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Klinisk Biokemi i Norden · 1 2015
Doktorgradsavhandling
Aspects of the use and interpretation of INR and
D-dimer in primary and secondary care
Ann Helen Kristoffersen
Institutt for samfunnsmedisinske fag, Universitetet i Bergen
Laboratorium for klinisk biokjemi, Haukeland Universitetssjukehus, Bergen
Noklus (Norsk kvalitetsforbedring av laboratorievirksomhet utenfor sykehus), Bergen
INR and monitoring of vitamin K antagonists
(VKAs)
Treatment with VKAs is recommended to reduce
the risk of recurrent episodes in patients with venous
thromboembolism, and to reduce the risk of ischemic
stroke in patients with mechanical heart valves and/
or atrial fibrillation. VKA treatment is challenging
because of the large inter- and intra-individual varia-
tion in dose requirements, caused by genetic poly-
morphisms (CYP2C9 and VKORC genes) and inter-
ference from medication, alcohol, diet and disease.
The treatment therefore has to be monitored with
INR measurements to avoid over- and under-dosing
which increase the risk of bleeding and thromboem-
bolism, respectively. The aims of paper I and II were
to evaluate physicians’ practical performance and
knowledge of VKA treatment and INR monitoring
in different countries.
Two case histories followed by a questionnaire
were sent to physicians in primary care in Norway
(both papers) and to physicians in primary and
secondary care in 12 other countries (paper II). The
patients described in the case histories were treated
with VKAs because of mechanical heart valve, atrial
fibrillation or pulmonary embolism. The physicians
were asked about their practice (VKA dosing and
INR monitoring) both regarding patients on stable
VKA treatment (patient A) and patients with an
unexpected supra-therapeutic INR (patient B), as
well as about their assessment of bleeding risk and
risk of ischemic stroke in atrial fibrillation. In paper
I, 1547 (41%) of 3781 Norwegian general practitio-
ners responded, while in paper II, 3016 physicians
(8 – 38%) from 13 countries responded (82% from
primary care, 18% from secondary care). In patient
A, the frequency of INR measurements stated by the
physicians varied from minimum 4 weeks (median)
to maximum 6 weeks (median), with the exception
of the United Kingdom (6 and 10 weeks, respecti-
vely). Most physicians changed the dose of VKA
at
or right below or right above the therapeutic limits,
but the range of INR changes stated by the clinicians
to change VKA dose (critical differences, CDs) were
substantial. In paper II (therapeutic range 2.0 – 3.0),
only about 20% waited with changing the VKA dose
until INR were < 1.8 or > 3.4, except in Denmark
where this percentage was about 50. In Hungary and
Belgium, 30 - 40% of the physicians would change the
dose when the INR was still
within
the therapeutic
range (Fig. 1). In both papers, the therapeutic limits
where used as guidance for dose change, rather than
Ann Helen Kristoffer-
sen disputerte fredag 27.
september 2013 for PhD
graden ved Universitetet i
Bergen. Avhandlingens tit-
tel:
Aspects of the use and
interpretation of INR and
D-dimer in primary and
secondary care.
Discussed in relation to dif-
ferent phases in laboratory medicine.
Veile-
dere: Sverre Sandberg, Geir Thue og Per Hyltoft
Petersen
