=====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. {{ :wiki:haematology:coagulation_cascade.png.jpg?400|}} ==== 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) <@anno:[10;;anno_dylan]>{{ :wiki:haematology:antiplatelet.png?|}} *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/\\ [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236360/ |aspirin pharmacol]]\\ [[https://bjcardio.co.uk/2016/01/revised-anticoagulation-module-2-antiplatelet-therapy/2/|Briish J cardiol anticoag module]]\\ [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429347/|NCBI article tranexamic acid]]\\ [[https://www.nice.org.uk/guidance/ta236/documents/acute-coronary-syndromes-ticagrelor-final-appraisal-determination-document2|NICE review Ticagrelor]]\\ [[https://www.ahajournals.org/doi/10.1161/JAHA.120.017559|JAHA oral anticoags - challenges]]\\