Other drugs can antagonize the effect of warfarin. Other examples include anticonvulsants, omeprazole, cimitidine, simvastatin, propylthiouracil, urokinase, streptokinase, amiodarone, thiazides, tricylclic antidepressants, danazol, and allopurinol.
Analgesics including acetaminophen, aspirin and ibuprofen can prolong the PT. Other medications can affect the action of warfarin in the liver. Antifungal medications such as fluconazole, miconazole, norfloxacin and itraconzole can also prolong the PT. Examples include cephalosporins, ciprofloxacin, erythromycin, ofloxacin, sulfonamides, tetracyclines neomycin, chloramphenicol and metronidazole. One common cause of vitamin K deficiency is chronic administration of broad-spectrum antibiotics, which decreases the intestinal flora that synthesize vitamin K. It may take up to one month for a physician to reach an optimal therapeutic level of warfarin for an individual patient. However, until the patient reaches a steady state, PT/INR fluctuations are expected. Warfarin dosage changes may also be required in response to the PT/INR results. Typically, monitoring is performed daily, until several days after the therapeutic range is reached. Due to significant patient variability in response to warfarin therapy, the PT/INR must be closely monitored until a steady state has been reached. If administered on a daily basis, it usually takes 5-10 days for the warfarin level in the patient’s bloodstream to reach a steady state. Warfarin starts working in the liver within 24 hours, but the maximum effect of a single dose may not be seen for 2-4 days. Warfarin acts in the liver by inhibiting the synthesis of vitamin K dependent clotting factors, which include factors II, VII, IX and X, and other proteins essential for the clotting process. The prothrombin time may also be prolonged due to the presence of a coagulation inhibitor such as a specific factor inhibitor or the lupus anticoagulant. The prothrombin time may be prolonged by deficiency of a single or multiple coagulation factors (Factor VII, Factor X, Factor V, Factor II or fibrinogen).
PT reagents are more sensitive to Factor VII deficiency than to deficiencies of factors V, X, prothrombin and fibrinogen. The PT assesses the coagulation factors of the extrinsic pathway (factors VII) and the common pathway (activated factor X, activated factor V, prothrombin and fibrinogen).
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The prothrombin time (PT or protime) is the actual time, measured in seconds, for an anticoagulated sample of patient plasma to clot after the addition of calcium and an activator of the extrinsic pathway, which is called thromboplastin.
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