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Coagulation

Coagulation laboratory tests

PT - Prothrombin time


Reviewer: Jeremy Parsons, M.D. (see Reviewers page)
Revised: 11 February 2013, last major update November 2012
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.

General
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● Most commonly performed laboratory coagulation test
● Measures clotting time from factor VII activation through fibrin formation (i.e. extrinsic and common pathway)
● Used as screening test and to monitor warfarin anticoagulation; can only detect single factor deficiencies if level is 15-45% of normal
● Anticoagulant is usually 3.2% sodium citrate (recommended by Clinical and Laboratory Standards Institute; 3.8% sodium citrate causes prolonged PT if samples are < 80% filed compared to 100% filled; no difference in result with 3.2% citrate between filled volumes of 70% and 100%, Arch Pathol Lab Med 1997;121:956)
● Test should use a thromboplastin that is insensitive to heparin in therapeutic range
● PT is more sensitive to deficiencies in common pathway than aPTT

Warfarin monitoring
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● Warfarin is monitored using INR (international normalized ratio), which standardizes PT results for patients on oral anticoagulants
● Goal is INR of 2-3
● Calculated as INR = (patient PT/mean normal PT)ISI, where ISI is the International Sensitivity Index which is used to calibrate a particular batch of thromboplastin reagent to a universal standard (see below)
● PT/INR should be checked daily at onset of warfarin use until dose and INR are stable (usually at least a week since half life of factors II and X are long), then need to check decreases gradually to every 4 weeks
● May be improved by instrument-specific International Sensitivity Index (ISI) values, in-house calibrators or calibration curves (Arch Pathol Lab Med 2004;128:308); ISI measures sensitivity of PT reagent to factor deficiencies (1.0 is sensitive, 3.0 is insensitive, value determined by manufacturer)

Interpretation
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● Reference interval should be established using at least 120 subjects for each reference population or subclass, and verified using at least 20 subjects
● Usual reference range is 10-14 seconds, up to 16 seconds at birth and decreasing to adult values at age 6 months
Limitations: lupus anticoagulants, use of hirudin or argatroban - must use alternative assays, such as chromogenic factor X assays
Prolonged PT: usually due to deficiencies of factors I (fibrinogen), II, V, VII, X, less commonly due to an inhibitor or anticoagulant (heparin, hirudin, argatroban) and rarely lupus anticoagulant or specific factor inhibitor
Prolonged PT with normal PTT: warfarin or vitamin K deficiency (decreases function of factors II, VII, IX, X, protein C, protein S), liver dysfunction (decreases hepatic synthesis of all coagulation factors except factor VIII) and DIC
● Markedly prolonged values may be due to long acting warfarin-like rodenticide toxicity (Arch Pathol Lab Med 2004;128:e181)

Algorithm for working up a prolonged PT
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● (1) add heparinase; if PT corrects to normal, prolongation is due to presence of heparin
● (2) mixing study (determine if etiology if factor deficiency or factor inhibitor); mix patient plasma with equal amount of normal plasma and determine the PT of the mixture after incubation for 2 hours
● (a) if PT of mixture is normal, prolonged PT is due to factor deficiency; do assays for factors I, II, V, VII, X
● (b) if PT of mixture is still prolonged, suggests presence of inhibitor (rare)
● (c) if PTT of mixture is initially normal but becomes prolonged after incubation for 1-2 hours, may be due to factor V inhibitor (rare)

End of Coagulation > Coagulation laboratory tests > PT - Prothrombin time


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