10. disorders of haemostasis cont. Flashcards
3 types of inherited coagulation defects
Haemophilia A
Haemophilia B
von Willebrand’s disease
what factor does haemophillia A affect
factor 8
in terms of genetics what kind of disorder is haemophillia A
x linked recessive disorder
(but can alsos be spontatneous mutation with no family history)
why is there vaiability on haemophillia A symptoms
depends on factor 8 level
sever haemophillia symptoms
- Bleeding into joints and less frequently muscles
- Knees, elbows and ankles most commonly affected
- Majority of bleeds that require treatment.
- Presenting symptoms: pain in affected areas.
- Intracranial bleeding: main cause of death from the disease.
what is bleeding into joints called
haemarthrosis
how is haemophillia A diagnosed
- prolonged APTT
- confirmed by factor 8 clotting assay
- IF family suspects haemophillia, then chorionic biopsy at 8-10 weeks can be done to analyse DNA
at what % of factor 8 will symptoms start to show
under 50%
so between 25-50, will see bleeding after severe trauma
what symptoms to we see in mild haemophillia
5-25% factor 8 in blood
- severe bleeding after surgery
- slight bleeding after minro trauma
symotoms seen in moderate haemophillia A
1-5% factor 8 in blood
- severe bleeding after slight trauma
symptoms in severe haemophillia A
less than 1% of factor 8
severe frequent spontaneous bleeds in joints and muscles
how is haemophillia A treated during a bleed
recombinant factor 8 used to replace factor 8
how is mild haemophillia A treated
DDAVP
a vasopressin
which molibilises factor 8 from endothelial cells
what factor does haemophillia B affect
factor 9
how does haem B present compared to haem A
no difference
clinically undistinguishable
(but much less common)
in terms of genetics what kind of disorder is haemophillia A
X linked recessive bleeding disorder
how is haem B diagnosed
APTT prolonged
Diagnosis is confirmed by factor IX clotting assay.
how is haem B treated
factor 9 replacement
in terms of genetics, what kind of disease is VWD
autosomal dominant
affects 1 in 100 but is only clinicall significant in 1 in 10,000
3 different types of VWD
- type 1 and 3 = based on number of molecules
= partial reduction or near absence of VWD molecules - type 2 = abnormal function of the protein
why would VWD diagnosis inclued testing for factor 8
VWD is a carrier for factor 8
so would be decreased in VWD as well
what could be tested to diagnose VWD
would have impaired platelet aggregation
what is the bleeding characteristics in VWD
extent is variable
- might have spontaneous in mucous membranes and skin
- severe haemorrage after surgiccal procedures
what is used to treat VWD
DDAVP
mobilises both VWf and factor 8
which type of VWD is the DDAVP treatment effective for
Type1 = reduced amount, but still some, so can mobilise what is inside cells already
what could cause acquired coagulation disorders
- vit K deficiency
- disseminated intravascular coagulation
- liver disorders
what is thrombus made up of
platelets and fibrin
thromboembolism definition
occlusion of a vessel by a blood clot which has moved from its starting position
what is thrombophilia
a condition that increases your risk of blood clots
what is virchows triad
outlinesthe presence of three factors that predisposes a person to develop vascular thrombosis =
- endothelial injury (changes in blood vessel walls)
- hypercoagubility (changes in blood constituents)
- venous stasis (sitting for long times)
2 diseases caused by arterial thrombosis
stroke
myocardial infarction
stroke
- Disturbance in blood supply to brain
- Thrombotic stroke: thrombus usually forms around atherosclerotic plaque with gradual blockage of artery
Myocardial infarction
- Caused by an infarct (death of tissue due to ischemia)
- after obstruction of coronary artery
how can myocardial infarction be treated
only if within 12 hrs of intial attack
then thrombolytic theraoy (e.g. tPA) can be initiated
where is deep vein thrombosis most common
lower limbs
symptoms of DVT
swelling
pain
pulmonary embolism
pulmonary embolism symptoms
- dysponea
- tachypnoea
- pleuritic chest pain
risk factors for venous thrombosis
- hereditary
= factor 5 leiden - or raised levels of other factors
- oral contraceptives
- malignancy
- stasis
what is factor 5 leiden
- most common inherited cause of increased risk of venoue thrombosis
- point mutation in factor 5 gene
- which means factor 5 less susceptible to cleavage by protein C
- homo = 50x increase risk of thrombosis
- het = 7 x increased risk
what is used for antithrombotic therapy
anticoagulants = prevention
thrombolytic agents = dissolve thrombus
2 anticoagulants
heparin
warfarin
how do thrombolytic agents work
- act as plasminogen activators, converting plasminogen into plasmin
- Plasmin will then dissolve the fibrin of a blood clot
2 commonly used thrombolytic agents
streptokinase
tissue plasminogen activator
