7 - Haemostasis Basics

Question 1

5 main components of haemostasis

Answer 1

Platelets
Von Willebrand Factor
Tissue Factor
Clotting Proteins
Anticoagulant proteins

Question 2

Primary haemostasis

Answer 2

Platelets and vasoconstriction form platelet plug

Question 3

Thrombocytopenia

Answer 3

Below 150x109 per litre

Question 4

Thrombocytosis

Answer 4

Over 450x109 per litre

Question 5

What are platelets released from

Answer 5

Megakaryocyte (can release 1000+ platelets)

Question 6

What is the function of granules

Answer 6

Secrete proteins needed for a plug

Question 7

4 steps of primary haemostasis

Answer 7

Vessel Injury
Platelet release reaction
Platelet aggregation
Vasoconstriction

Question 8

What is the role of Von Willebrand Factor

Answer 8

Assists the platelets to attach to an injured site by binding to collagen and each other

Question 9

What is released in the platelet release reaction and what is their function

Answer 9

Adenosine Phosphate - causes platelets to aggregate
Serotonin - Vasoconstriction
Thromboxin A2 - Vasoconstriction and platelet aggregation

Question 10

Extrinsic pathway

Answer 10

When blood vessels are injured

1) TF reacts with F7 -> F7a
2) 7a converts F10 -> 10a

Question 11

Intrinsic pathway

Answer 11

When clots form without tissue injury

1) F12 -> 12a
2) 12a activates 11 -> 11a
3) 11a activates 9 -> 9a
4) 9a and factor 8 convert 10 to 10a

Question 12

Common Pathway

Answer 12

1) 10a turns prothrombin to thrombin

2) thrombin turns fibrinogen to fibrin

Question 13

What is the amplification stage

Answer 13

The small amount of thrombin produced from the extrinsic pathway activates factors 5,7,8,11 and 13

Question 14

What is the role of antithrombin

Answer 14

Thrombin produces antithombin which converts plasminogen to plasmin (destroys cross links in fibrin formed by factor 13) and stops X to Xa

Question 15

Test for the extrinsic pathway

Answer 15

Prothrombin Time

Question 16

Test for intrinsic pathway

Answer 16

Activated Partial Prothrombin Time

Question 17

What are the normal values for bleeding time

Answer 17

3-10minutes

Question 18

What is the normal range for INR

Answer 18

0.8-1.2

Question 19

Haemophillia A

Answer 19

Deficiency of factor 8

Question 20

Haemophilia B

Answer 20

Deficiency of factor 9

Question 21

What holds plasminogen in it’s inactive form

Answer 21

alpha-2 antiplasmin

Question 22

D-dimer

Answer 22

Product of fibrin breakdown

Low levels indicate no thrombosis

Question 23

What structures to platelets contain to stop bleeding

Answer 23

Proteins on surface allow them to stick
Granules secrete proteins
Contain proteins to allow them to change shape

Question 24

How do platelets change their shape when activated

Answer 24

First like a plate
activated by contact with materials such as collagen (due to break in blood vessel wall)
Extend long filaments which interlock and erythrocytes can be trapped

Question 25

How long is platelet lifespan

Answer 25

8-14 days | removed by reticuloendothelial system

Question 26

Structure of platelet

Answer 26

Lipid bilayer + microtubular system 9 glycoproteins Cell membrane receptors - GpIIb/IIIa, gbIb

Question 27

What does a dense granule contain

Answer 27

ADP and calcium

Question 28

What do alpha granules contain

Answer 28

``` P selectin PDGF Factor V VWF Fibrinogen ```

Question 29

How is vWF bound to platelets and what does it do

Answer 29

Vessel injury Platelets adhere to collagen + vWF via gb1b gPIIb/IIIa exposed via vwf binding forms a second binding site for vwf Fibrinogen bound to promote platelet aggregation

Question 30

GpIb deficiency

Answer 30

Bernard Soulier Syndrome

Question 31

GpIIb/IIIa deficiency

Answer 31

Glanzmann's

Question 32

Treatment for vWF disease

Answer 32

DDAVP Tranexamic acid vWF containing concentrate

Question 33

Types of VWF disease

Answer 33

Type 1 - mild/moderate deficiency Type 2 - present but defective Type 3 - total absence

Question 34

Where is tissue factor and what is its function

Answer 34

Present on subendothelial tissue Expressed by cells which are not normally exposed to flowing blood Physical injury exposes TF to flowing blood Initiates clotting via factor 7

Question 35

Role of vWF

Answer 35

vWF binds to GpIb, subsequent activation via G-protein --> shape change --> disc to sphere --> pseudopods--> complex of GpIb, IIbIIIa, vWF, fibrinogen

Question 36

vWF agonists

Answer 36

``` collagen ADP thrombin adrenaline TXA2 ```

Question 37

What does factor 10 need to turn prothrombin to thrombin

Answer 37

calcium | factor 5a

Question 38

What is the INR

Answer 38

Practical form of prothrombin time

Question 39

What INR do you aim for in patients taking warfarin

Answer 39

2-3

Question 40

Function of tissue plasminogen activator

Answer 40

Released from normal endothelial cells | Catalyses plasminogen to plasmin

Question 41

When is TPA released

Answer 41

when the wound has healed | no longer need a clot

Question 42

What other molecules affect plasmin

Answer 42

- urokinase plasminogen activator, kallikrein, and factor XIIa

Question 43

What is the function of antithrombin

Answer 43

Inhibits thrombin, 9,10, 11 Member of serine protease inhibitors Binds to heparan sulfate on vascular endothelium

Question 44

Function of vitamin C

Answer 44

Activated by thrombin Serine protease Inactivates 5 and 8

Question 45

Function vitamin S

Answer 45

cofactor for protein C (apc)

Question 46

What are vitamin C and S dependent on

Answer 46

Vitamin K