Haemostasis: Flashcards
What is haemostasis?
Prevents and stops bleeding
How quickly after injury does hemostasis occur?
Seconds to hours
What are the three main processes in hemostasis?
Vasoconstriction, platelet aggregation, leucocyte migration
What happens when there is too little hemostasis?
Excessive bleeding, clotting defects and platelet deficiency
What happens if there is too much hemostasis?
Thrombus formation, atherosclerosis, septicemic shock
How many platelets are in a ml of blood?
250 million
What is thrombocytopenia?
Struggle with blood clotting
What happens to the structure of a platelet when it is activated?
Morphological change - changes from a smooth to rough surface with extensions due to rearrangement of actin and myosin
How are platelets activated?
- Platelets adhere to damaged collagen
- Binding sites include involvement of von Willebrand factor (vWF)
- vWF released from endothelial cells and present in plasma
- Platelets become activated
How is platelet activation an example of positive feedback?
Activated platelets release biochemicals into area for increased vasoconstriction, which results in more collagen being exposed and more platelets being activated
What does ADP do in platelet plug formation?
Makes platelets sticky
What does serotonin do in platelet plug formation?
Activates vasoconstriction
What does thromboxane A2 do in platelet plug formation?
It is a prostaglandin - vasoconstrictor and activates
How does a platelet plug form?
- Adhesion, activation, aggregation
- ADP makes platelets sticky
- Serotonin activates vasoconstriction
- Thromboxane A2 is a prostaglandin - vasoconstricts and activates
- Platelet adhesion activates platelets (morphological and biological change)
What is a platelet plug?
Cell fragments of megakaryotes present in the blood with no nucleus/organelles/DNA/proteins
What are the two pathways in the coagulation cascade?
Intrinsic and extrinsic
When is the intrinsic pathway triggered?
When blood in cells is exposed to collagen
Why must venepuncture test tubes be coated with anti-coagulant?
To stop initiation of the intrinsic pathway
Where does the extrinsic pathway occur?
Tissues
What is factor 13 activated by?
Thrombin
What happens during the intrinsic pathway?
Co-factors 12, 11 and 9 are activated which converts 10 to its active form
What does thrombin do?
Converts fibrinogen to fibrin to form a mesh
Do RBCs contribute to the hemostasis process?
No
Where is fibrinogen produced?
Liver
Describe the process of the final common pathway in the coagulation cascade
Prothrombin activator converts prothrombin to thrombin
Reaction requires calcium
Thrombin converts fibrinogen into fibrin
This forms cross-linked fibrin clot
What happens during the intrinsic pathway?
Activated by contact with a damaged surface
factor XII - factor XI - factor IX (+factor VIII and vWF)
What happens during the extrinsic pathway?
Activated by release fo tissue factors
Factor VII - common pathway
What does prostacyclin do?
From intact endothelium, inhibits platelet adhesion and aggregation
What does nitro oxide do?
From intact endothelium inhibits platelet adhesion
How does the liver assist with clotting?
Synthesises clotting factors and bile salts
What do bile salts do?
Increase rate of uptake of vitamin K from GI tract and move it to blood
What does warfarin do?
Vit K antagonist
Anticoagulant
How is a clot removed?
- Cell growth and cell division repairs damaged vessel
- Clot retracts and dissolves
- Plasmin (an enzyme) trapped in the clot acts on fibrin to break it into soluble fragments
- Plasmin takes around a week to act
How is plasmin made?
Plasminogen reacts with TPA
How does the endothelium prevent clot formation?
Intact it separates collagen, tissue factors and vWF
How does glycocalyx prevent clot formation?
Inhibits adhesion of platelets
How do prostacyclin and nitric oxide prevent clot formation?
Inhibits platelet activation and aggregation
How do CD39 and ecto-ADPases prevent clot formation?
Metabolize ADP
How does TPA prevent clot formation?
Dissolves fibrin
How does heparin sulphate prevent clot formation?
Co-factor for antithrombin
Why is antithrombin an anti-coagulant?
Inactivates thrombin
Inactivates factor Xa and IXa
Which factors do coumarin drugs impact?
II, VII, IX and X
What is a thromboembolism?
Abnormal clot formation
What is a thrombus?
Clot attached to vessel
What is an emboli?
Free-floating clots
Examples of anti platelet drugs
Aspirin, clopidogrel
Examples of anticoagulant drugs
Warfarin, heparin
Examples of fibrinolytic drugs
Urokinase, streptokinase, genetically engineered tissue plasminogen activator (t-PA)
Why should aspirin not be taken before surgery?
Reduces platelets binding to sub-endothelial components
Impairs platelet aggregation
Prolongs bleeding
Where is heparin used?
Catheters, dialysis, heart-lung machines
Examples of calcium ion reducers
EDTA, citrate, oxalate
What do siliconised containers do?
Reduce platelet activation
Processes inside haemostasis
Vasoconstriction
Platelet aggregation
Leucocyte migration
Processes inside inflammation
Early = neutrophil, late = macrophage
Chemoattractant release
phagocytosis
Processes inside proliferation
Collagen and ECM synthesis
Angiogenesis
Fibroblast proliferation
Granulation tissue formation
Processes inside remodelling
Epithelialisation
ECM remodelling
Increase in wound strength
