Absorption of Direct Oral Anticoagulants in Cancer Patients after Gastrectomy

Direct oral anticoagulants (DOACs) are safe and effective in cancer patients treated for venous thromboembolism (VTE) or atrial fibrillation (AF). Gastrectomy is the treatment of choice in patients with localized upper gastrointestinal cancer. DOACs are absorbed in the upper gastrointestinal tract, but to what extent is unclear. In a retrospective analysis, hospital data were searched for adult patients who underwent gastrectomy for gastroesophageal or pancreatic cancer, and DOAC therapy for VTE or AF after gastrectomy. DOAC blood levels were determined by chromogenic assays before and after administration, and thromboembolic and bleeding complications were recorded. Eleven patients (median age 76 years) received a factor Xa inhibitor (FXaI; apixaban (3), edoxaban (3), rivaroxaban (4)) or the factor IIa inhibitor dabigatran (1) for VTE (7) or AF (4) after gastrectomy. Eight patients on FXaI had anti-Xa (aXa) trough levels within the expected range (ER). In all of them, aXa levels increased upon DOAC administration. Two patients on 30 mg edoxaban had low aXa trough levels. Administration of 20 mg of rivaroxaban resulted in trough levels in the ER in one of them. None of the FXaI patients had thromboembolism, while two experienced bleeding (arterial puncture site, gastrointestinal). One dabigatran AF patient with trough and peak concentrations below the ER had strokes during 110 mg and 150 mg dabigatran administration. While on apixaban, aXa levels were in the ER, and no clinical complications occurred. DOACs, particularly FXaI, were adequately absorbed in cancer patients after gastrectomy. Our observation of recurrent thromboembolic events in a patient treated with dabigatran warrants cautious use in this specific patient population.

[1]  P. Sandset,et al.  Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation , 2021, Journal of thrombosis and haemostasis : JTH.

[2]  S. Thurner,et al.  Relative risk of arterial and venous thromboembolism in persons with cancer vs. persons without cancer-a nationwide analysis. , 2021, European heart journal.

[3]  Lara A. Kahale,et al.  American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. , 2021, Blood advances.

[4]  R. Babor,et al.  Evidence of impaired dabigatran absorption following laparoscopic Roux‐en‐Y gastric bypass surgery: the Auckland regional experience (2011–2018) , 2020, British journal of haematology.

[5]  A. Torbicki,et al.  Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. , 2020, The New England journal of medicine.

[6]  S. Noble,et al.  Anticoagulation of cancer patients with non‐valvular atrial fibrillation receiving chemotherapy: Guidance from the SSC of the ISTH , 2019, Journal of thrombosis and haemostasis : JTH.

[7]  G. Raskob,et al.  Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism , 2019, Journal of Vascular Surgery: Venous and Lymphatic Disorders.

[8]  Wonkyung Byon,et al.  Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review , 2019, Clinical Pharmacokinetics.

[9]  H. Versteeg,et al.  Atrial fibrillation and cancer - An unexplored field in cardiovascular oncology. , 2019, Blood reviews.

[10]  R. Souza,et al.  Cancer-associated thrombosis: the when, how and why , 2019, European Respiratory Review.

[11]  L. Alberio,et al.  The effect of bariatric surgery on the direct oral anticoagulant rivaroxaban: the extension study. , 2018, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[12]  P. Galajda,et al.  How to proceed with long-term anticoagulation in patient after total gastrectomy and atrial fibrillation? , 2018, European Journal of Clinical Pharmacology.

[13]  P. Metharom,et al.  Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment , 2018, Cancers.

[14]  G. Lyman,et al.  Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  S. Kitchen,et al.  International Council for Standardization in Haematology (ICSH) Recommendations for Laboratory Measurement of Direct Oral Anticoagulants , 2018, Thrombosis and Haemostasis.

[16]  W. Ageno,et al.  Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians , 2018, Journal of thrombosis and haemostasis : JTH.

[17]  A. Rottenstreich,et al.  The effect of bariatric surgery on direct-acting oral anticoagulant drug levels. , 2017, Thrombosis research.

[18]  E. Weledji The principles of the surgical management of gastric cancer , 2017, International journal of surgery. Oncology.

[19]  Craig R. Lee,et al.  Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance. , 2017, The American journal of medicine.

[20]  N. Al-Sanea,et al.  Effect of major gastrointestinal tract surgery on the absorption and efficacy of direct acting oral anticoagulants (DOACs) , 2017, Journal of Thrombosis and Thrombolysis.

[21]  I. Wilding,et al.  Evaluation of regional gastrointestinal absorption of edoxaban using the enterion capsule , 2015, Journal of clinical pharmacology.

[22]  S. Yusuf,et al.  The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). , 2014, Journal of the American College of Cardiology.

[23]  I. Uraizee,et al.  Novel oral anticoagulants after gastric bypass surgery: Caveat emptor , 2014 .

[24]  Z. DeFilipp,et al.  Subtherapeutic anticoagulation with dabigatran following Roux-en-Y gastric bypass surgery. , 2013, Journal of cardiology cases.

[25]  J. Beyer-Westendorf,et al.  Pharmacokinetics of rivaroxaban after bariatric surgery: a case report , 2013, Journal of Thrombosis and Thrombolysis.

[26]  A. Clemens,et al.  Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[27]  A A Rimm,et al.  Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. , 1999, Medicine.

[28]  J. Samet,et al.  Food and Drug Administration , 2007, BMJ : British Medical Journal.