Haemostasis

Question 1

what is haemostasis and what is it for?

Answer 1

→Protective process evolved in order to maintain a stable physiology
→curtail blood loss
→restore vascular integrity
→ultimately preserve life

Question 2

what does DIC stand for?

Answer 2

→disseminated intravascular coagulation

Question 3

The Horseshoe Crab

Answer 3

→Limulus Polyphemus

→ ‘A primitive coagulation pathway can be initiated by endotoxin’

Question 4

what are the Four Key Components of haemostasis?

Answer 4

→Endothelium
→Coagulation
→Platelets
→Fibrinolysis

Question 5

what does a blood clot consist of?

Answer 5

→Fibrin mesh
→Platelets
→Red blood cells

Question 6

what are the simplified steps of haemostasis?

Answer 6

→Tissue injury 
→Vasoconstriction 
→Platelet activation 
→Haemostatic plug 
→Coagulation 
→Stable clot formation 
→Clot dissolution

Question 7

Primary haemostasis:

Answer 7

→Vasoconstriction (immediate)
→Platelet adhesion (within seconds)
→Platelet aggregation and contraction (within minutes)

Question 8

Secondary haemostasis:

Answer 8

→Activation of coagulation factors (within seconds) →Formation of fibrin (within minutes)

Question 9

Fibrinolysis:

Answer 9

→Activation of fibrinolysis (within minutes)

→Lysis of the plug (within hours)

Question 10

what is the purpose of the vessel wall?

Answer 10

→Normal Endothelium:
→ inhibits coagulation
→ prevents platelet aggregation

Provides a barrier to reactive elements in the subendothelium
→collagen fibronectin
→ tissue factor

Question 11

Haemostasis at rest

Answer 11

triggers and cofactors separated

Question 12

what are the functions of Von Willebrand Factors?

Answer 12

→Forms a bridge between damaged vessel wall (collagen) and platelets (primary haemostasis)
→Stabilises and protects Factor VIII from rapid clearance

Question 13

Loss of VWF function

Answer 13

→results in a bleeding disorder

Question 14

VWF synthesis and storage

Answer 14

Synthesis
→Endothelial cells contain Weibel Palade bodies

→Megakaryocytes
→Platelet a granules

→Plasma VWF entirely derived from endothelial cells

Question 15

Distribution of VWF

Answer 15

→Constitutive path (95%)
→Regulated path (5%)
→Weibel-Palade bodies (storage granules of endothelial cells)

Question 16

Platelet activation

Answer 16

→Resting
→Platelet Activation
→Adhesion + spreading (increase SA)

Question 17

what happens when a vessel wall is damaged?

Answer 17

→various signalling molecules are expressed / exposed, →including tissue factor and collagen

Question 18

describe Initiation of coagulation

Answer 18

→The TF leads to the production of a small local amount of thrombin, which is the initiation step of the coagulation process

Question 19

describe adhesion

Answer 19

The exposed signalling molecules attract circulating platelets, which attach themselves to the exposed sub-endothelial tissue

Question 20

describe secretion

Answer 20

These platelets become activated
→ principally through the presence of the thrombin
→ release further attractant chemicals
→which attract more platelets

Question 21

describe aggregation

Answer 21

→These new platelets bind to the adhered platelets and themselves become activated

Question 22

describe contraction

Answer 22

→Through the conformational changes inherent in activation

→the loose platelet plug contracts to form a dense, adherent plug

Question 23

what do activated platelets present?

Answer 23

→negatively-charged phospholipid membrane at the site of the injury
→on which the process of coagulation (secondary haemostasis) can occur, if needed

Question 24

what does the fibrin mesh do?

Answer 24

→Fibrin mesh binds and stabilises platelet plug and other cells

Question 25

what does Fibrinogen (I) do?

Answer 25

Forms clot (fibrin)

Question 26

FVII deficiency

Answer 26

FVII deficiency causes bleeding

Question 27

how does a tissue factor drive coagulation?

Answer 27

→TF is outside the lumen
→Formation of TF-FVIIa complex
→ Recruitment of FX and formation of thrombin

Question 28

Initiation of coagulation occurs when

Answer 28

→sub-endothelial tissue is exposed to the circulation at a site of injury.
→These tissues express tissue factor at their surface, which binds to endogenous activated FVII

Question 29

what happens after FVII is activated?

Answer 29

→the complex binds small amounts of FX and FV to the exposed endothelial surface,

→ produce small quantities of thrombin

Question 30

The thrombin activates

Answer 30

→platelets that are attracted to the site by the process, as well as other plasma-borne clotting factors

Question 31

what do the activated factors (among them FVIII and FIX) enable the binding of ?

Answer 31

→enable the binding of activated FX and FV to the surface of platelets whose activation has produce conformational changes in their surface membranes to expose the ‘reaction sites’ necessary for continuation of the process

Question 32

the ‘thrombin burst’

Answer 32

→This leads to the ‘thrombin burst’ that is necessary for the large-scale production of fibrin and so the development of an effective clot

Question 33

coagulation phases

Answer 33

→ initiation
→amplification
→ propagation

Question 34

Fibrinolysis

Answer 34

→Main function clot limiting mechanism repair and healing mechanism
→Series of tightly regulated enzymatic steps
→Feedback potentiation & inhibition

Question 35

what are the key players in fibrinolysis?

Answer 35

→Plasminogen
→ Tissue plasminogen activator (t-PA) & urokinase (u-PA) →Plasminogen activator inhibitor -1 and -2 α2-plasmin inhibitor