Anti-coagulation

Question 1

Warfarin - General Points

1. How does it function
2. Which factors have the shortest half life?
3. how metabolised and how does this relate to interactions?

Answer 1

Warfarin - General Points

1. Inhibits Vitamin K epoxide reductase complex, leading to reduced production of factors X, IX, VII, II, and protein C and S
2. C + VII have shortest half life
3. Metabolised in the liver, therefore enzyme inducers reduce function and inhibitors increase function; Over 700 interactions

Question 2

Warfarin - Adverse effects

1. What is the main risk when on warfarin?
2. Name some other side-effects/
3. What factors increase risk?
4. What common factors affect INR control?

Answer 2

Warfarin - Adverse effects

1. Bleed - particularly IC haemorrhage
2. N, D, Rash, Alopecia, Congenital malformations (6-14/40 - fetal warfarin syndrome, include facial malformation, congenital heart defects and growth retardation)
3. Alcohol, liver disease, falls risk, age etc
4. Binge drinking, green leafy vegetables, vitamin supplements

Question 3

Warfarin - Contraindications

Absolute?

Relative?

Answer 3

Warfarin - Contraindications

Absolute - pregnancy (under 14 weeks), active PUD/varices/proliferative retinopathy

Relative: pregnancy after 14/40, alcoholism, liver disease, compliance, F/Up issues

Question 4

Warfarin - Dosing

1. What is necessary for first 5 days?
2. What is target INR?
3. Initial blood tests?
4. What dosing protocols are there?
5. What happens if underfil citrate tube?

Answer 4

Warfarin - Dosing

1. Heparin for first 5 days, due to relative protein C deficiency, which is pro-thrombotic state
2. INR 2-3 unless MV replacement
3. Baseline INR, LFT, FBC
4. Dosing protocol depends on IP, OP, AF. Follow e-library guidelines. Broadly, IP - 10mg first dose, OP - 5mg, AF - 3mg for one week. Wtih all, titrate based on INR
5. Spuriously High result - therefore repeat

Question 5

Warfarin - Implications for patient

Answer 5

Warfarin - Implications for patient

Regualr medication that puts them at risk of potentially life-threatening bleed and other SE

Awkward dosing

Regular blood tests

Dietary restriction

Complete compliance is necessary

OAT - yellow book

Question 6

Warfarin - Reversal

What options are there for reversal of warfarin?

Drawback of using Vit K?

Considerations when stopping bleed?

Risks of FFP?

ALternatives to Warfarin?

Answer 6

Warfarin - reversal

1. Stop the medication! Vitamin K (e.g. menadiol phosphate; oral or IV), FFP, Prothombin complex concentrate (PCC). Always give Vit K with second 2
2. Take several days to re-warfarinise
3. Bleeding severeity, why patient on anti-coags, how quickly need to stop the bleeding. Oral vit K takes 24h, IV takes 24h
4. Fluid overload
5. Other coumarins e.g. Sinthrone; Hirudins e.g. Phenindione; both inhibit Vitamin K factors

Question 7

Heparin - general

How works?

How do contraindications compare to warfarin?

How eliminated?

How reverse?

Answer 7

Heparin - general

1. Potentiates anti-thrombin III; UFH results in inactivation of Xa and IIa, whereas LMWH mainly affects Xa
2. Similar, but can be used in pregnancy
3. renal excretion, therefore must lower dose in renal failure
4. Protamine sulphate, but only after Haematology advice, becasue if dose wrong, can cause increased bleeding

Question 8

Heparin - Adverse effects

What are main 4?

What is more common in UFH, and describe its pathophysiology?

When suspect HITTS? How treat?

Answer 8

Heparin - Adverse effects

1. Allergy, OP, Hyprkalemia, HITTS
2. HITTS - Heprain induced thrombocytopaenia and thrombosis syndrome. Heparin binds to platelet factor 4, resulting in AB formation to the compound. Immune complex formation with IgG. IC binds Fc receptor on platelets, leading to removal by splenic macrophages as well as platelet aggregation and thrombosis
3. Suspect if platelet drop >30% at 5-10 days. Treat by stopping heparin and starting hirudin. Add in warfarin if thrombosis also present, stopping hirudin once warfarin loaded

Question 9

Heparin - Dosing

Prophylaxis - in renal failure?

ACS

DVT/VTE?

How decide on dose?

How monitor e.g. in pregnancy, extreme weight, very young, active bleed?

Answer 9

Heparin - Dosing

1. 40mg, 20 mg -
2. 1mg/kg bd –> once daily
3. 1.5mg/kg OD -> 1mg/kg OD
4. Round to nearest vial - 60, 80, 100, 120, 150
5. anti-Xa assay

Question 10

Other Anti-coagulants

2 anti-Xa factors?

Anti-thrombin potentiator?

thrombin inhibitor?

4 weaknesses?

Main studies and what SE increased?

Answer 10

Other Anti-coagulants

1. Rivaroxaban, Apixiban
2. Fondaparinux
3. Dabigatran
4. No monitoring, no reversal agent, all accumulate in renal failure, no surgery recommendations (becasue so new)
5. RE-LY and ROCKET-AF - dabigatran and Rivaroxaban better than warfarin in terms of adverse events and as good as if not better in terms of preventing stroke. Main SE increased was dyspepsia, but all other SE reduced