Anti-coagulants

Question 1

Steps in coagulation (simple)

Answer 1

Question 2

Diseases possibly caused by thrombus

Answer 2

Question 3

Inherited risks for thrombogenesis

Answer 3

Question 4

Acquired risks for thrombogenesis

Answer 4

Question 5

What’s Factor V Leiden disease

Answer 5

Factor V Leiden:

• the most common inherited risk factor for thrombogenesis among UK’s females (and among European ethnicity)
• mutation in factor V gene (that helps blood to clot)
• increase in blood coagulability (hyper-coagulability)

Question 6

Pathophysiology in Factor V Leiden disease

Answer 6

• Mutation -> protein C (which normally inhibits factor V) is not able to bind to it -> hypercoagubility
• It is AD, with incomplete penetrance (not everyone with the mutation will be symptomatic)
• Result: Recurrent venous thromboses

Question 7

Diagnosis of Factor V Leiden disease

Answer 7

Caucasian patient below age 45 with thrombotic event

• lab tests (aPTT - time it takes for blood to clot is decreased)
• genetic testing for a mutation (PCR)

Question 8

Management of Factor V Leiden disease

Answer 8

Management:

• no cure -> prevention of thrombotic events
• lifelong treatment with anti-coagulants

e. g. Warfarin and Heparin (during periods of increased risks for VT e.g. major surgery)
* cannot be prescribed an oestrogen containing pill

Question 9

Why D-dimer is usually done?

Answer 9

D- dimers are done rather for patients who we do not suspect to have a clot -> to exclude it definitely

Question 10

Ix in DVT

Answer 10

Question 11

PE Investigations

Answer 11

Question 12

Wells score

• components
• meaning

Answer 12

Question 13

Pathway for treatment of PE without shock

Answer 13

Question 14

What risk score and components are used to assess for anti-coagulant need

Answer 14

CHA₂DS₂

Question 15

Possible anti-coagulation drugs for people with score 2 or more on CHA₂DS₂

Answer 15

People with score 2 or above should be offered anti-coagulation with:

• apixaban
• dabigatran etexilate
• rivaroxaban
• Vitamin K antagonist

* Aspirin monotherapy should not be offered in these patients solely for stroke prevention

Question 16

What score assesses the risk of major bleeds for a patient on anti-coagulant?

Answer 16

Question 17

Ix and diagnostic findings of PE and DVT

Answer 17

• chest X ray can show lung infract (sometimes)
• sometimes typical ECG changes
• Doppler scan -> if we compress on the veins and it collapses means that there is a clot (as normally it should not collapse)
• V/Q scans (mismatch between perfusion and ventilation)
• CT Pulmonary Angiogram - preferred by doctors as: able to pick up other abnormalities and also visualise the location of a clot

Question 18

Examples (3) of ADP antagonist drugs

Answer 18

Question 19

Example of COX inhibitor (1)

Answer 19

Question 20

Example of Phosphodiesterase inhibitor

Answer 20

Question 21

Examples (3) of GP IIb/IIIa inhibitors

Answer 21

Question 22

Mechanism of action of Aspirin

Answer 22

Aspirin:

• inhibition of COX1 (in small dose)
• inhibition of COX2 (high dose) - analgesia effect (so e.g. headache we need higher dose of

aspirin)

Aspirin permanently blocks enzymes that convert arachidonic acid -> thromboxane (prothrombotic inductors released by platelets)

*as there is high turnover of platelets in the body (everyday 10% is new ones) -> need to carry on with aspirin

Question 23

Examples (4) of ADP antagonists

+ simple MoA

Answer 23

1. Ticlopidine
2. Clopidogrel
3. Prasugrel
4. Ticagrelor

MoA: inhibition of ADP induced platelet aggregation

Question 24

Common use of ADP antagonists

Answer 24

• They are used for patients with cardiovascular disease, as part of dual-anti-platelet therapy (blocking two pathways leading to platelet activation)

​

• Clopidogrel and Ticagrelor are the most commonly used

Question 25

(2) anti - platelets used in treatment of acute MI

Answer 25

In acute MI (e.g. A&E) : ***- Aspirin*** ***- Ticagrelor*** (preferred as rapid onset)

Question 26

Potential side effects of Ticlopidine and Prasugrel

Answer 26

Both ADP antagonists - not usually used in acute MI Rx due to SEs: * ***Ticlopidine*** is not used that much anymore due to neutropenia in 2.4% of patients * ***Prasugrel*** also not used as increased risk of TIA in elderly patients

Question 28

What is ***Warfarin*** potentiated by?

Answer 28

**Potentiated** by: * antibiotics * fluconazole * cimetidine they inhibit p450 (therefore less metabolism of other drugs)

Question 29

What is Warfarin antagonized by?

Answer 29

Antagonised by: * anti-TB drugs * anti- epileptics they will induce p450 (so more metabolism of other drugs)

Question 30

Therapies used in Warfarin overdose

Answer 30

* vitamin K * prothrombin complex concentrate * FFP

Question 31

What Warfarin is mostly metabolized by?

Answer 31

is mostly metabolised by liver (so choice for patients with CKD)

Question 32

***Warfarin*** MoA

Answer 32

Question 33

Risks (2) associated with ***Warfarin*** therapy

Answer 33

_Risks with Warfarin:_ - bleeding - lots of patients may not be complaint with treatments - may receive sub-therapeutic level of treatment

Question 34

What a dose of Warfarin will depend on?

Answer 34

_Dose of warfarin will depend on:_ Age, BMI, gender, nutritional status, concomitant medications, compliance, comorbid disease

Question 35

Side effects of Warfarin

Answer 35

* haemorrhage * skin necrosis * teratogenicity (contraindicated with pregnancy -\> give Heparin through pregnancy instead) * leukopaenia * overdose - reversed FFP or prothrombin complex concentrate (Octaplex) or IV vitamin K

Question 36

***Heparin*** MoA

Answer 36

**Mechanism of action:** * Binds and enhances antithrombin III * Inhibits clotting factors IXa, Xa, XIa and thrombibn

Question 37

Unfractionated vs LMWH ***Heparin*** use

Answer 37

_Options of heparin:_ A. **Unfractioned** - IV route, it acts in short time (30 minutes onset of action with half time 4 hours) - used for acute thrombotic events \*blood tests are checked regularly to monitor treatment’s effectiveness B. **Low molecular weight Heparin** - used more commonly due to its half time (12 hours), once again due to sub-cutaneous injection

Question 38

Heparin side effects

Answer 38

Side effects: * bleeding * thrombocytopaenia * osteoporosis * hair loss

Question 39

Drug used to reverse heparin effects

Answer 39

***Protamine***

Question 40

Use of GP IIb/IIIa inhibitors

Answer 40

are usually used only via IV route, on the patients going for angioplasty or any other vascular surgery (sue use in cardio-thoracic surgery)

Question 41

MoA of GP IIb/IIIa inhibitors

Answer 41

Question 42

***DOACs*** MoA

Answer 42

Mechanism of action: * Dabigatran blocks factor II * Other drugs from NOAC class block conversion of factor X - Xa (so prothrombin)

Question 43

Advantages of DOAC use

Answer 43

- no need to monitor levels - partially metabolized by the liver, partially by kidney \*however much more expensive than Warfarin

Question 44

**Dabigatran** use and advantages

Answer 44

Question 45

'...xaban' use and advantage

Answer 45

DOACs

Question 46

Half-life, class and use of ***fondaparinux***

Answer 46

***Fondaparinux*** - belongs to Heparins - long half-life (17 h) - efficacy comparable to unfractioned and LMWH for treating DVT and PE - more cost effective than LMWH

Question 47

Fondaparinux MoA

Answer 47

binds to antithrombin -\> enhances its activity towards factor Xa \*no activity against thrombin or platelets

Question 48

***Fibrinolytics*** - use - MoA - SE

Answer 48

Fibrinolytics used only on stroke unit SE: acute bleeding

Question 49

Names (4) of ***thrombolytic*** drugs

Answer 49

Question 50

Use and MoA of ***thrombolytics***

Answer 50

Question 51

SE and contraindications of thrombolytics

Answer 51