Haemostasis and Thrombosis Flashcards
Main 3 components of coagulation?
Coagulation - making the clot
Anticoagulants - limiting the size of the clot
Fibrinolysis - remodel the clot and resolve the clot
What can contribute to clotting?
Endothelial surface (when activated)
Platelets
Von Willebrand factors
Coagulation Factors
What can aid bleeding?
Natural anticoagulants (help control the clot)
What is the function of fibrinolysis?
Remodel or remove clot
If there is a problem with clotting how will this manifest?
Patient has bleeding tendency
If there is a problem with natural anticoagulants/bleeding how will this manifest?
Patient has clotting tendency
First response to injury?
Vasoconstriction
During vasoconstriction how do platelets react?
Release serotonin and thromboxane A2 which activates them - forms platelet plug
Why do we feel pain during vasoconstriction?
Sympathetic interpretation to help vasoconstriction
What is the next step of clotting after vasoconstriction
Formation of platelet plug
How is a platelet plug formed?
When collagen is exposed platelets release serotonin and thromboxane A2 which activates them - they change shape and become adhesive
When does the first response to injury occur in terms of clotting?
When collagen is exposed (damaged endothelium)
How can platelets bind directly to the endothelium?
Von Willebrand factor
What does the platelet plug bind to?
Exposed collagen
What are the 3 parts of the coagulation cascade?
Intrinsic Extrinsic and common
What is the first clotting factor of the common pathway?
10
What activates the extrinsic pathway?
Tissue factor
What is the end result of the common pathway?
Clotting factors activate thrombin which activates fibrin
What 4 things do we need to healthy coagulation?
Platelets - number and function
Von willebrand factor
coagulation factor
Clot stability
What type of condition is Haemophilia? How does it cause problems?
X-linked condition - genetic = deficiency of clotting factor 8 and 9
How is haemophilia classified?
Severity based on normal concentration of coagulation factor %
How does a patient with very severe haemophilia (concentration of coagulation factor less than 1%) react?
Spontaneous bleeding
How does a patient with moderately severe haemophilia react?
Severe bleeding after surgery
Risk of haemophilia in young?
Not yet diagnosed so spontaneous bleeding in joints leads to arthritis
How is haemophilia now treated?
Recombinant gene therapy treatment - gene cloned
How is haemophilia C transmitted?
Blood transfusion
Hemlibra is a new gene therapy for haemophilia treatment. How does it work?
It is an antibody that binds factor 9 and 10 and leads to activation and formation of fibrin
Why is hemlibra (new gene therapy treatment) better than previous treatments?
Doesn’t get injected into the vein only under the skin once every 2 weeks = less often so better quality of life
How does von Willebrand disease present?
Mucosal bleeding - bruising, nosebleeds, heavy periods, GI bleeding
Function of Von Willebrands factor?
Helps bind Platelets to endothelium and each other
How can Von Willebrand disease be classified?
Type I = mild deficiency in VWD
Type II - normal number but mutation effecting the function of VWD
Type III - severe deficiency
How can problems with platelets be classfied?
Low number or functional defects
What drugs is given to treat functional defects of platelets?
Aspirin
In general how should a patient with bleeding disorders be managed during surgery (5)
Close liaison with haemophilia centre
Platelets transfusion or DDAVP (increase VWF)
Atraumatic technique to secure local haemostasis
Oral tranexamic acid = antifibrinolytic = stabilise clot
Warfarin mechanism of action?
inhibit thrombin (vit K reductase inhibitor)
How is warfarin dealt with in surgery?
Don’t alter - check INR
Why is it advisable to not stop warfarin treatment (especially when INR is normal)?
Can increase risk of thrombosis
Name 2 type of DOAC?
Direct thrombin inhibitors
Xa inhibitors
Dabigatran is a direct thrombin inhibitor, describe its mechanism of action?
Reversible thrombin inhibitor
Mechanism of action fo Xa inhibitors?
Bind to activated factor 10
