Session 5: Haemostasis Flashcards
Define haemostasis.
The stopping of haemorrhage. A physiological response to a damaged blood vessel.
Haem = blood
Stasis = halt
Halting of blood
What is the main difference between fibrinogen and fibrin filaments?
Fibrinogen is soluble and therefore travel in the blood freely.
Fibrin filaments are insoluble and will therefore trap red blood cells forming a clot.
Outline the three steps of haemostasis. (In a severed artery e.g.)
- The artery contracts
- Primary haemostat plug of activated platelets forms at the hole of injury. It sticks to the injured vessel and the connective tissue outside of it.
- Secondary haemostatic plug forms as fibrin filaments stabilise the friable platelet plug into a blood clot. Forms in around 30 minutes.
Why does the artery contract in haemostasis? How does this differ from severing a vein?
To decrease the pressure downstream. This doesn’t occur in veins as the blood pressure is already much lower.
What are the three main players in haemostasis?
Platelets, the process of blood clotting and the vascular wall.
What are platelets activated by?
Collagen surfaces within extravascular areas.
ADP
Thromboxane A2
Thrombin
What is ADP released by in the activation of platelets?
From already activated platelets and also by injured red blood cells which will amplify the platelet response.
What is thromboxane A2 released by?
By already activated platelets
Explain what happens in the clotting process after the platelets are activated?
They start sticking to the exposed basement membrane or collagen via von Willebrand factor which is concentrated on the basement membrane. The von Willebrand factor helps in adhesion.
The platelets starts to aggregated with other platelets via cross linking. This forms a plug. Also fibrinogen starts to bind to the platelets and sticks them together.
Swelling of the clot starts to occur and it changes into a sticky, spiny sphere.
The platelet granules will start to secrete factors like fibrinogen, ADP and thromboxane A2 in order to increase the platelet plug’s size and aid in clotting. This is an example of positive feedback.
What is the mechanism of aspirin?
Irreversibly inactivates cyclooxygenase which is one of the enzymes responsible for production of thromboxane A2. This means that platelet aggregation will be decreased.
Give the most important factors of blood clotting.
Platelets Von Willebrand Factor Fibrinogen Collagen ADP Thromboxane A2 Thrombin
What is the role of thrombin?
To cleave circulating plasma protein fibrinogen into the insoluble fibrin.
Why doesn’t thrombin keep activating fibrinogen in the blood?
Because it needs to be activated in order to start cleaving fibrinogen.
What activates thrombin?
In short it is Factor Xa but it is a long pathway to get there with multiple factors.
What is required in the synthesis of the factors for blood clotting?
Vitamin K.
What other important co-factors are needed for effective clotting?
Phospholipids and calcium.
What is the difference between the intrinsic and the extrinsic pathways of clotting?
The intrinsic pathway involves factors which are all contain within the blood. It is triggered by a negatively charged surface and no vessels needs to be broken open for it to occur.
The extrinsic pathway involves factors which are not contained within the blood. It relies on a tissue factor called thromboplastin (formerly Factor III) which is present outside of the blood. The thromboplastin is released from damaged cells adjacent to the area of haemorrhage.
How does the vascular wall play a role in haemostasis?
The arterial wall contracts.
The subendothelium traps platelets with the help of von Willebrand factor.
The endothelium also release tissue factor (thromboplastin) to help in blood clotting.
However the vascular wall and endothelium in particular doesn’t only promote blood clotting but also the opposite.
Endothelium release plasminogen activator which will in its turn activate fibrinolysis which dissolves a clot. Endothelium also release protein C which interferes with the clotting cascade as an anticoagulant.
Give examples of factors that oppose clotting. What happens if these are not present?
Antithrombin III
Protein C
Protein S
If any of these lack a person might experience repeated episodes of thrombosis.
Explain fibrinolysis.
The clotting cascade sets fibrinolysis in motion because fibrin increases the activity of tissue plasminogen activator. tPA activates plasminogen into plasmin. Plasmin will then break down the fibrin into fibrin degradation products also called FDPs or D-dimers.
There are other plasminogen activators. Which?
Urokinase found in urine.
Streptokinase obtained from streptococci.
D-dimers are increased in certain conditions like?
Where there is thrombosis.
DIC, DVT and pulmonary embolism.
What happens to fibrinolysis after surgery?
The activity drops and remains low for about 7-10 days. Increased risk of thrombosis because of this.
Explain the extrinsic pathway of clotting.
Endothelial cell injury leads to release of thromboplastin. This tissue factor turns factor VII into factor VIIa (activated).
Factor VIIa activates factor X into factor Xa.
Factor Xa turns prothrombin into thrombin.
Thrombin cleaves fibrinogen into fibrin.
Explain the intrinsic pathway.
A negatively charged surface turns Factor XII into Factor XIIa.
This turns Factor XI into factor XIa
Factor XIa turns factor IX into factor IXa.
Factor IXa with the help of Factor VIIIa then turns factor X into Factor Xa.
