Anticoagulants - Warfarin: Nursing pharmacology

Anticoagulants are medications that work by interfering with the function of clotting factors in the coagulation cascade, preventing the formation of thrombi, or blood clots. These medications are used to prevent or treat thromboembolic events, such as deep vein thrombosis, pulmonary embolism, ischemic stroke, transient ischemic attack, coronary artery disease or myocardial infarction.

They're also used in clients with coagulation disorders, including antiphospholipid syndrome and disseminated intravascular coagulation; as well as in clients who underwent coronary angioplasty or cardiac valve replacement; and during surgical procedures like cardiopulmonary bypass, percutaneous coronary intervention, extracorporeal membrane oxygenation, and in clients undergoing dialysis.

One of the most important anticoagulants is warfarin, which is given orally, and works as a vitamin K antagonist.

Normally, vitamin K is used by the liver as a cofactor for the synthesis and activation of the clotting factors II, VII, IX, and X, as well as the anticoagulant proteins C and S. During this process, the active form of vitamin K, called vitamin K hydroquinone, is converted into vitamin K epoxide, which is then recycled back into vitamin K hydroquinone by another enzyme called epoxide reductase.

Warfarin antagonizes the function of vitamin K by inhibiting the epoxide reductase enzyme and preventing vitamin K hydroquinone from getting recycled. As a result, there’s no synthesis and activation of the clotting factors II, VII, IX, and X, but also the anticoagulant proteins C and S. Out of all the vitamin K-dependent proteins, protein C has the shortest half-life so it is the first to be depleted in clients taking warfarin. This results in an initial period of hypercoagulation before the anticoagulant effect kicks in. To prevent this, bridging anticoagulation with LMWH is usually prescribed for a short period while starting warfarin therapy.

Now, the main side effect of warfarin is undue bleeding, which can present as petechiae, ecchymosis, epistaxis, as well as bleeding gums, blood in stools, hematemesis, and uncontrollable internal bleeding from falls or even minor trauma. Thankfully, antidotes are available to reverse the action of most anticoagulants if the bleeding gets severe. The antidote for warfarin is vitamin K1, also called phytonadione.

Other side effects of warfarin include hair loss, fever, bone marrow depression, and gastrointestinal effects like anorexia, abdominal cramps, vomiting, and diarrhea. In addition, clients are at risk for thrombi and emboli in various parts of the body, since warfarin also inhibits protein C. In particular, thrombosis of blood vessels in the skin leads to warfarin-induced skin necrosis, while microemboli in the feet can cut off blood supply causing purple toe syndrome. Finally, warfarin is teratogenic, since it can cross the placenta and cause fetal hemorrhage, bone deformities, congenital heart defects, brain malformation in the fetus, or even spontaneous abortion.

Now, due to the risk of bleeding, all anticoagulant medications are contraindicated in clients with active internal bleeding, recent trauma in the past three months, as well as those with a history of intracranial hemorrhage or ischemic stroke, gastrointestinal ulcers and coagulopathies or bleeding disorders. In addition, anticoagulants should be used with caution in clients taking antiplatelet medications like aspirin and clopidogrel; or thrombolytic medications like alteplase, reteplase, and tenecteplase; which can increase the risk of bleeding.

Now, warfarin is broken down in the liver by a class of enzymes called CYP450, so it should not be combined with medications that interact with it. On the one hand, any medications that inhibit this enzyme, such as cimetidine, omeprazole, metronidazole, trimethoprim/sulfamethoxazole, and amiodarone can cause the accumulation of warfarin in the body, leading to undue bleeding. On the other hand, medications that enhance the activity of CYP450, such as griseofulvin, barbiturates, phenytoin, and carbamazepine, can speed up the metabolism of warfarin, decreasing its effects.

In addition, clients should limit their consumption of vitamin K-rich foods like green leafy vegetables, as they reduce warfarin's effects, as well as cranberry juice, as it increases warfarin's effects. Warfarin is also contraindicated for use in clients undergoing surgery of the eye, brain, or spinal cord, as well as when undergoing spinal anesthesia or spinal puncture, as it can cause a spinal and epidural hematoma, which can lead to permanent paralysis. Finally, warfarin is also contraindicated during pregnancy and breastfeeding due to its teratogenic effects.