Haemolytic Anaemias Flashcards
Clinical features of extravascular haemolysis?
Splenomegaly
Jaundice due to unconjugated bilirubin
Clinical and lab findings of intravascular haemolysis?
Increased free plasma haemoglobin (haemoglobinaemia)
Haemoglobinuria (dark red urine)
Decreased haptoglobin (binds free haemoglobin)
Lab findings of all haemolytic anaemias?
Increased unconjugated bilirubin Increased urobilinogen Increased LDH Reticulocytosis (increased MCV and polychromasia) May have pigmented bile gallstones
Inherited causes of haemolytic anaemias?
Membrane defect: hereditary spherocytosis, hereditary eliptocytosis
Enzyme defect: G6PD deficiency, pyruvate kinase deficiency
Haemoglobinopathies: sickle cell disease, thalassaemias
Acquired causes of haemolytic anaemias?
Immune: autoimmune (warm or cold), alloimmune (haemolytic transfusion reactions)
Non immune: mechanical (metal valves, trauma), PNH, MAHA. Infections (malaria), drugs
Characteristic blood cell in hereditary spherocytosis?
Spherocytes with loss of central pallor
Type of haemolysis seen in hereditary spherocytosis and the clinical finding?
Extravascular
Splenomegaly- spherocytes consumed by splenic macrophages
How is hereditary spherocytosis diagnosed?
Osmotic fragility test
DAT is negative
Treatment for hereditary spherocytosis?
Splenectomy
What are people with hereditary spherocytosis susceptible to?
Increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors
Inheritance of hereditary spherocytosis?
Autosomal dominant
Inheritance of G6PD deficiency?
X linked
Characteristic blood film of G6PD deficiency?
Heinz bodies
Role of G6PD?
Helps RBCs make glutathione which protects them from OXIDANT damage.
Features seen in G6PD attack?
Rapid anaemia and jaundice
Type of haemolysis in G6PD deficiency?
Intravascular
Get dark urine
How to diagnose G6PD deficiency?
Enzyme assay 2-3 months after a crisis.
Features of pyruvate kinase deficiency?
Autosomal recessive
SEVERE NEONATAL JAUNDICE, splenomegaly, haemolytic anaemia
Inheritance of sickle cell anaemia and the mutation that occurs?
Autosomal recessive
Mutation in beta chain of haemoglobin, single amino acid change of glutamic acid to valine (hydrophobic)
Difference between sickle cell trait and disease?
Trait: HbAS- usually asymptomatic
Disease: HbSS- severe
What increases the risk of sickling?
Hypoxaemia, dehydration and acidosis
What does hydroxurea treatment do?
Increase levels of HbF
HbF protects against sickling; high HbF at birth is protective for the first few months of life.
Type of haemolysis present in sickle cell disease?
Extravascular
What is seen on the blood film for sickle cell disease?
Sickle cells and target cells
How can sickle cell be diagnosed?
Sickle cells and target cells on blood film
Sickle solubility test
Hb electrophoresis
Smear of beta thalassaemia?
Microcytic, hypochromic RBCs and target cells
Diagnosis of beta thalassaemia?
Hb electrophoresis
What test is used for autoimmune haemolytic anaemia?
Coombs test/direct antiglobulin test
Will be positive
Blood film of warm auto immune haemolytic anaemia?
Spherocytes
IgG binds RBCs in the relatively warm temperature of the central body (warm agglutinin); membrane of antibody coated RBC is consumed by splenic macrophages resulting in spherocytes.
What is warm auto immune haemolytic anaemia associated with?
CLL, SLE, METYHLDOPA
Antibody in warm auto immune haemolytic anaemia?
IgG
Antibody in cold agglutinin disease?
IgM
What infections are associated with cold agglutinin disease?
Mypoplasma pneumoniae and infectious mononucleosis (EBV), hepatitis C
What is the cause of paroxysmal nocturnal haemoglobinuria?
ACQUIRED loss of protective GPI surface markers of blood cells which usually protects against complement.
Get COMPLEMENT MEDIATED LYSIS
Chronic intravascular haemolysis especially at night
Haemolysis seen in warm AIHA?
Extravascular
Haemolysis seen in cold AIHA?
Intravascular
Causes of microangiopathic haemolytic anaemia?
Haemolytic uraemic syndrome
Thrombotic thrombocytopenic purpura
Disseminated intravascular coagulation
Blood film features of microangiopathic haemolytic anaemia?
SCHISTOCYTES
THROMBOCYTOPENIA
What is MAHA?
Pathological formation of platelet microthrombi in small vessels, causing mechanical destruction of red blood cells.
How do you distinguish HUS and TTP from DIC?
Normal APTT, PT and fibrinogen.
Abnormal in DIC
What is TTP caused by?
Deficiency of ADAMTS13 which is needed to chop up vWF multimers, so get abnormal platelet adhesion and microthrombi which chop up the RBCs.
What is the pentad of symptoms in in TTP?
MAHA FEVER RENAL IMPAIRMENT NEUROLOGICAL SYMPTOMS (PREDOMINANT PROBLEM) THROMBOCYTOPENIA
What is haemolytic uraemic syndrome caused by?
Commonly by Escherichia coli 0157:H7
Classically in children
Features of haemolytic uraemic syndrome?
Symptoms occur after a diarrhoeal illness MAHA Thromboctyopaenia Acute renal failure Self limiting in children
Antibody involved in haemolytic disease of the newborn?
IgG
ONLY IgG CAN CROSS THE PLACENTA!
Features of HELLP syndrome?
HAEMOLYSIS, ELEVATED LIVER ENZYMES, LOW PLATELETS
Life threatening complication associated with pregnancy.
MAHA, INCREASED AST, INCREASED ALT, DECREASED PLATELETS, NORMAL APTT, NORMAL PT
Differentials include DIC: in DIC the APTT is INCREASED, the PT is INCREASED, fibrinogen is DECREASED, AFLP (marked transaminitis)
Management- supportive delivery of the foetus
