Thrombosis- Haemostatis In The Wrong Place

Question 1

What is primary haemostasis?

Answer 1

Aggregation of platelets

Question 2

What is secondary haemostasis?

Answer 2

The conversion of fibrinogen into fibrin

Question 3

What are the three basic steps of fibrinolysis?

Answer 3

1- aggregation of platelets
2- fibrinogen -> fibrin mesh by thrombin
3- thrombin is itself converted from prothrombin

Question 4

What do anticoagulants do?

Answer 4

Prevent thrombosis

Question 5

What does fibrinolysis do?

Answer 5

Reverses thrombosis

Question 6

What are the three main features of arterial thrombosis?

Answer 6

Mostly result from atheroma rupture or damage to the endothelium.
Mostly primary, platelet rich ‘white’ thrombosis
May block downstream arteries

Question 7

What are the main features of venous thrombosis?

Answer 7

Often results from stasis or a hypercoagulant state
Mostly secondary, platelet poor ‘red’ thrombus
May move to lungs

Question 8

What happens if the endothelial cells get damaged and the subendothelial cells get exposed?

Answer 8

The blood may either coalesce around it and form a clot or von willebrand factors will bind to platelets and start a clot

Question 9

What does heparin bind to?

Answer 9

Antithrombin

Question 10

What do antithrombin and heperan do?

Answer 10

Inhibit clotting prostaglandins, platelets and nitric oxide

Question 11

What does tissue plasminogen activator cause?

Answer 11

Plasminogen to be converted to plasmin, which acts in the clot to give D-dimers

Question 12

What are d-dimers?

Answer 12

Breakdown products of a clot

Question 13

What are the components of Virchows triad?

Answer 13

Stasis, endothelial damage and the hypercoagulant state

Question 14

How does stasis cause clotting?

Answer 14

Static blood lacks kinetic energy and tends to clot

Question 15

How does endothelial damage lead to clotting?

Answer 15

When you have surgery or a cannula you are exposing the subendothelial cells

Question 16

When may you be in a hypercoagulant state?

Answer 16

In infection/ sepsis, drugs or if you have a genetic predisposition

Question 17

Why is there an increased risk of stasis around venous valves?

Answer 17

The blood eddys around them so doesn’t move as efficiently

Question 18

What happens if venous return is blocked?

Answer 18

The affected organ becomes congested with fluid and there is an increased pressure so more filtration

Question 19

What are the four fates for a thrombus?

Answer 19

Resolution, embolism, organised or recanalised and organised

Question 20

What happens when a thrombus is resolved?

Answer 20

Thrombolysis

Question 21

What happens when a thrombus embolises?

Answer 21

Moves to another location and blocks the vessel

Question 22

What happens when a thrombus is organised?

Answer 22

Becomes covered by the endothelium

Question 23

What are the risks with a proximal DVT?

Answer 23

Higher risk of pulmonary embolism and post-thrombotic syndrome

Question 24

What are symptoms of proximal DVT?

Answer 24

Pain, swelling and maybe even ulcers

Question 25

Where are proximal DVTs found?

Answer 25

Upper leg

Question 26

Where are distal DVTs found?

Answer 26

Lower leg

Question 27

What are the risks of distal DVT?

Answer 27

Not much- they rarely cause PE or post-thrombotic syndrome

Question 28

What is post-thrombotic syndrome?

Answer 28

Inflammation along with damage to the venous valves from the thrombus itself

Question 29

What causes post thrombotic syndrome?

Answer 29

Valvular incompetence combined with a persistent venous obstruction

Question 30

What does post thrombotic syndrome induce?

Answer 30

Rupture of small superficial veins, subcutaneous haemorrhage and an increase of tissue permeability

Question 31

What symptoms follow post-thrombotic syndrome?

Answer 31

Pain, swelling, discolouration and even ulceration

Question 32

What causes pulmonary embolus?

Answer 32

Small venous thrombolus getting through the heart and caught in the lung

Question 33

What happens in platelet adherence?

Answer 33

- von willebrand factors on subendothelial cells activate platelets - circulating von willebrand factors may bind to exposed subendothelial cells - activated endothelial cells can also express von willebrand factors

Question 34

What happens in platelet activation?

Answer 34

- activated platelets release thromboxane A2 and adenosine disphosphate which induce receptors for fibrinogen - bind to receptors and increase expression of GPIIb/IIIa - platelets can also be activated by thrombin, collagen and many other mediators

Question 35

What happens in platelet aggregation?

Answer 35

Fibrinogen acts as a tether holding platelets together- it is the soluble precursor to fibrin and is in the circulation

Question 36

What happens in platelet substrate for coagulation?

Answer 36

- clumps of platelet form a negatively charged surface | - coagulation involves the conversion of fibrinogen to fibrin and then cross linking the fibrin clot

Question 37

What are the 7 steps in the common coagulation pathway?

Answer 37

1- factor IXa activates factor X by proteolysis to create factor Xa 2- factor Xa cleaves prothrombin to form thrombin (IIa) 3- thrombin cleaves fibrinogen into fibrin 4- fibrinogen promotes blood clotting by forming bridges between (and activating) blood platelets through binding to their GPIIb/IIIa surface membrane fibrinogen receptor 5- thrombin cleaves factors V and VIII to give Va and VIIIa 6- Va and VIII together with Ca2+ form a tenase complex and a prothrombinase complex 7- once enough thrombin has been generated, XIII is activated, which cross links the fibrin fibres into a solid clot

Question 38

What do VIIIa and Va amplify?

Answer 38

The existing reactions making them hard to overpower

Question 39

What is a GLA domain?

Answer 39

10-12 glutamic acids on the N-terminus of the molecule converted to gamma carboxy glutamic acid

Question 40

What is the GLA domain dependant on?

Answer 40

Vitamin K

Question 41

What is the extrinsic pathway?

Answer 41

Tissue factor is a receptor for VIIa which is bound to negatively charged platelet phospholipid surface along with calcium. Then VIIa activated Xa and the common pathway starts

Question 42

What is the extrinsic pathway triggered by?

Answer 42

Transcription factors which activates factor VII

Question 43

When is the intrinsic pathway activated?

Answer 43

When you put blood onto a charged surface (like glass)

Question 44

What do lab tests distinguish between?

Answer 44

Activating the intrinsic or extrinsic pathways in order to assess where a defect may be

Question 45

What is antithrombin expressed by?

Answer 45

Endothelial cells

Question 46

What does antithrombin inhibit?

Answer 46

A lot of the enzymes in the coagulation cascade