HAEMATOLOGY - BLEEDING DISORDERS Flashcards
Outline the pattern of bleeding in coagulation and platelet disorders?
Platelet disorders cause prolonged bleeding from cuts, bleeding into the skin e.g. purpura, and bleeding from mucous membranes
Coagulation disorders cause bleeding into joints and muscles which is more likely to be delayed.
What are some vascular bleeding defects?
Osler-Weber-Rendu syndrome
Connective tissue disease e.g. Ehlers Danlos syndrome or Marfan syndrome
Acquired: Senile purpura, Infection, Steroids, Scurvy, Henoch-Schonlein purpura
What is Osler-Weber-Rendu syndrome also known as?
Hereditary haemorrhagic telangiectasia
What is hereditary haemorrhagic telangiectasia?
A rare autosomal dominant disorder caused by mutations in genes that regulate angiogenesis, leading to the formation of fragile, dilated blood vessels called telangiectasias and arteriovenous malformations that can cause various clinical manifestations.
If they have 3 or more of the following its a diagnosis:
- epistaxis
- telangiectasia
- visceral lesions e.g. Arteriovenous malformations or GI telangiectasia
- FHx first degree relative
What mucous membranes does Osler-Weber-Rendu syndrome usually affect?
Nose and GIT
What are the main complications of Osler-Weber-Rendu syndrome?
Iron deficiency anaemia from epistaxis and chronic GI bleeding
Recurrent epistaxis
GI bleeds
Arteriovenous malformations in various organs e.g. brain, liver, lungs - can cause stroke, brain abscess, HF, respiratory distress
What is senile purpura?
Benign easy bruising that affects older adults
This is because the skin and blood vessels become more fragile
What is Henoch-Schonlein purpura?
A type 3 hypersensitivity reaction that is often preceded by an acute respiratory tract infection
It’s a type of small vessel vasculitis
Where is the rash characteristically in Henoch-Schonlein purpura?
Purpura on legs and buttocks
It’s raised
Whats the pathophysiology of Henoch Schonlein purpura?
IgA mediated small vessel vasculitis - IgA-antibody immune complexes caused by antigenic exposure from an infection or medication deposit in the small vessels of the skin, joints, kidneys, and gastrointestinal tract.
What are the 3 broad categories for causes of thrombocytopenia?
Reduced platelet production in bone marrow
Excessive peripheral destruction of platelets
Sequestration in an enlarged spleen
What can cause impaired production of platelets?
Aplastic anaemia
bone marrow failure due to drugs/disease e.g. chemo or leukaemia
Tumour infiltration into bone marrow
MDS
Myeloma
Myelofibrosis
HIV infection
What can cause excessive destruction of platelets?
ITP
Drug induced destruction
Secondary immune e.g SLE, CLL
Alloimmune neonatal thrombocytopenia
Post-transfusion purpura
DIC
TTP
HUS
What is ITP?
Thrombocytopenia due to immune destruction of platelets spleen produces IgG antibodies against GP2b/3a
What is acute ITP?
Usually affects children
Happens 2-3 weeks after a viral infection
Resolves spontaneously within 2 months
What is chronic ITP/
Seen in females of reproductive age
Lasts >6 months
Can be primary or secondary (triggered by another condition e.g. SLE, HIV)
Usually affects adults
How does ITP present?
Usually asymptomatic
In some cases it can cause purpura
In severe cases it can cause epistaxis
How is ITP investigated?
Isolated Thrombocytopenia
(In cases with significant bleeding it can cause anaemia)
Diagnosis is based on exclusion of other causes of thrombocytopenia
Normal or increased megakaryocytes - not necessary for confirming diagnoses
Platelet autoantibodies - not necessary for confirming diagnoses
Hep C and HIV testing to rule out secondary ITP
How is ITP managed?
Children and adults with platelet counts of more than 30 x 109/L generally require no treatment
Treat underlying condition in secondary ITP
When treatment is needed…
Oral corticosteroids
IV immunoglobulin
Second line:
Splenectomy (removes macrophages that destroy platelet)
TPO receptor agonists
Platelet transfusions (when platelets <10,000)
What is neonatal alloimmune thrombocytopenia?
Fetomaternal incompatibility for platelet-specific antigens, usually for human platelet alloantigen 1a, and is the platelet equivalent of HDN. The mother is HPA-1a-negative and produces antibodies that destroy the HPA-1a-positive fetal platelets.
What is post-transfusion purpura?
Rare and occurs 7-10 days after a transfusion of platelet-containing blood components
Associated with a platelet specific alloantibody, usually anti-HPA-1a
It always occurs in people who have been previously immunised by blood transfusion or pregnancy
What is thrombotic thrombocytopenic purpura?
A rare but serious blood disease that causes many small blood clots throughout the body
Caused by a severe deficiency of enzyme ADAMTS13 which usually breaks down vWF when no longer needed
What are the signs and sympotms of TTP?
Fever, neuro signs, thrombocytopenia, haemolytic anaemia and renal disease
What are the 2 types of TTP and which is more common?
Immune mediated TTP - more common
Congenital TTP
What is immune mediated TTP?
Acquired TTP which is an autoimmune disorder that usually develops in late childhood or adulthood
The immune system attacks ADAMTS13 enzyme
What is congenital TTP?
Present from birth and inherited in an autosomal recessive pattern
Low levels of ADAMTS13 enzyme
How is TTP diagnosed?
Blood tests to show deficiency of <10% ADAMTS13 activity
Present of anti-ADAMTS13 antibodies in iTTP
How is TTP treated?
Plasmapheresis
Steroids
Rituximab
How does plasmapheresis work for TTP management?
It provides a source of ADAMTS13 and removes associated autoantibodies in iTTP
What is haemolytic uraemic syndrome?
Characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury.
What are the types of HUS?
Diarrhoea + HUS (typical HUS)
Diarrhoea - HUS (atypical HUS)
What is typical HUS?
When HUS is triggered by bloody diarrhoea
Usually affects children
What causes typical HUS?
Most common cause is enterohemorrhagic E.coli (0157;H7)
Outline the pathology of HUS?
HUS can be triggered by an infection with certain strains of E. coli bacteria (such as E. coli O157:H7), or exposure to other toxins that damage the lining of blood vessels.
damage to the endothelial cells lining the blood vessels = inflammation and release of substances that promote blood clotting.
The damaged endothelial cells also cause the activation and aggregation of platelets, which contribute to the formation of blood clots.
The combination of activated platelets and clotting factors leads to the formation of microthrombi in the small blood vessels, particularly in the kidneys.
The microthrombi damage the red blood cells as they pass through the blood vessels, leading to hemolysis and a decreased number of platelets in circulation. They can also block blood flow to the kidneys, leading to kidney damage and dysfunction.
What is atypical HUS?
No preceding diarrhoea
Damage to endothelial cells; this can be caused by infections, medications, autoimmune causes, genetic mutations
Glomerular endothelium is damaged and in response blood clots form in the kidneys
Whats the classic findings in HUS?
Microangiopathic haemolytic anaemia - schistocytes, anaemia symptoms, jaundice
Thrombocytopenia - easy bruising and purpura
Acute renal failure - uraemia
If they have TTP too then they will have neurological findings and fever
How is HUS diagnosed?
Signs of kidney damage - proteinuria and haematuria, elevated cr and urea in blood
Blood smear - schistocytes or helmet cells
Bacteria culture in diarrhoea +
In TTP-HUS - ADAMTS13 can be measured
How is HUS treated?
Supportive as shiga-like toxin clears in days to weeks
(Using antibiotics can actually worsen the problem)
In TTP-HUS give plasmapheresis