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Klinisk Biokemi i Norden · 4 2014
Doktorgradsavhandling:
Analytical quality control of INR measurements
in primary care
Anne Vegard Stavelin
Norsk kvalitetsforbedring av laboratorievirksomhet utenfor sykehus (Noklus), Bergen
Anne Vegard Stavelin disputerte
29. november 2013 for ph.d.-gra-
den ved Universitetet i Bergen.
Avhandlingen i sin helhet er til-
gjengelig elektronisk fra Bergen
Open Research Archive
.
handle.net/1956/7607.
In Norway, most patients on oral
anticoagulation with warfarin are treated in primary
care. The treatment is monitored with the laboratory
method prothrombin time, expressed as International
normalized Ratio (INR). It is important that the INR
methods have good analytical quality because the
treatment (medical dose) depends on the INR result.
Overdosing can cause severe bleedings and under
dosing can lead to thrombosis. The laboratories in
primary care control the analytical quality of their
INR methods by performing internal quality control
(IQC) and external quality assessment (EQA). There
are, however, some challenges regarding these quality
control systems. The aim of this thesis was to evaluate
and suggest improvements of the analytical quality
control of INR methods used in primary care. Some
of the findings will also apply for POC methods in
general.
The primary care laboratories perform IQC mainly
by two different approaches; 1) a commercial lyophi-
lized control material is analyzed on the INR method
and the result is compared with some control limits,
2) a fresh patient sample is analyzed both on the INR
method and on a hospital method, and the difference
between the methods is compared with some control
limits. The latter approach is called split sample pro-
cedure. The primary care INR method is considered
“in control” if the result is within the limits and “out
of control” if the result is outside the limits (error
alarm). The aim of paper I (1) was to evaluate and
compare these two IQC approaches in their ability to
detect systematic errors. Power functions were crea-
ted by computer simulations based on empirical data
from 18 primary care laboratories using the INR met-
hods Thrombotrack, CoaguChek S, or Hemochron
Jr. Signature. The control rules 1
2S
, 1
3S
, exponential
weighted moving average, and the deviation limits
of ± 10% and ± 20% were evaluated by their proba-
bility of error detection and false alarms. The results
showed that the probability of detecting systematic
errors was higher when lyophilized control materials
were used compared to patient split samples. The pro-
bability of false alarms was, however, the same. The
conclusion in paper I was that IQC of INR methods
in primary care should be performed by using control
materials rather than the split sample procedure. The
split sample procedure with native patient samples
should be restricted to method bias estimation.
International guidelines recommend that pri-
mary care laboratories should participate in an EQA
scheme whenever available. The aim of paper II (2)
was to investigate if and how the European countries
provide this service for point-of-care (POC) INR
methods. Thirty European countries were asked,
and nineteen countries reported that they do not
provide EQA schemes for POC INR methods, while
12 organizations from nine countries (Austria, Czech
Republic, Denmark, Finland, Hungary, Netherlands,
Norway, Switzerland and United Kingdom) repor-
ted that they offer this service. All 12 organizations
answered a questionnaire regarding their schemes,
and the results showed that there is a vide variation
in how the schemes are organized. However, the most
