndrome(UGT 1A1 TA7/TA7 genotype)
What is the epidemiology of sickle cell disease
Rarely presents before 4-6 months
Distribution matches that of endemic plasmodium falciparum malaria - Gene will provide protection against malaria
Up to 25% Africans (sub-Saharan) and 10% Caribbeans carry the sickle gene
Common in Africa, Caribbean, Middle East
Around 300,000 births affected worldwide annually
Most common monogenic disorders
What are the early manifestation symptoms of sickle cell disorder
May be diagnosed on Guthrie spot
Dactylitis (pain in bones) in the small bones of hands and feet
Splenic sequestration (pallor, tachycardia, shock)
Infection e.g. S. pneumoniae
What are the general symptoms of sickle cell disorder
Anaemia: fatigue, SOB, pallor, dizziness
Recurrent infection (due to autosplenectomy) e.g. with pneumococcus, influenza etc.
Chronic/recurrent leg ulcers
Gallstones: RUQ pain, especially after eating
Dactylitis in ribs, spine, pelvis and long bones in adults
Myalgia and arthralgia
Chronic cholecystitis
What are the symptoms in an acute sickle cell crisis
Pain crisis due to vaso-occlusion by erythrocytes → ischaemic tissue damage:
- Painful, swollen joints (bone infarction, acute pain crisis)
- Dactylitis
- Acute osteomyelitis
- Abdominal pain (gallstones, ascending cholangitis, acute cholecystitis, empyema, acute pancreatitis)
What are the signs of sickle cell disorder on examination
Obs: Fever
General
- Anaemia: pallor, SOB
- Maxillary hypertrophy with overbite (extramedullary haematopoeisis)
- Jaundice (gallstones)
- Dehydration (renal damage)
- Cotton wool spots on retina (vaso-occlusive)
Abdominal
- Splenomegaly in early disease (sequestration crisis) -> will shrink as the patient gets older
- Tender hepatomegaly (acute hepatitis)
- Abdominal distension (acute hepatitis)
- Priapism
Joints
- Dactylitis
- Osteomyelitis
- Short digits or joint/muscle tenderness and swelling (vaso-occlusive crisis)
What constitutes an emergency in sickle cell disorder
Septic shock (BP <90/60)
Neurological signs or symptoms
SpO2 <92% on air
Symptoms/signs of anaemia with Hb <5 or fall >3g/dl from baseline
Priapism >4 hours
What investigations should be done for sickle cell disorder
Bloods
- FBC + reticulocytes: leucocytosis, anaemia, high reticulocytes
- Blood film: sickled cells, boat cells, Howell jolly bodies (hyposplenism), target cells (hyposplenism)
- Solubility test: solution turgid, <10-15% HbS → if positive then electrophoresis
- Electrophoresis: Presence of HbS and/or HbA
- High performance liquid chromatography (HPLC): HbF predominates, HbA/HbS
Other
- X-ray hip: exclude avascular necrosis (Infarctions seen by irregular margins or moth-eaten destruction with overlying periosteal new bone formation)
- CXR (Acute chest syndrome)
What is the management for sickle cell disorder
Conservative
Education
Crisis trigger avoidance e.g. cold, windy, excessive activity, dehydration
Coping: distraction techniques
Maintain fluid intake, hygiene and nutrition
Genetic counselling for family
Psychological support
Medical
Vaccination
Hydroxyurea (increased HbF levels and reduces frequency and duration of crises)
Folic acid
Prophylactic antibiotics (for <3yo or >5 with severe infections)
Analgesia
Surgical
bone marrow transplant
Joint replacement in avascular necrosis
Which vaccinations should be given to patients with sickle cell disorder
Pneumococcal polysaccharide vaccine at 2 years
Influenza annually from 6 months
Meningitis ACWY
What are the indications for haematopoietic stem cell transplantation in SCD
CNS disease
Recurrent severe vaso-occlusive crisis
Recurrent acute chest syndrome when hydroxyurea fails