Haemopoiesis and Haemolytic Anaemia Flashcards
Foetal haemoglobin
2 alpha and 2 gamma globin chains, should be less than 1% in adults, it is the main form before birth
HbA
2 alpha, 2 beta chains
HbA2
2 alpha, 2 delta
Definition of haemoglobinopathies
inherited disorders in haemoglobin, typically autosomal recessive
Thalassemia
Reduced or absent expression of normal globin chains
Sickle cell disease
Abnormal globin chain variants with altered function
a-Thalassemia
Humans have 4 a-globin genes, 2 on each chr16
1 deleted alpha globin gene
Silent carrier state, no symptoms, carrier of disease
2 a-globin deleted
a-Thalassemia trait, minimal or no anaemia, microcytosis and hypochromia in RBC
3 a-globin genes deleted
Haemoglobin H disease, moderately severe, microcytoc, hypochromic anaemia with target cells and Heinz bodies
4 a-globin genes deleted
Hydrops fetalis, severe, usually results in intrauterine death
Consequences of Thalassemia
Extramedullary haemopoiesis resulting in splenomegaly, hepatomegaly, impaired growth, iron overload
Thalassemia treatments
- Red cell transfusion from childhood
- Folic acid (supports erythropoiesis)
- Stem cell transplant
Sickle cell disease
Autosomal recessive resulting in mutation of beta globin gene
Why is sickle cell disease a problem?
In low oxygen state, irreversibly sickled cells that are less deformable can get stuck in small blood vessels
Symptoms of sickle cell disease
Stroke, skin ulcers, acute chest syndrome
Autoimmune haemolytic anaemias
Caused by autoantibodies binding to red cell membrane proteins, spleen recognises these as abnormal -> reduced life span of RBC
Myeloproliferative neoplasms
Overproduction of one or several blood elements with dominance of a transformed clone
Cause of myeloproliferative neoplasms
Point mutation in one copy of JAK2 gene
JAK2 mutation
Normal activated my EPO on receptor of RBC surface, mutated is activated without EPO binding
Polycythaemia
Increase in circulating RBC concentration, usually have raised haemotocrit
Polycythaemia vera
Usually in older patients, bone marrow overproduction due to genetic mutation
Clinical features of polycythaemia vera
- arterial/venous thrombosis
- splenomegaly
- gout
Secondary polycythaemia
Caused by increased levels of erythropoietin
Symptoms of secondary polycythaemia
Chronic lung disease, renal hypoxia, renal cell cancer
Cause of essential thrombocythaemia
Associated with JAK2 and CAL-R mutations
Clinical features of thrombocythaemia
Increased platelets in blood, increase in megakaryocytes, thrombotic events
Myelofibrosis
Genetic mutation in JAK2, excess of platelet derived growth factor, causes increased reticulin, heavily fibrotic bone marrow
Myelofibrosis clinical features
Massive splenomegaly or hepatomegaly, RBC look like tear drops in blood film
Primary myelofibrosis
Clonal baemopoietic stem cell proliferation, may be end result of polycythaemia vera or essential thrombocythaemia
Clinical features of primary myelofibrosis
Fatigue, sweats, weight loss, early satiety due to splenomegaly
Chronic myeloid leukaemia
High white cell count, splenomegaly, bone pain or hyperviscosity (sticky blood)
BCR:ABL1 fusion
Translocation of Abl gene on chr9 and Bcr on chr22 to make a Philadelphia chromosome that drives proliferation
Tyrosine kinase inhibitors
Used to treat myeloproliferative disorders
