prothrombin time (PT)

Reference interval

• 11.0-12.8 seconds (method-dependent)

Principle

Assessment of activity of vitamin K-dependent coagulation factors

• factor II
• factor V
• factor VII
• factor X

The assay is performed by adding a source of tissue factor to citrated plasma, adding an excess of Ca+2 & measuring the time to clot formation.

The in vitro prothrombin time assay differs from the in vivo coagulation cascade. Factor VIIa in the presence of tissue factor activates factor X to factor Xa in the in vitro assay, whereas in thein vivo pathway, factor IX is also required for activation of factor X to factor Xa in addition to factor VIIa & tissue factor. Thus factor IX levels do not affect the prothrombin time.

Increases

• decreases in factor II, factor V, factor VII or factor X activity to < 40% of normal
  • liver disease
    • prothombin time is a measure of liver synthetic capacity
  • vitamin K deficiency or warfarin (coumadin) therapy
• plasma fibrinogen levels < 50 mg/dL or dysfibrinogenemia
• circulating anticoagulant
• failure to adjust anticoagulant to hematocrit
• drugs that increase PT (effects may be additive to warfarin)
  • acetaminophen toxicity
  • acetohexamide
  • aminosalicylic acid
  • anabolic steroids
  • anistreplase
  • asparaginase
  • aspirin (large doses)
  • carbenicillin
  • cephalosporins (esp cefamandole, cefmetazole, cefoperazone, cefotetan, moxalactam)
  • cholestyramine & cholestipol (rare)
  • cyclophosphamide
  • ethanol (large quantities)
  • halothane
  • heparin (concentration-related, more frequent with intermittent doses)
  • hetastarch (transient)
  • interferon alfa 2b
  • laxatives
  • methotrexate
  • niacin
  • oral anticoagulants: warfarin
  • plicamycin
  • pyrazinamide
  • quinidine & quinine
  • thiazides
  • ticarcillin
  • tolazamide
  • tolbutamide
• drugs that may interact with warfarin to enhance its anticoagulant effect
  • allopurinol, amiodarone, chloral hydrate (initial effect), chloramphenicol (inhibits metabolism), cimetidine, clofibrate, disulfiram, erythromycin, ethacrynic acid, glucagon, mefenamic acid, metronidazole, miconazole, nalidixic acid, oxyphenbutazone, phenyramidol, phenytoin (transient initial effect), sulfinpyrazone, sulfonamides, tamoxifen, thyroxine, phenylbutazone

Causes of increased PT & PTT:

• decreases in factor II, factor V, factor X
• deficiency in fibrinogen
• vitamin K deficiency (late)
• severe liver disease
• disseminated intravascular coagulation
• warfarin
• heparin overdose

Decreases

• prolonged storage at 4 degrees C
  • cold activation of factor VII
• tissues contaminated with tissue thromboplastin by poor venipuncture technique
• hemolyzed specimens
• high level of antithrombin
• drugs that may interact with warfarin to diminish its anticoagulant effect
  • aminoglutethimide, barbiturates, carbamazepine, corticosteroids, ethanol, ethchlorvynol, glutethimide, phenytoin (chronic use), griseofulvin, rifampin, cholestyramine (impairs absorption), chlorinated hydrocarbon pesticides

Differential diagnosis

• prolonged prothrombin time, normal aPTT [4[
  • factor VII deficiency
  • disseminated intravascular coagulation (DIC)
  • liver disease
  • vitamin K deficiency
  • warfarin
• normal prothrombin time, prolonged aPTT
  • factor VIII deficiency
  • factor IX deficiency
  • factor XI deficiency
  • factor XII deficiency
  • von Willebrand's disease (if factor VIII low)
  • heparin
• prolonged prothrombin time, prolonged aPTT
  • factor V deficiency
  • factor X deficiency
  • factor II deficiency
  • fibrinogen deficiency
  • severe liver disease
  • disseminated intravascular coagulation (DIC)
  • vitamin K deficiency
  • warfarin toxicity
  • heparin overdose
• normal prothrombin time, normal aPTT
  • platelet dysfunction (acquired or congenital)
  • von Willebrand's disease (factor VIII not too low)
  • scurvy
  • Ehlers-Danlos syndrome
  • hereditary hemorrhagic telangiectasia
  • factor XIII deficiency

More general terms

• clinical coagulation test
• liver (function) tests (LFT, liver panel, hepatic function panel)

Additional terms

• coagulation cascade
• International normalized ratio (INR)
• partial thromboplastin time (PTT)

Component of

• PT/aPTT/fibrinogen in plasma
• liver (function) tests (LFT, liver panel, hepatic function panel)
• DIC panel
• coagulation screening panel

Patient information

prothrombin time (PT) patient information