Haemolysis

Question 1

Define haemolysis

Answer 1

Premature red cell destruction
i.e. shortened red cell survival

Question 2

Why are red cells susceptible to damage?

Answer 2

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)

Question 3

Define compensated haemolysis

Answer 3

Increased red cell destruction compensated by increased red cell production i.e Hb maintained

Question 4

What is haemolytic anaemia?

Answer 4

Destruction of red blood cells (haemolysis), resulting in a low haemoglobin concentration (anaemia)

Question 5

Several inherited conditions cause the red blood cells to be more fragile and break down faster than normal, leading to..

Answer 5

Chronic haemolytic anaemia

Question 6

Inherited conditions that can cause chronic haemolytic anaemia

Answer 6

Hereditary spherocytosis
Hereditary elliptocytosis
Thalassaemia
Sickle cell anaemia
G6PD deficiency

Question 7

The features that act as a result of the destruction of red blood cells are…

Answer 7

Anaemia
Splenomegaly
Jaundice

Question 8

Ix for Haemolytic anaemia

Answer 8

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)

Question 9

What is the most common type of haemolytic anaemia?

Answer 9

Hereditary spherocytosis

Question 10

Hereditary spherocytosis is an autosomal dominant/recessive

Answer 10

Autosomal dominant

Question 11

What is hereditary spherocytosis?

Answer 11

Fragile, sphere-shaped red blood cells that easily break down when passing through the spleen.

Question 12

Anaemia, jaundice, gallstones and splenomegaly. A notable feature is aplastic crisis in the presence of the parvovirus

Answer 12

Hereditary Spherocytosis

Question 13

Raised mean corpuscular haemoglobin concentration
Raised reticulocyte count
Spherocytes on a blood film

Answer 13

Hereditary Spherocytosis

Question 14

Tx for Hereditary Spherocytosis

Answer 14

Folate supplementation

Blood transfusions when required and splenectomy

Gallbladder removal (cholecystectomy) if necessary

Question 15

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

Answer 15

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

Question 16

G6PD deficiency is autosomal dominant/recessive

Answer 16

X-linked recessive

Question 17

Acute episodes of haemolytic anaemia triggered by infections, drugs or fava beans

Answer 17

G6PD deficiency

Question 18

Key medication triggers for G6PD deficiency

Answer 18

Ciprofloxacin, sulfonylureas (e.g., gliclazide) and sulfasalazine

Question 19

Jaundice (often in the neonatal period), gallstones, anaemia, splenomegaly and Heinz bodies on a blood film

Answer 19

G6PD deficiency

Question 20

Ix for G6PD deficiency

Answer 20

G6PD enzyme assay

Question 21

What is autoimmune haemolytic anaemia?

Answer 21

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

Question 22

Which type of autoimmune haemolytic anaemia is more common?

Answer 22

Warm autoimmune haemolytic anaemia - usually idiopathic

Question 23

Cold-reactive autoimmune haemolytic anaemia is also called..

Answer 23

Cold agglutinin disease

Question 24

Cold AIHA can be secondary..

Answer 24

Lymphoma, leukaemia, systemic lupus erythematosus and infections (e.g., mycoplasma, EBV, CMV and HIV)

Question 25

Mx of autoimmune haemolytic anaemia

Answer 25

Blood transfusions Prednisolone Rituximab (a monoclonal antibody against B cells) Splenectomy

Question 26

What is alloimmune haemolytic anaemia?

Answer 26

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

Question 27

What is Paroxysmal Nocturnal Haemoglobinuria?

Answer 27

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

Question 28

Red urine in the morning Anaemia Thrombosis (DVT, PE, hepatic vein thrombosis) Smooth muscle dystonia (e.g., oesophageal spasm and erectile dysfunction)

Answer 28

Paroxysmal Nocturnal Haemoglobinuria

Question 29

The red urine caused by Paroxysmal Nocturnal Haemoglobinuria contains..

Answer 29

Hemoglobin and haemosiderin

Question 30

Mx for Paroxysmal Nocturnal Haemoglobinuria

Answer 30

Eculizumab (targets C5) or bone marrow transplantation

Question 31

What is Microangiopathic Haemolytic Anaemia?

Answer 31

Abnormal activation of the clotting system, with blood clots (thrombi) partially obstructing the small blood vessels and causing destruction of RBCs

Question 32

Microangiopathic haemolytic anaemia is usually secondary to an underlying condition, such as..

Answer 32

Haemolytic uraemic syndrome (HUS) Disseminated intravascular coagulation (DIC) Thrombotic thrombocytopenic purpura (TTP) Systemic lupus erythematosus (SLE) Cancer

Question 33

_________ are a key finding on the blood film in patients with microangiopathic haemolytic anaemia

Answer 33

Schistocytes

Question 34

Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both ____________ and ____________ replacements

Answer 34

Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both bioprosthetic and metallic valve replacement

Question 35

Mx of Prosthetic Valve Haemolysis

Answer 35

Monitoring Oral iron and folic acid supplementation Blood transfusions if severe Revision surgery may be required in severe cases

Question 36

What are the consequences of haemolysis

Answer 36

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)

Question 37

T or F: Retics are diagnostic of haemolysis- response to bleeding

Answer 37

False

Question 38

Define Extravascular cell destruction

Answer 38

Taken up by reticuloendothelial system (spleen and liver predominantly)

Question 39

Define Intravascular cell destruction

Answer 39

Red cells destroyed within the circulation

Question 40

Intravascular/Extravascular cell destruction is the most common one

Answer 40

Extravascular

Question 41

What is Extravascular cell destruction?

Answer 41

Unconjugated bilrubinaemia * Jaundice * Gall stones Urobilinogenuria Normal products in excess

Question 42

What is Intravascular cell destruction?

Answer 42

Red cells are destroyed in the circulation spilling their contents Abnormal products

Question 43

Haemoglobinaemia Methaemalbuminaemia Haemoglobinuria Haemosiderinuria

Answer 43

Intravascular cell destruction

Question 44

T or F: Intravascular cell destruction may be life threatening

Answer 44

True

Question 45

What causes intravascular cell destruction

Answer 45

Mismatched blood transfusion G6PD deficiency Red cell fragmentation: heart valves, TTP, DIC, HUS Paroxysmal nocturnal haemoglobinuria Cold autoimmune haemolytic anaemia

Question 46

What causes extravascular cell destruction

Answer 46

Haemoglobinopathies Hereditary spherocytosis Haemolytic disease of newborn Warm autoimmune haemolytic anaemia

Question 47

Pathophysiology of haemolytic anaemia

Answer 47

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

Question 48

Other than intra and extravascular, what are the other classification by site of red cell defect?

Answer 48

Premature destruction of normal red cells (immune or mechanical) Abnormal cell membrane Abnormal red cell metabolism Abnormal haemoglobin

Question 49

What causes warm autoimmune haemolysis?

Answer 49

Idiopathic (commonest) Autoimmune disorders (SLE) Lymphoproliferative disorders (CLL) Drugs (penicillins, etc) Infections

Question 50

What causes cold autoimmune haemolysis?

Answer 50

Idiopathic Infections (EBV, mycoplasma) Lymphoproliferative disorders

Question 51

What causes abnormal cell membranes?

Answer 51

Liver Disease (Zieve’s Syndrome) Vitamin E deficiency Paroxysmal Nocturnal Haemoglobinuria

Question 52

How can abnormal cell metabolism cause red cell defect?

Answer 52

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