Preanalytical variables and off-site blood collection: influences on the results of the prothrombin time/international normalized ratio test and implications for monitoring of oral anticoagulant therapy

Clin Chem. 2005 Mar;51(3):561-8. doi: 10.1373/clinchem.2004.043174. Epub 2005 Jan 13.


Background: The quality of oral anticoagulant therapy management with coumarin derivatives requires reliable results for the prothrombin time/International Normalized Ratio (PT/INR). We assessed the effect on PT/INR of preanalytical variables, including ones related to off-site blood collection and transportation to a laboratory.

Methods: Four laboratories with different combinations of blood collection systems, thromboplastin reagents, and coagulation meters participated. The simulated preanalytical variables included time between blood collection and PT/INR determinations on samples stored at room temperature, at 4-6 degrees C, and at 37 degrees C; mechanical agitation at room temperature, at 4-6 degrees C, and at 37 degrees C; time between centrifugation and PT/INR determination; and times and temperatures of centrifugation. For variables that affected results, the effect of the variable was classified as moderate when <25% of samples showed a change >10% or as large if >25% of samples showed such a change.

Results: During the first 6 h after blood collection, INR changed by >10% in <25% of samples (moderate effect) when blood samples were stored at room temperature, 4-6 degrees C, or 37 degrees C with or without mechanical agitation and independent of the time of centrifugation after blood collection. With one combination of materials and preanalytical conditions, a 24-h delay at room temperature or 4-6 degrees C had a large effect, i.e., changes >10% in >25% of samples. In all laboratories, a 24-h delay at 37 degrees C or with mechanical agitation had a large effect. We observed no clinically or statistically relevant INR differences among studied centrifugation conditions (centrifugation temperature, 20 degrees C or no temperature control; centrifugation time, 5 or 10 min).

Conclusions: We recommend a maximum of 6 h between blood collection and PT/INR determination. The impact of a 24-h delay should be investigated for each combination of materials and conditions.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use
  • Blood Specimen Collection / methods*
  • Centrifugation
  • Drug Monitoring / methods
  • Humans
  • Indicators and Reagents
  • International Normalized Ratio*
  • Prothrombin Time* / instrumentation
  • Temperature
  • Thromboplastin
  • Time Factors
  • Transportation


  • Anticoagulants
  • Indicators and Reagents
  • Thromboplastin