Coagulation Flashcards
What are the major stages of Haemostasis?
- Damage to Blood Vessel Wall
- Platelet Adhesion to blood vessel wall
- Platelet Activation
- Platelet Plug Formation
- Coagulation Cascade
What is the First Step of the Initiation Phase of the Coagulation Cascade?
What does this step activate?
Activation of Factor VII in the presence of tissue factor.
Contributes to the activation of Factors IX and X
Where does vWF act on the Coagulation Cascade?
Factor VIIIa
Where does Antithrombin act on the Coagulation Cascade?
Factors IXa and Xa and Thrombin (IIa)
Where does Activated Protein C act on the Coagulation Cascade?
What is its mechanism of action?
Va and VIIIa
Inhibits amplification phase
Proteolyses peptide binds in FVa and FVIIIa
deactivates them
Where is Calcium required in the Coagulation Cascade?
Activation of Factor X and II (prothrombin to thrombin)
What does the Thrombin Burst cause?
Positive Feedback
Amplification phase
Activates more Platelets
Activates Factors XI, VIII and V
What factor causes a loose mesh to become a stable clot?
Factor XIIIa
How to Platelets stick to Exposed Collagen?
Glycoprotein Ia
How to vWF and Fibrinogen promote platelet aggregation?
Glycoprotein IIb and IIIa
What are the 3 aims of clot regulation?
- prevent clot formation in normal vessels
- restrict clot to damaged area
- remove clot as tissue repair is completed
What is the role of the Liver in clotting?
Synthesises clotting factors by synthesising bile salts
Bile salts released into the GI tract in bile
Allows absorption of vitamin K (with pancreatic juices)
Post-translational modification produces clotting factors in blood
How is a clot broken down?
Plasminogen in incorporated into a clot
This is activated into plasmin
Plasmin causes the breakdown of fibrin into fibrin degradation products (FDPS)
FDPs are soluble forms of fibrin
What activates plasminogen?
tPA - tissue plasminogen activator
urokinase/streptokinase - fibrinolytic drugs
What activates fibrinogen?
Thrombin
What is the role of the endothelium in preventing clot formation and propagation?
Separates tissue factor and circulating FVII
Cover vWF - prevent platelet adhesion
Collagen not exposed
Glycocalyx - prevents platelet adhesion
Prostacyclin and Nitric Oxide - prevent platelet adhesion and aggregation
CD39 - metabolises ADP released by activated platelets
tPA - involved in clot breakdown
Thrombomodulin - activates protein C, absorbs excess thrombin
Heparin sulfate - cofactor for antithrombin
What is Purpura and what are the different types?
Collective term for bleeding into the skin or mucous membranes
Petechia - small haemorrhages up to pin head size
Ecchymoses - larger haemorrhages
What is thrombocytopenia?
How does it present?
Low blood platelet count
Petechiae in skin and other tissues
What are the indications for Anticoagulant Therapy? (3)
Prophylaxis
Post-Thromboembolic event
During therapeutic procedures
How do anticoagulant drugs work, generally?
What are the different types of anticoagulant drugs?
Prevent or reduce coagulation of blood
Prolong clotting time
Do not stop the formation of a platelet plug
Act on the clotting cascade to prevent fibrin production
Heparin
Warfarin
DOACs
What are the two types of heparin?
Unfractioned heparin
Low molecular weight heparin
What is the mechanism of action of Heparin?
Increases effectiveness of antithrombin-III
Inactivates thrombin and Factors VIII, IX, X, XI, XII
How is unfractioned Heparin administered?
Subcutaneously or Intravenously
What is used to monitor unfractioned heparin?
APTT activated partial thromboplastin time
