CV - Heparins and fondaparinux: enoxaparin, dalteparin, fondaparinux, unfractionated heparin Flashcards
1
Q
Heparins and fondaparinux: enoxaparin, dalteparin, fondaparinux, unfractionated heparin
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: enoxaparin, dalteparin, fondaparinux, unfractionated heparin
Mechanism of Action
A
- Thrombin and factor Xa are key components of common coagulation pathway leading to formation of a fibrin clot.
- By inhibiting their function, heparins and fondaparinux prevent the formation of blood clots. Unfractionated heparin (UFH) activates antithrombin that, 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: enoxaparin, dalteparin, fondaparinux, unfractionated heparin
Important adverse effects
A
- The main adverse effect of heparins and fondaparinux is bleeding.
- This risk may be lower with fondaparinux than with LMWH or UFH.
- As with many injectables, these drugs may cause injection site reactions. Rarely, heparins may cause a dangerous syndrome characterised by low platelet count and thrombosis (heparin-induced thrombocytopenia).
- This immune reaction is less likely with LMWH and fondaparinux than UFH.
4
Q
Heparins and fondaparinux: enoxaparin, dalteparin, fondaparinux, unfractionated heparin
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: enoxaparin, dalteparin, fondaparinux, unfractionated heparin
Contraindications
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: enoxaparin, dalteparin, fondaparinux, unfractionated heparin
Px and Administration
A
- LMWH and fondaparinux are prescribed for regular administration. Some hospitals have a dedicated prescription chart for anticoagulants.
- They are given by SC injection. The dose is dependent on indication and the patient’s weight. For prophylaxis of VTE in medical inpatients, common choices are enoxaparin 40 mg SC daily or dalteparin 5000 units SC daily.
- Higher doses are used in treatment of VTE and ACS. UFH is sometimes given by IV infusion, and is therefore prescribed in the infusion section of the chart.
7
Q
Heparins and fondaparinux: enoxaparin, dalteparin, fondaparinux, unfractionated heparin
Communication
A
- In the context of VTE prophylaxis, explain that you are offering a daily injection that will reduce the risk of blood clots.
- In longer-term therapy (e.g. for the treatment of VTE in cancer, when LMWH may be preferred over warfarin), discuss the risks and benefits of anticoagulation.
- Advise patients to avoid activities that may increase their risk of bleeding, such as contact sports, and to inform healthcare professionals they come into contact with that they are taking anticoagulants.
- If appropriate, train patients how to self-administer SC injections.
8
Q
Heparins and fondaparinux: enoxaparin, dalteparin, fondaparinux, unfractionated heparin
Monitoring
A
- The activated partial thromboplastin ratio (APTR) indicates the anticoagulant effect of UFH and is measured frequently (e.g. every 6 hours initially) during an infusion of UFH.
- The infusion rate should be altered to achieve the target APTR (usually 1.5–2.5).
- The anticoagulant effects of LMWH and fondaparinux rarely require monitoring.
- If required (e.g. in pregnancy), LMWH can be monitored by anti-Xa activity. The full blood count and renal profile should be checked in all cases. In prolonged therapy (>4 days), platelet count should be monitored.
- If thrombocytopenia occurs, the drug must be stopped and specialist advice sought immediately.
