7/28/2019 Prothrombin Time INR

1/1

prothrombin time (PT, Pro-time, International normalized ratio [INR]) Test type: Blood

11.0-12.5 seconds; 85%-100%

Full anticoagulant therapy: >1.5-2 times control value; 20% to 30%INR: 0.8-1.1

Possible critical values:

>20 seconds

INR: >5.5

Preferred INR according to indication for anticoagulation

Deep-vein thrombosis prophylaxis: 1.5-2.0Orthopedic surgery: 2.0-3.0

Deep-vein thrombosis: 2.0-3.0

Atrial fibrillation: 2.0-3.0

Pulmonary embolism: 2.5-3.5

Prosthetic valve prophylaxis: 3.0-4.0

Alcohol intake can increase PT levels.

A high-fat diet may decrease PT levels.

Drugs that may cause increased levels include allopurinol, aminosalicylic acid, barbiturates, beta-lactam antibiotics,cephalosporins, cholestyramine, chloral hydrate, cephalosporins, chlorpromazine, cimetidine, clofibrate, colestipol, ethyl alcohol,

glucagon, heparin, methyldopa, neomycin, oral anticoagulants, propylthiouracil, quinidine, quinine, salicylates, and

sulfonamides.

Drugs that may cause decreased levels include anabolic steroids, barbiturates, chloral hydrate, digitalis, diphenhydramine,

estrogens, griseofulvin, oral contraceptives, and vitamin K.

Increased levels: Cirrhosis, Hepatitis, Vitamin K deficiency, Salicylate intoxication, Bile duct obstruction, Coumarin ingestion,Disseminated intravascular coagulation, Massive blood transfusion, Hereditary factor deficiency

Procedure and patient careBefore: Explain the procedure to the patient. Tell the patient that no fasting is required. Obtain the blood specimen before the patient is given the daily dose of warfarin.During: Collect a venous blood sample in a light bluetop tube.After: Apply pressure to the venipuncture site. Remember, hemostasis will be delayed if t he patient is taking warfarin or if the patient has any coagulopathies. Patientstaking warfarin will have their doses regulated by PT and INR values. If the PT is greatly prolonged, evaluate the patient for bleeding tendencies. Teach patients on warfarinto check themselves for bleeding. The anticoagulant effect of warfarin can be reversed by the slow parenteral administration of vitamin K. Instruct patients on warfarintherapy not to take any other medications unless approved by their physician.

prothrombin time (PT, Pro-time, International normalized ratio [INR]) Test type: Blood

The PT is used to evaluate the adequacy of the extrinsic system and common pathway in the clotting mechanism. The PT measures the clotting ability of factorsI (fibrinogen), II (prothrombin), V, VII, and X. When these clotting factors exist in deficient quantities, PT is prolonged. Many diseases and drugs are associatedwith decreased levels of these factors. These include the following:

Hepatocellular liver disease (e.g., cirrhosis, hepatitis, and neoplastic invasive processes) Factors I, II, V, VII, IX, and X are produced in the liver. With severe

hepatocellular dysfunction, synthesis of these factors will not occur. Obstructive biliary disease (e.g., bile duct obstruction secondary to tumor or gallstones or intrahepatic cholestasis secondary to sepsis or drugs)As a result of the

biliary obstruction, the bile necessary for fat absorption fails to enter the gut, and fat malabsorption results. Vitamins A, D, E, and K are fat soluble and also are notabsorbed. Because the synthesis of factors II, VII, IX, and X depends on vitamin K, these factors will not be adequately produced and serum concentrations willfall.Parenchymal (hepatocellular) liver disease can be differentiated from obstructive biliary disease by determination of the patient's response to parenteral vitaminK administration. If PT returns to normal after 1 to 3 days of vitamin K administration (10 mg IM twice a day), one can safely assume that the patient hasobstructive biliary disease that is causing vitamin K malabsorption. If, on the other hand, PT does not return to normal with the vitamin K injections, one canassume that severe hepatocellular disease exists and that the liver cells are incapable of synthesizing the clotting factors no matter how much vitamin K is available.

Oral anticoagulant administrationThe coumarin derivatives dicumarol and warfarin (Coumadin, Panwarfin) are used to prevent coagulation in patients withthromboembolic disease. These drugs interfere with the production of vitamin Kdependent clotting factors, which results in a prolongation of PT, as previouslydescribed. The adequacy of coumarin therapy can be monitored by following the patient's PT. For anticoagulation, the INR typically should be between 2.0 and 3.0for patients with atrial fibrillation, and between 3.0 and 4.0 for patients with mechanical heart valves. However, the ideal INR must be individualized for eachpatient (Table 26).

PT test results are usually given in seconds, along with a control value. The control value usually varies somewhat from day to day because the reagents usedmay vary. The patient's PT should be approximately equal to the control value. Some laboratories report PT values as percentages of normal activity, because thepatient's results are compared with a curve representing normal clotting time. Normally, the patient's PT is 85% to 100%.

To have uniform PT results for physicians in different parts of the country and the world, t he World Health Organization has recommended that PT resultsinclude the use of the international normalized ratio (INR) value. The reported INR results are independent of the reagents or methods used. Most hospitals are nowreporting PT times in both absolute and INR numbers.

Such factors as weight, body mass index, age, diet, and concurrent medications are known to affect warfarin dose requirements during anticoagulation therapy.Warfarin interferes with the regeneration of reduced vitamin K from oxidized vitamin K in the vitamin K oxidoreductase (VKOR) complex. A recently identifiedgene for the major subunit of VKOR, called VKORC1, has been identified and may explain up to 44% of the variance in warfarin dose requirements. Furthermore,

warfarin is metabolized in part by the cytochrome P-450 enzyme CYP2C9. The CYP2C9*2 and CYP2C9*3 genetic mutations have been shown to decrease theenzyme activity of these metabolizing enzymes, which has led to warfarin sensitivity and, in serious cases, bleeding complications. A warfarin pharmacogenomictest panel is available that can identify any mutations in the VKORC1 1639, CYP2C9*2, or CYP2C9*3 genes. The warfarin pharmacogenomic test can be used aspart of an algorithm to determine the best initial warfarin dose and does not replace the need for routine PT testing for the calculation of the INR.

Point-of-care home testing is now available for patients who require long-term anticoagulation with warfarin. Like glucose monitoring, a finger stick isperformed. A drop of blood is placed on the testing strip and inserted into the handheld testing device. The PT and INR are provided in a few minutes. The treatingphysician is notified by phone and any therapeutic changes can be instigated the same day.