Inherited Haemoglobin Disorders Flashcards
Describe the haemoglobin structure
Hb is a complex of globin chain
Eachh globin has a haem group
Each haem group has iron
Haem carry oxygen
What is the main haemoglobin in adults
Haemoglobin a
What is the number of alpha and beta chains in haemoglobin
2 Alpha
2 Beta
How many genes does alpha chain have and on what chromosome
2 genes on chromosom 16
How many genes does beta globin have
1 gene on chromosome 11
What are the ways we can classify haemoglobin disorders
Qualitative: changes to the globin chain amino acid sequence e.g sickle cells disease
Quantitatice: complete or partial reduction of a globin chain i.e thalasemia
What is sickle cell disease due to
Substitution of amino acid valine for glutamic acid at position 6 of the beta globin chain
What is sickle cell diease
When both beta globin chains are abnormal instead of making hba they make the variatn haemoglobinss
What is a sickle cell trait
This is someone who is a carrier
Only one beta chain is abnormla and they make both hba and hbs
What protection does sickle cell trait show
Protection to malaria
What are the symptoms of sickle cell trait
Usually asymptomatic
In phsyiological stress e.g sepsis what can people with sickle cell trait develop
Splenic infarction
Increased risk of clots
In sickle cell disease what can happen to the capillaries
Become occluded
What is the life span of the RBC in sickle cell disease
Short
Due to the short lifespain in sickle cell disease what can occur due to haemolytic anaemia
Jaundice- due to increased bilirubin
Pigment gallstones
What happens to the cell production in sickle cell disease due to haemolytic anaemia
Compensation
What features does compensation in cell production in sickle cell disease result in
Reticulocytosis
Potentional for folate deficiency
What are the acute presentation of sickle cell disease
Painful vasooclussive crises Infection Acute chest syndrome Stroke Acute splenic and hepatic sequestration Aplastic crises i.e bone marrow swtiched off Priapism Growth delay
What is a vasooclusive sickle cell crises
When the small vessel in the body become blocked so it can be painful
What is the management of vasooclusive sickle crises
Analgesia for pain
Fluids
Oxygen
Low molecule hepatic
What are the complications of sickle cell disease
Sepsis
Renal impairment
VTE
Acute sickle chest syndrome
What is a an acute chest syndrome
Acute lung injury from pneumonia
What symptoms do peope with acute chest syndrome present with
Cough SOB Chest pain Rib pain Fever
What will the CXR show in someone with acute chest syndrome
Consolidation
Infiltrates
What is the management for acute chest syndrome
Transfusion
What can sickle cell disease lead to if chronic
End organ damage: Chronic kidney disease Chronick sickle lung Right heart failure Cardiomegaly Retinopathy Gallstone Leg ulcers
What is the management of chronic sickle cell disease
Education
Support
Screening: in children with cranial doppler for stroke, adults with echocardiography for pulmonary hypertension
What are the other interventions for sickle cell
Folic acid Analgesia Penicillin prophylaxis Blood transfusion Hydroxycarbamide- for severe recurrent painful virses or acurte chest syndrome
What is alpha thalassemia
Reduction in the alpha globin chain production so you have a lack of hbA. There are excess gamma and beta chains that form abnormal haemoglobin
How many alpha globin genes are there in alpha chains
2
In total then how many alpha genes is there in one rbc
4 (2 alpha gene in 1 alpha chain and there are 2 alpha chains in total) this makes up 4 genes)
What is the type of alpha thalassemia according to
How many alpha chains are deleted
What is the deletion of 1 alpha gene called
Heterozygous a+
What is the deletion of 1 alpha genes from both alpha genes
Homozygous a+ (-a/-a)
What is the deletion of 2 alpha gene from one alpha chain
Heterozygous a- (- -/aa)
What is the deletion of 2 alpha gene and 1 alpha gene from alpha chain
( - -/- a) haemoglobin h disease
What is the deletion of 4 alpha genes in total
- / - - hb barts hydrops
What does hb barts hydrops result in
Still birth
What features does heterozygous a+, ao and homozygous a+ result in
Low MCV
What is beta thalassemia
Reduction of beta globin chain production
What is b0 mutations result in
Total loss of beta chain production from the gene
What does b+ mutation result in
Partial reduction of beta chain production from the gene
How many beta genes does one beta chain have
1
What is b/b0
B thal trait
What is b0/b0
Beta thalasemia major
What is b0/b+
Beta thalassemia intermedia
What happens when you have absent or reduced beta chain production
You have excess alpha chains which are unstable and interfere with red blood cell maturation so you get erythropoiesis and haemolysis leading to anaemia
What is the presentation of beta thalassemia at birth
Healthy as they have hbf and become anaemic as hbf reduces and present with failure to thrive
What is the management of beta thalassemia
Blood tranfusion to reverse progressive anaemia
What is the complication of blood transfusion
Iron overload
What are the complications of beta thalassemia iron overload
Endocrine dysfunction: hypogonadism, hypo parathyroiism, hypothyroidism Diabetes Bony overgrowth Cardiac disease Liver disease; cirrhosis, HCC
What are the ways we can reduce iron overload
Iron chelation
What are the 3 types of treatment for iron chelation
Desferrioxamine
Desferasirox
Deferiprone
What is the acute presentation of thalassemia
Infection Heart failure Diabeted Hypoadrenal crises Hypocalcaemia
What is the MCV in sickle cell disease
Normal
What is the mcv in thalasemia
Microcytic
