Clinical use and laboratory testing of oral anticoagulation therapy: experience from Finland

Helin, Tuukka; Joutsi‐Korhonen, Lotta; Lassila, Riitta

doi:10.21037/aob.2019.07.01

Cited by 8 publications

(11 citation statements)

References 49 publications

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“…The aim of this retrospective real‐world study was to provide more insight on the effect of genetic factors on end points associated with the use of DOACs. We have linked genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters to explore potential associations of genetic variants with responses to dabigatran, rivaroxaban, and apixaban, which are the three most used DOACs in Finland 23 …”

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confidence: 99%

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Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users

Lähteenmäki

Vuorinen

Pajula

et al. 2021

Clin Pharma and Therapeutics

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This study aimed to analyze associations between genetic variants and the occurrence of clinical outcomes in dabigatran, apixaban, and rivaroxaban users. This was a retrospective real-world study linking genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters. We investigated several single-nucleotide variants (SNVs) in the ABCG2, ABCB1, CES1, and CYP3A5 genes potentially associated with bleeding or thromboembolic events in direct oral anticoagulant (DOAC) users based on earlier research. We used Cox regression models to compare the incidence of clinical outcomes between carriers and noncarriers of the SNVs or haplotypes. In total, 1,806 patients on apixaban, dabigatran, or rivaroxaban were studied. The ABCB1 c.3435C>T (p.Ile1145=, rs1045642) SNV (hazard ratio (HR) 0.42, 95% confidence interval (CI), 0.18-0.98, P = 0.044) and 1236T-2677T-3435T (rs1128503-rs2032582-rs1045642) haplotype (HR 0.44, 95% CI, 0.20-0.95, P = 0.036) were associated with a reduced risk for thromboembolic outcomes, and the 1236C-2677G-3435C (HR 2.55, 95% CI, 1.03-6.36, P = 0.044) and 1236T-2677G-3435C (HR 5.88, 95% CI, 2.35-14.72, P < 0.001) haplotypes with an increased risk for thromboembolic outcomes in rivaroxaban users. The ABCB1 c.2482-2236G>A (rs4148738) SNV associated with a lower risk for bleeding events (HR 0.37, 95% CI, 0.16-0.89, P = 0.025) in apixaban users. ABCB1 variants are potential factors affecting thromboembolic events in rivaroxaban users and bleeding events in apixaban users. Studies with larger numbers of patients are warranted for comprehensive assessment of the pharmacogenetic associations of DOACs and their relevance for clinical practice.Direct oral anticoagulants (DOACs) are increasingly used in the context of various clinical conditions and procedures, including atrial fibrillation (ischemic stroke prevention), deep vein thrombosis, and pulmonary embolism. DOACs have favorable pharmacodynamic and pharmacokinetic properties and do not require continuous therapeutic monitoring except in specific

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confidence: 99%

“…We have linked genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters to explore potential associations of genetic variants with responses to dabigatran, rivaroxaban, and apixaban, which are the three most used DOACs in Finland. 23…”

mentioning

confidence: 99%

Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users

Lähteenmäki

Vuorinen

Pajula

et al. 2021

Clin Pharma and Therapeutics

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“…The introduction of direct oral anticoagulant (DOAC) medications and of global coagulation tests has given a new dimension to perioperative transfusion medicine. 6 Whether during acute bleeds and urgent surgery, anticoagulation needs to be discontinued, antidote may be necessary, and when and how resumption of anticoagulation should occur are all questions to which the laboratory provides answers. Assessing the traditional coagulation factor profile and global hemostatic assays are useful in evaluating coagulation capacity, beyond factor levels in inherited bleeding disorders.…”

Section: Coagulation Disorders Unit In Finland-our Missionmentioning

confidence: 99%

Development of a Coagulation Disorders Unit

Szanto,

Helin,

Joutsi-Korhonen

et al. 2024

Semin Thromb Hemost

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Our Coagulation Disorders Unit in Helsinki, Finland, provides 24/7 services for local and national hospitals and colleagues upon requests regarding bleeding and thrombosis diagnostics and management, including follow-up. The unit has a tight connection between the clinic and laboratory, and its maintenance and sharing knowledge and observations have been priorities, already for over 20 years and will continue to be of major importance. The consultation service is provided by phone during daytime and on-call hours, and in written form sent electronically to the consulting stakeholders. Thrombosis and hemostasis-targeted outpatient clinics are also available for the patients referred to the center. Writing local guidance and official guidelines, Nordic, European and international collaboration, and educational activities including social communication are critical elements for the Coagulation Disorders Unit. Alertness to acute coagulation abnormalities, such as occurred during COVID-19 and vaccine-induced thrombosis and thrombocytopenia, and development of strategies to manage cross-disciplinary problems are topics which call upon broad networking. The Nordic community has an ongoing historical meeting, which has been circulating among coagulation centers for the past 56 years. At the European level, the European Association of Haemophilia and Allied Disorders focuses on bleeding disorders and their management, including safety surveillance. The International Society of Thrombosis and Haemostasis offers excellent basic and clinical benchmarks for any Coagulation Disorders Unit. We hope that the description of the development and implementation of our Coagulation Disorders Unit in Helsinki achieves international interest and broadens international collaboration. Finally, we congratulate STH on its great contributions around the globe and for providing a vivid forum to foster the discipline of thrombosis and hemostasis.

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“…The European Society of Cardiology (ESC) and the American College of Cardiology (ACC) recommend DOACs over VKAs in eligible atrial fibrillation patients, and the American College of Chest Physicians (CHEST) suggests DOACs over VKAs in patients with venous thromboembolism and no malignancy 4 . Apart from these major indications of anticoagulation, DOACs are being evaluated in other clinical settings 5,6 …”

Section: Introductionmentioning

confidence: 99%

Quantification of direct‐acting oral anticoagulants: Application of a clinically validated liquid chromatography‐tandem mass spectrometry method to forensic cases

Wiesen

Fietz

Jübner

et al. 2020

Drug Testing and Analysis

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In certain forensic cases, a quantification of direct‐acting oral anticoagulants (DOACs) can be necessary. We evaluate the applicability of a previously described liquid chromatography–tandem mass spectrometry (LC‐MS/MS) methodology for the determination of DOACs in plasma to postmortem specimen. Postmortem internal quality control (PIQC) samples were prepared in pooled blank postmortem heart blood, femoral blood, cerebrospinal fluid (CSF), and urine as well in plasma. To examine the application of the clinical method to forensic cases, the main validation parameters were reinvestigated using PIQC samples. Postmortem samples of 12 forensic cases with evidence of previous rivaroxaban intake and unknown bleeding disorders were analyzed. Interday variability remained within the acceptance criterion of ±15%. Matrix effects were comparable in blank plasma and postmortem matrix extracts. After 4 weeks of storage in the refrigerator, no relevant decrease of DOACs was evident. After 96 h of storage at room temperature, a slight decrease in edoxaban concentration was observed in CSF and urine, while plasma edoxaban decreased by about 50%. Median (range) rivaroxaban concentrations determined in specimen of forensic cases were as follows: heart blood (n = 6), 17.2 ng/ml (

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Clinical use and laboratory testing of oral anticoagulation therapy: experience from Finland

Cited by 8 publications

References 49 publications

Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users

Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users

Development of a Coagulation Disorders Unit

Quantification of direct‐acting oral anticoagulants: Application of a clinically validated liquid chromatography‐tandem mass spectrometry method to forensic cases

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