Study of bioaccumulation of dalteparin at a therapeutic dose in patients with renal insufficiency

Schmid, Pirmin; Brodmann, Doreen; Odermatt, Y.; Fischer, Andreas; Wuillemin, Walter A.

doi:10.1111/j.1538-7836.2009.03556.x

Cited by 31 publications

(20 citation statements)

References 12 publications

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“…In elderly patients (≥75 years), STEMI patients, excess doses of LMWH were not independent predictors of major adverse vascular events. Results from the current study are consistent with those from previous studies in which patients with RI have a higher risk for thromboembolic complications [24-26], and support the recommendation for dose adjustments based on anti-Xa activity and not calculated based on a simple dose scheme for LMWH used in RI patients [27]. Our results indicate that using LMWH at a fixed, lower dose in patients without severe RI may be safe and effective.…”

Section: Discussionsupporting

confidence: 90%

Dosing practice of low molecular weight heparins and its efficacy and safety in cardiovascular inpatients: a retrospective study in a Chinese teaching hospital

Cai

Qian

et al. 2012

BMC Cardiovasc Disord

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BackgroundLow-molecular-weight heparins (LMWHs) are safe and effective anticoagulant options for cardiovascular patients when applied as body weight-adjusted doses. However, there are some barriers that make it difficult to implement weight-adjusted doses in clinical practice. Therefore, it is vital to learn the dosing practices of LMWH and its efficacy and safety in clinical practice.MethodsA retrospective study was conducted in cardiovascular inpatients who had received at least one dose of LMWH during a 6-month period. Appropriateness of LMWH dosing was determined and major clinical outcomes (major adverse vascular events and major bleeding) during hospitalization were evaluated.ResultsA total of 376 admissions representing 364 patients received LMWH treatment. Of these, 17.0% (64/376) of admissions did not have body weight records. Of the 312 admissions included for the outcome study, only 34 cases (10.9%) received the recommended doses of LMWH, while 51 cases (16.3%) received mild underdoses, 223 cases (71.5%) received major underdoses and 4 (1.3%) received excess doses. There were 10 major adverse vascular events, which occurred more often in patients receiving excess doses of LMWH than in patients receiving recommended, mild or major underdoses (50%, 2.9%, 2.0% and 2.7%, respectively, P < 0.001). After multivariable analysis, severe renal insufficiency was an independent risk factor for major adverse vascular events [odds ratio (OR), 31.93; 95% confidence interval (CI), 5.99-170.30; P < 0.001]. No major bleeding was recorded.ConclusionsUnderdose of LMWH is commonly used in cardiovascular inpatients, which was suboptimal according to guidelines. Using LMWH at a fixed, low dose for treatment purposes in patients without severe renal insufficiency was not associated with a higher risk of adverse vascular events in the current study, though larger studies with extended follow-ups are required to fully assess the long-term consequences of LMWH underdosing.

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Section: Discussionsupporting

confidence: 90%

Dosing practice of low molecular weight heparins and its efficacy and safety in cardiovascular inpatients: a retrospective study in a Chinese teaching hospital

Cai

Qian

et al. 2012

BMC Cardiovasc Disord

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“…No patients (0%; 95% ci: 0% to 3.0%) showed bioaccumulation (that is, anti-factor xa > 0.40 IU/mL), and the median trough anti-factor xa concentration was undetectable (<0.10 IU/mL) 61 . Similar findings have been reported elsewhere 62 .…”

Section: 23supporting

confidence: 93%

Evidence-Based Guidance on Venous Thromboembolism in Patients with Solid Tumours

Shea‐Budgell

Easaw

2014

Current Oncology

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Venous thromboembolism (vte) is a serious, life-threatening complication of cancer. Anticoagulation therapy such as low molecular weight heparin (lmwh) has been shown to treat and prevent vte. Cancer therapy is often complex and ongoing, making the management of vte less straightforward in patients with cancer. There are no published Canadian guidelines available to suggest appropriate strategies for the management of vte in patients with solid tumours. We therefore aimed to develop a clear, evidence-based guideline on this topic. A systematic review of clinical trials and meta-analyses published between 2002 and 2013 in PubMed was conducted. Reference lists were handsearched for additional publications. The National Guidelines Clearinghouse was searched for relevant guidelines. Recommendations were developed based on the best available evidence. In patients with solid tumours, lmwh is recommended for those with established vte and for those without established vte but with a high risk for developing vte. Options for lmwh include dalteparin, enoxaparin, and tinzaparin. No one agent can be recommended over another, but in the setting of renal insufficiency, tinzaparin is preferred. Unfractionated heparin can be used under select circumstances only (that is, when rapid clearance of the anticoagulant is desired). The most common adverse event is bleeding, but major events are rare, and with appropriate follow-up care, bleeding can be monitored and appropriately managed.

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“…Unexpectedly, as relatively contraindicated in CKD stage 4–5 patients due to reduced elimination of the drug , 45% of these patients in our cohort were on long‐term treatment with LMWH, as were 53% of CKD stage 3B patients. LMWH therapy resulted in an increased risk of fatal bleeding in CKD stage 3 patients, compared with non‐CKD patients.…”

Section: Discussionmentioning

confidence: 86%

Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer‐associated venous thromboembolism during anticoagulant treatment

Kooiman

Exter

Cannegieter

et al. 2013

Journal of Thrombosis and Haemostasis

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Summary Background Information on recurrent venous thromboembolic events (VTEs) and major bleeding risks during anticoagulant treatment in patients with cancer‐associated VTEs and chronic kidney disease (CKD) is scarce, although it is of relevance in establishing better tailored management strategies in these patients. Objectives We compared risks of recurrent VTEs and major bleeds in cancer‐associated VTE patients with and without CKD. Methods A total of 1684 patients diagnosed with a cancer‐associated VTE between 2001 and 2011 were followed for 180 days after VTE diagnosis. Patients were treated mainly with low‐molecular‐weight heparin (LMWH) or vitamin‐K antagonists (VKA). Primary outcomes were recurrent VTE and major bleeding. Secondary outcome was fatal bleeding. Results Recurrent VTEs occurred in 15.9/100 patient years (py) in patients without CKD (eGFR > 60 mL min−1), 19.5/100 py in those with CKD stage 3A (eGFR 45–60 mL min−1), 14.9/100 py in those with CKD 3B (eGFR 30–45 mL min−1), and 6.8/100 py in patients with CKD 4–5 (eGFR < 30 mL min−1). Major bleeding occurred in 11.4/100 py in patients without CKD, 18.5/100 py in those with CKD stage 3A, 16.0/100 py in those with CKD 3B, and 40.8/100 py in patients with CKD 4–5. Fatal bleeding occurred in 1.1/100 py, 3.4/100 py, 6.3/100 py and 15.7/100 py, respectively. These increased bleeding risks in CKD patients were mainly observed in those on LMWH treatment, not VKA. Conclusions The risk of major bleeding was increased in CKD patients with VTE and cancer, and was most prominent in those treated with LMWH and an eGFR < 30 mL min−1. These results indicate that LMWH should be used with caution in this specific population.

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Study of bioaccumulation of dalteparin at a therapeutic dose in patients with renal insufficiency

Abstract: To cite this article: Schmid P, Brodmann D, Odermatt Y, Fischer AG, Wuillemin WA. Study of bioaccumulation of dalteparin at a therapeutic dose in patients with renal insufficiency.

Cited by 31 publications

References 12 publications

Dosing practice of low molecular weight heparins and its efficacy and safety in cardiovascular inpatients: a retrospective study in a Chinese teaching hospital

Dosing practice of low molecular weight heparins and its efficacy and safety in cardiovascular inpatients: a retrospective study in a Chinese teaching hospital

Evidence-Based Guidance on Venous Thromboembolism in Patients with Solid Tumours

Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer‐associated venous thromboembolism during anticoagulant treatment

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