Antithrombotic anticoagulants

Antithrombotic anticoagulants
Updated resume for treatment

1. Marwa Mahmoud Khalifa Faculty Of Medicine Alexandria University Antithrombotic Agents

2. HEPARINS Fondaparinux LMWH ( dalteprin , enoxaprin & tinzaparin ) Unfractionated heparin Synthetic pentasaccharide Manufactured by enzymatically or controlled depolymerization Naturally occurring GAGs extracted from porcine intestine. MW 3000-5000 MW 15,000 SC SC IVI/ SC T ½ 17 h T ½ 3-5 h T ½ 45-60 min No monitoring Monitored APTT According to type Bolus 80 IU/kg/h Then 18 IU/kg/h Protamine but less effective Antidote : protamine No HIT SE : same but less common SE : hyperkalemia, HIT& osteoprosis

3. HEPARINS Mechanism of action Specific pentasaccharide sequence binds with high affinity to antithrombin , produces conformational changes that releases reactive centre loop potentiating its activity Inhibition FXa

4. HEPARINS Danaparoid Hepainoid Used with HIT Indirectly inhibit FXa , thrombin No effect on PT / APTT

5. Direct thrombin inhibitors Argatroban Bivalirudin Metabolized by liver (cytochrome P450) Metabolized 80% proteolysis 20% by kidney T ½ 50 min T ½ 25 min Indication : HIT , renal impairment Indication : ACS undergoing PCI Continuous IVI Continuous IVI Monitored by APTT Monitored by APTT

6. Vitamin K antagonists Vit K is needed for post translational modification of vit K dependent factors (II, VII, IX, X, protein C & S) Vit K antagonists : warfain , acenocoumarol , phenindione , fluindione & phenprocoumon . Affected by diet Many drug drug interactions Monitored by INR. Target INR for DVT, PE, stroke prevention in AF (2-3) Higher target for mechanical heart valves Take days to be effective, heparin is given initially. SE : skin necrosis, purple toe syndrome, rash hair loss and hepatitis Teratogenic

7. Vitamin K antagonists If anticoagulant has to be stopped for surgery or invasive procedure should be stopped 5 days before BRIDGING therapy with short acting anticoagulant (LMWH) Can be resumed the evening of surgery or next day Emergency anticoagulation reversal major bleeding 25-50 U/kg four factor prothrombin complex concentrate 5 mg IV vit K Non major bleeding : 1-3 mg IV vit K INR >8 , no bleeding : 1-5 mg oral vit K

8. Bridging therapy : Last episode VTE within previous 3 months AF with previous stroke / TIA / multiple risk factors Mitral MHV / non bileaflet aortic MHV/ bileaflet aortic MHV with other risk factors

9. Warfarin dosing algorithm Day 4 Day 3 Days 1 & 2 Dose ( mg) INR Dose ( mg) INR Give 5 mg each day if baseline INR <1.3 10 <1.6 10 <1.5 7 1.6-1.7 5 1.5-2 6 1.8-1.9 3 2.1-2.5 5 2-2.3 1 2.6-3 4 2.4-2.7 >3 3 2.8-3 2 3.1-3.5 1 3.6-4 >4

10. Non vit K antagonist oral anticoagulants Predictable dose resposes No need for routine monitoring No food interactions Limited drug interactions Fixed dose Rapid onset & short T ½ Not ass with HIT Kidney excreted with variable degrees

11. Edoxaban Apixaban Rivaroxaban Dabigatran Inhibit FXa Inhibit FXa Inhibit FXa Inhibit IIa Target 9-11h 10-14h 7-13h 12-17 h T1/2 60 mg od 5 mg bd 20 mg od 150 mg bd Dose AF 60 mg od 10 mg bd for 7 d then 5 mg bd 15 mg bd for 3 w then 20 mg od 150 mg bd Dose VTE Yes No No Yes LMWH for initial treatment 35% 25% 33% 80% Renal excretion Low High High low Protein binding

12. Time of stopping NOACs before elective surgery Minor surgery Major surgery 24 48 Dabigatran 24 48 Rivaroxaban 24 48 Apixaban 24 48 Edoxaban

13. Management of bleeding with N OACS The anticoagulant activity should be determined by most appropriate lab assay ( calibrated anti Xa , dilute plasma thrombin time ) Bleeding not severe : stop drug and detemine cause of bleeding Severe bleeeding : Mechanical compression S urgical haemostasis Correction of additional coagulopathy FFP doesn’t reverse the effect