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21st World Congress of the World Society of Cardio-Thoracic Surgeons


Monitoring of Coumadin Anticoagulation


The clotting system is a powerful natural defense. Without the ability of blood to clot, minor injuries could be associated with life threatening bleeding. Nature has managed this threat by evolving an elaborate clotting system which responds to any injury by forming a clot to seal off the damaged blood vessels (using a host of different proteins in combination with blood cells called platelets). Thus any medication which alters the normal function of this natural protective mechanism must be carefully administered and monitored.

Vitamin K in the diet is normally absorbed by the liver and used as a necessary factor in the production of key clotting proteins. As these proteins circulate in the blood, they provide a potential defense against bleeding through an opening in a damaged blood vessel. Coumadin® impairs the production of these liver-dependent clotting proteins. As the concentration of these proteins in the blood decreases, the blood takes longer to clot. This is the basis for the anticoagulant action of Coumadin®.

It has been known for a long time that the dose needed for blood thinning is different in each patient. The rate of absorption of the drug, the dietary Vitamin K load, and the livers response to Coumadin® does vary from person to person. In order to obtain the clinical anticoagulant effect without overdosage (and subsequent bleeding complications), laboratory tests have been used to monitor the results of Coumadin® in each patient.

For many years, the principal test used to monitor the Coumadin® effect was the Prothrombin Time. Other common nicknames for this test are Pro-Time or "PT". This test is performed on blood drawn from the patient and quickly mixed with a special solution which stops the initial clotting process, usually by chemically binding all the calcium molecules in the blood. The medical laboratory then processes the specimen by removing the red blood cells (with a centrifuge). The remaining fluid is called "plasma" and contains all the clotting proteins (along with many different proteins and other molecules).

The patients plasma is treated with a chemical agent called "thromboplastin" which immediately activates the clotting proteins. A timer is started when the thromboplastic reagent is added. The elapsed time needed to form a firm clot is measured. Normal plasma will clot in about 11 to 13 seconds after exposure to thromboplastic chemicals. If the patient is treated with Coumadin® , it takes longer for the blood to clot.

After starting therapy with Coumadin, it takes several days to see the initial effect on the blood test. It is common practice for physicians to begin with an initial high dose until the Pro-Time begins to rise, then back down to lower doses. Follow-up of the Pro-Time is key to guiding how much Coumadin® will be necessary for treatment, but without causing excessive anticoagulation and bleeding complications.

Most patients receiving Coumadin® are managed within upper and lower Prothrombin values called the "target range". The target range may differ depending on the diagnosis and clinical circumstances. However, most patients with, say a heart valve replacement, will have their Coumadin® dose adjusted until a Prothrombin Time of 18 to 20 seconds is reached.

Although the Pro-Time is the most popular method of monitoring therapy, it can also be a difficult test to use in some circumstances. The main problem is variation of the results between different institutions. It has now been shown that the same test run in different hospitals or laboratories can yield different results. For example, the measured Pro-Time might be 18 seconds at one institution, 20 seconds at another and 16 seconds at a third institution. If the patient obtains blood tests that are processed at more than one site, the potential for variations exists. Some of these variations can mislead the treating physician into changing the patients Coumadin® dose improperly.

European centers have been using a standardization method for many years. The International Normalized Ratio...or INR was developed at the Karolinska Institute of Sweden to reduce variability in Pro-Time results. The INR standardizes the methods for comparison amongst different laboratories. By running the patients blood test against a known standard, a value can be calculated which is more consistent from place-to-place than the traditional Pro-Time values were.

When treating a patient with Coumadin®, it is best to manage the medication according to the INR ratio. For most clinical conditions, an INR of 2.5 to 3.0 indicates the appropriate dosage. INR values above 5.0 can be dangerous. INR values of 1.0 indicate no Coumadin® effect at all. Just for information sake, most clinical laboratories still report the Pro-Time result along with the INR value. Also, most doctors and patients still refer to the blood testing as "getting a Pro-Time" for the sake of clarity and tradition. However, Coumadin® dosage is adjusted according to INR more often than to the Pro-Time result.

When first starting therapy with anticoagulation, it is important to obtain frequent blood tests in order for proper the dosage to be determined. Your treating physician will review the INR result, and increase or decrease the dosage of medication to reach the "target range". Most patients will be asked to have their blood test drawn twice a week initially. As the dose becomes more routine, the testing intervals can be spaced out.

If you take your medication only at night, the physican can conveniently make an adjustment in your dosage on the same day as the blood test. Otherwise, the dosage must be altered starting on the following day. After each dose change, another Pro-Time test is recommended in 2 to 3 days to monitor the result of the new dosage.

Most blood testing labs will still draw blood from a vein in your arm. This is the most reliable and traditional source for obtaining blood for the Pro-Time test. However, there are now some laboratories which have the capability to use droplets of blood from a finger tip puncture. For some patients, this is less emotional and/or painful. Ask the technician in your doctors office or clinical laboratory if they have the "finger-stick" Pro-Time assay available.

The most important advice on Pro-Time testing is followup. As a patient on a powerful blood thinning medication, you should continue to work with one physician who takes charge of the dosing of this medication. The INR results and the new dosage should be available to you within 24 hours of your blood draw. In addition, you should come back for further Pro-Time tests after any dosage adjustment is made. If any other medications are added or removed from you regimen, it is best to recheck the INR to make sure that the body's handling of Coumadin® has not been affected in any way.

Gradually, as you are taking Coumadin® for a longer period of time, it is possible to take the drug without frequent blood tests. Once a steady dosage schedule is finally reached, most patients administer the same dose for long periods of time without blood testing. Some physicians will keep their patients on a schedule of every 3 months for repeat testing. However, more frequent testing is indicated if the patient develops a serious infection, new illness, is started or withdrawn from medications which affect Coumadin®, etc. If you have any questions about how often your blood tests should be performed, or what INR target range is being used for treatment of your condition, then please address these questions to your treating physician.


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