Warfarin prothrombin time

One patient stabilised on warfarin (prothrombin time 20 seconds) was found to have an increased prothrombin time of 32 seconds 8 days after starting intravenous benzylpenicillin 24 million units daily for subacute bacterial endocarditis. The benzylpenicillin was continued, and the warfarin dose reduced for 18 days. However, the prothrombin time dropped below the therapeutic range, and the warfarin dose was increased back to the original dose, still with continuation of the benzylpenicillin for a further 3 weeks. ... 

In a study in 15 healthy subjects stabilised on warfarin, ketoprofen 100 mg twice daily for 7 days had no effect on prothrombin times or coagulation cascade parameters, and there was no evidence of bleeding. This contrasts with an isolated case of bleeding in a patient taking warfarin (prothrombin time increased from 18 to 41 seconds) a week after starting ketoprofen 25 mg three times daily. ... 

In 26 healthy subjects, pantoprazole 40 mg daily for 8 days caused no change in the response to a single 25-mg dose of warfarin given on day 2. The pharmacokineties of R- and 5-warfarin were unaltered, and no changes in the pharmaeodynamies of the warfarin (prothrombin time, factor Vff) were seen." However, the manufaeturer notes that there have been reports of inereased INR and prothrombin time in patients taking pantoprazole and warfarin. ... 

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

Before administering the first dose of warfarin, die nurse questions the patient about all drags taken during the previous 2 to 3 weeks (if the patient was recendy admitted to the hospital). If the patient took any drug before admission, the nurse notifies the primary healdi care provider before the first dose is administered. Usually, the prothrombin time (PT) is ordered and die international normalized ratio (INR) determined before tiierapy is started. The first dose of warfarin is not given until blood for a baseline PT/ INR is drawn. The dosage is individualized based on die results of the PT or die INR. 

The nurse monitors the prothrombin time (PT) during therapy. Optimal PT for warfarin therapy is... 

A number of laboratory tests are available to measure the phases of hemostasis described above. The tests include platelet count, bleeding time, activated partial thromboplastin time (aPTT or PTT), prothrombin time (PT), thrombin time (TT), concentration of fibrinogen, fibrin clot stabifity, and measurement of fibrin degradation products. The platelet count quantitates the number of platelets, and the bleeding time is an overall test of platelet function. aPTT is a measure of the intrinsic pathway and PT of the extrinsic pathway. PT is used to measure the effectiveness of oral anticoagulants such as warfarin, and aPTT is used to monitor heparin therapy. The reader is referred to a textbook of hematology for a discussion of these tests. 

FIGURE 7-9. Initiation of warfarin therapy. INR, International Normalized Ratio PT, prothrombin time. (Reproduced from Haines ST, Zeolla M, Witt DM. Venous thromboembolism. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 391, with permission.)... 

Application of topical salicylates can lead to systemic effects, especially if the product is applied liberally. Repeated application and occlusion with a wrap or bandage also can increase systemic concentrations.41 Salicylate-containing counterirritants should be used with caution in patients in whom systemic salicylates are contraindicated, such as patients with severe asthma or aspirin allergy.42 Topical salicylates have been reported to increase prothrombin time in patients on warfarin and should be used with caution in patients on oral anticoagulants.43... 

Prothrombin time PT is performed by adding thromboplastin (tissue) factor and calcium to citrate-anticoagulated plasma, recalcifying the plasma, and measuring the clotting time. The major utility of PT is to measure the activity of the vitamin K-dependent factors II, VII, and X. The PT is used in evaluation of liver disease, to monitor warfarin anticoagulant effect, and to assess vitamin K deficiency. 

Metronidazole Nausea/vomiting Metallic taste Refrain from using alcoholic beverages potential for disulfiram-like reaction Substrate for CYP2C9 and inhibitor of CYP2C9, 3A3/4 and 3A5-7 potential interactions may include warfarin (enhanced prothrombin time) and lithium (increased concentrations)... 

FIGURE 14-3. Initiation of warfarin therapy. (INR, international normalized ratio PT, prothrombin time.)... 

PO loading dose 400 mg tid x 15-30 days, then 200-400 mg qd (5-10 mg/l ) pneurrwnitis when dose >400 mg/d elevation of digoxin level, prolongation of prothrombin time (70-100%) with warfarin pultrwnary fibrosis, hepatitis, ocular opacities proarrhythmic monitor thyroid and liver function... 

As tinzaparin may theoretically affect the prothrombin time (PT)/INR, draw blood for PT/INR determination just prior to the next scheduled dose of tinzaparin for patients receiving tinzaparin and warfarin. 

Monitoring Monitor prothrombin time or other suitable anticoagulation test if tigecycline is administered with warfarin. 

PT prothrombin time (to measure anticoagulant drug warfarin)... 

As noted above, OC failure may lead to accidental pregnancy and exposure of the developing fetus to potentially teratogenic properties of CBZ ( 383). Therefore, OC levels should be closely monitored and patients should notify their physician of spotting, an indicator of OC failure. Prothrombin time and the International Normalized Ratio (INR) should be monitored when patients are on warfarin and CBZ concomitantly. Patients stabilized on an antipsychotic may decompensate when CBZ is added. This may necessitate an increase in the antipsychotic dose and is one indication for TDM of antipsychotic drug levels ( 384). Conversely, when CBZ is discontinued, the dose of these other agents may need to be lowered to avoid toxicity. In summary ... 

Warfarin Antimalaria drugs 8 oz of freshly prepared GFJ from concentrate t.i.d. for 1 wk N/A Prothrombin time <->, international normalized ratio (120)... 

Coumarins are competitive inhibitors of vitamin K, which is required for the formation in the liver of the amino acid, gamma-carboxyglutamic acid. This is necessary for the synthesis of prothrombin and factors VII, IX and X (Figure 17.1). After starting treatment the anticoagulant effect is delayed until the concentration of normal coagulation factors falls (36-72 h). The effects can be reversed by vitamin K (slow maximum effect only after 3-6 h) or by whole blood or plasma (fast). Gut bacteria synthesise vitamin K and thus are an important source of this vitamin. Consequently, antibiotics can cause excessive prolongation of the prothrombin time in patients otherwise adequately controlled on warfarin. 

Treatment with warfarin should be initiated with standard doses of 5-10 mg rather than the large loading doses formerly used. The initial adjustment of the prothrombin time takes about 1 week, which usually results in a maintenance dose of 5-7 mg/d. The prothrombin time (PT) should be increased to a level representing a reduction of prothrombin activity to 25%... 

Primary prevention of venous thrombosis reduces the incidence of and mortality rate from pulmonary emboli. Heparin and warfarin may be used to prevent venous thrombosis. Subcutaneous administration of low-dose unfractionated heparin, low-molecular-weight heparin, or fondaparinux provides effective prophylaxis. Warfarin is also effective but requires laboratory monitoring of the prothrombin time. 

Drug Interactions Increased prothrombin time after warfarin administration Phenytoin Cyclosporine Tolbutamide Tacrolimus Glyburide Glipizide Rifampin Cisapride Terfenadine Astemizole Theophylline ... 

Warfarin antagonists include vitamin K, barbiturates, glutethimide. rifampin, and cholestyramine. Warfarin potentiators include phenylbutazone. oxyphenbutazone, anabolic steroids, clofibrate, aspirin, hepatotoxins, disnlfirain, and metronidazole. In patients undergoing anticoagulation therapy with warfann, it has been found that cimetidine (used in therapy of duodenal ulcer) may increase anticoagulant blood levels and consequently prolong the prothrombin time. 

To assess the potential for an interaction between raloxifene and warfarin, 15 healthy postmenopausal women each received single doses of warfarin 20 mg before and during 2 weeks of dosing with raloxifene 120 mg/day (37). Raloxifene reduced the oral clearance of R- and A -war-farin respectively by 7.1 and 14% and the oral volume of distribution by 7.4 and 9.8%. Raloxifene reduced the maximum prothrombin time by 10% and the area under the prothrombin versus time curve from 0-120 hours by an average of 8%. The authors concluded that raloxifene may produce a small increase in systemic warfarin exposure but a reduced pharmacodynamic effect. Since the effects are slight this interaction is unlikely to have clinical consequences. 

There have been several reports of altered prothrombin time in patients taking warfarin and melatonin. In some cases bleeding or purpura was the presenting symptom, despite a reduced prothrombin time (5). 

In 12 patients chronically maintained on warfarin, atorvastatin 80 mg/day for 2 weeks reduced mean prothrombin times slightly, but only for the first few days of the 2-week treatment period (35). Thus, atorvastatin had no consistent effect on the anticoagulant activity of warfarin and adjustments in warfarin doses should not be necessary. 

In contrast, in 12 patients chronically maintained on warfarin, atorvastatin 80 mg/day for 2 weeks had no important effect on mean prothrombin time (92). 

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