HAEMOSTASIS

Question 1

What is Haemostasis?

Answer 1

Haemostasis is the process of initiation & termination of blood coagulation with removal of clot as part of vascular remodeling

A protective process that ensures minimal blood loss from sites of vascular injury without compromising blood flow generally.

Question 2

The physiological process of haemostasis results in what?

Answer 2

The physiologic process results in:

• Maintenance of vessel integrity & patency
• Prevention of further blood loss from damaged vessels & initiation of repair, while
• Blood flow through the blood vessel is maintained

Question 3

The 2 components Primary haemostasis

Answer 3

Primary haemostasis
* Blood vessels (vasoconstriction)
* Platelets (Formation of platelet plug)

Question 4

What are the five major components of haemostasis?

Answer 4

Blood vessels,
Blood platelets,
Coagulation factors,
Coagulation inhibitors,
Fibrinolysis

Question 5

Discuss Vasocontriction in Primary haemostasis, what 2 things does it result in?

Answer 5

Vasoconstriction

• Vessel wall has 3 layers: intima, media & adventitia contributing to haemostasis
• Vasoconstriction is a result of direct vessel injury
• Vasoconstrictors released from platelets, endothelium helps e.g. vasoactive amines, Thromboxane A2
• Pain also result in reflex sympathetic vasoconstriction
• Attempt is made to breach gap especially in big arteries
• Vasoconstriction essentially results in two things:

1. Reduced blood flow to site of injury thereby minimizing blood loss
2. Slowing down of blood flow allows platelets and clotting factors the opportunity to make contact with site of injury

Question 6

Electron dense granules consist of

Answer 6

Ca2+
ADP
Serotonin

Question 6

Discuss Platelet and platelet plug formation in Primary haemostasis

What is the function of the various glycoprotein inhibitors?

Answer 6

Produced in the bone marrow by fragmentation of the cytoplasm of megakaryocytes

Megakaryocytes mature by endomitotic synchronous replication

Each megakaryocyte can give rise to 1000 – 5000 platelets

Differentiation of human stem cell to production of platelets averages 10 days

Aggregation & Activation:
Platelet is activated on exposure to damaged wall (collagen)

Aggregate at site of injury to form platelet plug sufficient to plug small holes

Attach to vessel wall (collagen) by glycoprotein Ia receptor and to vWF (sub-endothelium) via Ib, IIb/ IIIa complex

They also aggregate using the IIb/ IIIa glycoprotein receptors

Platelet contains α-granules & dense granules that contribute to haemostasis
Platelet shape change exposes a phospholipid surface for coagulation factors activation

Question 7

Specific α granules contain

Answer 7

Fibrinigen
FV
VWF
Heparin antagonist (PF4)
PDGF
Other proteins

Question 8

Discuss the coagulation cascade

Answer 8

Extrinsic

1. Due to injury, tissue factor (FIII) is exposed and activated
2. Activated tissue factor activates FVII to FVIIa
3. They form a complex an

Intrinsic

1. Intrinsic (contact activation) pathway begins with exposure of blood to the contact factor with activation of FXII & FXI
2. FXII is activated to FXIIa
3. FXIIa activates FXI to FXIa
4. FXIa activates FIX to FIXa
5. FIXa is complexed with FVIIIa (activated by Thrombin) brought by VWF
6. FIXa and FVIIIa activate FX to FXa
7. FXa activates FII (prothrombin) to FIIa (thrombin)
8. Thrombin activates FI (fibrinigen) to FIa (fibrin)
9. Fibrin is converted to stabilized fibrin/cross-linked fibrin clot by FXIIIa ( FXIII to FXIIIa is activated by thrombin)

Question 9

Discuss Fibrinolysis

Answer 9

1. Plasminogen is converted to plasmin by activators either from the vessel wall (intrinsic activation) or from the tissues (extrinsic activation
2. The most important route follows the
   release of TPA from endothelial cells whcih binds to fibrin.
3. Release of TPA occurs after such stimuli
   as trauma, exercise or emotional stress.
4. Plasmin enables the conversion of Fibrin to Fibrin degrading products
5. Streptokinase can also be used to convert Plasminogen to Fibrin

Question 9

Discuss Coagulation Inhibitors

Answer 9

3 main processes keep the pathway in check

Protein C: activated by thrombin to APC which inactivates FVa & FVIIIa

Antithrombin: degrades factors IIa, IXa and Xa.

Tissue factor pathway inhibitor(TFPI) inhibits FVIIa-related activation of factors IX & X after its original initiation.

Protein C&S is activated by thromin via thrombomodulin which initiated the destruction of FV & FVIII, antithrombin then destroys FX and FIX