Haematology 5 (Sickle Cell Disease) Flashcards
why/how does sickle cell disease occur?
- missense mutation at codon 6 (of gene for beta globe chain)
- Glu replaced by Val
describe the stages in the process of sickling of RBCs
- Distortion
- initially = reversible polymerization w oxyHbS formation - Dehydration
- increased adherence to vascular endothelium.
the reduction in life span of rbc leads to :
increased hemolysis
what are the 3 different consequences of hemolysis?
- anaemia
- gallstones
- aplastic crisis
Why does anaemia occur in hemolysis?
- due to reduced erythropoietic drive
- HbS has low affinity for O2
- so hypoxia = doesn’t stimulate erythropoietin release as much (from kidney)
what are the 2 methods of pathogenesis of sickle cell disorders ?
- increased hemolysis
2. blockage of microvascular circulation (vaso-occlusion)
Why does gallstone occur in hemolysis?
- increased hemolysis = increase Bilirubin release
- increased risk of gallstone formation
Why does aplastic crisis occur in hemolysis?
- parvovirus B19 = respiratory virus
- can cause aplastic crisis in people with sickle cell disease
- infects developing RBCs in bone marrow
- blocks production of RBC
- with sickled cell: can lead to steep drop in hb –> anaemia
What are 3 possible consequences of blockage of microvascular circulation?
- distorted RBCs get clumped together –> block vessels –> infarction
- tissue damage,
- pain,
- dysfunction
Which three main organs/parts does tissue infarction affect?
- Spleen
- Bones / Joints
- Skin
How does tissue infarction affect the spleen?
- spleen = one of 1st affected organ
- spleen = subject to repetitive vaso-occlusve damage from (early-life) infarction
- -> loss of splenic function = predisposed to infection of capsulated bacteria
How does tissue infarction affect bones + joints?
- Bone + joint = most common clinical presentation site of tissue infarction
- presents with DACTYLITIS
- over time –> can lead to avascular necrosis
- -> these patients = susceptible to osteomyelitis
What is DACTYLITIS?
- inflammation of finger or toe –> due to bone infection
What is avascular necrosis?
- lack of blood supply –> death of bone tissue
What is osteomyelitis?
- inflammation of the bone due to infection
How does Pulmonary hypertension correlate with the severity of hemolysis?
- free plasma Hb –> from intravascular hemolysis
- scavenges NO
- causes vasoconstriction
(associated with increased mortality)
Clinical course _____ and _____ even within same family.
Clinical course VARIABLE and UNPREDICTABLE even within same family.
Describe and give examples of early presentation of sickle cell disorders.
- clinical problem = usually AFTER 3-6 months
- onset occurs as HbF –> switches with adult Hb synthesis
- early manifestation = dactylics, splenic sequestration, infection (S.pneumoniae)
List Sickle emergencies:
- septic shock
- neurological signs/symptoms
- SpO2 <92% on air
- anaemia (symptoms) w Hb < 5
- Priapism > 4hours
Define Acute Chest Syndrome
New pulmonary infiltrate on chest X-ray with:
- Fever
- Cough
- Chest Pain
- Tachypnoea
List laboratory features of sickle cell disease:
List laboratory features of sickle cell disease:
- Hb Low (6-8g/dl)
- Reticulocytes High (except in aplastic crisis)
- Blood Film (sickled, boat, target cells, howell jolly bodies)
Diagnosis: How does solubility test work?
- reducing agent added
- oxyHb —> deoxy Hb
- Solubility decreases
- Solution –> turbid (cloudy)
- doesn’t differentiate AS from SS
(AS: sickle cell trait // SS: Sickle cell anaemia)
What is a definitive diagnosis of sickle cell disorder ?
- Electrophoresis
or - High Performance Liquid Chromatography (HPLC)
–> separates proteins according to charge
Describe methods of management of painful crisis:
PAINFUL CRISIS MEASURES:
- Pain relief (opioids)
- hydration
- keep warm
- (if hypoxic) Oxygen
- exclude infection (via tests)
