Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An international study

Harenberg, Job; Du, Shanshan; Wehling, Martin; Zolfaghari, Shabnam; Weiß, Christel; Krämer, Roland; Walenga, Jeanine M.

doi:10.1515/cclm-2015-0389

Cited by 30 publications

(33 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our Clinical Pathway also recommended LMWH over rivaroxaban in patients with urinary tract lesions. Rivaroxaban and other DOACs are cleared in part and are active in the urine . LMWHs are also cleared in the urine but are inactive without the protein antithrombin, which is not normally present in the urine.…”

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

Rivaroxaban treatment of cancer‐associated venous thromboembolism: Memorial Sloan Kettering Cancer Center institutional experience

Soff

Mones

Wilkins

et al. 2019

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background Low‐molecular‐weight heparin has been the preferred treatment of cancer‐associated thrombosis (CAT); however, emerging data support the use of direct oral anticoagulants (DOACs). Objectives The Memorial Sloan Kettering Cancer Center Clinical Pathway has served as the institutional guideline for the use of rivaroxaban to treat CAT since 2014. Key elements are to recommend against use of a DOAC in patients with active gastrointestinal (GI) or genitourinary tract lesions, and a prespecified dose reduction in the elderly (75+ years old). We present our institutional experience for treatment of CAT. Methods From January 2014 through September 2016, 1072 patients began rivaroxaban treatment for CAT; 91.9% had a solid tumor, 8.1% had hematologic malignancies, and 75% of patients with solid tumors had metastatic disease. All patients with CAT treated with rivaroxaban were included in this analysis, regardless of adherence to the Clinical Pathway. Results The 6‐month cumulative incidence of recurrent venous thromboembolism and major bleeding were 4.2% (95% confidence interval [CI], 2.7%‐5.7%) and 2.2% (95% CI, 1.1%‐3.2%), respectively. The incidence of clinically relevant non–major bleeding leading to discontinuation of rivaroxaban for at least 7 days was 5.5% (95% CI, 3.7%‐7.1%), and 73.3% of major bleeds occurred in the GI tract. The 6‐month cumulative mortality rate was 22.2% (95% CI, 19.4%‐24.9%). The elderly had similar rates of recurrent thrombosis and bleeding as those aged under 75 years. Conclusion Our institutional experience suggests that in appropriately selected patients, rivaroxaban may be used for treatment of CAT with promising safety and efficacy.

show abstract

Section: Discussionsupporting

confidence: 89%

“…Bioavailability of rivaroxaban is approximately > 80%, but active drug remains in the upper GI lumen. Similarly, rivaroxaban and other DOACs are excreted in the urine at biologically active concentrations . In the presence of known luminal lesions of the GI or GU tract, an LMWH was recommended instead.…”

Section: Methodsmentioning

confidence: 99%

Rivaroxaban treatment of cancer‐associated venous thromboembolism: Memorial Sloan Kettering Cancer Center institutional experience

Soff

Mones

Wilkins

et al. 2019

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…38 Concentrations of rivaroxaban and apixaban as measured by urinary assays are 5- to 15-fold higher as compared to plasma. 65 …”

Section: 0 Anti-xa Agentsmentioning

confidence: 99%

Measurement and reversal of the direct oral anticoagulants

2017

View full text Add to dashboard Cite

Direct oral anticoagulants (DOACs) offer non-inferior efficacy and improved safety compared to vitamin K antagonists (VKAs) for prevention and treatment of venous thromboembolism and prevention of stroke and systemic embolism in non-valvular atrial fibrillation. Unlike VKAs, DOACs do not require routine laboratory monitoring of anticoagulant effect and dose adjustment. In certain situations, however, laboratory assessment of anticoagulant effect may be desirable. Here we review the utility of currently available assays for assessment of DOAC effect and recommend an optimal assessment strategy for each drug, including calibrated dilute thrombin time or ecarin-based assays for dabigatran and calibrated anti-Xa activity assays for the factor Xa inhibitors. We also discuss reversal strategies, both specific and non-specific, for each drug, including the preferential use of idarucizumab for reversal of dabigatran and two agents, andexanet and ciraparantag, currently under development for reversal of rivaroxaban, apixaban and edoxaban.

show abstract

“…Unfortunately, only serum samples were available for our analyses. Because some serum vials contain thrombin‐based clotting activators, the use of serum, instead of plasma, may have led to the detection of lower concentrations than those actually present in the patient's blood, as have been observed with the use of functional assays . Thirdly, the analytical method used in our study measured free dabigatran concentrations, not including the active acylglucuronide metabolites , which normally would lead to somewhat lower dabigatran concentrations .…”

Section: Discussionmentioning

confidence: 94%

Fatal Adverse Event with Dabigatran in Elderly Patient with Reduced Kidney Function

Havig

Lea

Krpo

et al. 2018

Basic Clin Pharma Tox

View full text Add to dashboard Cite

An elderly man with decreased kidney function was admitted to hospital with gastrointestinal bleeding. After remaining stable for 2 days in hospital, he became haemodynamically unstable and an adverse effect of dabigatran was suspected, but efforts to treat the patient failed and the following morning he passed away. In conjunction with the autopsy, blood samples from his hospital stay were analysed for dabigatran, revealing the highest concentration (6400 ng/mL) apparently reported to date. Supra-therapeutic dosing was, however, never suspected. Dabigatran is largely excreted through the kidneys. A possible cause of the high dabigatran concentrations could be a rapid decrease in kidney function that seemingly occurred over a period of 2 months, sometime between his initiation of treatment (eGFR 51-55 mL/min/1.73 m ) and subsequent hospital admission (eGFR 31 mL/min/1.73 m ). The increasing dabigatran concentrations in the patient was, however, not apparent to the prescribing doctor, as therapeutic drug monitoring of dabigatran is not recommended in current guidelines and no such analyses were performed. There may be a need to evaluate blood concentrations of dabigatran, in the light of the reported differences in interindividual concentrations, along with the increased risks of thromboembolic events with lower concentrations and major bleeding events with higher concentrations. Functional assays to assess concentrations of dabigatran in blood have been developed and are available in some hospitals to be used in suspected overdoses or before emergency surgeries. Methods to determine concentrations of dabigatran specifically have also been developed and can additionally be used for therapeutic drug monitoring in an outpatient setting, especially in high-risk individuals.

show abstract

Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An international study

Cited by 30 publications

References 19 publications

Rivaroxaban treatment of cancer‐associated venous thromboembolism: Memorial Sloan Kettering Cancer Center institutional experience

Rivaroxaban treatment of cancer‐associated venous thromboembolism: Memorial Sloan Kettering Cancer Center institutional experience

Measurement and reversal of the direct oral anticoagulants

Fatal Adverse Event with Dabigatran in Elderly Patient with Reduced Kidney Function

Contact Info

Product

Resources

About