Thromboembolism

Question 1

What is a characteristic of platelets

Answer 1

Platelets do not have a nucleus. So they cannot regenerate. Hence when you take aspirin. The anti platelet effect is irreversible

Question 2

What is haemostasis

Answer 2

The arrest of blood flow from a damaged vessel

Question 3

What is vascular spasm?

Answer 3

When a vessel wall is damaged , vasoconstriction occurs

Question 4

What is coagulation

Answer 4

Solidification of blood through an amplifying cascade

Question 5

What is the main event during coagulation

Answer 5

• soluble fibrinogen becomes insoluble fibrin
• this fibrin mesh work traps blood cells and platelets

Question 6

What is the extrinsic pathway

Answer 6

Activated after tissue trauma
In vivo
Happens very fast

Question 7

What is the intrinsic pathway

Answer 7

Activated upon contact with abnormal surface
In vivo and in vitro
Very slow

Question 8

What do the intrinsic and extrinsic merge to form?

Answer 8

Common pathway

Question 9

What is the cascade process of the intrinsic pathway?

Answer 9

XII—>XIIa
Which triggers:
XI——> XIa
Which triggers
IX——> IXa

Which forms X—->Xa which is the common pathway

Question 10

What is the cascade process of extrinsic pathway

Answer 10

VII—->VIIa

Then activates
X—->Xa

Question 11

What does the coagulation cascade happen in the presence of ?

Answer 11

Calcium ions

Question 12

What happens after the common pathway? (Clot)

Answer 12

X——>Xa
Which triggers
II (prothrombin) —-> IIa (thrombin)

Which causes activation of (XIII—>XIIIa)
Soluble fibrinogen——> fibrin

Question 13

What is the function of thrombin

Answer 13

Activates factor 13
Causes fibrinogen to form fibrin
Causes vasoconstriction
Strengthens the fibrin strands

Question 14

What is thrombin inhibited by?

Answer 14

Antithrombin III

Question 15

What is thrombosis

Answer 15

An inappropriate blood clot

Question 16

What is a thrombus

Answer 16

Fixed clot in a unbroken blood vessel

Question 17

What is an arterial thrombosis

Answer 17

White platelet plug

Question 18

What is venous thrombosis

Answer 18

Red coagulation

Question 19

What is an embolus

Answer 19

A thrombus that breaks apart and cam cause ischaemia

Question 20

How do you treat someone who has a defect in their clotting factors (genetics)

Answer 20

Vitamin K (orally or iv)

Question 21

Types of thromboembolism

Answer 21

MI
STROKE
DVT
PE

Question 22

How would you treat arterial (white) disorders

Answer 22

Antiplatelet
Antifibrinolyctic

Question 23

How would you treat a venous (red ) thromboembolism disorder?

Answer 23

Oral anticoagulant
I.V anti coagulant

Question 24

Risk factors of thromboembolism

Answer 24

Contraceptives
Prosthetic device
Atherosclerosis

Question 25

How does heparin work?

Answer 25

Inactivates thrombin (IIa) by increasing activation antithrombin III ( has to happen simultaneously)

Question 26

How does LMWH differ to heparin?

Answer 26

LMWH has a different structure (fragment of heparin) so cannot bind to thrombin to activate anti thrombin III

Question 27

How does LMWH work?

Answer 27

Binds to antithrombin III and It inhibits the action of factor 10 and thrombin

Question 28

What are direct thrombin inhibitors or doacs

Answer 28

They do not depend on the activation of antithrombin

Question 29

How does warfarin work

Answer 29

It interferes with the post translational carboxylic of glutamic acid residues in clotting factor 2,7,9 and 10 by inhibiting vitamin k reductase . This causes the inhibition of vitamin K epoxied to its original form being vitamin k hydroquinone

Question 30

Factors that potentiate warfarin (make it too potent)

Answer 30

Drugs that inhibit platelet function (aspirin) Drugs that inhibit the reduction of vitamin k (cephalosporins) Drugs that inhibit hepatic metabolism (most antibiotics)

Question 31

What lessens the effect of warfarin

Answer 31

Vitamin K

Question 32

How do platelets form?

Answer 32

1. Trauma/damage 2. Platelets are activated and arachidonic acid is produced 3. This produces cyclic endoperoxides 4. Thromboxane 2 is synthesised 5. Leads to more GP IIb and IIIa receptors 6. Platelets will then form a linkage with these receptors and form platelet aggregation

Question 33

What is the Moa of aspirin

Answer 33

Inhibits the production of thromboxane 2 (TXA2)

Question 34

What is the mechanism of action of abciximab (antiplatelet)

Answer 34

Antagonises the GP IIb/IIIa receptors

Question 35

What is the Moa of clopidogrel, ticagrelor

Answer 35

Irreversible inhibition of P2Y receptors N.B IN THE BNF

Question 36

How do antiplatelets and anticoagulants and fibrolyctics differ

Answer 36

Anticoagulants and antiplatelets stop clots from forming in the first place. But fibrinolytic work when the clot is already formed.

Question 37

How do fibronolyctics work

Answer 37

They act on the existing clot. Causing it to dissolve by activating plasminogen to turn into plasmin Plasmin breaks cross links in fibrin causing it to dissolve

Question 38

What are the benefits of heparin (UFH) compared to LMWH

Answer 38

UFH is quickly reversible and has a shorter half-life

Question 39

Why are some patients prescribed heparin and warfarin

Answer 39

Warfarin takes about 5-7 days to take its effect. So patients need to take both but once the warfarin is on full effect the heparin stops. Known as patient bridging

Question 40

Why is the volume of distribution of warfarin small

Answer 40

Binds to plasma albumin so lower volumw

Question 41

What are the benefits of prescribing DOACS instead of warfarin

Answer 41

Fixed daily dose Fewer drug interaction Fast acting No need for regular blood tests

Question 42

What is the moa of rivaroxaban

Answer 42

Direct factor xa inhibitor. This in turn interrupts the intrinsic and extrinsic pathway