Blood clotting pathways

Question 1

what is haemostasis?

Answer 1

the arrest of bleeding

Question 2

how many steps are in the complex process of haemostasis?

Answer 2

3

Question 3

what are the 3 steps involved in haemostasis?

Answer 3

1. vascular spasm
2. formation of a platelet plug
3. blood coagulation (clotting)

Question 4

what is vascular spasm?

Answer 4

vasoconstriction of blood vessels after injury

Question 5

what happens during vascular spasm? 3 things

Answer 5

muscle cells contract
reduces blood flow limiting blood loss
opposing endothelial surfaces pressed together and adhere

Question 6

what is the process vascular spasm mediated by? 2 things

Answer 6

platelet derived products serotonin and thromboxane A2 (TXA2)

Question 7

normal endothelium produces? 2 things

Answer 7

vasodilators
inhibitors of platelet aggregation

Question 8

what is another name for platelets?

Answer 8

thrombocytes

Question 9

what are platelets?

Answer 9

small fragments derived from bone marrow cells megakaryocytes

Question 10

do platelets have nuclei?

Answer 10

no

Question 11

what allows platelets to contract?

Answer 11

high concentration of actin and myosin

Question 12

platelets can be activated by what 4 factors?

Answer 12

1. thrombin
2. ADP
3. collagen
4. PAF - platelet activating factor

Question 13

what happens to platelets when activated? 5 things

Answer 13

change shape to sphere with extended pseudopodia
granules release compounds for haemostasis
aggregate
adhere to the vessel walls
synthesise thromboxane A2

Question 14

how is the platelet plug formed? 3 things

Answer 14

platelets aggregate and adhere to vessel walls
form primary haemostatic plug stabilised by fibrin
platelets release chemicals that enhance coagulation

Question 15

what affect does thromboxane and ADP have on blood platelets?

Answer 15

increase adhesiveness

Question 16

what does vWF (von Willebrand Factor) do?

Answer 16

enables aggregation and adhesion
by binding to platelet receptors and endothelium receptors

Question 17

what is arterial thrombosis?

Answer 17

blood clot within an artery

Question 18

what is used to treat arterial thrombosis? how?

Answer 18

anti-platelet drugs
decrease platelet aggregation and inhibit thrombus formation

Question 19

example of an anti-platelet drug?

Answer 19

aspirin

Question 20

Why is collagen important for small blood vessels?

Answer 20

structure and function of small blood vessels

Question 21

collagen deficiencies can cause

Answer 21

excessive bleeding

Question 22

what does blood coagulation form?

Answer 22

secondary fibrin-rich haemostat plug in small vessels
secondary fibrin thrombus in arteries and veins

Question 23

what are the 3 pathways for blood coagulation?

Answer 23

intrinsic pathway
extrinsic pathway
final common pathway

Question 24

what is the intrinsic pathway activated by?
blood coagulation

Answer 24

Factor XII comes into contact with sub-endothelial collagen or a foreign surface

Question 25

what is the extrinsic pathway activated by? blood coagulation

Answer 25

tissue damage which exposes flowing blood to a protein called tissue factor (TF)

Question 26

what does the final common pathway result in? blood coagulation

Answer 26

conversion of fibrinogen to fibrin

Question 27

what does thrombin do? 5

Answer 27

converts fibrinogen to fibrin activates factor XIII enhances its own activation +ve feedback enhances platelet activation initiates deactivation of the clotting cascade

Question 28

what does fibrin do?

Answer 28

forms a loose mesh that traps blood cells

Question 29

what does factor XIII do to fibrin?

Answer 29

catalyses cross-links between adjacent fibrin strands

Question 30

what happens in the intrinsic pathway? blood coagulation

Answer 30

aggregated platelets secrete Platelet Factor (PF3)

Question 31

what does the intrinsic pathway result in?

Answer 31

activation of Factor X which can digest prothrombin to active thrombin

Question 32

what happens in the extrinsic pathway?

Answer 32

traumatised tissue releases Tissue Factor activates Factor X

Question 33

what does the extrinsic pathway enable us to do?

Answer 33

clot blood that has escaped into tissues

Question 34

This diagram shows a blood clot

Answer 34

Question 35

are fibrinogen and fibrin soluble?

Answer 35

fibrinogen is soluble fibrin is insoluble

Question 36

steps in the conversion of fibrinogen to fibrin?

Answer 36

thrombin cleaves 4 polypeptide chains from fibrinogen -> fibrin monomer -> fibrinopeptides spontaneously assemble into ordered fibrous arrays -> fibrin fibrin cross linked by activated Factor XIII

Question 37

how is thrombin present normally in the blood?

Answer 37

as an inactive precursor: prothrombin

Question 38

what is the role of Vitamin K in the conversion of prothrombin to thrombin?

Answer 38

it is required by an enzyme to convert the N-terminus of prothrombin into y-carboxyglutamate Which binds to Ca2+ on the phospholipid surface

Question 39

what is the role of gamma-carboxyglutamate?

Answer 39

binds better to Ca2+ anchors prothrombin to phospholipid surfaces and facilitates conversion to thrombin

Question 40

after the glutamate N-terminus of prothrombin has been converted to gamma-carboxyglutamate and is bound to Ca2+ what is the last step to produce thrombin?

Answer 40

activated Factor X removes the calcium binding domain releasing thrombin

Question 41

what is the role of Ca2+ in the conversion of prothrombin to thrombin?

Answer 41

prothrombin binds to Ca2+ prothrombin anchored to platelet membrane surface close proximity to clotting factors (Xa+V) which cleave prothrombin releasing thrombin

Question 42

name two vitamin K antagonists

Answer 42

dicoumarol warfarin (rat poison also used medically as anticoagulant)

Question 43

how does warfarin work?

Answer 43

leads to the synthesis of prothrombin without gamma-carboxyglutamate so it doesn't bind to Ca2+

Question 44

4 things that prevent inappropriate clotting Don’t need to learn

Answer 44

anti-thrombin (inactivates thrombin) heparin (activates anti-thrombin) protein C and protein S (degrade some clotting factors) tissue factor pathway inhibitor (blocks FX activation)

Question 45

what is fibrinolysis?

Answer 45

dissolving the clot

Question 46

what happens in fibrinolysis?

Answer 46

plasminogen converted to plasmin by FXII and tPA plasmin slowly degrades fibrin

Question 47

2 uses of tissue plasminogen activator (tPA) Don’t need to know

Answer 47

thrombolytic drug to remove clots prevents inappropriate fibrin formation

Question 48

what is thromboembolism?

Answer 48

blood clot forms in an intact blood vessel

Question 49

what is thrombosis?

Answer 49

abnormal blood clot attached to a vessel wall which narrows and can occlude the vessel

Question 50

what is embolus?

Answer 50

freely floating clot or mass that can completely block a small vessel and suddenly block blood flow

Question 51

what are the 4 stages of wound healing?

Answer 51

1. rapid haeomostasis 2. appropriate inflammation 3. proliferation 4. tissue remodelling