BLEEDING DISORDERS Flashcards
What are the five main components of normal haemostasis?
Coagulation factors
Coagulation inhibitors
Fibrinolysis
Platelets
Blood vessels
Where are the coagulation factors mainly produced?
In the liver
How are coagulation factors normally found in the blood stream?
In their inactivated form
What is the ultimate goal of the both sides of the coagulation cascade?
To generate thrombin, which allows fibrinogen to become fibrin and form a clot are the aggregated platelets
What are the two pathways of the coagulation cascade?
Extrinsic pathway - tissue factor pathway caused by cellular injury releasing tissue factor
Intrinsic pathway - contact system
What are the coagulation factors involved exclusively in the extrinsic or tissue factor pathway?
Tissue factor (FIII) - activates FVII
FVII - used to activate factor X
What are the coagulation factors involved exclusively in the intrinsic or contact pathway?
FXII - activates FXI
FXI - activates FIX
FIX - used with FVIII to activate factor X
FVIII - used with FIX to activate factor X
What are the factors that make up the common pathway of the coagulation cascade?
FX
FV
FII (Prothrombin) – FIIa (Thrombin)
Fibrinogen – Fibrin
FXIII
What investigations may be useful as screening tools in patients with a history of bleeding?
FBC and blood film - thrombocytopenia
Prothrombin time
Activated partial thromboplastin time
Thrombin time
Quantitative fibrinogen assay
D-Dimer
U+Es and LFTs
What does the prothrombin time (PT) represent?
Measure of the extrinsic pathway of coagulation.
Therefore activity of factors VII, X, V and II
What does the activated partial thromboplastin time (APTT) represent?
Measure of the intrinsic pathway of coagulation
Therefore activity of factors XII, XI, IX, VIII, X, V and II
When monitoring heparin therapy do we use PT or APTT?
APTT
What is the inheritance pattern of haemophilia?
X-linked recessive
What is the coagulation factor affected in haemophilia A?
Factor VIII
What is the coagulation factor affected in haemophilia B?
Factor IX
What is the alternative name for haemophilia B?
Christmas disease
How do we grade haemophilia?
By Factor VIII:C (or FIX:C)
More than 5% is mild
Between 1 - 5% is moderate
Less than 1% is severe
What are the bleeding tendencies of someone with mild haemophilia?
Bleed after surgery
What are the bleeding tendencies of someone with moderate haemophilia?
Bleed after minor trauma
What are the bleeding tendencies of someone with severe haemophilia?
Spontaneous joint/muscle bleeds - this can lead to crippling arthritis if not treated
When do most children with haemophilia present?
Towards the end of the first year of life, when they start to crawl or walk (and hence fall over)
When neonates present with haemophilia, what are the common sites of bleeding?
Intracranial haemorrhage
Bleeding post-circumcision
Prolonged oozing from heel prick test
How do we treat someone with haemophilia?
Recombinant FVIII or FIX whenever there is a bleed
Prophylactic recombinant factor for all those with severe disease
In mild disease, desmopressin can stimulate release of FVIII:C and von Willebrand factor.
What are the complications of recombinant factor VIII or IX?
5 - 20% develop antibodies to the recombinant factor, which reduces or completely inhibits effect treatment
Transfusion-transmitted infections such as hepatitis A, B and C, HIV and prions
Vascular access can be difficult. Central venous access may be required which may become infected or thrombosed.
What are the two main functions of von Willebrand factor?
Facilitates platelet adhesion to damaged endothelium
Acts as carrier protein for FVIII:C, protecting it from inactivation and clearance.
What is the inheritance pattern of von Willebrand disease?
Usually autosomal dominant
When is the most common type of von Willebrand disease (type 1) usually diagnosed?
Not until puberty or even adulthood
What are the clinical features of von Willebrand disease?
Bruising
Excessive, prolonged bleeding after surgery
Mucosal bleeding such as epistaxis and menorrhagia
Unlike haemophilia, soft tissue haematomas and haemarthrosis are uncommon
How do we manage a patient with von Willebrand disease?
Depends on severity.
Type 1 (mild) - usually treated with desmopressin
More severe - plasma-derived FVIII (contain vWF unlike recombinant FVIII)
What are the main acquired disorders of coagulation affecting children?
Vitamin K deficiency leading to haemorrhagic disease of the newborn.
Liver disease
Immune thrombocytopenia
Disseminated intravascular coagulation
What is vitamin K used for in terms of coagulation?
Essential for production of active forms of factors II, VII, IX, X
Why might children become deficient in vitamin K?
Inadequate intake - neonates, long term chronic illness
Malabsorption - coeliac disease, cystic fibrosis, obstructive jaundice
Vitamin K antagonists - warfarin
What is the definition of thrombocytopenia?
Platelet count less than 150 x 10^9/L
What are the different grades of thrombocytopenia by platelet count?
Mild is 50 - 150 x 10^9/L - low risk of bleeding unless there is major operation or severe trauma
Moderate is 20 - 50 x 10^9/L - risk of excess bleeding during operations or trauma but low risk of spontaneous bleeding
Severe is less than 20 x 10^9/L - risk of spontaneous bleeding
What are the clinical features of thrombocytopenia?
Bruising
Petechiae
Purpura
Mucosal bleeding - epistaxis, bleeding from gums
What is the most common cause of thrombocytopenia in children?
Immune thrombocytopenia (ITP)
What is the incidence of ITP?
4 per 100, 000 children per year
What is the pathophysiology of ITP?
Usually caused by destruction of circulating platelets by anti-platelet IgG autoantibodies. Usually follows 1-2 weeks after a viral infection.
What is the peak age of incidence for ITP in children?
Between 2 and 10 years old
What are the clinical features of ITP?
Widespread petechiae and purpura
Superficial bruising
Epistaxis and other mucosal bleeding
How do we diagnose ITP in children?
It is a diagnosis of exclusion. FBC will show low platelet count. The differentials to exclude include:
Leukaemia - any atypical features should prompt bone marrow examination
DIC
Wiskott-Aldrich syndrome
Bernard-Soulier syndrome
SLE
How do we manage a child with ITP?
ITP is usually self-limiting, remitting spontaneously after 6-8 weeks.
Normally do not require admission
Treatment should be given if there is evidence of major bleeding or persistent bleeding that affects daily life (eg epistaxis)
Treatment options:
Oral prednisolone
IV anti-D
IVIG
Platelet transfusion (only in life-threatening scenarios)
If steroids are to be started in someone with suspected ITP, what investigation must be done first and why?
Bone marrow examination as steroid therapy can mask undiagnosed ALL. Steroid therapy will compromise the long-term outcome of such patients.
What do we define as chronic ITP?
When platelet count remains low 6 months after diagnosis
What percentage of children with ITP will develop chronic ITP?
20%
How do we manage children with chronic ITP?
Usually supportive therapy is all that is needed
Drug treatment includes Rituximab and thrombopoietic growth factor
Must also perform regular screening for SLE
What is disseminated intravascular coagulation?
A process characterised by the widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body. This leads to compromise of tissue blood flow and can ultimately lead to multiple organ damage. In addition, as the coagulation process consumes clotting factors and platelets, normal clotting is disrupted and severe bleeding can occur from various sites.
Disseminated intravascular coagulation occurs as a complicating factors for other underlying conditions. What conditions can lead to DIC in children?
Cancer - both solid and blood (particularly acute promyelocytic leukemia)
Massive tissue injury - eg burns
Sepsis
Transfusion reaction
Severe allergic or toxic reaction - eg snake venom
What investigations might be ordered to further assess someone with suspected disseminated intravascular coagulation? For each state what might be found in a positive result.
Prothrombin time increase
Activated partial thromboplastin time increase
Low fibrinogen
Rapidly declining platelet count
Positive D-dimer
Blood film shows schistocytes
Reduction in naturally occuring anticoagulants protein C and S and antithrombin.
How is disseminated intravascular coagulation treated?
Treat underlying cause
Supportive care includes FFP, cryoprecipitate and platelets.
