Clinical study
Extended outpatient therapy with low molecular weight heparin for the treatment of recurrent venous thromboembolism despite warfarin therapy

https://doi.org/10.1016/S0002-9343(01)00840-3Get rights and content

Abstract

Purpose

The optimal management of patients who have recurrent thromboembolism while being treated with oral anticoagulation therapy is unknown. This study reports managing such patients with extended duration low molecular weight heparin therapy.

Subjects and methods

This study was a retrospective review of the prospective databases of three tertiary care teaching hospitals over a 27-month period. All patients who had recurrent symptomatic thromboembolism while being treated with warfarin were identified. All patients were treated with low molecular weight heparin (dalteparin), 200 U/kg daily. Data were collected for recurrent venous thromboembolism, bleeding, and survival.

Results

Eight hundred eighty-seven patients were managed for acute thromboembolism. In 32 patients, symptomatic, objectively documented thromboembolism recurred while they were taking warfarin; 63% of the patients with recurrence had cancer, compared with 30% of patients without recurrence. All recurrences were treated with dalteparin. In 3 patients (9% [95% confidence interval: 2% to 25%]), symptomatic recurrence developed while they were being treated with low molecular weight heparin. Nineteen patients (59%) died while receiving anticoagulation therapy; all deaths but 1 were due to malignancy, and none was due to pulmonary embolism or bleeding.

Conclusions

These results suggest that recurrent venous thromboembolism is more likely to develop in cancer patients while being treated with warfarin and that long-term therapy with low molecular weight heparin may be effective in managing warfarin-failure thromboembolic disease.

Section snippets

Patients and eligibility

All patients with recurrent symptomatic venous thromboembolism while being treated with warfarin were identified by a review of the prospective databases of three tertiary care thrombosis clinics (London Health Sciences Center, Ottawa Civic Hospital, and Queen Elizabeth II Health Sciences Center) from June 1996 to August 1998. To be eligible for this series, patients must have had objectively documented deep vein thrombosis or pulmonary embolism. The initial event must have been treated with

Results

Symptomatic recurrent venous thromboembolism developed in 32 patients while on a warfarin regimen. The average age of patients was 56 years (range, 17 to 85, SD = 17). Fifteen (47%) were men. At the time of initial presentation, 27 patients (84%) had deep vein thrombosis, 4 (13%) had pulmonary embolism, and 1 (3%) had both. Four patients (13%) had episodes of venous thromboembolism prior to the index case (Table). Twenty (63%) patients had cancer (15 cases were metastatic), 9 (13%) were

Discussion

Recurrence of venous thromboembolism in patients while taking warfarin was first reported among cancer patients 7, 8. Recent studies have reported that symptomatic venous thromboembolism recurs in approximately 5% of patients despite adequate oral anticoagulation 1, 2. Malignancy is a well-known risk factor for venous thromboembolism and is associated with a significantly higher frequency of recurrent events (9% vs. 1% with no malignancy) at 3 months 1, 2, 9. Other conditions associated with

References (15)

  • J Ansell et al.

    Managing oral anticoagulant therapy

    Chest

    (2001)
  • P Prandoni et al.

    The long-term clinical course of acute deep venous thrombosis

    Ann Intern Med

    (1996)
  • Low molecular weight heparin in the treatment of patients with venous thromboembolism

    N Engl J Med

    (1997)
  • M Levine et al.

    A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis

    N Engl J Med

    (1996)
  • M.M Koopman et al.

    Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home

    N Engl J Med

    (1996)
  • P.S Wells et al.

    Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparinA comparison of patient self-injection to home care injection

    Arch Intern Med

    (1998)
  • C Kearon et al.

    A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism

    N Engl J Med

    (1999)
There are more references available in the full text version of this article.

Cited by (75)

  • Rivaroxaban plus aspirin versus acenocoumarol to manage recurrent venous thromboembolic events despite systemic anticoagulation with rivaroxaban

    2023, Thrombosis Research
    Citation Excerpt :

    Recurrent DVT despite anticoagulation has been related to active cancer, subtherapeutic anticoagulation, use of concomitant anticancer drugs, younger age at presentation (<65 years), and PE as the initial DVT [31–37]. It has been suggested that increasing the dose of low-molecular-weight heparin (LMWH) may be an alternative in patients with recurrent DVT [38–45]; however, to date, there has been no systematic review or randomized trial focused on the treatment of patients with recurrent DVT and PE during anticoagulant therapy. The combination of rivaroxaban plus aspirin has been previously explored in patients with increased risk of atherothrombotic and venous thromboembolic events.

  • Treatment of venous thromboembolism in cancer patients: The dark side of the moon

    2021, Cancer Treatment Reviews
    Citation Excerpt :

    The proportion of patients with recurrent VTE during treatment with factor Xa inhibitors was lower, but still relevant with an overall pooled incidence of about 6% [3]. Evidence to guide treatment of recurrent VTE in cancer patients is weak and largely based on few retrospective studies [87–90]. In a cohort of 70 cancer patients with recurrent VTE, patients who recurred on VKAs or sub-therapeutic dose LMWH received full-dose LMWH for 4–12 weeks, while those who developed recurrent VTE despite full-dose LMWH were treated according to a dose-escalating approach by increasing the dose of about 25% for at least 4 weeks [88].

  • Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report

    2020, Chest
    Citation Excerpt :

    There are no studies assessing the treatment of recurrent VTE despite anticoagulation with DOACs. One retrospective study reported reasonable outcomes (recurrent VTE of 9% [95% CI, 2 to 25]) when using therapeutic weight-adjusted LMWH in patients with recurrent VTE despite oral anticoagulation with vitamin K antagonists.66 Two small retrospective cohort studies have also reported reasonable outcome by increasing the dose of LMWH to 125% and 130% in patients with recurrent events despite therapeutic weight-adjusted LMWH.67,68

  • Management of suspected and confirmed recurrent venous thrombosis while on anticoagulant therapy. What next?

    2019, Thrombosis Research
    Citation Excerpt :

    There are, however, compelling retrospective cohort studies that collectively provide some evidence, albeit weak, upon which to guide practice. Luk and colleagues reported a retrospective cohort study of 82 patients who developed recurrent VTE despite VKAs therapy, who were then switched to full-dose dalteparin for at least 4 weeks [29]. The risk of subsequent recurrent VTE was 9% (3/32; (95% CI 2–25%) over an unspecified duration of follow-up in these patients.

  • Clinical outcomes of venous thromboembolism with dalteparin therapy in multiple myeloma patients

    2015, Thrombosis Research
    Citation Excerpt :

    VTE treatment and second prophylaxis with LMWH may be a more effective and practical alternative to oral anticoagulant therapy. Unlike vitamin K antagonists (VKA), LMWH have predictable pharmacokinetic properties and drug interactions [9], and they can be effective in patients with cancer who have recurrent VTE while receiving warfarin [10,11]. Poor gastrointestinal absorption is not a concern with subcutaneously injected LMWH.

View all citing articles on Scopus
1

Dr. Michael Kovacs is an Internal Scholar with the Department of Medicine at the University of Western Ontario. Dr. Philip Wells is a Canada Research Chair.

View full text