Anticoagulants are used for treating and preventing embolic events. The most common oral anticoagulatory agents are vitamin K antagonists such as warfarin and phenprocoumon. Non-vitamin K antagonist oral anticoagulants (NOACs) like dabigatran and rivaroxaban have also gained popularity in recent years. Vitamin K antagonists inhibit the enzyme vitamin K epoxide reductase, thereby blocking hepatic synthesis of the active, reduced form of vitamin K (needed for carboxylation of coagulation factors II, VII, IX, and X, protein C, protein S). This effect can last for several days, which complicates exact dosing and makes regular monitoring necessary. Vitamin K antagonists are also metabolized by C-P450 (CYP) enzymes and therefore interact with a broad range of foods and drugs. NOACs act selectively via inhibition of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban). Because of their comparatively short half-life and fewer interactions, NOACs are easier to control and administer than warfarin and do not require regular monitoring to ensure their efficacy and safety. For all substances, it is important to consider the dose-dependent risk of bleeding, especially when combining different substances that affect hemostasis (e.g., aspirin, clopidogrel, ticagrelor).
Overview of commonly used oral anticoagulants
|Overview of commonly used oral anticoagulants|
|Mechanism of action||Advantages||Disadvantages|
|Vitamin K antagonists (coumarins)|| |
| || |
|Direct oral anticoagulants|
|Direct oral thrombin inhibitors||Dabigatran || || |
|Direct oral factor Xa inhibitors|| |
General notes regarding oral anticoagulation
- Indications for all oral anticoagulants
- Expected laboratory changes
The most important side effect of all oral anticoagulants is a dose-dependent increase in bleeding risk.
DRAW: Dabigatran, Rivaroxaban, Apixaban, and Warfarin are the most important oral anticoagulants.
RivaroXaban, apiXaban, and edoXaban are .
WARsaw is an EXTRaordinary Place To check out: WARfarin affects the EXTRinsic pathway; therefore, PT should be regularly checked.
WEPT: Warfarin Extrinsic pathway PT
|Heparin vs. warfarin|
|Anticoagulant||Route of administratIon||Mechanism of action||Monitoring||Reversal agents|
|Heparin|| || || |
Dose-dependent increased risk of bleeding
- Small wounds cease to bleed spontaneously and no additional measures are required
- Severe cases of hemorrhage are usually retroperitoneal, intracranial, or gastrointestinal.
- Countermeasures for extensive or life-threatening bleeding include
Warfarin-induced skin necrosis
- Seen within the first few days of treatment with high doses of warfarin
- Warfarin inhibits all vitamin K-dependent coagulation factors; : anticoagulants protein C and protein S have a relatively short half-life and are depleted more quickly than procoagulants factors II, IX, and X → increased factor V and VIII activity → initial hypercoagulable state → formation of microthrombi → vascular occlusion, tissue infarction, and blood extravasation; ; ;
- Increased risk in patients with underlying hereditary protein C deficiency
- Presentation: painful purpura, hemorrhagic blisters, and large areas of necrosis; mostly affects subcutaneous adipose tissue
- Immediate management: discontinue warfarin, administer IV vitamin K, unfractionated heparin, and source of protein C (protein C concentrate, FFP); surgical debridement and grafting in therapy-refractory cases
- Prevention: temporary with therapyheparin for immediate anticoagulation until warfarin has started to act and the initial hypercoagulable state has been bridged
Direct factor Xa inhibitors and direct thrombin inhibitors
Dose-dependent increased risk of bleeding
- Interventional steps to stop the bleeding
- If life-threatening bleeding occurs, administer PCC
- General management and specific medication antidotes
RivaroXaban and apiXaban can be reversed with andeXanet alfa.
We list the most important adverse effects. The selection is not exhaustive.
|Indications of oral anticoagulants |
|Direct thrombin inhibitors|| |
|Direct factor Xa inhibitors|
- Coagulopathies; hepatic dysfunction with impaired hepatic production of coagulation factors
- Acute bleeding
- Suspected vascular lesions, increased risk of severe bleeding
- Severe renal insufficiency
- Concurrent administration of several anticoagulants
- Pregnancy and breastfeeding
- Specific contraindications
We list the most important contraindications. The selection is not exhaustive.
- Decrease of anticoagulant effect
Increase of anticoagulant effect
- Several antidepressants and antibiotics, PPIs, amiodarone, grapefruit: impair metabolic breakdown via inhibition of cytochrome P450
- Acetaminophen: metabolite of acetaminophen interrupts vitamin K cycle via inhibition of vitamin K-dependent carboxylase
- Sulfonamides, sulfonylureas: competitively block or displace warfarin at plasma protein binding sites
- Damage to gut flora (e.g., antibiotic therapy): impaired bacterial vitamin K synthesis
“Chronic alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs): Chronic alcohol use, St. John's wort, Phenytoin, Phenobarbital, Nevirapine, Rifampin, Griseofulvin, and Carbamazepine are P450 inducers (↓ warfarin levels).
“sickfaces.com group”: Sulfonamides, Isoniazid, Cimetidine, Ketoconazole, Fluconazole, Alcohol (binge drinking), Ciprofloxacin, Erythromycin, Sodium valproate, Chloramphenicol, Omeprazole, Metronidazole, and Grapefruit juice are P450 inhibitors.
- Bridging anticoagulation: the administration of heparin for the duration of the transient hypercoagulable state caused by warfarin therapy. Heparin prevents coagulation by activating antithrombin.
Preoperative bridging therapy
- Stop coumarin administration 5–6 days before surgery.
- Administer a therapeutic dose of the bridging drug 3 days before surgery; , with the last dose administered 24 hours before the procedure.
- Resume the bridging drug and warfarin after surgery; ; administer the bridging drug for 4–6 days post-surgery.