Haemoglobinopathies and Iron Overload Flashcards
What inheritance pattern are most haemoglobinopathies?
AR
What chromosome is the alpha chain gene on?
16
What chromosome is the beta chain gene on?
11
What investigations are done for suspected haemoglobinopathies
FBC
Blood film
HPLC
Gel electrophoresis
What is the basic mechanism behind thalassaemia?
Decreased globin chain synthesis causes ineffective erythropoiesis
What type of anaemia does thalassaemia cause?
Microcytic hypochromic haemolytic anaemia
What type of mutation causes alpha thalassaemia?
Deletion
What types of Hb are effected by alpha thalassaemia?
HbA
HbA2
HbF
What disease does alpha thalassaemia cause a slight selective pressure against?
Malaria
What are the 3 main forms of alpha thalassaemia?
Asymptomatic trait
HbH disease
Barts hydrops fetals
What alpha mutations cause asymptomatic alpha thalassaemia?
- α/αα or
- -/αα or
- α/-α
What alpha chain mutation causes HbH disease?
–/-α
What is seen in asymptomatic alpha thalassaemia on HPLC and serum ferritin?
Normal ferritin
Normal HPLC
What is the Mx of asymptomatic alpha thalassaemia?
No Tx
What effect does HbH disease have on Hb?
Causes excess beta chain production - haemoglobin H - which can’t carry O2
Beta 4
How does HbH disease present?
Moderate / severe anaemia Splenomegaly Gallstones Intermittent jaundice Decreased growth
What causes splenomegaly in HbH disease?
Extramedullary hematopoiesis
What causes intermittent jaundice in HbH disease?
Haemolysis due to oxidative damage
What effect does HbH diseases have on reticulocytes?
Increased numbers
What is seen on stain blood film in HbH disease?
Heinz bodies
Red cell inclusions
What effect does HbH disease have on MCH and MCV?
Decreased
What was the management of HbH disease in the past?
Splenectomy
What is the severest form of alpha thalassaemia?
Barts hydrops fetalis
What alpha chain mutation causes Barts hydrops fetalis?
–/–
No alpha chain synthesis, no HbF or HbA
What forms of haemoglobin are present at birth in hydrops fetalis?
γ4 + HbH β4 tetramers
Most cases of hydrops fetalis die in utero. T or F
True
What type of mutation causes beta thalassaemia?
Point mutation
What forms of Hb are effected by beta thalassaemia?
Only HbA
What are the 3 forms of beta thalassaemia?
β thalassaemia trait
β thalassaemia intermedia
β thalassaemia major
What mutations cause β thalassaemia trait?
β+/β b-/bb
β0/β –/bb
What mutations cause β thalassaemia intermedia?
β+/β+ -b/-b
β0/β+ –/-b
What mutations cause β thalassaemia major?
β0/β0 –/–
How does β thalassaemia trait present?
No S+S
What effect does β thalassaemia trait have on MCV, MCH, HbA2 and ferritin?
Low MCV
Low MCH
Raised HbA2
Normal ferritin
What are the pathological consequences of β thalassaemia major?
Extramedullary haematopoiesis
Chronic erythroid hyperplasia
Organ damage
How old are patients when β thalassaemia major presents?
6 - 24 months
Should be more HbA
How does β thalassaemia major present?
Pallor Failure to thrive Splenomegaly Bone deformity Frontal bossing SC compression
What effect does β thalassaemia major have on Hb, MCV, WCC, platelets and ferritin?
Low Hb Low MCV Normal WCC Low platelets Normal ferritin
What is seen on blood film in β thalassaemia major?
Pappenheimer bodies
What is the Mx of β thalassaemia major?
Lifelong regular transfusion
What is the purpose of transfusions in β thalassaemia major?
Prevent iron overload and ineffective erythropoiesis
What is the highest cause of mortality in beta thalassaemia?
Fe overload
How does Fe overload present?
Impaired growth DM OP Cardiomyopathy Arrhythmia Cirrhosis Hepatocellular carcinoma
What is the Fe chelating drug given SC or IV that causes Fe complex excretion?
Desferrioxamine
Why type of mutation causes sickling disorders?
Point mutation
A mutation of glutamine to valine producing βS causes what group of disorders?
Sickling disorders
What mutation causes sickle trait?
1 abnormal β gene β/βs
What are the symptoms of sickle trait?
Asymptomatic
May sickle in severe hypoxia eg altitude
What is seen on blood film in sickle trait?
Normal
What effect does sickle trait have on MCH?
Normal
What mutation causes sickle cell anaemia? What is the mode of inheritance?
Autosomal recessive
βs/βs
What consequences does sickle cell anaemia have on Hb?
No HbA
>80% HbS
What effect does sickle cell anaemia have on:
- the spleen
- RBC lifespan
- iron
Hyposplenism if repeated infarcts
Decreased RBC lifespan
No Fe overload
What is the pathology of a sickle crisis?
BV occlusion; infarct
What are the common sites of sickle crisis?
Triggered by hypoxia, dehydration, infection, hypothermia, fatigue
Dactylitis digits Bone marrow Lung Spleen CNS
What drug is given as prophylaxis in sickle cell anaemia hyposplenism?
Penicillin since increased infection risk
What is sickle cell disease
Heterozygous HbS + diff β chain mutation
What condition causes a primary iron overload?
Hereditary haemochromatosis
most autosomal recessive
What effect does hereditary haemochromatosis have on hepcidin, transferrin saturation and serum ferritin?
Low hepcidin
Transferrin saturation more than 50%
Serum ferritin more than 300 in M and 200 in F
Hereditary haemochromatosis generally presents in people age _____. It is mostly asymptomatic until there is ______
Middle age
Irreversible organ damage
Iron overload greater than 5 grams causes _______ which causes increased free radicals
Oxidative stress
What is the Mx of hereditary haemochromatosis?
Weekly venesection 450-500ml
Iron overload causes irreversible organ damage. Which organs are effected and how does this present?
Cirrhosis Cardiomyopathy Impotence Arthralgia DM
What is the iatrogenic cause of secondary iron overload?
Regular RBC transfusions
Why is venesection not the management of secondary iron overload?
Already anaemic
What is the management of secondary iron overload?
Iron chelating drugs
What is the SC / IV iron chelating agent?
Desferrioxamine
