Prothrombin Time With INR

Such infrequent discrepancies are usually due to pretest variables related to sample collection, processing, and storage. The most frequently seen examples include 

• Underfilled, uncapped, or expired collection tubes¹
• Hemolysis (most common to syringe or butterfly needle collections)
• Clotted or partially clotted specimen (due to specimen not being mixed after collection)

A comprehensive review of pretest variables and their impact on plasma-based coagulation assays can be purchased from the Clinical and Laboratory Standards Institute (CLSI; document H21-A5 [CLSI.org]).

A prolonged PT with INR result can be caused by a medical condition, medications, and other factors as summarized below.^2,3

Medical conditions:

• Vitamin K deficiency, which may be secondary to malabsorption or antibiotic therapy; administration of vitamin K will lead to a significantly shorter PT or normalization within 12-24 hours
• Liver disease (due to diminished production of clotting factors)
• Hematocrit >55% (common in newborns and patients with polycythemia vera)
• Disseminated intravascular coagulopathy (DIC)
• Dysfibrinogenemia (production of abnormal fibrinogen)/abnormal fibrinolysis
• Clotting factor deficiencies (factors II, V, VII, X, fibrinogen)
• Neonates less than 3 months of age will have slightly increased PT/INR due to decreased coagulation factors

Drugs:

• Direct thrombin inhibitors (ie, dabigatran, argatroban)
• Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, fondaparinux)
• Excessive unfractionated heparin (ie, >2.0 IU/mL; however, low molecular weight heparin [LMWH] will cause minimal or no elevation)

Other:

• Gross lipemia.
• Markedly elevated bilirubin.
• Lupus anticoagulants.
• Most reagents used in the PT with INR test contain excess phospholipid that neutralizes lupus anticoagulants. However, strong lupus anticoagulants can cause a mild prolongation or accentuate the prolongation of the PT when patients are taking warfarin. To monitor warfarin in these situations, a FACTOR X ACTIVITY, CHROMOGENIC (test code 10663) can be used rather than, or in addition to, the PT with INR test. 

Consider testing for vitamin K-dependent clotting factors (II, VII, X) and a non-vitamin K-dependent clotting factor (V). When combined with clinical history, these tests can help differentiate a coagulopathy due to vitamin K deficiency, hepatic insufficiency, or a single factor deficiency.

Depending on the clinical context, a fibrinogen or DIC evaluation (D-dimer, platelet count, fibrinogen, aPTT, and PT) may be helpful.³

Quest does not use the term “critical values,” because this implies an understanding of the medical context of each patient. We use the term “priority values.” We have 2 different priority value levels, which trigger different notification protocols. For more information as to how priority values are handled, please click here.

We established priority values for this test after considering the following:

• Some therapeutic indications target a higher intensity PT with INR result (INR of 3.0 to 4.0).
• The likelihood of bleeding has been reported to rise steeply as the PT with INR value increases to above⁴ 5.0.
• However, data from a large registry of warfarin-treated patients suggest that the short-term risk for major bleeding is low (0.96% after 1 month of therapy) for someone with a single INR value between⁵ 5.0 and 9.0.

The INR is calculated using the following formula:

ISI is the international sensitivity index. This value is specific for both the reagent and instrument used to determine the INR. The ISI of the PT reagent used at Quest is ~1.0. 

Yes, for patients with stable liver disease. The PT with INR is generally prolonged in patients with stable chronic liver disease because clotting factor production is diminished. However, if the liver disease is unstable, the concentration of clotting factors would be variable and the PT with INR would be an unreliable measure.