Haemolysis Flashcards
Define haemolysis
Premature red cell destruction
i.e. shortened red cell survival
Why are red cells susceptible to damage?
They need to have a biconcave shape to transit the circulation successfully
They have limited metabolic reserve and rely exclusively on glucose metabolism for
energy (no mitochondria)
Can’t generate new proteins once in the circulation (no nucleus)
Define compensated haemolysis
Increased red cell destruction compensated by increased red cell production i.e Hb maintained
What is haemolytic anaemia?
Destruction of red blood cells (haemolysis), resulting in a low haemoglobin concentration (anaemia)
Several inherited conditions cause the red blood cells to be more fragile and break down faster than normal, leading to..
Chronic haemolytic anaemia
Inherited conditions that can cause chronic haemolytic anaemia
Hereditary spherocytosis
Hereditary elliptocytosis
Thalassaemia
Sickle cell anaemia
G6PD deficiency
The features that act as a result of the destruction of red blood cells are…
Anaemia
Splenomegaly
Jaundice
Ix for Haemolytic anaemia
Full blood count shows a normocytic anaemia
Blood film shows schistocytes (fragments of red blood cells)
Direct Coombs test is positive in autoimmune haemolytic anaemia (not in other types)
What is the most common type of haemolytic anaemia?
Hereditary spherocytosis
Hereditary spherocytosis is an autosomal dominant/recessive
Autosomal dominant
What is hereditary spherocytosis?
Fragile, sphere-shaped red blood cells that easily break down when passing through the spleen.
Anaemia, jaundice, gallstones and splenomegaly. A notable feature is aplastic crisis in the presence of the parvovirus
Hereditary Spherocytosis
Raised mean corpuscular haemoglobin concentration
Raised reticulocyte count
Spherocytes on a blood film
Hereditary Spherocytosis
Tx for Hereditary Spherocytosis
Folate supplementation
Blood transfusions when required and splenectomy
Gallbladder removal (cholecystectomy) if necessary
Hereditary elliptocytosis is similar to hereditary spherocytosis except that the red blood cells are ___________. It is also autosomal dominant. The presentation and management are the same as hereditary spherocytosis
Hereditary elliptocytosis is similar to hereditary spherocytosis except that the red blood cells are ellipse-shaped. It is also autosomal dominant. The presentation and management are the same as hereditary spherocytosis
G6PD deficiency is autosomal dominant/recessive
X-linked recessive
Acute episodes of haemolytic anaemia triggered by infections, drugs or fava beans
G6PD deficiency
Key medication triggers for G6PD deficiency
Ciprofloxacin, sulfonylureas (e.g., gliclazide) and sulfasalazine
Jaundice (often in the neonatal period), gallstones, anaemia, splenomegaly and Heinz bodies on a blood film
G6PD deficiency
Ix for G6PD deficiency
G6PD enzyme assay
What is autoimmune haemolytic anaemia?
When antibodies are created against the patient’s red blood cells. These antibodies lead to red blood cell destruction (haemolysis)
There are two types, warm and cold, based on the temperature at which the auto-antibodies destroy red blood cells
Which type of autoimmune haemolytic anaemia is more common?
Warm autoimmune haemolytic anaemia - usually idiopathic
Cold-reactive autoimmune haemolytic anaemia is also called..
Cold agglutinin disease
Cold AIHA can be secondary..
Lymphoma, leukaemia, systemic lupus erythematosus and infections (e.g., mycoplasma, EBV, CMV and HIV)
Mx of autoimmune haemolytic anaemia
Blood transfusions
Prednisolone
Rituximab (a monoclonal antibody against B cells)
Splenectomy
What is alloimmune haemolytic anaemia?
Occurs due to foreign red blood cells or foreign antibodies
The two scenarios where this happens are transfusion reactions and haemolytic disease of the newborn
What is Paroxysmal Nocturnal Haemoglobinuria?
Caused by a specific genetic mutation in the haematopoietic stem cells in the bone marrow
Results in a loss of the proteins on the surface of red blood cells that inhibit the complement cascade, allowing activation of the complement cascade on red blood cells and their destruction
Red urine in the morning
Anaemia
Thrombosis (DVT, PE, hepatic vein thrombosis)
Smooth muscle dystonia (e.g., oesophageal spasm and erectile dysfunction)
Paroxysmal Nocturnal Haemoglobinuria
The red urine caused by Paroxysmal Nocturnal Haemoglobinuria contains..
Hemoglobin and haemosiderin
Mx for Paroxysmal Nocturnal Haemoglobinuria
Eculizumab (targets C5) or bone marrow transplantation
What is Microangiopathic Haemolytic Anaemia?
Abnormal activation of the clotting system, with blood clots (thrombi) partially obstructing the small blood vessels and causing destruction of RBCs
Microangiopathic haemolytic anaemia is usually secondary to an underlying condition, such as..
Haemolytic uraemic syndrome (HUS)
Disseminated intravascular coagulation (DIC)
Thrombotic thrombocytopenic purpura (TTP)
Systemic lupus erythematosus (SLE)
Cancer
_________ are a key finding on the blood film in patients with microangiopathic haemolytic anaemia
Schistocytes
Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both ____________ and ____________ replacements
Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both bioprosthetic and metallic valve replacement
Mx of Prosthetic Valve Haemolysis
Monitoring
Oral iron and folic acid supplementation
Blood transfusions if severe
Revision surgery may be required in severe cases
What are the consequences of haemolysis
Erythroid hyperplasia (increased bone
marrow red cell production)
Excess red cell breakdown products eg billirubin (clinical features differ by aetiology and site of red cell breakdown)
T or F: Retics are diagnostic of
haemolysis- response to bleeding
False
Define Extravascular cell destruction
Taken up by reticuloendothelial system (spleen and liver predominantly)
Define Intravascular cell destruction
Red cells destroyed within the circulation
Intravascular/Extravascular cell destruction is the most common one
Extravascular
What is Extravascular cell destruction?
Unconjugated bilrubinaemia
* Jaundice
* Gall stones
Urobilinogenuria
Normal products in excess
What is Intravascular cell destruction?
Red cells are destroyed in the circulation spilling their contents
Abnormal products
Haemoglobinaemia
Methaemalbuminaemia
Haemoglobinuria
Haemosiderinuria
Intravascular cell destruction
T or F: Intravascular cell destruction may be life threatening
True
What causes intravascular cell destruction
Mismatched blood transfusion
G6PD deficiency
Red cell fragmentation: heart valves, TTP, DIC, HUS
Paroxysmal nocturnal haemoglobinuria
Cold autoimmune haemolytic anaemia
What causes extravascular cell destruction
Haemoglobinopathies
Hereditary spherocytosis
Haemolytic disease of newborn
Warm autoimmune haemolytic anaemia
Pathophysiology of haemolytic anaemia
Free haemoglobin is released which then binds to haptoglobin. As haptoglobin becomes saturated, haemoglobin binds to albumin forming methaemalbumin (detected by Schumm’s test)
Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria
Other than intra and extravascular, what are the other classification by site of red cell defect?
Premature destruction of normal red cells
(immune or mechanical)
Abnormal cell membrane
Abnormal red cell metabolism
Abnormal haemoglobin
What causes warm autoimmune haemolysis?
Idiopathic (commonest)
Autoimmune disorders (SLE)
Lymphoproliferative disorders (CLL)
Drugs (penicillins, etc)
Infections
What causes cold autoimmune haemolysis?
Idiopathic
Infections (EBV, mycoplasma)
Lymphoproliferative disorders
What causes abnormal cell membranes?
Liver Disease (Zieve’s Syndrome)
Vitamin E deficiency
Paroxysmal Nocturnal Haemoglobinuria
How can abnormal cell metabolism cause red cell defect?
Failure to cope with oxidant stress (G6PD deficiency)
Failure to generate ATP: metabolic processes fail
Even the metabolic pathways of normal cells if sufficiently stressed e.g.by dapsone or salazopyrin can get oxidative damage
