Haemostasis

Question 1

Define haemostasis

Answer 1

Fine balance between fibrinolytic factors and anticoagulant factors (which causes bleeding) and coagulant factors and platlets (which can cause thrombosis)

Question 2

Describe the 5 steps of a basic haemostatic plug formation

Answer 2

1. Response to injury to endothelial cell lining - vessel constriction
2. Vascular smooth muscle cells contract - limiting blood flow to injured vessels
3. Formation of an unstable platlet plug - primary haemostasis (surface for coagulation)
4. Stabilisation of platlet plug with fibrin - secondary haemostasis (stops bleeding)
5. Vessel repair and dissolution of clot (restores vessel injury)

Question 3

Describe the structure of the endothelium and its role

Answer 3

The endothelial layer has lots of subendothelial structures which consists of basement membrane, the endothelial layer creates a barrier between the blood and the procoagulant structures. The collagen layer in the subendothelial layer in platlet interaction with damaged blood vessel. The factors expressed on the surface of cells that underlie blood vessels but not normally in circulation itself.

Question 4

Describe the effects of vessel constriction

Answer 4

Mainly important in small vessels, local contractile response to injury.

The platlet originated in megakarocytes, which undergoes maturation in bone marrow that leads to granulation, the platlet has no nucleus, has storage granules with ADP and proteins such as factor V and VWF. Important glycoproteins receptors on the platlet surface.

Question 5

Describe the process of primary haemostasis

Answer 5

1. Platlet adhesion: VWF circulate in plasma in globular conformation, binding sites are hidden from platlet Gp1b, vascular injury damages endothelium and exposes sub-endothelial collagen this binds to VWF. The sheer blood flow unravels the VWF and exposes platlet binding site. This binding of VWF and Gp1b causes recruitment of platlets and those can bind to collagen via GpVI and a1 and b1
2. Platlet activation: collagen and thrombin activate platlet, platlet bound to collagen/ VWF release ADP and thromboxane activating platlets
3. Activated platlets with glycoproteins receptors aIIbB3 and GpIIb/IIIa recruit further platlet, aIIbB3 bind to fribinogen and a platlet plug develops

PLATLET ACTIVATION ENHANCES COAGULATION
THROMBIN CATALYSES FIBRIN FOR STABILISATION

Question 6

Describe the change in shape of a platlet after its activaet

Answer 6

Platlet changes shape upon adhesion, activation and aggregation

Rolling ball shape > hemisphere shape > spreading platlet shape

Question 7

Describe the coagulation cascade that occurs in primary haemostasis

Answer 7

Coagulation cascade relies on liver for protein production, endothelial cells - VWF, TM, TF. Megakaryocytes - VWF and fv. Clotting factors circulate as inactive precursors either as serine zymogens or co-factors activated by specific proteolysis.

Initiation of coagulation: f7/ f7a bind cell surfaces via GIa domain and interact with TF. TF makes f7a more active. The f7a-TF complex activates f10 and f9 by removing activation peptide. F10a can activate prothrombin to generate thrombin, activation is inefficient - only small quantities of thrombin is generated, thrombin activates f5 to f5a and f8 to f8a. The f8-f9 produces more f10 LOOK AT DIAGRAM

Question 8

Describe the regulators of coagulation

Answer 8

TFPI - TF-F7a
AT - f9a, f10a and thrombin
APC and protein S - f5a and f8a

Protein C pathway : look at slide

Question 9

Describe the mechanism of anti-thrombin

Answer 9

AT.

Question 10

Describe the process of fibrinolysis

Answer 10

Plasminogen > plasmin fibrin ……?????.