Haemoglobinopathies Flashcards
List 8 types of haemoglobin
HbA - normal adult Hb
HbA2 - minor Hb 2-3% in adults, 2 alpha, 2 delta
HbF - fetal Hb, transitions to normal Hb at 6 months, 2 alpha, 2 gamma
HbBarts - 4 gamma chains, leads to hydrops, not consistent with life
HbE - variant Hb with 2 alpha, 2 beta but with a base substitution Glu to Lys in the beta chain
HbC - variant with beta chain mutation
HbS - Hb variant with beta chain mutation Glu to Val, aggregates and forms sickle cells
HbH - 4 beta chains, forms inclusions in RBC, aka HBH disease
What is normal haemoglobin made up of?
2 alpha globin chains
2 beta globin chains
Each chain contains a central heme group consisting of a protoporphyrin bound to a single ferrous iron
What chromosome is the alpha globin gene on?
16
What underlies the pathology of thalassemia?
An imbalance in chain production
Ie. alpha thal is loss of a proportion of alpha chains
What are the four types of alpha thal inheritance?
Silent carrier - loss of one alpha gene, no signs, normal Hb electrophoresis
Mild alpha thal = loss of 2 genes, microcytic, mild anaemia
- alpha thal 1 = loss of 2 genes on 1 allele, cis deletion, common in SE Asia
- alpha thal 2 = loss of one gene from each allele, trans deletion, common in Africa (lower risk of Bart’s or Hbh disease)
HbH disease = loss of 3 alpha genes, HbH accumulates in RBC leading to haemolysis, anaemia, iron overload
HbBarts = no alpha genes, incompatible with life
What is meant by thalassemia intermedia?
Have anaemia but are not transfusion dependant unless in times of stress ie. pregnancy, oxidative drugs, sepsis etc
What chromosome are the beta globin genes on?
11
What are the types of B-thalassemia?
B-thal minor/trait
B+/B or B/B0 (B0 is no beta chain produced, + is some beta chain produced)
Leads to mild anaemia, abnormal Hb electrophoresis, compensatory increase in HbF and HbA2
B-thal intermedia
B+/B+ or B+/B0
Can have signs similar to major but are not transfusion dependant
B-thal major
B0/B0
Symptoms manifest after 6 months of life when transition from HbF to HbA
Profound life long transfusion dependant anaemia, hepatomegaly and growth deformities
Clinical features of significant thalassemia?
Chronic haemolysis - indirect bilirubin, splenomegaly, pre-mature gallstones
Bone marrow expansion from erythropoietic drive - frontal bossing, maxillary overgrowth, long bone fractures
Diabetes, hypogonadism, growth failure
Hepatomegaly
Hyperuraecimia
Enlarged kidneys
Cardiac dilitation
Aplastic crisis with parvovirus B19 infection
Lab features of thalassemia?
Hypochromic, microcytic cells
Target cells
Red cell fragments
Heinz bodies (globin precipitates in cells)
Iron studies - raised ferritin, iron, transferrin sat
Haemolysis
Management of thalassemia?
Immunisations
Supplement folic acid
Transfuse aiming for haematocrit of 27-30% (to suppress erythropoeisis)
Splenectomy if high transfusion requirement
Avoid oxidative drugs
Trial chemotherapy (hydroxyura) to increase level of HbF
Stem cell transplant can cure
What is the pathology of sickle cell?
Mutated beta globin gene polymerises when deoxygenated causing a sickled shape
Causes micro vascular occlusion and haemolysis
Inheritance of sickle cell anaemia
Autosomal recessive
- requires homozygote to exhibit disease or combination of one allele with other Hb variant
Clinical manifestations of sickle cell?
Painful crisis - vaso-occlusive episodes
Acute chest syndrome - sickling in the lung
Splenic sequestration crisis - trapping of blood in spleen
Stroke, priapism, leg ulcers, arthropathy
Lab features of sickle cell?
Sickle cells, target cells
HbF, HbS and no HbA on electrophoresis
Can do sickling solubility tests
