Haemostasis

Question 1

What is haemostasis?

Answer 1

It is a life-preserving processes designed to maintain blood flow. It responds to tissue injury, curtails (reduces) blood loss, restores vascular integrity and promotes healing, and limits infection.

It’s a protective process evolved in order to maintain a stable physiology.

Question 2

What are the four key components of haemostasis?

Answer 2

• endothelium
• coagulation
• platelets
• fibrinolysis

Question 3

What makes a blood clot?

Answer 3

• fibrin mesh
• platelets
• red blood cells

Question 4

What are the three stages of the haemostatic system?

Answer 4

PRIMARY HAEMOSTASIS;

• vasoconstriction (immediate)
• platelet adhesion (within seconds)
• platelet aggregation and contraction (within minutes)

SECONDARY HAEMOSTASIS:

• activation of coagulation factors (within seconds)
• formation of fibrin (within minutes)

FIBRINOLYSIS:

• activation of fibrinolysis (within minutes)
• lysis of the plug (within hours)

Question 5

Describe primary haemostasis.

Answer 5

With haemostasis at rest, the triggers and cofactors are separated by endothelial cells.
If the endothelial tissue is gone, we expose the blood to components of the subendothelial tissue. When collagen, which was in the subendothelial tissue, is exposed, it attracts Von Willebrand factors (vWFs).
Normally, vWFs circulate in the blood as globules, but when there is an injury, it exposed a sticky part of its molecule which recognises collagen, so it will stick to the site of injury.
The vWFs bind platelets. When the platelets bind, they change morphologically (become activated); they become flatter for a larger surface area. They also release important mediators of coagulation.
More platelets bind and get activated, and eventually, coagulation occurs on the platelet surfaces.
This plug of platelets, localised to the site of injury, provides the phospholipid surface upon which secondary haemostasis takes place.

We say that vWF activity occurs under shear stress because, in areas of injury, the blood flow becomes more turbulent.

Question 6

What is secondary haemostasis?

Answer 6

It is the stabilisation of the platelet plug with fibrin blood coagulation, contracting the clot.

After primary haemostasis, there is then the activation of coagulation factors which then froms the fibrin clot. This is blood coagulation. Prothrombin is converted into thrombin. Thrombin, along with Ca2+, causes fibrinogen to be converted to fibrin.

Question 7

Where are most coagulation proteins made?

Answer 7

Most coagulation proteins are made in the liver. Vitamin K is also needed, because some factors require activation via Vitamin K.

If someone has liver disease, they may have bleeding problems because no factors are being made.

Question 8

Describe fibrinolysis.

Answer 8

It is the process of clot dissolution, which allows for repair and the proper healing process (ie. replacing the clot with normal tissue).
Its main functions are the clot limiting mechanism and the repair and healing mechanism.
There are a series of tightly regulated enzymatic steps, such as feedback, potentiation and inhibition.
The key players in this process are:
- Plasminogen
- Tissue plasminogen activator (t-PA) and urokinase (u-PA)
- Plasminogen activator inhibitor -1 and -2
- α2-plasmin inhibitor

Question 9

Describe the process of fibrinolysis.

Answer 9

Plasminogen is converted into Plasmin, with the help of tissue plasminogen activator (t-PA).
D dimers are generated when cross-linked fibrin is degraded.
FDP (fibrin degradation products) are generated if non-cross-linked fibrin or fibrinogen is broken down.

We can test blood for D dimers to see if a blood clot is degrading properly.

t-PA and a bacterial activator, streptokinase, are used in therapeutic thrombolysis for myocardial infarctions (to help remove the blood clot).

Question 10

What are the two ways in which a blood clot can form?

Answer 10

• through Tissue Factor-driven clot formation

- through surface activation

Question 11

Describe the balance of haemostasis, and what happens when it is unbalanced.

Answer 11

In normal haemostasis, fibrinolytic factors and anticoagulant proteins (preventing blood clot), and coagulation factors and platelets (creating blood clot) are in equilibrium.

If there is an increase in coagulation factors and platelets, this can lead to thrombosis (formation of a blood clot inside a blood vessel). One of the conditions this could lead to is chronic venous insufficiency (CVI), which can cause atrophic changes, hyperpigmentation, ulceration and infection. This occurs because the legs don’t get the nutrients, etc. needed.

If there is an increase in fibrinolytic factors and anticoagulant proteins, this can lead to easy bruising (ecchymosis).

Question 12

Describe a coagulation screen.

Answer 12

A coagulation screen can assess for deficiences of coagulation factors. There are three times that can be measured:
PROTHROMBIN TIME (PT)
- sensitive to the extrinsic pathway and, to a lesser extent, the common pathway
- tissue factor driven

ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT):

• sensitive to the intrinsic pathway and, to a lesser extent, the common pathway
• contact activated

THROMBIN TIME (TT);
- sensitive to defects in conversion of fibrinogen to fibrin