Enoxaparin dosing in the elderly using adjusted body weight

Leri, Frederick; Voyce, Stephen J.; Scialla, Salvatore J.; Glavich, William; Dzielak, Edward; Smego, Raymond A.; Guzek, John

doi:10.1007/s11239-009-0320-8

Cited by 9 publications

(9 citation statements)

References 25 publications

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“…Most evidence on altered pharmacokinetics in patients with renal insufficiency on LMWH exists for the use of enoxaparin [18] . When a therapeutic full dose of enoxaparin was administered, anti-Xa levels were significantly higher among patients with severe renal insufficiency (creatinine clearance <30 mL/min) than those without [7][8][9]19] . A meta-analysis of therapeuticdose enoxaparin studies showed that major bleeding was significantly higher among patients with severe renal insufficiency compared to patients with better renal function (OR 3.88, 95% CI 1.78-8.45).…”

Section: Discussionmentioning

confidence: 94%

Empirically Reduced Dosages of Tinzaparin in Patients with Moderate-to-Severe Renal Insufficiency Lead to Inadequate Anti-Xa Levels

Olie

Meertens

Henskens³

et al. 2017

Nephron

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Background: Due to the higher molecular weight of tinzaparin, the low molecular weight heparin (LMWH) is less dependent on renal excretion than other LMWH preparations. However, several international guidelines recommend the same preemptive dosage reduction for all therapeutic dose LMWHs prescribed in renal insufficient patients, to ensure that there is no accumulation of anticoagulant activity and increased risk of bleeding. This study is aimed at assessing whether a preemptive dosage reduction of tinzaparin in all renal insufficient patients (comprising 25% reduction in patients with Modification of Diet in Renal Disease - estimated glomerular filtration rate (MDRD-eGFR) 30-60 mL/min/1.73 m² and 50% reduction in patients with MDRD-eGFR <30 mL/min/1.73 m²) leads to adequate anti-Xa levels. Methods: We selected the anti-Xa levels of in-hospital patients (≥18 years) with moderate-to-severe renal insufficiency (MDRD-eGFR <60 mL/min/1.73 m²), on therapeutic dosages of tinzaparin. Anti-Xa levels were measured using a chromogenic assay. Results: Preemptive dosage reduction resulted in a median anti-Xa activity of 0.50 IU/mL (interquartile range [IQR] 0.38-0.60). In 92.3% of patients the anti-Xa level was below the target anti-Xa level of >0.85 IU/mL for therapeutic indications. Unadjusted dosages led to a median anti-Xa activity of 0.74 IU/mL (IQR 0.56-0.92). The preemptive dosage reduction was significantly associated with anti-Xa activity below therapeutic range (p = 0.007). No difference in anti-Xa activity was observed between patients with moderate (0.71 IU/mL, IQR 0.61-0.95) versus severe (0.65 IU/mL, IQR 0.41-1.06) renal insufficiency in whom an unadjusted dose had been administered (p = 0.77). None of the anti-Xa levels were above the upper margin of the presumed therapeutic range of 2.0 IU/mL. Conclusion: In renal insufficient patients, the preemptive dosage reduction of tinzaparin leads to inadequate anti-Xa levels.

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Section: Discussionmentioning

confidence: 94%

Empirically Reduced Dosages of Tinzaparin in Patients with Moderate-to-Severe Renal Insufficiency Lead to Inadequate Anti-Xa Levels

Olie

Meertens

Henskens³

et al. 2017

Nephron

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“…Numerous clinical studies support this hypothesis, including some conducted in elderly patients [4,13,16]. In studies conducted with the therapeutic full dose of enoxaparin, anti‐FXa activity levels were significantly higher among patients with severe renal insufficiency (CrCl ≤ 30 mL min −1 ) than among those without [21–23], and a linear correlation was shown by Chow et al. between CrCl and anti‐FXa levels ( P < 0.0005) after multiple therapeutic doses of enoxaparin in patients with a mean age of 75 years [22].…”

Section: Discussionmentioning

confidence: 97%

“…Our study provides additional data confirming that anti‐FXa activity at peak level is not a good predictor of bleeding in patients treated with tinzaparin, even given that it was not designed to investigate this clinical endpoint. Nevertheless, it is accepted that excessive peak anti‐FXa levels are associated with an increased risk of bleeding: this has been shown in large cohorts of patients with acute coronary syndrome receiving enoxaparin, and has led to the suggestion of dose adjustments when enoxaparin is used (grade 2C), either empirically or on the basis of anti‐FXa activity levels [3,4,23,26,27]. However, depending on the pharmacodynamic profile of each LMWH, the threshold of anti‐FXa level not to be exceeded varies from one LMWH to another.…”

Section: Discussionmentioning

confidence: 99%

No accumulation of the peak anti‐factor Xa activity of tinzaparin in elderly patients with moderate‐to‐severe renal impairment: the IRIS substudy

Siguret

Gouin‐Thibault

Pautas

et al. 2011

Journal of Thrombosis and Haemostasis

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Summary. Background: In the elderly, concerns have been raised regarding the risk of accumulation of low molecular weight heparins, owing to their renal elimination. Although data exist for tinzaparin, they are observational. Objectives: To assess whether: (i) there was an accumulation of anti‐factor Xa activity; and (ii) there was any relationship between anti‐FXa activity and age, weight, creatinine clearance or clinical outcomes in patients with moderate‐to‐severe renal impairment receiving tinzaparin (175 IU kg−1 per 24 h) for acute venous thromboembolism. Methods: In 38 centers participating in the Innohep in Renal Insufficiency Study (IRIS), peak plasma anti‐FXa activity was measured on day 2/day 3 and on day 5 or at visit S (VS) (end of tinzaparin treatment). There was considered to be absence of accumulation if the 90% confidence interval (CI) of the (anti‐FXa day 5/VS)/(anti‐FXa day 2/3) ratio did not exceed the predefined limit of 1.25. Results: Eighty‐seven patients, with a mean age of 83 ± 5 years (range: 75–99 years) and a mean creatinine clearance (CrCl) of 40.8 mL min−1, 24.1% of whom had severe renal impairment, were included. The mean duration of tinzaparin treatment was 8.4 days. No significant accumulation was detected: the mean accumulation ratio was 1.06 (90% CI 1.01–1.11). There was no correlation between the accumulation ratio and age, weight, or CrCl. The mean anti‐FXa activity did not differ significantly between the eight patients who experienced clinically relevant bleeding and those who did not. Conclusions: No accumulation of anti‐FXa activity was observed in elderly patients with renal impairment receiving therapeutic doses of tinzaparin, suggesting that there is no need for systematic anti‐FXa monitoring in these patients. The high proportion of high molecular weight moieties in tinzaparin may account for its reduced dependence on renal elimination.

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“…This dose was not associated with bleeding risks. [14][15][16] Almost 50% of patients with lower limb DVT are asymptomatic. Although DVT prophylaxis is recommended in bariatric surgery, data with regard to monitoring and appropriate dosing of LMWH are limited.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of Low–Molecular Weight Heparin and Incidence of Lower Limb Deep Venous Thrombosis and Pulmonary Embolism After Laparoscopic Bariatric Surgery

Khoursheed¹,

Al-Bader²,

Al-Asfar³

et al. 2013

Surgical Laparoscopy, Endoscopy &Amp; Percutaneous Techniques

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Enoxaparin dosing in the elderly using adjusted body weight

Cited by 9 publications

References 25 publications

Empirically Reduced Dosages of Tinzaparin in Patients with Moderate-to-Severe Renal Insufficiency Lead to Inadequate Anti-Xa Levels

Empirically Reduced Dosages of Tinzaparin in Patients with Moderate-to-Severe Renal Insufficiency Lead to Inadequate Anti-Xa Levels

No accumulation of the peak anti‐factor Xa activity of tinzaparin in elderly patients with moderate‐to‐severe renal impairment: the IRIS substudy

Therapeutic Effect of Low–Molecular Weight Heparin and Incidence of Lower Limb Deep Venous Thrombosis and Pulmonary Embolism After Laparoscopic Bariatric Surgery

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