Haemostasis

Question 1

Describe how blood clots

Factors that influence whether blood is hyper or hypocoagulable

Main tests of coagulation, esp PT and APTT

Answer 1

.

Question 2

What substances does the endothelium secrete to stop cells from sticking to it and causing clot formation

Answer 2

Fibrinolytic heparin molecule
Thrombomodulin
Nitric oxide
Prosatcyclin

Question 3

Haemostasis (slowing + stopping flow of blood to imitate wound healing) involves 3 rapid steps

Answer 3

1. Vascular spasm (vasoconstriction)
2. Platelet plug formation
3. Coagulation

Question 4

Describe the 1st step of haemostasis

Answer 4

Vasoconstriction

-reflex contraction of the vessel to prevent more blood from going there to stop excess bleeding

Question 5

Describe the 2nd step of haemostasis

Answer 5

Platelet plug formation:

1. PLATELET ADHERENCE
   - -> Tear in endothelium reveals the subendothelial collagen which releases von willebrand factor (VWF) that binds to platelets causing them to change form with adhesive extensions and adhere to the subendothelial collagen
2. PLATELET ACTIVATION
   - -> Subendothelial collagen binds to receptors on the platelet surface which ACTIVATE it and make it sticky. During activation, granules within the platelet degranulate to release chemicals like ADP, serotonin, VWF and other coag factors causing nearby platelets to adhere and become activated as well
3. PLATELET AGGREGATION
   - -> Thromboxane activates other platelets and causes them to aggregate together. Receptors on the platelet bind to VWF to holding the platelets together and anchor them to the damaged endothelium

Question 6

Describe the 3rd step of haemostasis

Answer 6

Coagulation (blood clot formation)

• coag factors (mainly prothrombin, thrombin + fibrinogen) circulate as inactive enzyme precursors, which, upon activation, take part in the coagulation cascade to form the FIBRIN MESH ON TOP OF PLATELET PLUG
• once first coag factor is activated in the cascade, produced a domino reaction that activates subsequent coag factors
• final domino is factor X which then activates prothrombin (zymogen) and converts it into THROMBIN using factor V
• thrombin cleaves fibrinogen into FIBRIN, forming the mesh that binds to and strengthens the platelet plug

Question 7

What on the platelet surface do things like VWF and other coag factors bind to

Answer 7

Glycoprotein binding sites

Question 8

Platelets contain an alpha granule and dense granule which contain cytokines and chemical mediators that are released when activated to signal other platelets

What chemicals do each of these granules contain respectively

Answer 8

Alpha granule - VWF, thrombin

Dense granule - ADP, serotonin, calcium

Question 9

During platelet plug formation, the phospholipid membrane gets flipped to face outwards which is important in the coagulation stage as this activates coag factors like PROTHROMBIN

What enzyme catalyses this?

Answer 9

Scramblase

Question 10

Platelets may also bind to subendothelial VWF to anchor them to the damaged endothelium

Answer 10

Arachadonic acid converted into thrombocytopenia axon by COX enzyme

Question 11

The coag factors in the coagulation cascade (stage 3) are considered what substances

Answer 11

Inactive enzyme precursors (ZYMOGENS)

Question 12

Prothrombin converted into thrombin by what

Answer 12

Factor V

Question 13

Fibrinogen cleaved into fibrin by what

Answer 13

Thrombin

Question 14

Coagulation can occur even without injury so the body produces natural anticoagulants to prevent unnecessary coagulation

Those that genetically lack the ability to produce these molecules will be more susceptible to coagulation

Name some natural anticoagulants

Answer 14

Activated protein C
Antithrombin
Tissue factor pathway inhibitor (TFPI)
Plasmin
Prostacyclin 
Thrombomodulin

Question 15

During clot formation, what needs to be switched off to LOCALISE the clot

Answer 15

Natural anticoagulants (produced by body)

Question 16

How does the natural anticoagulant, TFPI, work?

Answer 16

Limits the action of tissue factor (TF) and the factors it produces (TF part of coagulation cascade)

Question 17

How does the natural anticoagulant, protein C, work?

Answer 17

Citamin K-dependent serine protease enzyme that degrades Factor V and factor VIII (so prevents prothrombin –> thrombin)

Question 18

How does the natural anticoagulant, antithrombin, work?

Answer 18

Sserine protease inhibitor that degrades thrombin and other coag factors

Question 19

Following haemostasis, what process occurs to break down clots

Answer 19

Fibrinolysis

Question 20

Describe fibrinolysis

• what does the damaged endothelium release very slowly
• what does above do

Answer 20

tPA
-this degrades circulating plasminogen –> plasmin which CLEAVES THE FIBRIN MESH –> fibrin breakdown products, e.g. d-dimer

Question 21

What is secondary fibrinolysis

Answer 21

Pharmacological treatment of thrombus, e.g. recombinant tPA, streptokinase

Question 22

Aspirin is antiplatelet, where in the haemosatsis pathway does it inhibit?

Answer 22

Inhibits platelet aggregation by stopping COX from converting arachadonic acid into thromboxane

Question 23

Antilpatelets like clopidogrel, prasugrel, ticagrelor inhibit what part of the haemostasis pathway?

Answer 23

ADP (P2Y12) pathway

-binds to platelet receptor in order to stop ADP from binding to platelet and activating them

Question 24

How does warfarin inhibit thrombosis?

Answer 24

Warfarin is a vitamin K antagonist and vitamin K is involved in the synthesis of many of the coag factors

Question 25

How do heparins inhibit thrombosis?

Answer 25

Inhibits thrombin

Question 26

How do DOACs inhibit thrombosis?

Answer 26

Inhibit factor Xa which converts prothrombin to thrombin

Apart from dabigatran which inhibits thrombin instead

Question 27

Main tests of coagulation (2)

Answer 27

PT

APTT (activated prothrombin time)

Question 28

What does primary and secondary haemostasis mean?

Answer 28

Primary refers to platelet plug formation

Secondary refers to fibrin mesh formation