Regular Article
Dose escalation of low molecular weight heparin in patients with recurrent cancer-associated thrombosis

https://doi.org/10.1016/j.thromres.2014.04.028Get rights and content

Abstract

Introduction

Patients with cancer-associated thrombosis are at a high risk of developing recurrent events despite anticoagulant therapy. Escalation of the dose of low molecular weight heparin (LMWH) has been suggested as a potential treatment option to manage these patients. We sought to confirm the benefit and risk of this management strategy in patients with recurrent cancer-associated thrombosis.

Material and Methods

A retrospective cohort study of consecutive cancer outpatients seen for management of a symptomatic recurrent cancer-associated thrombosis while on anticoagulation was undertaken. Objectively confirmed episodes of recurrent thrombosis were treated with either dose escalation of LMWH or initiation of therapeutic dose of LMWH in patients already anticoagulated with LMWH or vitamin K antagonist (VKA) respectively. Included patients were followed for a minimum of 3 months after the index recurrent event.

Results

Fifty-five cancer patients with a recurrent venous thromboembolism (VTE) despite anticoagulation were included. At the time of the recurrence, 89% of patients were on LMWH. The median time between the initial cancer-associated thrombosis to the index recurrent event was 2.3 months (range 0.1 to 30.4 months). Four patients (7.3%; 95% CI: 2.0 to 17.6%) had a second recurrent VTE during the 3-month follow-up period. Three patients (5.5%; 95% CI 1.1 to 15.1%) had major bleeding complications after dose escalation of LMWH. There were no recurrent fatal VTE or major bleeding episodes.

Conclusion

Escalating the dose of LMWH seems effective and safe for managing patients with recurrent cancer-associated thrombosis despite anticoagulant therapy.

Introduction

Cancer patients are at increased risk of developing a venous thrombosis compared to the general population [1], [2]. Although low molecular weight heparins (LMWH) have improved patient outcomes, patients with cancer-associated thrombosis remain at an increase risk of developing recurrent thrombosis despite anticoagulant therapy [3], [4], [5]. Approximately 10 to 17% of patients with cancer-associated thrombosis managed with a vitamin K antagonist (VKA) and 6 to 10% of patients treated with therapeutic doses of LMWH will have recurrent VTE during the initial 3 to 6 month of therapy [6], [7], [8]. Previous retrospective cohort studies have suggested that switching cancer patients with recurrent cancer-associated thrombosis while on VKA to therapeutic doses of LMWH seemed safe and effective [9], [10]. Similarly, an observation cohort study has also shown that escalating the dose of LMWH (by approximately 25% or increased to therapeutic doses if receiving lower doses) might be a potential treatment option to manage patients with recurrent cancer-associated thrombosis despite LMWH [9]. Although only one retrospective cohort study (n = 47) has shown potential benefit of dose escalation of LMWH, it has been proposed as a management strategy to treat patients with recurrent cancer-associated thrombosis despite anticoagulation [11], [12], [13]. We sought to confirm the benefits and risks associated with this empiric approach.

Section snippets

Material & Methods

A retrospective cohort study of consecutive cancer outpatients seen for management of a symptomatic recurrent cancer-associated thrombosis while on anticoagulation was undertaken from July 2008 to December 2012. Patients were included if they had: 1) documented active malignancy (receiving therapy (chemotherapy or radiotherapy) or with metastatic disease); 2) objectively proven first episode of symptomatic cancer-related thrombosis (Proximal lower/upper extremity deep vein thrombosis (DVT) or

Results

Fifty-five cancer patients with a recurrent cancer-associated thrombosis despite ongoing anticoagulation were included. Baseline characteristic are depicted in Table 1. The median age was 63 years old (range 22-83). Twenty-eight (50.9%) were female and thirty (54.5%) had metastatic disease at the time of the initial cancer-associated thrombosis. Twenty eight (50.9%) were undergoing chemotherapy at the time of the recurrent event and three (5.5%) underwent a surgical procedure within the previous

Discussion

Our cohort study confirms that recurrent cancer-associated thrombosis can be effectively and safely managed by switching from VKA to LMWH or escalating the dose of LMWH.

Dose escalation of LMWH has been suggested as a treatment option to manage patients with recurrent cancer-associated thrombosis despite anticoagulation following confirmation of drug compliance and exclusion of heparin-induced thrombocytopenia (HIT) [11], [12], [13]. However, this approach was only described and reported in a

Conflict of Interest Statement

All authors have fulfilled the conditions required for authorship and the authors report no potential conflicts of interest.

Acknowlegements

MC is a recipient of a New Investigator Award from the Heart and Stroke Foundation of Canada and of a Tier 2 Research Chair in Thrombosis and Cancer

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