Haemolytic anaemia Flashcards
What causes the signs and symptoms of haemolytic anaemias?
Increased RBC destruction and compensatory increased RBC production
What are the symptoms of RBC destruction?
Pallor of mucous membranes
Jaundice (high unconjugated serum bilirubin)
Pigment gallstones (increased bilirubin in bile)
Splenomegaly (increased RBC destruction)
Reticulocytosis (Erythrocyte precursors)
No plasma haptoglobins
What are the symptoms of increased RBC production?
Folate deficiency Bone deformities (erythroid hyperplasia causes expansion of marrow cavities
Is haemolytic anaemia micro/macro/normocytic? Why?
Macrocytic, increased erythropoeisis so increased reticulocytes in circulation
What are the symptoms of intravascular haemolytic anaemia?
Haemoglobulinaemia Absence of haptoglobins Haemoglobinurai Haemosiderinuria Methaemalbuminaemia (some of Hb oxidised and binds to albumin)
Name two cytoskeleton defects causing haemolytic anaemia?
Spherocytosis, elliptocytosis
What is spherocytosis? What is found on investigation?
Autosomal dominant disorder, commonly a disorder of spectrin
Spherocytes and increased osmotic fragility
What are the symptoms of spherocytosis?
How can it be treated?
Asymptomatic or jaundice and anaemia at birth
After infancy: low grade anaemia with crises
Splenectomy
What is elliptocytosis?
Autosomal dominant disorder, high proportion of elliptical cells
What enzyme deficiencies can cause haemolytic anaemia?
Pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency
What is pyruvate kinase deficiency? How does it cause anaemia?
Rare, autosomal recessive, affects glycolytic pathway
Lack of ATP production
Erythrocytes become rigid and are destroyed
What does blood film show in PK deficiency?
Poikilocytosis, acanthocytes
What is G6PD deficiency, what defect does it cause?
X-linked, affects hexose monophosphate shunt
Which variant of G6PD deficiency is more severe?
Mediterranean
Describe the pathogenesis of G6PD deficiency?
Oxidant stress means red cells cannot produce NADPH via HMP shunt
Inadequate GSH to combat oxidative stress
Oxidant damage to membrane and haemoglobin
What can precipitate haemolysis is G6PD deficiency?
Infection, acidosis, drugs, fava beans (only med type)
Is haemolysis in G6PD deficiency intra or extravascular?
Intravascular
Why may assay be unreliable during a crisis in G6PD deficiency?
Higher numbers of reticulocytes which have a higher amount of enzyme
What is the management of a G6PD crisis?
Support circulation and eliminate cause
What is paroxysmal nocturnal haemolobinuria? Describe the pathogenesis and what you may see on investigation
Rare, acquired RBC membrane defect
Mutation in gene coding for PIG-A causing lack of GP
GPI anchors proteins to membrane which prevents lysis by complement
Chronic intravascular haemolysis
May have leucopenia and thrombocytopenia
What are the causes of warm AIHA?
Idiopathic, AI disease (e.g. lupus), leukaemia (CLL), lymphomas, drugs
What are the causes of cold AIHA?
Idiopathic, lymphoma, leukaemia, infection (mycoplasma, EBV)
What are the symptoms of warm AIHA?
Anaemia, jaundice, splenomegaly, Evans’ syndrome (warm AIHA+ITP)
What is the management of warm AIHA?
Steroids, immunologicals (azothiaprine), monoclonal anti-B cell (rituximab), splenectomy
What are the symptoms of cold AIHA?
Sx worse in cold, Raynaud’s, acrocyanosis due to vascular sludging from RBC agglutination
What is the management of cold AIHA?
Keep warm, eliminate cause, rituximab effective in idiopathic/B-lymphoproliferative
What is paroxysmal cold haemoglobinuria?
Haemolysis is at a higher temperature but binding occurs in the cold
usually presents in children post viral illness
What are the auto antibodies in cold vs warm AIHA?
Warm: IgG
Cold: IgM
What are further causes of haemolytic anaemia apart from hereditary and autoimmune?
Alloimmune (ABO incompatibility, haemolytic of newborn)
Drug induced
Mechanical trauma e.g. mechanical heart valve, microangiopathic (TTP, DIC), march haemoglobinuria
Chemicals and toxins e.g. lead, snake venoma
Infection e.g. malaria
Burns
