Blood Clots

Question 1

Venous Thromboembolism

Answer 1

Venous Thromboembolism (VTE) includes Deep-vein thrombosis (DVT) + Pulmonary Embolism and occurs as a result of thrombus formation in a vein

Question 2

• High risk patients of VTE include

Answer 2

• > 60 years old,
• limited mobility,
• obese,
• malignant disease,
• thrombophilic disorder
• history of VTE.
• Pregnanacy and postpartum period are also risk factors
• It is essential to look at the risk of bleeding vs VTE

Question 3

Examples of VTE treatment

Answer 3

• Mechanical: Stockings
• Pharmacological:
• LMWH can be used for prophylaxis in general + orthopaedic surgery
• Unfractionated heparin can be used in patients with renal failure
• Oral anticoagulants: apixaban, dabigatran + rivaroxaban are indicated for prophylaxis in hip/knee replacement surgery.

Question 4

Heparin

Answer 4

 Heparin has a fast onset of action and a short duration of action compared to a LMWH
 Used in patients with a high risk of bleeding as its effects can be reversed quicker… In the case of a haemorrhage, Protamine is given to reverse the effects of this drug (but only partially effective for LMWH)
 Pregnant women can take Heparin for VTE as it does not cross the placenta. But LMWH are preferred due to their risk of osteoporosis and heparin-induced thrombocytopenia.
 LMWH are given in preference to Heparin for the treatment of VTE due to reasons highlighted above. Examples include: Dalteparin + Enoxaparin.
 The duration of action for LMWH is LONGER… hence a ONCE daily dosing regimen (convenience).

Question 5

Side effects of heparin

Answer 5

thrombocytopenia (reduced platelet count), hypokalaemia and haemorrhage.

Question 6

Warfarin uses and action

Answer 6

• Warfarin can be used for AF, DVT + PE. It antagonises the effect of Vitamin K (needed to produce clotting factors) and it usually takes at least 48-72 hours for the full effect to be seen. If a quicker effect is needed… heparin should be used.
- Counselling point: taking ONCE daily at the SAME TIME each day

Question 7

INR ranges and monitoring

Answer 7

• 2.5 for AF, DVT and PE
• 3.0 for mechanical aortic valves and
• 3.5 for recurrent DVT or PE in patients currently receiving anticoagulation and with INR >2

• INR monitoring should be carried out daily or on alternate days at first, then gradually increased to longer durations up to 12 weeks apart.
• Any changes to the patient’s condition or lifestyle may derange the INR and indicate more frequent monitoring (e.g. decreased liver function, change of medication, diet, smoking or alcohol intake).
- Recent weight loss, acute illness, diarrhoea and vomiting may also upset INR levels.

Question 8

ADR of warfarin

Answer 8

The main adverse effect of warfarin is haemorrhage (bleeding). If there is any sign of bleeding warfarin should be stopped immediately, and the patient should be started on vitamin K1.

Question 9

 If they are not bleeding, but their INR > 8

Answer 9

give vitamin K1 by mouth and withhold warfarin until INR <5

Question 10

If they are not bleeding and their INR > 5

Answer 10

then withhold 1 or 2 doses of warfarin.

Question 11

Elective surgery whilst on warfarin

Answer 11

• Usually warfarin is stopped 5 days prior to any elective (planned) surgery and is restarted almost immediately after the procedure. Patients stopping warfarin prior to surgery who are considered to have a higher risk of VTE may require interim therapy (‘bridging’) with a LMWH – this should be stopped 24 hours before surgery and resumed 48 hours after surgery.
• If emergency surgery is required, the patient will need vitamin K1 with prothrombin complex depending on the timescale

Question 12

Anticoagulant and antiplatelet therapy

Answer 12

Ideally anticoagulant therapy (slows clotting) should not overlap with antiplatelet therapy (prevent clotting). The risk of bleeding with Aspirin + Warfarin is less than with Clopidogrel + Warfarin.

Question 13

Warfarin in renal impairment

Answer 13

Warfarin can be used in Renal impairment: increased frequency of INR monitoring needed in severe impairment.

Question 14

Avoid warfarin

Answer 14

• Avoid in pregnancy + avoid cranberry juice (increases anticoagulant effect). Avoid changing diet of liver, sprouts, broccoli and leafy green vegetables (rich in Vitamin K).

Question 15

Enzyme inducers (Crap GP’s Shout BS)

Answer 15

Carbamazepine
Rifampicin
Alcohol
Phenytoin
Griseofulvin
Phenobarbital
Sulphonylurea’s
St John’s Wort
Barbiturates
Smoking

Question 16

Enzyme inhibitors (Sickfaces.comGF)

Answer 16

Sodium Valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol
Chloramphenicol
Erythromycin
Sulphonamide’s
Ciprofloxacin
Omeprazole
Metronidazole
Grapefruit Juice
Fluoxetine

Question 17

MHRA/CHM ADVICE: WARFARIN

Answer 17

REPORTS OF CALCIPHYLAXIS (JULY 2016): An EU-wide review has concluded that on rare occasions, warfarin use may lead to calciphylaxis—patients should be advised to consult their doctor if they develop a painful skin rash; if calciphylaxis is diagnosed, appropriate treatment should be started and consideration should be given to stopping treatment with warfarin. The MHRA has advised that calciphylaxis is most commonly observed in patients with known risk factors such as end-stage renal disease, however cases have also been reported in patients with normal renal function.

Question 18

• Warfarin is CI in patients

Answer 18

at immediate risk of haemorrhage, including after trauma and in patients requiring surgery. Patients with liver disease who are less able to metabolise the drug are at risk of over-anticoagulation/bleeding. In pregnancy, warfarin should not be used in the first trimester as it causes fetal malformations, including cardiac and cranial abnormalities. It should not be used towards term, when it may cause maternal haemorrhage at delivery.

Question 19

Antiplatelet drugs

Answer 19

 These drugs decrease platelet aggregation and inhibit thrombus formation.
 Aspirin at a dose of 75mg is given for secondary prevention of CVD, but there is no proven benefit of its use in primary prevention. It can be given with Prasugrel/Ticagrelor for the prevention of thrombotic events in patients with acute coronary syndrome (ACS).
 It is contraindicated in patients with active peptic ulceration, haemophilia and children <16 years due to the risk of Reye’s syndrome.
 Clopidogrel is an antiplatelet drug used to prevent thrombotic events in patients with a history of ischaemic disease.
 Clopidogrel with aspirin is used following an ST- elevated MI or for AF when warfarin is not suitable

Question 20

Stroke and Transient Ischaemic attack (TIA)

Answer 20

 A TIA (‘mini stroke’) should be treated with Aspirin immediately. A stroke or TIA should be treated initially with ALTEPLASE (a thrombolytic) 4.5 hours after symptoms occurred, and Aspirin 300mg OD for two weeks, after the two weeks anticoagulant therapy can be added if needed.
 Long-term management is Clopidogrel 75mg OD and a Statin (regardless of patient’s cholesterol).

Question 21

Other oral anticoagulants

Answer 21

1. Dabigatran is a thrombin inhibitor; apixaban and rivaroxaban are inhibitors of activated factor X.
2. Apixaban and rivaroxaban may be affected by enzyme inducers/inhibitors.
3. Rivaroxaban is once daily dosing whereas the others are twice daily, and it is slightly cheaper.

Question 22

Aspirin 75mg dispersible tablets (Antiplatelet)

Answer 22

• Thins blood so it doesn’t clot too easily, helps to prevent strokes and heart attacks.
• Aspirin 75mg usually taken OD, preferably at the same time each day. Can be chewed or dispersed in a glass of water.
• Take with or just after food as aspirin can cause dyspepsia (indigestion). If indigestion is severe or prolonged contact doctor.
• A few people are allergic to aspirin - this is more common in asthmatic people. Although unlikely, difficulty breathing, and skin rashes can occur. If this happens stop taking the tablets and contact doctor.
• Do not give to children <16 years due to risk of Reye’s syndrome unless specifically indicated (e.g. for Kawasaki disease).
• Long-term use of low-dose aspirin is recommended in patients with established CVD (secondary prevention)
• Overdose signs - hyperventilation, tinnitus, deafness, vasodilatation, and sweating. Coma is uncommon but indicates very severe poisoning.
• BP states if no strength is stated dispense 300mg strength
• Can be sold to public (max pack size of 32; pharmacists can sell multiple packs -total quantity of 100 capsules or tablets in justifiable circumstances).
• Do not take anything else containing aspirin while taking this medicine