Prothrombin Time and International Normalized Ratio

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Prothrombin Time and International Normalized Ratio

Synonym/acronym: Protime, PT.

Common use

To assess and monitor coagulation status related to therapeutic interventions and disorders such as vitamin K deficiency.


Plasma (1 mL) collected in a completely filled blue-top (sodium citrate) tube. If the patient’s hematocrit exceeds 55%, the volume of citrate in the collection tube must be adjusted.

Normal findings

(Method: Clot detection) 10 to 13 sec.
  • International normalized ratio (INR) = Less than 2 for patients not receiving anticoagulation therapy, 2 to 3 for patients receiving treatment for venous thrombosis, pulmonary embolism, and valvular heart disease.
  • INR = 2.5 to 3.5 for patients with mechanical heart valves and/or receiving treatment for recurrent systemic embolism.


Prothrombin time (PT) is a coagulation test performed to measure the time it takes for a firm fibrin clot to form after tissue thromboplastin (factor III) and calcium are added to a sample of plasma. Coagulation factors in the patient’s sample, including prothrombin (factor II) react with the reagents and complete the process of coagulation in proportion to the amount of available coagulation factors. The PT is used to evaluate the tissue factor pathway, formerly called the extrinsic pathway of the coagulation sequence in patients receiving oral warfarin (Coumadin) anticoagulants. Prothrombin is a vitamin K–dependent protein produced by the liver; measurement is reported as time in seconds or percentage of normal activity.

The goal of long-term anticoagulation therapy is to achieve a balance between in vivo thrombus formation and hemorrhage. It is a delicate clinical balance, and because of differences in instruments and reagents, there is a wide variation in PT results among laboratories. Worldwide concern for the need to provide more consistency in monitoring patients receiving anticoagulant therapy led to the development of an international committee. In the early 1980s, manufacturers of instruments and reagents began comparing their measurement systems with a single reference material provided by the World Health Organization (WHO). The international effort successfully developed an algorithm to provide comparable PT values regardless of differences in laboratory methodology. Reagent and instrument manufacturers compare their results to the WHO reference and derive a factor called an international sensitivity index (ISI) that is applied to a mathematical formula to standardize the results. Laboratories convert their PT values into an international normalized ratio (INR) by using the following formula: INR = (patient PT result/normal patient average)(ISI) PT evaluation can now be based on an INR using a standardized thromboplastin reagent to assist in making decisions regarding oral anticoagulation therapy.

The metabolism of many commonly prescribed medications is driven by the cytochrome P450 (CYP450) family of enzymes. Genetic variants can alter enzymatic activity that results in a spectrum of effects ranging from the total absence of drug metabolism to ultrafast metabolism. Impaired drug metabolism can prevent the intended therapeutic effect or even lead to serious adverse drug reactions. Poor metabolizers (PM) are at increased risk for drug-induced side effects due to accumulation of drug in the blood, whereas ultra-rapid metabolizers (UM) require a higher-than-normal dosage because the drug is metabolized over a shorter duration than intended. In the case of prodrugs that require activation before metabolism, the opposite occurs: PM may require a higher dose because the activated drug is becoming available more slowly than intended, and UM may require less because the activated drug is becoming available sooner than intended. Other genetic phenotypes used to report CYP450 results are intermediate metabolizer (IM) and extensive metabolizer (EM). Genetic testing can be performed on blood samples submitted to a laboratory. test method commonly used is polymerase chain reaction. Counseling and informed written consent are generally required for genetic testing. CYP2C9 is a gene in the CYP450 family that metabolizes prodrugs like the anticoagulant warfarin. Three major gene mutations are associated with warfarin response and are estimated to account for up to 45% of variations in Caucasians and up to 30% of variations in African Americans. The CYP450 genes are distributed differently and in predictable frequency among various ethnic groups; incidence of mutation in CYP2C9*2 allele in Caucasians is 8% to 19%, in Asians is less than 0% to 4%, and in African Americans is 0% to 12%; incidence of mutation in CYP2C9*3 allele in Caucasians is 5% to 16%, in Asians is 1% to 8%, and in African Americans is 0% to 6%; incidence of mutation in VKORC1 (as predicted by 1639G > A mutation) is 37% in Caucasians, 89% in Asians, and 14% in African Americans. CYP450 testing is available and should be used in conjunction with other factors, including all prescription and over-the-counter medications being used; mode of drug administration; use of tobacco products, foods, and supplements; age, weight, environment, activity level, and diseases with which the patient may be dealing.

Some inferences of factor deficiency can be made by comparison of results obtained from the activated partial thromboplastin time (aPTT) and PT tests. A normal aPTT with a prolonged PT can occur only with factor VII deficiency. A prolonged aPTT with a normal PT could indicate a deficiency in factors XII, XI, IX, and VIII as well as VIII:C (von Willebrand factor). Factor deficiencies can also be identified by correction or substitution studies using normal serum. These studies are easy to perform and are accomplished by adding plasma from a healthy patient to a sample from a suspected factor-deficient patient. When the PT is repeated and corrected, or within the reference range, it can be assumed that the prolonged PT is due to a factor deficiency (see monograph titled “Coagulation Factors”). If the result remains uncorrected, the prolonged PT is most likely due to a circulating anticoagulant.

This procedure is contraindicated for



  • Differentiate between deficiencies of clotting factors II, V, VII, and X, which prolong the PT, and congenital coagulation disorders such as hemophilia A (factor VIII) and hemophilia B (factor IX), which do not alter the PT
  • Evaluate the response to anticoagulant therapy with coumadin derivatives and determine dosage required to achieve therapeutic results
  • Identify individuals who may be prone to bleeding during surgical, obstetric, dental, or invasive diagnostic procedures
  • Identify the possible cause of abnormal bleeding, such as epistaxis, hematoma, gingival bleeding, hematuria, and menorrhagia
  • Monitor the effects of conditions such as liver disease, protein deficiency, and fat malabsorption on hemostasis
  • Screen for prothrombin deficiency
  • Screen for vitamin K deficiency

Potential diagnosis

Increased in

  • Afibrinogenemia, dysfibrinogenemia, or hypofibrinogenemia (related to insufficient levels of fibrinogen, which is required for clotting; its absence prolongs PT)
  • Biliary obstruction (related to poor absorption of fat-soluble vitamin K; vitamin K is required for clotting and its absence prolongs PT)
  • Disseminated intravascular coagulation (related to increased consumption of clotting factors; PT is increased)
  • Hereditary deficiencies of factors II, V, VII, and X (related to deficiency of factors required for clotting; their absence prolongs PT)
  • Liver disease (cirrhosis) (related to decreased liver function, which results in decreased production of clotting factors and prolonged PT)
  • Massive transfusion of packed red blood cells (RBCs) (related to dilutional effect of replacing a significant fraction of the total blood volume; there are insufficient clotting factors in plasma-poor, packed RBC products. Blood products contain anticoagulants, which compound the lack of adequate clotting factors in the case of massive transfusion)
  • Poor fat absorption (tropical sprue, celiac disease, and chronic diarrhea are conditions that prevent absorption of fat-soluble vitamins, including vitamin K, which is required for clotting; its absence prolongs PT)
  • Presence of circulating anticoagulant (related to the production of inhibitors of specific factors, e.g., developed from long-term factor VIII therapy or circulating anticoagulants associated with conditions like tuberculosis, systemic lupus erythematosus, rheumatoid arthritis, and chronic glomerulonephritis)
  • Salicylate intoxication (related to decreased liver function)
  • Vitamin K deficiency (vitamin K is required for clotting; its absence prolongs PT)

Decreased in

    Ovarian hyperfunction Regional enteritis or ileitis

Critical findings


  • Greater than 5
  • Prothrombin Time

  • Greater than 27 sec
  • Note and immediately report to the health-care provider (HCP) any critically increased values and related symptoms.

  • It is essential that a critical finding be communicated immediately to the requesting health-care provider (HCP). A listing of these findings varies among facilities.

  • Timely notification of a critical finding for lab or diagnostic studies is a role expectation of the professional nurse. Notification processes will vary among facilities. Upon receipt of the critical value the information should be read back to the caller to verify accuracy. Most policies require immediate notification of the primary HCP, Hospitalist, or on-call HCP. Reported information includes the patient’s name, unique identifiers, critical value, name of the person giving the report, and name of the person receiving the report. Documentation of notification should be made in the medical record with the name of the HCP notified, time and date of notification, and any orders received. Any delay in a timely report of a critical finding may require completion of a notification form with review by Risk Management.

  • Important signs to note relate to bleeding in specific areas of the body and include prolonged bleeding from cuts or gums, hematoma at a puncture site, hemorrhage, blood in the stool, backache or flank pain, dark colored urine, joint pain, persistent epistaxis, heavy or prolonged menstrual flow, and shock. Monitor vital signs, unusual ecchymosis, occult blood, severe headache, unusual dizziness, and neurological changes until PT is within normal range. Intramuscular (IM) administration of vitamin K, an anticoagulant reversal agent, may be requested by the HCP.

Interfering factors

  • Drugs that may increase the PT in patients receiving anticoagulation therapy include acetaminophen, acetylsalicylic acid, amiodarone, anabolic steroids, anisindione, anistreplase, antibiotics, antipyrine, carbenicillin, cathartics, chloral hydrate, chlorthalidone, cholestyramine, clofibrate, corticotropin, demeclocycline, dextrothyroxine, diazoxide, diflunisal, disulfiram, diuretics, doxycycline, erythromycin, ethyl alcohol, hydroxyzine, laxatives, mercaptopurine, miconazole, nalidixic acid, neomycin, niacin, oxyphenbutazone, phenytoin, quinidine, quinine, sulfachlorpyridazine, thyroxine, and tosylate bretylium.
  • Drugs that may decrease the PT in patients receiving anticoagulation therapy include aminoglutethimide, amobarbital, anabolic steroids, antacids, antihistamines, barbiturates, carbamazepine, chloral hydrate, chlordane, chlordiazepoxide, cholestyramine, clofibrate, colchicine, corticosteroids, dichloralphenazone, diuretics, oral contraceptives, penicillin, primidone, raloxifene, rifabutin, rifampin, simethicone, spironolactone, tacrolimus, tolbutamide, and vitamin K.
  • Traumatic venipunctures can activate the coagulation sequence by contaminating the sample with tissue thromboplastin and producing falsely shortened PT.
  • Hematocrit greater than 55% may cause falsely prolonged results because of anticoagulant excess relative to plasma volume.
  • Incompletely filled collection tubes, specimens contaminated with heparin, clotted or hemolyzed specimens, or unprocessed specimens not delivered to the laboratory within 24 hr of collection should be rejected.
  • Excessive agitation causing sample hemolysis can falsely shorten the PT because the hemolyzed cells activate plasma-clotting factors.

Nursing Implications and Procedure

Potential nursing problems

ProblemSigns & SymptomsInterventions
Bleeding (Related to alerted clotting factors secondary to warfarin use or depleted clotting factors)Altered level of consciousness; hypotension; increased heart rate; decreased HGB and HCT; capillary refill greater than 3 sec; cool extremities; blood in urine, stool, sputum; bleeding gums; nosebleed; bruises easilyIncrease frequency of vital sign assessment with variances in results; monitor for vital sign trends; administer blood or blood products as ordered; administer prescribed vitamin K; monitor and trend HGB/HCT; assess skin for petechiae, purpura, hematoma; monitor for blood in emesis, or sputum; institute bleeding precautions (prevent unnecessary venipuncture; avoid IM injections; prevent trauma; be gentle with oral care, suctioning; avoid use of a sharp razor); administer prescribed stool softener; monitor and trend PT/INR in relation to warfarin dosage
Gas exchange (Related to deficient oxygen capacity of the blood secondary to blood loss)Irregular breathing pattern, use of accessory muscles; altered chest excursion; adventitious breath sounds (crackles, rhonchi, wheezes, diminished breath sounds); copious secretions; signs of hypoxia; altered blood gas results; confusion; lethargy; cyanosisMonitor respiratory rate and effort based on assessment of patient condition; assess lung sounds frequently; monitor for secretions, bloody sputum; suction as necessary; use pulse oximetry to monitor oxygen saturation; collaborate with physician to administer oxygen as needed; elevate the head of the bed 30 degrees or higher; monitor IV fluids and avoid aggressive fluid resuscitation; assess level of consciousness; anticipate the need for possible intubation
Tissue perfusion (Related to decreased hemoglobin secondary to bleeding; altered clotting factors)Hypotension; dizziness; cool extremities; pallor; capillary refill greater than 3 sec in fingers and toes; weak pedal pulses; altered level of consciousness; altered sensationMonitor blood pressure; assess for dizziness; assess extremities for skin temperature, color, warmth; assess capillary refill; assess pedal pulses; monitor for numbness, tingling, hyperesthesia, hypoesthesia; monitor and trend PT and INR; administer blood or blood products as ordered; administer vitamin K as ordered; administer IV fluids as ordered; use fluid bolus as appropriate; administer medication to support blood pressure as ordered
Health management (Related to inaccurate self-medication of warfarin; complexity of health-care system; complexity of therapeutic management; knowledge deficit; cultural family health patterns; mistrust of health-care provider)Inability or failure to recognize or process information toward improving health and preventing illness with associated mental and physical effectsCollaborate with health-care provider to develop a plan of care that supports health; ensure patient adheres to recommended medication regime; encourage patient to comply with health-care follow-up appointments


  • Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
  • Patient Teaching: Inform the patient this test can assist in evaluating coagulation and monitor therapy.
  • Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
  • Obtain a history of the patient’s cardiovascular, hematopoietic, and hepatobiliary systems, especially any bleeding disorders and other symptoms, as well as results of previously performed laboratory tests and diagnostic and surgical procedures.
  • Obtain a list of the patient’s current medications, including anticoagulants, aspirin and other salicylates, herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus). Such products should be discontinued by medical direction for the appropriate number of days prior to a surgical procedure. Note the last time and dose of medication taken.
  • Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
  • Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
  • Note that there are no food, fluid, or medication restrictions unless by medical direction.


  • Potential complications: N/A
  • Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
  • Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
  • Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection. Perform a venipuncture. Fill tube completely. Important note: When multiple specimens are drawn, the blue-top tube should be collected after sterile (i.e., blood culture) tubes. Otherwise, when using a standard vacutainer system, the blue-top tube is the first tube collected. When a butterfly is used and due to the added tubing, an extra red-top tube should be collected before the blue-top tube to ensure complete filling of the blue-top tube.
  • Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
  • Promptly transport the specimen to the laboratory for processing and analysis. If delays in specimen transport and processing occur, it is important to consult with the testing laboratory. Whole blood specimens are stable at room temperature for up to 24 hr. Some laboratories will accept refrigerated whole blood samples up to 48 hr from the time of collection. Criteria for rejection of specimens based on collection time may vary among facilities.


  • Inform the patient that a report of the results will be made available to the requesting HCP, who will discuss the results with the patient.
  • Frequent monitoring of the PT/INR is very important. Concern with monitoring is mostly involved with elevated values. However, decreased PT results can indicate a risk for thrombosis. There are three factors, known as Virchow’s triad, that increase the risk of developing a venous thrombus:
    • Hypercoagulability, or a tendency for blood to coagulate at an abnormally rapid rate
    • Venous stasis, or an impaired rate of blood flow through a vessel
    • Vessel wall trauma or injury
    Possible nursing interventions to decrease risk of thrombus include education for the patient regarding leg exercises, avoidance of constrictive clothing (e.g., stockings or tight socks), or avoidance of behaviors that might constrict blood flow, such as crossing of the legs or maintaining a dependent position for long periods of time.
  • Nutritional Considerations: Foods high in vitamin K should be avoided by the patient on anticoagulant therapy. Foods that contain vitamin K include cabbage, cauliflower, chickpeas, egg yolks, green tea, pork, liver, milk, soybean products, tomatoes, mayonnaise, vegetable oils, and green leafy vegetables such as leaf lettuce, watercress, parsley, broccoli, brussels sprouts, kale, spinach, and turnip greens.
  • Nutritional Considerations: Avoid alcohol and alcohol products while taking warfarin because the combination of the two increases the risk of gastrointestinal bleeding.
  • Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.
  • Patient Education

    • Instruct the patient to report bleeding from any areas of the skin or mucous membranes.
    • Inform the patient with prolonged PT/INR of the importance of taking precautions against bruising and bleeding, including the use of a soft bristle toothbrush, use of an electric razor, avoidance of constipation, avoidance of aspirin products, and avoidance of IM injections.
    • Inform the patient of the importance of periodic laboratory testing while taking an anticoagulant.
    • Reinforce the importance of refraining from alcohol use while on warfarin.
    • Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP.
    • Instruct the patient in the use of home test kits for PT/INR approved by the U.S. Food and Drug Administration, as appropriate.
    • Answer any questions or address any concerns voiced by the patient or family.
  • Expected Patient Outcomes

    • Knowledge
    • States signs and symptoms of bleeding that should be reported to the HCP
    • States understanding of the benefit of taking warfarin to the patient’s overall health
    • Skills
    • Demonstrates proficiency and accuracy in the self-administration of warfarin
    • Identifies foods high in vitamin K and includes them in the diet
    • Attitude
    • Discusses barriers to compliance with therapeutic management and makes efforts to adhere to recommendations
    • Complies with recommended follow-up appointments for PT and INR evaluation

Related Monographs

  • Related tests include, ALP, ALT, ANA, AT-III, AST, bilirubin, biopsy liver, bleeding time, calcium, coagulation factors, CBC, CBC platelet count, CT liver and biliary tract, cryoglobulin, d-dimer, fecal analysis, fecal fat, FDP, fibrinogen, GGT, gastric acid emptying scan, hepatitis antibodies (A, B, C, D), liver and spleen scan, lupus anticoagulant, aPTT, plasminogen, protein C, protein S, US abdomen, US liver, and vitamin K.
  • Refer to the Cardiovascular, Hematopoietic, and Hepatobiliary systems tables at the end of the book for related tests by body system.
Handbook of Laboratory and Diagnostic Tests, © 2013 Farlex and Partners