Table of contents
Notes
- Do not need to stop warfarin therapy for minor dental procedures (includes extractions)
- Source: NEJM+
Antiplatelet Agents
- Dipyridamole - Usually used if aspirin not tolerated
- Aspirin
- Irreversible platelet inhibitor (takes 6 days or so to back to normal)
- Not appropriate for VTE prophylaxis / treatment. (shown no benefit)
- Aspirin is effective for ARTERIAL thrombi (stroke, MI)
- Ticlopidine - Not used for stroke prevention - Bad S/E profile.
Anticoagulant Agents
TABLE UNDER CONSTRUCTION
| Agent | Class/Mech | Indications | Cautions | Reversal | Notes |
|---|---|---|---|---|---|
| Warfarin (Coumadin) | Vitamin K Antagonist (Factors II, VII, IX, and X) | - AFib - VTE - VTE proph - PE - Congenital Prothromboic | - Requires INR monitoring | Vitamin K FFP PCC (Octoplex) - works fast - less volume - more expensive | - Affects factors 10, 9, 7, 2, Protein C, Protein S (1972 Canada vs. Soviets) - Target INR 2-3 (or 2.5-3.5 for mech valves) |
| Unfractionated Heparin - 5000u SC q8-12h for high risk) then 1000 U/h (target PTT 1.5-2.5 *normal PTT) | Binds antithrombin-3 (AT3), Heparin-AT3 complex inactivates F II (thrombin), IXa, Xa, XIa, XIIa Thrombin inhibited at very low doses (before other factors so VTE proph very effective at low dose) | - Safer in Renal Failure - AFib/VTE VTE proph/ congenital/ cancer VTE | - Heparin-AT3 complex can bind Platelet Factor 4 - Ab formed against it causes Heparin- Induced Thrombocytopenia (HIT) - Requires PTT monitoring - PTT poorly predictable. | - Protamine (must be in monitored setting) | - Must monitor PTT and titrate - High Risk of Heparin Induced Thrombocytopenia (HIT) - Usually give as infusion or frequent bolus - Duration of action ~4hr - Fast on-off if needs to go for surgery. - Reversible with protamine [LMWH is not as reversible with protamine] (1mg IV protamine for 100 units of UFH in last 4 hrs. Give protamine over 1-3min, do not exceed 50mg/10min.) or 1mL (10mg) of protamine for each 1000IU of heparin
|
| LMWH - Enoxaparin (1.5mg/kg q24h)
- Dalteparin (200UI/kg q24h) (aka Fragmin)
- Tinzaparin (175 U/kg q24h)
| LMWH Inhibits: - Factor Xa - Antithrombin molecular sizes, smaller ones = more anticoagulation. | Same as UH | - Protamine Reverses anti- thrombin, but partially reverses Factor Xa activity | - Monitoring not needed - Can monitor anti-factor Xa activity if need (i.e. obese or renal failure) - Very predictable anticoagulation - Low risk of heparin-induced thrombocytopenia (HIT) | |
| Argatroban (NO trade name) | Synthetic Direct Thrombin Inhibitor | - HIT requiring anticoagulation | - Hepatically cleared | - Cleared by liver (no renal dosing) (adjust for hepatic insufficiency) | |
| Lepirudin (not used, replaced by Argatroban) | Direct Thrombin Derived from medicinal leech | - like Argatroban | - Renally Cleared (not used in renal pts) - IV bolus = risk of anaphylaxis | - Rarely used - | |
| Fondaparinux (chemically related to LMWH) Daily Dosing 5mg SC od (for <50kg) or 7.5 mg SC od (for 50-100kg), or 10mg if >100kg | Anti-Thrombin III potentiator (indirectly inhibits Factor Xa) Synthetic penta- saccharide | - NSTEMI - ... | - Renally cleared if GFR < 30 and < 50kg pts) | - Can be used to manage HIT, but does not carry the FDA indication. (easy - single daily dose) - Insufficient data to recommend it over argatroban - Same efficacy as enox for hip+knee surgeries. | |
| Bivalirudin | Direct Thrombin Inhibitor - Derived from hirudin in leech saliva | - STEMI/NSTEMI undergoing PCI | Some renal clearance Mostly plasma protein cleavage Halflife: Normal renal function: 25 minutes Severe (CrCl 10-29): 57 minutes IHD-dependent (off dialysis): 3.5 hours | - NO need - activity ends 1hr after d/c | - inhibits both circulating + clot-bound thrombin - quick onset, short halflife - Unlike heparin doesnt bind plasma proteins, so has a predictable response
|
| Dabigatran | Direct thrombin inhibitor | Idarucizumab Dialyzable!!! | |||
| Rivaroxaban | Direct factor Xa inhibitor | Andexanet alfa | |||
| Apixaban | Diret factor Xa inhibitor | Andexanet alfa |
Heparin Induced Thrombocytopenia (HIT)
- More common with Heparin than LMWH
- Antibodies bind complexes formed between heparin and platelet factor 4 (PF4).
- See decreasing platelet counts
- Surprisingly, HIT is a pro-coagulant phenomena - perhaps antibody-PF4 complexes release procoagulants from circulation. So need to monitor patients for arterial clots.
- Treat with argatroban (FDA approved) but some use fondaparinux (not FDA approved)
Pro-Coagulant Agents
- Tranexamic Acid
- Lysine derivative
- Competitively inhibits plasminogen --> Acts as anti-fibrinolytic.
Pneumatic Compression Devices
- Only shown to decrease VTE risk in surgical patients.
- Not been demonstrated to significantly reduce incidence of PE.
- Compliance is an issue.
INR & Warfarin
- Do not use Vitamin K in a non-bleeding patient unless INR > 9.0.
- IF INR > 9.0, can give Oral Vitamin K 2.5-5mg and withhold warfarin + follow INR.
- Most common drugs that raise INR: (based on population based study)
- Septra
- Amoxicillin
- Clarithromycin
- Norfloxacin
- Starting/Titrating Warfarin:
-
Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e152S-84S
Resources
- Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e195S-226S. PMID: 22315261
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