Lack of significant bleeding despite large acute rivaroxaban overdose confirmed with whole blood concentrations

Repplinger, Daniel; Hoffman, Robert S.; Nelson, Lewis S.; Hines, Elizabeth Quaal; Howland, MaryAnn; Su, Mark K.

doi:10.1080/15563650.2016.1187736

Cited by 16 publications

(21 citation statements)

References 9 publications

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“…Management of such patients in published case reports is highly variable. Several cases of massive rivaroxaban overdose have been managed successfully without bleeding and without administration of blood products or reversal agents, attributed in part to the saturation of gastrointestinal absorption at dosages above 50 mg . Cases involving apixaban and dabigatran have likewise been conservatively managed with success .…”

Section: Guidancementioning

confidence: 99%

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

Cuker

Burnett

Triller³

et al. 2019

American J Hematol

269

263

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Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non‐specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.

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Section: Guidancementioning

confidence: 99%

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

Cuker

Burnett

Triller³

et al. 2019

American J Hematol

269

263

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“…At present, neither randomized control trials nor clinical trials involve coagulation monitoring for rivaroxaban. Based on previous case reports describing hemorrhaging caused by rivaroxaban, few patients with bleeding who were treated at a normal dosage had prolonged PT[17-19]. Prolongation of both PT and aPTT was reported in only two patients, who had both consumed large oral doses of rivaroxaban (1960 mg and 1400 mg) as a method of suicide[20,21].…”

Section: Discussionmentioning

confidence: 99%

“…As the use of rivaroxaban increases, clinicians have begun to pay attention to changes in routine coagulation tests and their relationship with bleeding in patients. Some studies suggest that coagulation monitoring may be useful in elderly patients, those who are underweight, or those with renal dysfunction, suspected overdose or bioaccumulation, bleeding, higher HAS-BLED scores, planned invasive procedures and surgery, or those patients with multiple diseases for which multiple drugs are being taken[18,19,29].…”

Section: Discussionmentioning

confidence: 99%

Considerations for routine coagulation monitoring with rivaroxaban: A case report and review of the literature

Cao

Song

et al. 2019

WJCC

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BACKGROUNDRivaroxaban is a non-vitamin K antagonist oral anticoagulant that does not require coagulation monitoring based on current recommendations. Our goal is to explore whether routine coagulation monitoring should not be required for all patients receiving oral rivaroxaban, what relationship between routine coagulation abnormalities and bleeding, and how to deal with the above clinical situations through our case and review of the literature.CASE SUMMARYWe report a 67-year-old woman with a history of atrial fibrillation who presented to the hospital with worsening dyspnea and cough. Based on electrocardiogram, venous compression ultrasonography, and computed tomography pulmonary angiography, the diagnosis of atrial fibrillation, deep venous thrombosis, and acute pulmonary embolism was confirmed. Her coagulation assays and renal function were normal on admission; she was not underweight, did not have a history of hemorrhagic disease, and her CHA2DS2-VAS, HAS-BLED, and simplified Pulmonary Embolism Severity Index scores were 3, 0, and 0, respectively. Oral rivaroxaban (15 mg twice daily) was administered. The following day, she presented gastrointestinal and gum bleeding, combined with coagulation abnormalities. Following cessation of rivaroxaban, her bleeding stopped and tests improved over the next 2 d. Rivaroxaban was begun again 3 d after recovery. However, she again presented with gastrointestinal and gum bleeding and the abnormal tests, and the therapy was discontinued. At 30-d follow-up after discharge, she presented normal coagulation tests without bleeding.CONCLUSIONAlthough current guidelines recommend that using non-vitamin K antagonist oral anticoagulants including rivaroxaban do not require coagulation monitoring, a small number of patients may develop routine coagulation test changes and bleeding during rivaroxaban therapy, especially in the elderly. Clinicians should pay attention to these patients and further obtain evidence in practice.

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“…35,36 However, case reports have also shown that despite overdoses of rivaroxaban and apixaban (showing very high anti-Xa activity), sometimes no bleeding occurred. 37,38 An observational study reporting rivaroxaban and apixaban overdoses described a 7% bleeding rate; although anti-Xa values were not measured, these data support the fact that a high plasma level does not necessarily lead to a bleeding episode. 39 This may suggest that the anticoagulant effect of a given rivaroxaban concentration varies as a function of the individual prothrombotic state and that acutely elevated rivaroxaban trough levels are less predictive of bleeding than long-lasting overexposure.…”

Section: Rivaroxabanmentioning

confidence: 93%

Does One Dose Really Fit All? On the Monitoring of Direct Oral Anticoagulants: A Review of the Literature

2020

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Background There is an increasing amount of literature on direct oral anticoagulant (DOAC) laboratory monitoring. The aims of the present review were to evaluate published data on monitoring DOACs, to provide clinical guidance on how to interpret results, and to summarize why, when, and how to monitor DOACs. Methods The publications screened for this review were obtained through a PubMed search for articles published in English or French before April 2019 that had the following as their main themes: DOAC monitoring, DOAC exposure–effect relationship, DOAC drug interactions, and pharmacokinetics and pharmacodynamics of DOACs. Results DOACs show important inter- and intrapersonal concentration variability and a significant exposure–effect relationship. Concentrations out of the expected range have been shown to lead to an increased adverse event rate and a lower efficacy. No definitive therapeutic range exists for DOACs except for dabigatran for which trough levels of 40 to 200 ng/mL seem to be the consensus. Indications to monitor include suspected drug accumulation in special patient populations, suspected drug failure, and acute situations such as hemorrhagic or thrombotic events. Conclusion There is a likely benefit to monitor DOACs in order to improve their safety and efficacy but randomized controlled trials are required to determine the therapeutic range of these drugs and evaluate whether DOAC monitoring can improve outcomes in a clinical setting.

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Lack of significant bleeding despite large acute rivaroxaban overdose confirmed with whole blood concentrations

Cited by 16 publications

References 9 publications

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

Considerations for routine coagulation monitoring with rivaroxaban: A case report and review of the literature

Does One Dose Really Fit All? On the Monitoring of Direct Oral Anticoagulants: A Review of the Literature

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