Table of Contents
Coagulation
Parenteral Anticoagulants
Heparin
- (unfractionated) initiates anticoagulation rapidly but has a short duration of action
- can be used in those at high risk of bleeding because its effect can be terminated rapidly by stopping the infusion.
Heparinoids
- role in patients who develop heparin-induced thrombocytopenia.
LMWH
- as effective but preferred because have a lower risk of heparin-induced thrombocytopenia.
- standard prophylactic regimen does not require anticoagulant monitoring
- Compared with UFH, LMWHs have higher anti-Xa/anti-IIa ratios
- LMWHs also seem to differ in their effects on platelet function
- because of their marked pharmacological differences between LMWHs, there are no agreed equivalent doses
| Fondaparinux | synthetic pentasaccharide that inhibits activated factor X. Does not inactivate thrombin (factor IIa), has no effect on platelets and does not X-react with serum of patients with HIT |
|---|---|
| Tinzaparin | fewest indications 175 IU/kg/day for DVT |
| Dalteparin | VTE prevention |
| Enoxaparin | VTE prevention, DVT Rx, ACS |
Oral Anticoagulants
- newer oral anticoagulant drugs have the advantage of the ability to administer at fixed doses without the need of laboratory monitoring
| Rivaroxaban | - direct inhibitor of activated factor X (Xa). - fixed daily oral dose of 10 mg for VTE |
|---|---|
| Dabigatran | - selective, reversible, direct thrombin inhibitor - dosing schedules of dabigatran are 150 mg and 220 mg daily - reports of an association of dabigatran with an increased risk of myocardial infarction or acute coronary syndrome |
| Apixaban | direct factor Xa inhibitor -2.5 mg twice daily |
Antiplatelet agents
Antiplatelet drugs are classified on mechanism of action. (View cycle) close
- metabolic inhibitors
- ADP rec blockers
- platelet-platelet interaction inhibitors
| Aspirin | • Irreversible dose dependent inhibition of the TXA2 pathway • Low dose inhibits cycloxygenase-1 (COX-1) in such a way that only TXA2 production is inhibited and not PGI2 • Platelet function returns to normal 5-7/7 after cessation |
|---|---|
| Dipyridamole | • Phosphodiesterase inhibitor - prevents the inactivation of cAMP • second action - inhibition of thromboxane synthase, thus reducing platelet activation • effect is relatively short-lived - repeated dosing or slow-release preparations are required in order to achieve 24-hour inhibition of platelet function, therefore used more if CI to clopidogrel • Side effects relate to its vasodilatory properties • Platelet function returns to normal 24/24 after cessation |
| Clopidogrel | • Clopidogrel is a prodrug, one of whose metabolites is an inhibitor of ADP-induced platelet aggregation (binds to P2Y12 rec) • PPIs inhibit antiplatelet effects, debate about significance. • Platelet function returns to normal 5-7/7 after cessation |
| Ticagrelor | • oral antagonist at the P2Y12 adenosine diphosphate receptor • inhibits platelet aggregation and thrombus formation in atherosclerotic disease |
Anticoag strategies
- Without VTE prophylaxis, the overall VTE incidence in medical and general surgery hospitalized patients: 10%-40%, & major orthopaedic surgery: 40-60%
- routine VTE prophylaxis, fatal pulmonary embolism is uncommon in orthopaedic patients and the rates of symptomatic VTE within three months: 1.3-10%.
- Hypercoagulability can persist for 3/12 after some orthopaedic surgery
| Condition | Strategy |
|---|---|
| AF | |
| ACS | |
| TIA | |
| Lower limb immobilisation | * Routine use of VTE prophylaxis in ambulatory patients in a short leg cast is controversial * NICE guidance: 'consider' if risk of VTE outweighs risk of bleed |
| Spinal cord injury | VTE prophylaxis with LMWH once haemostasis restored, if no evidence of spinal haematoma |
Pro-coagulants
Tranexamic acid
A synthetic lysine analogue with several mechanisms of action:
- inhibits conversion of plasminogen to plasmin by preventing plasminogen from binding to the fibrin molecule
- inhibits plasmin activity directly, although only at higher doses
- inhibits fibrin cleavage
- blocks binding of α2-antiplasmin and inhibits inflammatory reactions
- 10x more potent than epsilon‐aminocaproic acid (EACA)
- renal clearance with half-life = 2-3/24
- usual dose - 1-1.5g bd, tds
Useful in:
- Gastrointestinal bleeding
- Menorrhagia
- Epistaxis
- Hereditary angioneurotic oedema
- other massive bleeding
References include:
https://bnf.nice.org.uk/treatment-summary/parenteral-anticoagulants.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827912/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941651/
aspirin pharmacol
Briish J cardiol anticoag module
NCBI article tranexamic acid
NICE review Ticagrelor
JAHA oral anticoags - challenges