• PT
• Pro time
• International Normalized Ratio
• INR

• Blue top tube
• 3-5 mL of venous blood

Additional information

• The ratio of anticoagulant (sodium citrate) to blood (1:9) is critical
• Handle sample gently to prevent hemolysis
• Place the sample on ice and send it to lab promptly
• Blue topped vacuum tubes keep the prothrombin levels stable at room temperature for 12 hrs if left capped.

• Prothrombin time (PT) is a test that measures the "extrinsic system" of clotting factors. These include factors I (fibrinogen), II (prothrombin), V, VII, and X. If any of these factors are deficient, the PT is prolonged.
• This test measures the time required for a firm fibrin clot to form after addition of tissue thromboplastin (factor III) and calcium to the blood sample
• Prothrombin is a vitamin K dependent protein primarily synthesized in the liver that is involved in blood coagulation
• In clinical practice; the most common use of this test is to monitor patients on warfarin (Coumadin®) therapy.
• The International Normalized Ratio (INR) is a method of standardizing prothrombin time results. It has been devised to compare prothrombin time results among labs using different test methods
• The INR value is calculated by the formula:

INR = (PT patient/PT normal)^ISI

Where:

• PT patient = Patient's prothrombin time
• PT normal = Mean normal PT for the laboratory system
• ISI = International Sensitivity Index assigned to the system

• The clinical utility of the PT test includes:
• Evaluation of the clotting ability of the following plasma coagulation factors (extrinsic pathway of the coagulation sequence):
• Factor I (Fibrinogen)
• Factor II (Prothrombin)
• Factor V
• Factor VII
• Factor X
• Evaluation of the response to anticoagulant therapy [Usually to warfarin (Coumadin®)], to achieve therapeutic efficacy
• Screening of individuals who are prone to bleeding, prior to surgical, obstetric, dental, or invasive diagnostic procedures
• Evaluation of the causes of bruising and abnormal bleeding such as
• Epistaxis
• Gastrointestinal bleeding
• Gingival bleeding
• Hematomas
• Hematuria
• Menorrhagia
• Any other abnormal bleeding
• Evaluation of:
• Liver disease
• Protein deficiency
• Fat malabsorption
• Disfibrinogenemia
• Screening for prothrombin deficiency
• Screening for vitamin K deficiency
• INR values allows more consistent monitoring of anticoagulant therapy with warfarin (Coumadin®)
• PT performed along with APTT is of more significance:
• Prolonged PT with normal APTT can occur only with factor VII deficiency
• Normal PT with prolonged APTT could indicate a deficiency in factors XII, XI, IX, and VIII as well as VIII: C (von Willebrand factor)

Additional information

• Coagulation disorders where the PT is not affected include the following:
• Christmas disease (factor IX deficiency)
• Hemophilia A (factor VIII deficiency)
• Platelet disorders (idiopathic thrombocytopenic purpura)
• Polycythemia vera
• Tannin disease
• von Willebrand's disease
• Related laboratory tests include:
• Alanine aminotransferase
• Aspartate aminotransferase
• Bilirubin
• Bleeding time
• Coagulation factors
• Complete blood count
• -glutamyltranspeptidase
• Partial thromboplastin time
• Platelet count
• Prothrombin consumption time
• Vitamin K

zConsult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

Therapeutic levels by condition

^* Varies with valve type and position

^** Some sources recommend 2.5-3.5 whereas others recommend 2.0-3.0 for pulmonary embolus

Conditions associated with prolonged PT levels include:

• Deficiency of coagulation factors
• Factor I (Fibrinogen)
• Factor II (Prothrombin)
• Factor V (Proaccelerin)
• Factor VII (Proconvertin)
• Factor X (Stuart Factor)
• Vitamin K deficiency
• Newborns of mothers with vitamin K deficiency
• Hemorrhagic disease of the newborn
• Premature newborns
• Liver disease:
• Alcoholic hepatitis
• Cirrhosis
• Biliary obstruction
• Current anticoagulant therapy with warfarin (Coumadin®)
• Disseminated intravascular coagulation (DIC)
• Zollinger-Ellison syndrome
• Hypofibrinogenemia and dysfibrinogenemias
• Poor fat absorption as in
• Celiac disease
• Chronic diarrhea
• Sprue
• Systemic lupus erythematosus
• Massive blood transfusion

Drugs and substances associated with an increase in PT include:

• Acetaminophen
• Acetylsalicylic acid (Aspirin)
• Alcohol in excess
• Allopurinol
• Amiodarone
• Anabolic steroids
• Anisindione
• Anistreplase
• Antipyrine
• Carbenicillin
• Cephalosporins
• Chlorthalidone
• Cholestyramine resin
• Cimetidine
• Clofibrate
• Corticotropin
• Demeclocycline
• Dextrothyroxine
• Diazoxide
• Diflunisal
• Diphenylhydantoin
• Diuretics
• Doxycycline
• Erythromycin
• Glucagon
• Heparin IV (within 5 hrs of sample collection)
• Hydroxyzine
• Indomethacin
• Isoniazid
• Laxatives
• Mefenamic acid
• Mercaptopurine
• Methimazole
• Metronidazole
• Miconazole
• Nalidixic acid
• Neomycin
• Niacin
• Oral hypoglycemics
• Oxyphenbutazone
• Para-aminosalicylic acid
• Phenothiazides
• Phenylbutazone
• Phenytoin
• Propylthiouracil
• Quinidine
• Quinine
• Sulfachlorpyridazine
• Thyroid hormones
• Vitamin A
• Warfarin

Falsely prolonged PT may be seen in the following:

• Alcoholism or excessive alcohol ingestion
• Plasma fibrinogen levels >100 mg/dl
• Salicylates >1 g/day
• Failure to fill the collection tube completely
• Inadequate mixing of the sample and the anticoagulant
• Delay in sending the sample to the lab

Conditions associated with reduced PT levels include:

• Ovarian hyperfunction
• Regional enteritis or ileitis
• Thrombophlebitis

Drugs and substances associated with reduced PT levels include:

• Amobarbital
• Antacids
• Antihistamines
• Barbiturates
• Caffeine
• Carbamazepine
• Cardiac glycosides
• Chloral hydrate
• Chlordane
• Colchicines
• Corticosteroids
• Diphenhydramine
• Diuretics
• Glutethimide
• Griseofulvin
• Oral contraceptives
• Penicillin
• Primidone
• Progestin-estrogen combinations
• Pyrazinamide
• Rifampin
• Simethicone
• Spironolactone
• Theophylline
• Tolbutamide
• Vitamin K
• Xanthines

Falsely reduced PT may be seen in the following conditions:

• Diarrhea and vomiting
• Venipuncture technique is traumatic
• Sample collected in the tube is not filled properly
• Prolonged storage of plasma at 4°C

Patients on warfarin (Coumadin®) therapy can antagonize warfarin (thus decreasing their PT/INR) by having dietary consumption of foods high in vitamin K such as:

• Broccoli
• Cauliflower
• Collards
• Chickpeas
• Green tea
• Kale
• Liver
• Parsley
• Pork liver
• Soybean products
• Spinach
• Swiss chart
• Turnip greens

• Berkovsky A et al. A modified method of prothrombin time/International Normalised Ratio determination in capillary blood and monitoring oral anticoagulant therapy. Clin Chem Lab Med. 2006;44(10):1214-7.
• Caldwell SH et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology. 2006 Oct;44(4):1039-46.
• Couris A et al. Dietary vitamin K variability affects International Normalized Ratio (INR) coagulation indices. Int J Vitam Nutr Res. 2006 Mar;76(2):65-74.
• Hutten BA et al. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol. 2000 Sep;18(17):3078-83.
• Koertke et al. INR self-management permits lower anticoagulation levels after mechanical heart valve replacement. Circulation. 2003 Sep 9;108 Suppl 1:II75-8.
• LabTestsOnline®. PT and INR. [Homepage on the Internet] ©2001-2006. Last reviewed on May 6, 2005. Last accessed on November 7, 2006. Available at URL: http://www.labtestsonline.org/understanding/analytes/pt/sample.html
• Meijer P et al. A National Field Study of Quality Assessment of CoaguChek Point-of-Care Testing Prothrombin Time Monitors. Am I Clin Pathol. 2006 Nov;126(5):756-61.
• Stein, PD et al. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 1998;114;602-610.