Flashcards in Haemostasis Deck (35)
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1

what is haemostasis and what is it for?

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

2

what does DIC stand for?

β†’disseminated intravascular coagulation

3

The Horseshoe Crab

β†’Limulus Polyphemus
β†’ β€˜A primitive coagulation pathway can be initiated by endotoxin’

4

what are the Four Key Components of haemostasis?

β†’Endothelium
β†’Coagulation
β†’Platelets
β†’Fibrinolysis

5

what does a blood clot consist of?

β†’Fibrin mesh
β†’Platelets
β†’Red blood cells

6

what are the simplified steps of haemostasis?

β†’Tissue injury
β†’Vasoconstriction
β†’Platelet activation
β†’Haemostatic plug
β†’Coagulation
β†’Stable clot formation
β†’Clot dissolution

7

Primary haemostasis:

β†’Vasoconstriction (immediate)
β†’Platelet adhesion (within seconds)
β†’Platelet aggregation and contraction (within minutes)

8

Secondary haemostasis:

β†’Activation of coagulation factors (within seconds) β†’Formation of fibrin (within minutes)

9

Fibrinolysis:

β†’Activation of fibrinolysis (within minutes)
β†’Lysis of the plug (within hours)

10

what is the purpose of the vessel wall?

β†’Normal Endothelium:
β†’ inhibits coagulation
β†’ prevents platelet aggregation

Provides a barrier to reactive elements in the subendothelium
β†’collagen fibronectin
β†’ tissue factor

11

Haemostasis at rest

triggers and cofactors separated

12

what are the functions of Von Willebrand Factors?

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

13

Loss of VWF function

β†’results in a bleeding disorder

14

VWF synthesis and storage

Synthesis
β†’Endothelial cells contain Weibel Palade bodies

β†’Megakaryocytes
β†’Platelet a granules

β†’Plasma VWF entirely derived from endothelial cells

15

Distribution of VWF

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

16

Platelet activation

β†’Resting
β†’Platelet Activation
β†’Adhesion + spreading (increase SA)

17

what happens when a vessel wall is damaged?

β†’various signalling molecules are expressed / exposed, β†’including tissue factor and collagen

18

describe Initiation of coagulation

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

19

describe adhesion

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

20

describe secretion

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

21

describe aggregation

β†’These new platelets bind to the adhered platelets and themselves become activated

22

describe contraction

β†’Through the conformational changes inherent in activation
β†’the loose platelet plug contracts to form a dense, adherent plug

23

what do activated platelets present?

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

24

what does the fibrin mesh do?

β†’Fibrin mesh binds and stabilises platelet plug and other cells

25

what does Fibrinogen (I) do?

Forms clot (fibrin)

26

FVII deficiency

FVII deficiency causes bleeding

27

how does a tissue factor drive coagulation?

β†’TF is outside the lumen
β†’Formation of TF-FVIIa complex
β†’ Recruitment of FX and formation of thrombin

28

Initiation of coagulation occurs when

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

29

what happens after FVII is activated?

β†’the complex binds small amounts of FX and FV to the exposed endothelial surface,

β†’ produce small quantities of thrombin

30

The thrombin activates

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

31

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

β†’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 β€˜reaction sites’ necessary for continuation of the process

32

the β€˜thrombin burst’

β†’This leads to the β€˜thrombin burst’ that is necessary for the large-scale production of fibrin and so the development of an effective clot

33

coagulation phases

β†’ initiation
β†’amplification
β†’ propagation

34

Fibrinolysis

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

35

what are the key players in fibrinolysis?

β†’Plasminogen
β†’ Tissue plasminogen activator (t-PA) & urokinase (u-PA) β†’Plasminogen activator inhibitor -1 and -2 Ξ±2-plasmin inhibitor