Anaemia and haemolytic anaemia Flashcards
What are the causes of microcytic anaemias?
Iron deficiency anaemia (most common)
Anaemia of chronic disease
Thalassemia
Sideroblastic anaemia
What is thalassemia and how does it cause anaemia?
it is an autosomal recessive disorder that leads to decreased alpha or beta chanin synthesis
Decreased numbers of haemoglobin chains leads to a microcytic anaemia with teardrop shaped RBCs occasionally present
How does sideroblastic anaemia occur and why does it form ringed sideroblasts?
It occurs due to a defect in heme synthesis in the mitochondria
In the bone marrow aspirate you can see ringed sideroblasts because there are iron granules trapped in the mitochondria surrounding the normoblast nucleus
What are the causes of macrocytic anaemia?
B12 or folate deficiency Can be due to decreased intake (vegans) Decreased absoption (pernicous anaemia) Decreased in alcoholics (target cells on histology)
What are the causes of normocytic anaemia?
Acute blood loss Aplastic anaemia (see marrow replaced by adipose tissue on biopsy) Chronic renal failure (epo reduction) Malignancy Haemolytic anaemia
What are the two main types of haemolytic anaemias?
Intrinsic - defect in the RBC causing the anaemia e.g. membrane defects (hereditary spherocytosis), abnormal haemoglobin (sickle cell), enzyme deficiency (glucose-6-phosphate dehydrogenase deficiency)
Extrinsic - stenotic valve and immune destruction
What is hereditary spherocytosis and what is its pathogenesis?
An autosomal dominant disorder in which there are membrane protein defects
This leads to spherocyte formation (loses disc shape and becomes sphere
Spherocytes are then removed by the spleen leading to a normocytic anaemia
What are the clinical findings in hereditary spherocytosis?
Jaudice most commonly occurs because of increased unconjugated bilirubin from the red blood cell breakdown
Increased risk of calcium bilirubinate gallstones
Splenomegaly present in 75% of cases
What is the treatment for hereditary spherocytosis?
Splenectomy
What is hereditary ellopsocytosis?
Genetic defect in the extracescular hemolysis
Leads to milder features than hereditary spherocytosis
What is paroxysmal noctural hemoglobinuria?
At night when there is a slight respiratory acidosis RBCs undergo lysis because there is a genetic defect (PIG gene) in the binding of the inhibitors of complement
This causes Iron deficiency and increased risk of vessel thrombosis
It is treated with corticosteroids, Eculizumab to prevent complement activation and bone marrow transplantation
What is paroxysmal cold hemoglobinuria?
Develop an IgG antibody secondary to disease that is directed against RBC antigens
This only works at cold tempertures so the anaemia usually occurs when moving from cold to warm temperatures (fever, chills, red urine)
Diagnosis by special lab tests for biothermal antibody
Treatment is blood transfusion and keep warm
What is the pathogenesis of sickle cell anaemia? What are the clinical findings?
there is a missense mutation in the beta globin chain and this causes the deoxygenated red cells to become sickle shaped.
The clinical findings are Dactylitis - painful swellings of hands
Chest pain caused by pneumonias
Avascular necrosis of the femoral head
What is the treatment and prevention of sickle cell disease?
Treatment is through pain relief and blood transfusions
Prevention is through hydroxyurea to increase fetal haemoglobin and vaccination
What is the pathogenesis behind a glucose-6-phosphate dehydrogenase deficiency?
It is an X liked recessive disorder that causes problems with intravascular and extravascular haemolysis.
It results in decreased NADPH synthesis so H2O2 is no longer neutralised. This damages RBC membranes through heinz bodies that are produced.
