Haemolysis

Question 1

What is haemolysis

Answer 1

Shortened survival of circulation red blood cells

Question 2

What is the haemolysis screen?

Answer 2

Reticulocytes - INCREASED
LDH - INCREASED
Haptoglobin - REDUCED
Bilirubin - INCREASED

Question 3

Causes of intravascular haemolysis

Answer 3

Low low haptoglobin
Positive urinary hemosiderin

RBC fragmentation - TTP, HUS and aHUS, DIC, direct damage
Paroxysmal Nocturnal Haematuria
Paroxysmal Cold Haemoglobinuria

Question 4

Causes of extravascular haemolysis

Answer 4

Low haptoglobin

Immune mediated - Warm and cold AIHA
RBC membrane disorders
RBC enzyme disorders
Metabolic defects
Bacterial and parasitic infections

Question 5

Paroxysmal noctural haemoglobinuria

Answer 5

Mutation in pig-A gene

–> defective production of phosphatidylinositol glycan A which is essential for the formation of the GPI anchor

–> loss of surface proteins which protect the cell from complement mediated lysis - CD55 and CD59

Results in haematuria and haemosiderinuria
Associated with aplastic anaemia
Morbidity from thrombosis

Treatment =
Eculizumab
Transfusions and thrombosis management

Question 6

Paroxysmal Cold haemoglobinuria

Answer 6

Formation of a biphasic IgG anti-P antibody

–> Binds to RBCs at low temperature and upon warming –> complement mediated lysis

Causes:

• Idiopathic
• Syphilis
• Viral infections

Treatment = cold avoidence and supportive care

Question 7

Causes of Warm Autoimmune haemolytic anaemia

Answer 7

Antibodies which react with RBCs at 37 degress

IgG and C3d –> uptake by macrophages

Causes:

• Idiopathic
• SLE
• CLL/lymphoma
• HCV
• CMV
• Methydopa
• EVANS syndrome - AIHA + ITP

Question 8

Diagnosis of warm AIHA

Answer 8

Anaemia + Haemolysis + spherocyte + splenomegaly

DAT postive - IgG or C3d

Treatment =

• prednisone
• Intragam
• Splenectomy and vaccination
• AZA
• Rituxumab
• Folate supps

Question 9

Cold AIHA

Answer 9

Antibodies which react with RBCs <37 degrees

C3d only

Secondary disease:

• MGUS and lymphproliferative disease
• EBV
• Mycoplasma
• SLE

Treatment:

• cold avoidence
• Rituximab

Question 10

RBC membrane defects

Answer 10

Hereditary spherocytosis

• loss of vertical interactions
• ankyrin, spectrin, band 3
• flow cytometry = EMA binding

Hereditary ellipocytosis
- Loss of horizontal interactions

Ovalocytosis

Question 11

Pyruvate kinase deficiency

Answer 11

Glycolytic pathway

–> reduced ATP –> RBC rigidity

–> Chronic haemolysis

Rare disorder

Question 12

G6PD Deficiency

Answer 12

Glucose-6-Phosphate dehydrogenase deficiency

G6PD –> produces NADPH during times of oxidative stress –> reduces glutathione which scavenges ROS

Deficiency –> acute haemolytic crisis during oxidative stress

X linked disorder

Precipitants =

• Acute illness
• Anti-malarials
• Sulfur drugs
• Aspirin
• Naphthalene
• Fava beans

Treatment - stop precipitant, IV fluids, transfuse