Presentation Details
| Dual Direct Oral Anticoagulant Therapy in Challenging Thrombosis: A Case Series Heather McPhaden1, Chornenki Nicholas1, Peterson Erica1, Lai Chieh Min Benjamin1, 2, Lee Agnes1. 1The University of British Columbia, Department of Medicine, Division of Hematology, Vancouver, BC, Canada.2The University of British Columbia Centre for Blood Research, Vancouver, BC, Canada |
Abstract
Background: Venous thromboembolism (VTE) is a substantial cause of morbidity and mortality. While most respond to standard anticoagulant regimens, some patients follow an extraordinarily accelerated course and develop thrombosis in multiple organs over the course of days to weeks. Management of this ‘thrombotic storm’ of refractory events often involves escalating doses or switching to another anticoagulant such as low-molecular weight heparins (LMWH) or argatroban. While traditional anticoagulants target multiple factors in the coagulation cascade, direct oral anticoagulants (DOACs) block the activity of a single clotting factor. Dual DOAC therapy, using a factor Xa inhibitor (such as rivaroxaban or apixaban) and a factor IIa inhibitor (dabigatran), has the potential to ‘mimic’ the mechanism of action of LMWHs but does not require parenteral administration and have approved rapid-acting reversal agents. Objectives: This study describes the experience of using dual DOAC therapy in refractory cases of thrombosis at a single institution. Methods: A retrospective chart review was conducted on eight patients with refractory thrombosis treated at Vancouver General Hospital, Vancouver, Canada with simultaneous dabigatran and an oral factor Xa inhibitor. We included all patients over the age of 18 who met the criteria by surveying local hematologists for eligible patients. The study was approved by the University of British Columbia Research Ethics Board (REB #: H23-02575). Results: Eight patients (median age 54 years, 75% male) with multiple breakthrough thrombotic events despite therapeutic anticoagulation were included. Thrombotic events comprised deep vein thrombosis (8/8), pulmonary embolism (7/8), arterial thrombosis (1/8), and cerebral venous thrombosis (1/8). All patients initiated standard therapeutic anticoagulation upon diagnosis of acute VTE with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin induced thrombocytopenia HIT screen but only two had HIT confirmed on serotonin release assay testing. Predisposing risk factors included remote prior VTE (2/8), antiphospholipid antibody syndrome (1/8), anabolic steroid use (1/8), homozygous factor V Leiden (1/8), oral contraceptive use (1/8), smoking (2/8), obesity (4/8), and metastatic malignancy (1/8). Dual DOAC therapy, initiated after failure of a median of 3 treatment lines (either dose increase or change in agent, see Figure 1), involved dabigatran and either apixaban or rivaroxaban. After initiation of dual DOAC, D-dimer levels were noted to decline rapidly (Figure 2) in all cases. Follow-up (median 35 months; range 6-107 months) indicated no recurrent thrombosis or bleeding complications during dual DOAC use. 7/8 patients later transitioned to a single anti-Xa agent, while 1/8 continued dabigatran alone. Three patients experienced subsequent thrombotic events after dual DOAC cessation. Conclusions: Dual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. The absence of bleeding complications and lack of recurrent VTE during dual DOAC therapy in our case series support the potential safety and efficacy of this approach. The drop in D-dimer levels also provides evidence that clot formation was attenuated. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.