Evidence map›Paper›PMID 30933373›Full record

ArticleBritish journal of clinical pharmacology2019

Warfarin dose requirement in patients having severe thrombosis or thrombophilia.

Tuukka A Helin, Lotta Joutsi-Korhonen, Heidi Asmundela, Mikko Niemi, Arto Orpana, Riitta Lassila

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Tuukka A HelinCoagulation Disorders Unit, Clinical Chemistry, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.ORCID 0000-0002-5273-8088
Lotta Joutsi-KorhonenCoagulation Disorders Unit, Clinical Chemistry, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.
Heidi AsmundelaCoagulation Disorders Unit, Hematology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Mikko NiemiDepartment of Clinical Pharmacology, Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.
Arto OrpanaGenetics and Clinical Chemistry, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.
Riitta LassilaCoagulation Disorders Unit, Clinical Chemistry, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.
University of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsWarfarin dose requirement varies significantly. We compared the clinically established doses based on international normalized ratio (INR) among patients with severe thrombosis and/or thrombophilia with estimates from genetic dosing algorithms.

methodsFifty patients with severe thrombosis and/or thrombophilia requiring permanent anticoagulation, referred to the Helsinki University Hospital Coagulation Center, were screened for thrombophilias and genotyped for CYP2C9*2 (c.430C>T, rs1799853), CYP2C9*3 (c.1075A>C, rs1057910) and VKORC1 c.-1639G>A (rs9923231) variants. The warfarin maintenance doses (target INR 2.0-3.0 in 94%, 2.5-3.5 in 6%) were estimated by the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) algorithms. The individual warfarin maintenance dose was tailored, supplementing estimates with comprehensive clinical evaluation and INR data.

resultsMean patient age was 47 years (range 20-76), and BMI 27 (SD 6), 68% being women. Forty-six (92%) had previous venous or arterial thrombosis, and 26 (52%) had a thrombophilia, with 22% having concurrent aspirin. A total of 40% carried the CYP2C9*2 or *3 allele and 54% carried the VKORC1-1639A allele. The daily mean maintenance dose of warfarin estimated by the Gage algorithm was 5.4 mg (95% CI 4.9-5.9 mg), and by the IWPC algorithm was 5.2 mg (95% CI 4.7-5.7 mg). The daily warfarin maintenance dose after clinical visits and follow-up was higher than the estimates, mean 6.9 mg (95% CI 5.6-8.2 mg, P < 0.006), with highest dose in patients having multiple thrombophilic factors (P < 0.03).

conclusionsIn severe thrombosis and/or thrombophilia, variation in thrombin generation and pharmacodynamics influences warfarin response. Pharmacogenetic dosing algorithms seem to underestimate dose requirement.

Indexed as

AdultAgedAlgorithmsAllelesAnticoagulantsBiological Variation, PopulationBlood CoagulationCytochrome P-450 CYP2C9Dose-Response Relationship, DrugFemaleHumansInternational Normalized RatioMaleMiddle AgedPolymorphism, GeneticRetrospective StudiesAnticoagulantsCYP2C9 protein, humanCytochrome P-450 CYP2C9ThrombinVitamin K Epoxide ReductasesVKORC1 protein, humanWarfarinCYP2C9dosing algorithmthrombophiliathrombosisVKORC1warfarin

Identifiers

PMID30933373
PMCPMC6624394
OpenAlexW2931597833

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.