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.
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.
van Geest-Daalderop
Johanna H H
JH
Thrombosis Service, Department of Laboratory of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. ankees.vangeest@planet.nl
Mulder
André B
AB
Boonman-de Winter
Leandra J M
LJ
Hoekstra
Martha M C L
MM
van den Besselaar
Anton M H P
AM
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D001800:Blood Specimen Collection / Q000379:methods*; D002498:Centrifugation; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007202:Indicators and Reagents; D019934:International Normalized Ratio; D011517:Prothrombin Time / Q000295:instrumentation; D013696:Temperature; D013925:Thromboplastin; D013997:Time Factors; D014186:Transportation
D000925:Anticoagulants; D007202:Indicators and Reagents; D013925:Thromboplastin