Abnormalities Of Haemostasis Flashcards
What substances do we need to form a blood clot
Platelets
VWF
Clotting factors: proteases (F2,7,9,10)- these are dependent on vitamin k, and f11. Co factors: f5,8, fibrinogen and factor 13.
White blood cells
What is the primary haemostasis
Formation of an initial haemostastis plug that contributes by platelets and VWF
What is the secondary homeostasis
Involvment of clotting factors to form a stable clot
What do we need for normal haemostasis
Normal vessel wall integrity
Adequate number of platetes and platelets funcitoning properly
Adequate number of clotting factors
Proper function of fibrinolytic pathway- this breaks down blood clots to stop thrombosis
What happens when a blood vessel is injured
- Localised vasoconstriction at the site of injury
- Exposure of collagen from blood vessel starts platelet adhesion to subendothelium of damaged blood vessel (primary haemostasis)
- Platelet aggregations/activation, this contributes to thrombus formaiton.
- Vasoconstriction and release of tissue factor from the vessel wal activates of coagulation cascade
- This cuases insoluble Fibrin formation (scaffol) formation which contributes to thormbus formation
- Fibrinolytic degradation of clot once the bleeding has stopped.
What lab test can be used to investiage the haemostatic system
Platelet count
Prothrombin count (PT)
Activated partial thromboplastin time (APPT)
Fibrinogen level
What is INR
International normalised ratio (pt of the patietn to the mean in the population)
Which particular patients should have their INR checked
Warfarin users
What pathway does the PT measure
Extrinsic pathway
What pathway does the APPT measure
Intrinsic pathway
What are the pathways in the clotting cascade
- Intrinsic pathway
- Extrinsic pathway
- Final common pathway
Describe what happens in the extrinsic pathway
- Releease of tissue factor from vessel wall causes cleavafe of factor 7 to acitvated factor 7
- Activated factor 7 cleaves factor 10 to factor 10a
What happens in the intrinsic pathway of the clotting cascade
- Factor 12 cleaves to form acitvated factor12
- Factor 12a cleaves factor 11 to factor 11a
- Factor 11a cleaves factor 9 to factor 9a
- Factor 9a cleaves factor 10 to factor 10a with factor 8
What happens in the final common pathway in the clotting cascade
- Both intrinsic and extrinsic pathway lead to the formation of factor 10a
- Factor 10a with factor 5 cleaves prothrombin into thrombin
- Thrombin cleaves fibrinogen to fibrin
- Thrombin also cleaves factor 13 to factor 13 a which in turn cleaves fibrin to form a stable fibrin clot by crosslinking fibrin
What receptors are on the surface of platelets
Gp1b receptor
Gp11b/3a receptoro
What does gp1b bind to
VWF
What does GP11B/3A bind to and what does it cause
Other platelets to cause platelet aggregation
Descirbe what happens in primar haemostasis
- There is exposed collagen on the damaged vessel wall
- VWF binds to the collagen receptors
- VWF changes configuration
- Platelets bind to WVF via gp1b receptor on platelet surface
- Platelet becomes activated and releases their secondary granules to cause platelet activatation and aggegation
- Platelets cross link with gp11b/3a receptor and VWF
- This forms a platelet clot that occludes the blood vessel
What 2 problems can occur with WVF to cause disease
- Quantitative deficiency of VWF
3. Qualitative defect of VWF
What are the types of quantitative deficiency of VWF that can occur
Type 1: partial
Type 3: complete absence of VWF
What are the types of qualitaitve defect of VWF that can occur i.e there are normal numbers of VWF but the function is abnormal
Type 2a: decreased interaction of VWF with platelets to from multimers of VWF (many wvf stuck togehter)
Type 2b: increased affinity of VWF for platelet gp1b
Type 2m: decreased interaction of vwf with platelets- not associated with mutlimers of VWF
Type 2n: decreased affinity of vwf for factor8
What are the secondary mediators involved in platelet activation and aggregation
Adp
Thrombin
Collagen
Txa2
What happens when the platelets release granules
The platelets become activated by chaning shape and increase SA to enable them to interact with other clotting factors
What are the types of granules platelets have
Alpha
Dense
What do dense granules release
Adp
Calcium
5HT
What do alpha granules release
FGN Factor 8 VWF Factor 5 PDGF
What are the types of congenital disorders platelets can have
- absence of granules
- abnormality of platelet receptor
If there is an absence of alpha granules what does this resultin
Grey platelet syndrome
If there is an absence of dense granules what does this result in
Storage pool disease
If there is an absence of GP1B receptor on platelet what does this result in
Bernard soulier syndrome
If there is an absence of gb11b/3a receptor of platelet what does this result in
Glanzmann thrombastenia
Which protein cleaves VWF multimers
ADAMTS13
What happens when VWF mutlimers keep on formin and there is a deficiency of ADAMTS13
Thrombosis occurs
What is TTP
An autoimmune condition with deficiency of ADAMTS13 so VWF mutlimers form and thrombus occurs
What is the treatment of TTP
Plasma exchange
What is the reduction in factor 8 called
Haemophillia
What is haemophillia
X-lined conditon i.e males can have condition and females will be carriers
What is the treatment of haemophilia
Giving missing clotting factor
Emicizumab
What is emicuzumab
An antibody that binds to factor 9 and 10 so it stimulates the down cascade independent to factor 8
How is fibrin formed
Thrombin cleaves fibrinogen to fibrin
What is fibrin
The scaffold of platelets
How does fibrinolysis occur
Plasminogen is cleaved by tpa to give plasmin
Plasmin breaks down fibrin to break the blood clot
What is a measure of the break down product of fibrinolysis
D-dimer
What does a d dimer tell us
That active coagulation and fibrinolysis has been occuring
What drugs can we have to stop fibrinolysis and therefore stabilise blood clots
Tranexamic acid
How does tranexamic acid work
Inactivates plasminogen
Who is tranexamic acid given to
Patients that are bleeding heavily
What is immune thrombocytopenia purpurin
A reduction in platelets due to antibodies that are directed against the glycoprotein, gp11b/3a or GP1B
What does VWF present as
Menorhhagia
What does haemophilia a present as clinically
Bleeding in the joints and muscles and is common in men
