Blood-Thinning Warfarin
A High-Maintenance Antithrombic Drug
Warfarin, better known under the trade name Coumadin, is an anticoagulant drug that works against the blood's clotting system. It is used for conditions that involve being prone to forming clots easily (hypercoagulability). Like some other prescription medications, it requires regular monitoring and dosing adjustments as needed.
(Note: From this point on, warfarin will be referred to as Coumadin simply because it is more common to refer to the drug as such.)
Mechanism of Action
There are two processes that slow down bleeding. There are platelets that clump together at the bleeding site. There are also clotting factors, or proteins, that form a fibrin clot. Clot-forming proteins are normally balanced by clot-breaking proteins, which break up a clot after a bleeding site heals. If there is imbalance between the clot-forming proteins and clot-breaking proteins, one would either form too many clots or bleed easily because clots cannot form.
Coumadin acts by halting production of the clotting factors that require vitamin K: factor II, factor VII, factor IX, and factor X. It also inhibits protein C and protein S, both of which break clots. When Coumadin is given, proteins C and S are inhibited first. Because of this, balance is shifted towards clot formation and the blood initially becomes hypercoagulable, but only briefly. Once Coumadin inhibits factors II, VII, IX, and X about 2 or 3 days later, clot formation is slower and the blood becomes truly thinned.
Initiation of Treatment
If a patient has a clot within a leg vein (deep vein thrombosis) or if that clot breaks off, travels to the lung, and gets stuck (pulmonary embolism), then he or she would need Coumadin to prevent a future clot. Although Coumadin is started right away, there are two problems. First, the patient is briefly hypercoagulable when Coumadin is first given, and this can make the existing clot bigger. Second, it takes a few days for the full blood-thinning effect of Coumadin to kick in. The solution to both of these is to start a second blood-thinner simultaneously with Coumadin. The anticoagulant used is one from the heparin class of drugs, like unfractionated heparin or Lovenox. This drug thins the blood in its own way, but it can do the job in the meantime until Coumadin takes full effect. Once the level of Coumadin in the blood is just right, heparin is stopped.
Coumadin can also be used for a short time following lower extremity surgery, like hip replacement, since the stress of major surgery plus not moving the legs for a while can produce a hypercoagulable state. Another indication for Coumadin is atrial fibrillation. This is a type of abnormal heart rhythm where the muscle cells of the two atria, the smaller top chambers of the heart, contract in a random fashion instead of in one effective contracting unit. Blood flow through the atria is slower than normal, enough for clotting factors to come together more often and easily form clots. For this condition, the patient can be put on Coumadin without concurrent heparin, because there is no existing clot that could worsen from Coumadin's brief hypercoagulability effect.
As for how long one would be on Coumadin, it depends on the condition and how often the clots form. A one-time event may warrant treatment for several months while repeated episodes, particularly with genetic conditions making the blood hypercoagulable, may warrant lifelong anticoagulation.
Monitoring and Testing
The process of forming a fibrin clot involves two different pathways of clotting factor interaction that merge into one common pathway. Two coagulation blood tests, the partial thromboplastin time (PTT) and the prothrombin time (PT), measure the time it takes for the clotting factors to do their work. The PTT corresponds to one of the separate pathways plus the common pathway while the PT corresponds to the other separate pathway plus the common pathway. The higher the PTT or PT is, the more time it takes for clotting factors in the specific pathway to do their part, which means clots form more slowly and the blood is thinner.
When one is given Coumadin, both the PTT and PT rise. The PT can be converted to a simpler number. By dividing the PT by the standard PT for normal individuals, the PT can be converted to the international normalized ratio (INR). The INR is used often since it's easier to remember an INR of 1.0, which is the normal value, rather than a PT of 10 seconds. The higher the INR is, the thinner the blood is. For Coumadin to be effective while minimizing bleeding risk, the INR should be between 2.0 and 3.0. This goes for most situations requiring Coumadin. However, if one is still hypercoagulable in this range, the goal INR range may be set higher. The idea is to find the INR range that is therapeutic, thinning the blood without bleeding complications.
Interfering Factors
While on Coumadin, the INR must be checked regularly. If the INR is therapeutic and stable, it may be checked less often. Even so, it does not mean one can be on Coumadin without testing. Many things interact with Coumadin, so the INR can actually be too low or too high at times.
Because Coumadin opposes vitamin K, altering vitamin K intake can affect the INR. If a patient's INR is in the therapeutic range and he or she suddenly eat more leafy green vegetables containing vitamin K, more clotting factors are formed and the blood is less thin, so the INR drops to a subtherapeutic level. If vitamin K intake is decreased, INR increases to a supratherapeutic level. This is why it is important to keep the diet as consistent as possible when on Coumadin.
The same goes for medications. Coumadin is ultimately broken down in the liver. Some drugs, however, stimulate certain liver enzymes that metabolize Coumadin. With less blood thinner, the INR drops. Others inhibit these liver enzymes, so with Coumadin staying in the body longer, INR may increase. The list of drug interactions is a long one. It's a good idea to let the doctor know all current medications other than Coumadin. Most importantly, be aware of any medication changes.
In any event, the INR would still be checked regularly so that the Coumadin dose can be adjusted accordingly. This is a medication requiring relatively high maintenance, but once a patient becomes accustomed to it, it can become a lifesaver.
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