Sunday, September 24, 2023

Factors Potentially Affecting Prothrombin Time (PT)

Factors potentially affecting or influencing PT may include the following:

  • Shortening of PT

    • Physiological
      • Pregnancy
      • Aging
      • Exercise

    • Pathological
      • VTE & ATE
      • Malignancy
      • Sepsis
      • Thyroid disorders

    • Therapeutic
      • rFVIIa
      • Estrogen medications

    • Spurious
      • Prolonged venous stasis of >3 mins
      • Coagulation before centrifugation
      • Hyperbilirubinemia
      • Hypertriglyceridemia
      • Hemolyzed sample
      • Excess vigorous mixing of blood
      • Chilling in refrigerator or placing on ice
      • Incomplete Platelet separation
      • Sample re-run after freezing
      • Tube leaded into long track/belt in completely automated system
      • Analytical error

  • Prolongation of PT

    • Physiological
      • None

    • Pathological
      • Vitamin K deficiency
      • Liver Disease
      • FI, FII, FVII, FV, FX deficiency
      • Afibrinogenemia
      • Dysfibrinogenemia
      • DIC
      • Lupus anticoagulant

    • Therapeutic
      • Warfarin & other VKAs
      • Direct FIIa inhibitors
      • Oral → Dabigatran
      • Parenteral
        • Hirudin
        • Bivalirudin
        • Argatroban
      • Anti-FXa drugs
      • Heparin, Heparinoids, LMWH, Pentasaccharides

    • Spurious
      • Heparin contamination
      • Clotted sample
      • EDTA contamination (calcium chelation)
      • Under filled tube (<90% of the nominal volume)
      • Failure to mix specimen after collection
      • Sample held too long before analysis
      • Sample placed on wrong temperature
      • Use of centrifuge brake
      • Analytical error

    • Unfractionated Heparin
      • Most reagents are less sensitive to UFH due to
        • Nature of PT assay
        • Inclusion of Heparin Neutralizing agent in most PT reagents
      • PT reagent is sensitive when concentrated Heparin contaminates the sample

    • LMWH
      • PT reagents are even less sensitive to LMWH than WFH

    • Heparinoids (anti-FXa activity)
      • PT reagents are even less sensitive to Heparinoids than WFH

    • Pentasaccharides (Fondaparinux)
      • PT reagents are even less sensitive to Fondaparinux than WFH

    • Clotted Sample
      • Serum or fully Clotted sample → No fibrinogen → No clot in PT, APTT or TT
      • Partially clotted sample → Falsely Prolonged PT, APTT & TT or Shortened APTT

    • Hemolyzed sample
      • Hemolyzed RBCs → Phospholipid membranes → Coagulation accelerated → Shortened PT
      • Hemolyzed RBCs → Platelet activation → Impaired PT results
      • Change in the color of plasma & particulate material → interferes with optical end-point detection methods

    • Over & underfilled sample tube
    • Lupus anticoagulant
      • Most PT reagents are insensitive to LA
      • Some PT reagents are sensitive to LA

    • Daptomycin therapy
      • Spuriously prolongs the PT
      • Depends upon 2 factors
        • Thromboplastin source
          • Especially prolonged PT when recombinant human or rabbit thromboplastins are used
        • Phospholipid type of the PT reagent
          • Prolongation occurs mostly when Phosphatidylglycerol is used as phospholipid in PT reagent

    • Vigorous shaking mixing of blood sample
      • Hemolysis & platelet activation → activation of coagulation cascade → PT falsely shortened

    • Chilling in refrigerator (≤40C) or placing the plasma on ice
      • Activation of FVII activation of coagulation cascade → PT falsely shortened 


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