Trisodium-citrate concentration, storage time, storage temperature, evacuated tube effects, inadequate sample, variations in manual technique
From nonuse of MNPT, error in MNPT due to (1) unrepresentative selection; (2) technical faults (see above); (3) nonuse of geometric mean
Incorrect choice of IRP; poor distribution of coumarin test samples across treatment range; inadequate numbers of test samples in ISI calibration; incorrect transformation of PTR of test plasmas to INR.
3. Drift of ISI since original calibration
4. Instrument (coagulometer) effects on INR at local site
5. Lupus anticoagulant effects on some thromboplastin reagents
6. Lack of reliability of the INR system when used at the onset of
warfarin therapy and for screening for a coagulopathy in patients with liver disease
7. Relative lack of reliability of INR > 4.5 as these values excluded from ISI calibrations instrument-specific ISI. The mean normal plasma PT is not interchangeable with a laboratory control PT, however, the use of other than a properly defined mean normal PT can yield erroneous INR calculations, particularly when less responsive reagents are employed. The mean normal PT should be determined with each new batch of thromboplastin with the same instrument used to assay the PT.
The concentration of citrate that is used to anticoagulate plasma affects the INR. In general, higher citrate concentrations (3.8%) lead to higher INR values, and underfilling the blood collection tube spuriously prolongs the PT because excess citrate is present. Using collection tubes containing 3.2% concentrations of citrate for blood coagulation studies and adequately filling tubes can reduce this problem.
Clinical applications of VKA therapy
The clinical effectiveness of VKAs in the treatment of a variety of disease conditions has been established by well-designed clinical trials. VKAs are effective for the primary and secondary prevention of venous thromboembolism, for the prevention of systemic embolism in patients with prosthetic heart valves or atrial fibrillation, for the prevention of acute myocardial infarction in patients with peripheral arterial disease and in men who otherwise are at high risk, and for the prevention of stroke, recurrent infarction, or death in patients with acute myocardial infarction. Although effectiveness has not been proven by a randomized trial, VKAs are also indicated for the prevention of systemic embolism in high-risk patients with mitral stenosis.
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Optimal therapeutic range
The optimal target range for warfarin is not the same for all indications. Not only is it likely to be influenced by the indication for its use, but also by patient characteristics. Thus, in patients who are at very high risk of bleeding it might be prudent to sacrifice some efficacy for safety. Bleeding, the most feared and major complication of oral anticoagulant therapy, is closely related to the intensity of anticoagulation.
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