Treatment for Haemostasis, thrmobosis, coagulation, stroke lecture

Question 1

What are the 4 classes of drug agents used to treat conditions involving thrmbus?

Answer 1

Anticoagulants
Platelet inhibitors (anti-platelet drugs)
Fibrinolytic enzymes
Antifibrinolytics

Question 2

What is the function of Anticoagulants?

Answer 2

These prevent thrombus (clot) formation, commonly known as blood thinners.

Question 3

What are the different types of Anticoagulatns?

Answer 3

Unfractionated Heparin (parenteral)
Low molecular weight heparins (parenteral)
Vit K antagonists (oral) e.g. warfarin
non-vit K antagonists (oral) e.g. Apixaban

Question 4

Unfractionated Heparins are of what origin?

What is their main function?

Answer 4

Medical heparin is of animal origin i.e. bovine lung.

They inhibit thrombin from converting fibrinogen into fibrin

Question 5

What inhibits their action naturally in the blood?

And what can we give to inhibit their action?

Answer 5

Heparinases inhibit heparin naturally in the blood.
Protamine Sulphate is used to reverse the effect of heparin mostly in heparin overdose by binding and inactivating heparin.

Question 6

What is a major adverse effect of prolonged heparin treatment?

Answer 6

Heparin-induced Thrombocytopenia - massive reduction in platelet count.
Happens in two stages -
first 2-3 days, won’t show any symptoms
then 5-7 days, will produce an immune-mediated response. Typically would stop giving the heparins.

Question 7

How long does it take for Unfractionated Heparin to work?

Answer 7

It is quick acting and short acting which is a benefit if there is a contra-indication or an issue as the infusion can be stopped immediately.

Question 8

Low- molecular weight Heparins: Where are their origins?

Answer 8

These were developed from UNfractionated Heparins so can be called Fractionated Heparins.

Question 9

What is the difference in the Low- molecular weight Heparin mechanism of action compared to Unfractionated Heparin?

Answer 9

LMWHs don’t inactivate thrombin, instead they inactivate Xa, which has a central role of linking the extrinsic and intrinsic pathway in the coagulation cascade.

Question 10

What is an advantage of LMWH compared to Unfractionated Heparin?

Answer 10

LMWHs are less likely to induce Thrombocytopenia.

Question 11

How would LMWHs be administered and why?

Answer 11

They are highly ionized so would not be absorbed from the GI, so must be given as an IV or Deep Subcutaneous Injection.

Question 12

What is the only issue with the administration of LMWHs?

Answer 12

If longer treatment was required, then the patinet would have to be taught how to use them at home.

Question 13

Vitamin K antagonists: how do thesework?

Answer 13

They work by inducing a deficiency in Vitamin K, therefore inhibiting factor II, VII, IX and X

Question 14

Where are Vitamin K antagonists active?

Answer 14

In-vivo

Question 15

How do Vitamin K antagonists cause a reduction in vit K?

Answer 15

They prevent Vitamin K reductase from breaking down Vitamin K to its active form.

Question 16

What is the most commonly used Vitamin K antagonist?

Answer 16

Warfarin - the S-isomer is the most potent at inhibiting Vitamin K reduction

Question 17

What is the disadvantages of Vit K antagonist?

Answer 17

Slow onset of action due to no action on already carboxylated factors - the already active Vitamin K.
They have an enormous range of drug interactions causing deccreased or increased anticoagulation effects.

Question 18

What is the aim of treatment of any thrombus i.e. DVT, PE etc

Answer 18

The aim is to resolve normal circulation to the limbs, prevent damage to valves and prevent PE or DVT. The ail is to break down the clot, and prevent any more clots form forming.

Question 19

What is the Immediate treatment for anticoagulation in an emergancy?

Answer 19

Would choose LMWHs over Unfractionated Heparins unless there is increased risk of bleeding or renal impairment, then would choose Unfractionated first due to the more control of being able to withdraw the drug if required and limit the action.

Question 20

What would be the treatment for a PE for a patient who is haemodynamically unstable

Answer 20

Offer Unfractionated Heparin, then depending on location of the thrombus, may initiate thrombolytic therapy. May have to intervene surgically to remove the clot especially if in a major vessel in the lung.

Question 21

What would be the treatment for a patient with confirmed DVT or PE within?

Answer 21

Vitamin K antagonist e.g. Warfarin that should be used for 3 months (prophylaxis) then asses the risk/benefit of continuing treatment.

Question 22

Platelet Aggregation Inhibitors: how do these work?

Answer 22

Prevent platelet aggregation by targeting a variety of mechanisms, mainly inhibiting Glycoprotein IIb/IIIa from coming together which is essential for clot formation.

Question 23

Give example drugs of Platelet Aggregation inhibitors:

Answer 23

Aspirin, Clopidogrel, Dihydromole

Question 24

Fibrinolytic enzymes: How do these work?

Answer 24

Clot-busting drugs. These PROMOTE plasminogen conversion to plasmin which is an enzyme that dissolves clots by removing fibrin.

Question 25

When would Fibrinolytic enzymes be given?

Answer 25

These would be given for DVT, Ischaemic stroke, also licensed for use after an S/T elevated myocardial infarction.

Question 26

Give the name of the drug used for DVT that is a fibrinolytic enzyme:

Answer 26

Streptokinase

Question 27

What is the issue with streptokinase?

Answer 27

Strepotkinase is antigenic so there will be antibody production against the drug within the first 4 days of use, therefore will not be active if used again within 1 year of first administration. Would have to use another Fibrinolytic enzymes e.g. alteplase.

Question 28

WHat is the first line treatment for the presentation of Stroke ot TIA (you don’t know which one it is until after further investigation)

Answer 28

1: Aspirin loading dose 300mg immediately, followed by a specialist assessement and investigation to find out if it is a stroke or TIA.

Question 29

WHat is the treatment for a confirmed case of TIA?

Answer 29

Immediate acute treatment with Altepase which is a fibrinolytic enzyme adiministered as an IV bolus 10% followed by an infusion of the remaining 90% over an hour (60 mins)

Question 30

When is treatment most effective for stroke and TIA?

When do the risk of treatment outweigh the benefits?

Answer 30

Most effective within 90mins of onset, much poorer outcome after 3.5 hours.
After 4.5 hours, no point due to risks.

Question 31

What is the new treatment that is promoted by the NHS for Clots in large vessles?

Answer 31

Thrombecotomy - remove the drug mechacnially to resotre the blood flow

Question 32

What are Antifibrinolytic drugs?

Answer 32

These are pro-coagulation = they prevent bleeding and are opposite to fibrinolytic drugs (that promote fibrinolysis) by prefenting fibrinolysis.

Question 33

Give an example drug of Antifibrinolytic drugs?

Answer 33

Tranexamic acid - a sythnetic lysine derivative.

Question 34

What is the mechanism of action of Antifibrinolytic drugs?

Answer 34

They reversibly block the lysine binding sites on plasminogen, therefore preventing its conversion to Plasmin, preventing the breakdown of clots.

Question 35

WHen are Antifibrinolytic drugs used?

Answer 35

To prevent heavy bleeding after surgery or dental operation, thrombolytic overdose, menorrhagia (heavy periods)

Question 36

Summary of treatment: What type of thrombosis is LMWH and UFH used?

Answer 36

short-to mid term primarily VENOUS THROMBOSIS

Question 37

Summary of treatment: What type of thrombosis is Warfarin - Vit K antagonist used for?

Answer 37

Long term prevention of mainly VENOUS THROMBOSIS

Question 38

Summary of treatment: What type of thrombosis is Anti-platelet drugs used for e.g. aspirin, clopdogrel, dihydromole?

Answer 38

Prevent arterial thrombosis, also used for NSTEMI and unstable angina