Warfarin

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Warfarin is an anticoagulant medication. This drug dissolved clots that may have formed or those that have broken off and migrating in the body which might block blood supply to a vital organ. This drug works best at low pressure blood that is usually found in veins and heart valves. It acts slowly when compared to heparin and may be taken by mouth.

Contents

Chemical nature

Warfarin was used initially by the public as an effective poison against rats and mice. However, its use has been replaced by more current and more potent poisons such as brodifacoum. After it was introduced in the market, researchers discovered that it was an effective and relatively safe treatment for formed or migrating blood clots. It was approved for human use in 1950 and has been widely prescribed as an anticoagulant.

Warfarin is derived from the molecule of dicoumarol, an active mycotoxin that was originally discovered in rotten animal feeds, made mostly of sweet clover, that was discovered by Frank Schofield in 1921. This compound was further identified by Karl Paul Link of the University of Wisconsin and his associates and named it dicoumarol. The generic name “warfarin” comes from the organization that funded its discovery, the Wisconsin Alumni Research Foundation (WARF) and the suffix -arin from its link with coumarin, a sweet smelling chemical from sweet clover.

Warfarin works by preventing formation of clotting factors II, VII, IX and X by affecting the available Vitamin K n the tissues as these are dependent on the vitamin for their synthesis. As the working clotting factors degrade over several days, these will be replaced by inactive factors and anticoagulant effect is produced. However, at the start of therapy, warfarin may promote clotting temporarily which makes sense if heparin is co-administered with this drug.

Uses and common dosages

Substances that bind to protein in the blood might displace this drug and make finding the correct dosage difficult, which makes self-monitoring of the prothrombin time very important. The values from the test will determine the dose adjustment that will safely work for the patient.

It may take several days before warfarin can exert its anticoagulating action. Its effectiveness may last for days which is why doctors often give hospitalized patients heparin with warfarin. Heparin covers the lag period of 3 to 5 days and then withdrawn after some time when warfarin takes effect.

The common indication for warfarin use is to treat and prevent formation and migration of blood clots in the veins. This drug may also be used to prevent embolic complications associated with atrial fibrillation or cardiac valve replacement. These are the commonly recommended doses:

As oral medication

Adults are given an initial dose of 5 milligrams per day. If rapid anti-coagulation is needed, 10 milligrams will be given for 2 subsequent days and the following doses adjusted based on the prothrombin time. However, the usual maintenance dose is about 2 to 10 milligrams daily. Elderly patients aged 65 and above have a much lower initial dose. Warfarin is not given to patients with severe renal or hepatic impairment.

As intravenous medication

When given as slow bolus injection, adults are initially injected 5 milligrams of warfarin for 1 to 2 minutes into the peripheral vein daily. If rapid anti-coagulation is needed, an initial dose of 10 milligrams may be given daily for 2 subsequent days. The following doses will be adjusted based on the prothrombin time of the patient. The usual maintenance dose is 2 to 10 milligrams per day.

Side effects

Common side effects of warfarin use are drop in hematocrit values, nausea, loss of appetite, and pain in the abdomen.

Purple toes syndrome might develop between 3 to 10 weeks after therapy with warfarin starts. This is due to small deposits of cholesterol breaking loose at small blood vessels. The drug may be discontinued if necrosis develops. Necrosis develops in patients with protein C deficiency. When left untreated, it will lead to gangrene and tissues would have to be amputated or removed.

If conditions such as changes in amount of urine, vision changes, confusion, slurred speech, and weakness on one side of the body develop, seek medical help immediately. Other conditions that may prompt health care providers to reconsider dose adjustment for warfarin therapy is when there is persistent nausea and vomiting, severe stomach pain, and yellowing of the skin and eyes.

Warfarin may create a false decrease of serum theophylline in th Schack and Waxler ultraviolet method. Patients on long term use of warfarin must monitor their prothrombin time. Any value less than 2 (based on the International Normalized Ratio of the prothrombin time) means insufficient anticoagulation while anything greater than 4 presents an increased risk for bleeding. Patients MUST report any signs of bleeding.

Precautions and contraindications

Despite its effectiveness, warfarin interacts with many medications and some food substances. Another complication that may arise during therapy is the variability of the patient's metabolism.

Avoid increase or decrease of foods rich in Vitamin K such as green leafy vegetables, liver, cranberry juice, and green tea. Other herbal supplements to look out for are danshen, dong quai, fenugreek, garlic, ginkgo biloba, ginseng, and St. John's wort. Drugs that allow blood to thin like salicylates, NSAIDs and other aspirin-like drugs must be used with extreme caution. It is advisable to maintain a healthy, balanced diet when taking this medication.

  • Phenytoin, quinidine, and corticosteroids - Alters the effect of warfarin which makes dose adjustment more often.
  • Sucralfate, estrogens, rifampicin, and barbiturates - Reduces the effect of warfarin.
  • Antibiotics, antifungal medications, anabolic steroids, and fibrate medicines - Enhances the effect of warfarin.

Warfarin therapy must be avoided in patients with the following diagnosed conditions:

Warfarin must be used with caution or will require dose adjustments in patients with the following conditions:

  • Heparin-induced thrombocytopenia
  • Deep vein thrombosis
  • Infectious disease
  • Disturbance of natural intestinal bacterial population
  • Surgery or trauma
  • Indwelling catheters
  • Hypertension
  • Deficiencies of vitamins C and K, proteins C or S
  • Older patients
  • Breastfeeding patients

If possible, avoid injections in the muscle but if it is necessary, it should be in the arms to easily check for bleeding. Avoid activities that pose risks for bleeding (such as shaving, contact sports, etc.).

Availability

Warfarin is available in the Philippines as a tablet in doses of 1, 2.5 and 5 milligrams. Coumadin ® and Warik ® are popular brands for warfarin tablets.

References