VTE prophylaxis Flashcards
1
Q
Heparins and fondaparinux
Common indications
A
- Venous thromboembolism (VTE): low molecular weight heparin (LMWH) is the first choice agent for pharmacological VTE prophylaxis in hospital inpatients, and for initial treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).
- Acute coronary syndrome (ACS): LMWH or fondaparinux are part of first-line therapy to improve revascularisation and prevent intracoronary thrombus progression
2
Q
Heparins and fondaparinux
MOA
A
- Thrombin and factor Xa are key components of the final common coagulation pathway that leads to formation of a fibrin clot. By inhibiting their function, heparins and fondaparinux prevent the formation and propagation of blood clots.
- Unfractionated heparin (UFH) activates antithrombin that, in turn, inactivates clotting factor Xa and thrombin.
- Low molecular weight heparins such as dalteparin and enoxaparin have a similar mechanism of action but preferentially inhibit factor Xa. Low molecular weight heparins have a more predictable effect and, unlike UFH, do not usually require laboratory monitoring.
- Consequently, LMWHs are now preferred in most indications. Fondaparinux is a synthetic compound that is similar to heparin. It inhibits factor Xa only. It appears to have similar efficacy to LMWH and has become the anticoagulant of choice in the treatment of ACS in many hospitals in the UK.
3
Q
Heparins and fondaparinux
Adverse effects
A
- The main adverse effects of heparins and fondaparinux is bleeding
- This risk may be lower with fondaparinux and LMWH or UFH
- Rarely heparins may cause thronbocytopenia and thrombosis
- Immune reactions are less likley with LMWH and fondaparinux
4
Q
Heparins and fondaparinux
Warnings
A
- Anticoagulants should be used with caution in patients at increased risk of bleeding, including those with clotting disorders, severe uncontrolled hypertension, or recent surgery or trauma.
- Heparins should be avoided around the time of invasive procedures, particularly lumbar puncture and spinal anaesthesia.
- In patients with renal impairment, LMWH and fondaparinux may accumulate and should be used at a lower dose, or unfractionated heparin used instead
5
Q
Heparins and fondaparinux
Interactions
A
- Combining antithrombotic drugs increases the risk of bleeding. This
should usually be avoided unless there is a special reason for combined
therapy, such as in the use of LMWH while initiating warfarin, or the use
of antiplatelet drugs (e.g. aspirin, clopidogrel) with fondaparinux/LMWH
in ACS. - In major bleeding associated with heparin therapy, protamine
can be given to reverse anticoagulation. This is effective for UFH but much less so for LMWH, it is ineffective against fondaparinux
6
Q
Heparins and Fondaparinux
A
- FBC and renal profile should be checked
- Platelets should be monitored. If thrombocytopenia occurs seek speacalist advice
7
Q
Warfarin
Common indications
A
- To prevent clot extension and recurrence in deep vein thrombosis
and pulmonary embolism (collectively, venous thromboembolism
[VTE]). - To prevent embolic complications (e.g. stroke) in atrial fibrillation.
- To prevent embolic complications (e.g. stroke) after heart valve
replacement. Treatment is short term after tissue valve replacement
and lifelong for mechanical valve replacement.
Warfarin is not used to prevent arterial thrombosis (e.g. myocardial
infarction, thrombotic stroke). As this is driven by platelet aggregation,
it is prevented by antiplatelet agents, such as aspirin and clopidogrel
8
Q
Warfarin
MOA
A
- Warfarin inhibits hepatic production of vitamin K-dependent coagulation
factors and cofactors. - Vitamin K must be in its reduced form for synthesis of coagulation factors. It is then oxidised during the synthetic process.
- An enzyme called vitamin K epoxide reductase reactivates oxidised vitamin K. Warfarin inhibits vitamin K epoxide reductase, preventing reactivation of vitamin K and coagulation factor synthesis
9
Q
Warfarin
Adverse effects
A
- The main adverse effect of warfarin is bleeding. A slight excess of
warfarin increases the risk of bleeding from existing abnormalities such
as peptic ulcers or following minor trauma (e.g. intracerebral
haemorrhage after minor head injury). - A large excess of warfarin can trigger spontaneous haemorrhage such epistaxis (nose bleed) or retroperitoneal haemorrhage.
10
Q
Warfarin
Warnings
A
- As there is a fine line between thrombosis and haemorrhage in patients
taking warfarin, potential risks and benefits must be carefully balanced. - Warfarin is contraindicated in patients 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
11
Q
Warfarin
Interactions
A
- The plasma concentration of warfarin required to prevent clotting is very
close to the concentration that causes bleeding (low therapeutic
index). - Small changes in hepatic warfarin metabolism by cytochrome
P450 enzymes can cause clinically significant changes in
anticoagulation. - Cytochrome P450 inhibitors (e.g. fluconazole, macrolides, protease inhibitors) decrease warfarin metabolism and increase bleeding risk.
- Cytochrome P450 inducers (e.g. phenytoin, carbamazepine, rifampicin) increase warfarin metabolism and risk of clots.
- Many antibiotics can increase anticoagulation in patients on warfarin by killing gut flora which synthesise vitamin K.
12
Q
Warfarin
Communication
A
- Advise patients that warfarin treatment is a balance between benefits
(preventing clots) and risks (bleeding). - It is important for patients to understand how food, alcohol and other drugs can affect warfarin treatment.
- Patients receive an anticoagulant book (‘Yellow Book’), which acts as an alert to their warfarin therapy and is used to record warfarin doses, blood test results, treatment indication and duration
13
Q
Fondaparinux
Indications
A
- VTE prophylaxis undergoing major orthopaedic surgery
- VTE prophylaxis- in medical patients
- Treatment of superficial-vein thrombosis
- Treatment of unstable angina, NSTEMI, STEMI
- Treatment of DVT + PE
14
Q
Fondaparinux
MOA
A
- Selective inhibitor of factor Xa
- The anti-thrombotic activity of fondaparinux is the result of anti-thrombin III mediated selective inhibition of factor Xa
- NB- it has no effect on platelets so can be used in heparin-induced thrombocytopenia
15
Q
Fondaparinux
Adverse effects
A
- Bleeding
