Supratherapeutic anticoagulation from low-molecular-weight heparin in lung transplant recipients

Singer, Jonathan P.; Huang, M.-Y.; Hui, Christine; Blanc, Paul D.; Boettger, Rebecca F.; Golden, J. A.; Watkins, Katherine D.; Hoopes, Charles W.; Leard, Lorriana E.

doi:10.1016/j.healun.2010.04.018

Cited by 10 publications

(16 citation statements)

References 17 publications

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“…Our results are consistent with those of Singer et al. , who also found a high rate (67%) of supratherapeutic anti‐Xa levels in lung transplant recipients. In contrast to Singer's study, the majority of patients in our cohort received an empirically reduced enoxaparin dosage, including many receiving less than 0.8 mg/kg.…”

Section: Discussionsupporting

confidence: 93%

“…Major bleeding episodes aligned with the expected rate cited in previous studies . Similar to other reports, we did not find a correlation between anti‐Xa levels and bleeding rates , although duration of enoxaparin was identified as risk factor for bleeding, resembling those seen in the non‐transplant population .…”

Section: Discussionsupporting

confidence: 90%

“…This creates a concern that transplant recipients may also be at increased risk of LMWH accumulation and subsequent adverse events. Only minimal data exist regarding monitoring and outcomes of LMWH in this population, with one study in showing that two‐thirds of lung transplant recipients on standard treatment doses of enoxaparin had supratherapeutic anti‐Xa levels . Thus, the purpose of this study was to further evaluate the relationship between treatment enoxaparin dosing, anti‐Xa levels, and the risk of adverse events in a larger transplant population.…”

mentioning

confidence: 99%

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Low molecular weight heparin dosing and monitoring in solid organ transplant recipients

Moten

Gaber

Putney

et al. 2013

Clinical Transplantation

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Anti-Xa monitoring for low molecular weight heparin (LMWH) is currently recommended in obese, renally impaired, and pregnant patients. Substantial evidence indicates that solid organ transplant (SOT) patients are at an increased risk of renal impairment, thus representing a population at risk of LMWH accumulation. The purpose of this study was to review our experience with LMWH dosing and monitoring in a cohort of transplant recipients. This was a retrospective, single-center review of 96 SOT patients receiving enoxaparin treatment and anti-Xa monitoring. The percent of patients with supratherapeutic anti-Xas (>1 IU/mL) was determined, as was the relationship between enoxaparin dosages and anti-Xa levels and bleeding. The cohort had a mean age of 62 yr and creatinine clearance of 59 mL/min and was primarily lung transplant recipients (73%). The mean enoxaparin dose was 0.82 mg/kg, which resulted in a mean anti-Xa level of 0.98 IU/mL. Despite the reduced enoxaparin dose, 44% of patients experienced a supratherapeutic anti-Xa level. Patients with supratherapeutic anti-Xas had higher doses than those within the therapeutic range (0.89 mg/kg vs. 0.77 mg/kg; p = 0.002). No major bleeds occurred. Supratherapeutic anti-Xa levels are common in transplant patients receiving enoxaparin therapy. Empirically reduced dosing of enoxaparin and monitoring may warrant consideration in this population.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

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Low molecular weight heparin dosing and monitoring in solid organ transplant recipients

Moten

Gaber

Putney

et al. 2013

Clinical Transplantation

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“…Previous data have demonstrated that patients with low anti-Xa activity increased 30-day mortality [19]. This may be due to the fact that the underdose of LMWH in our study doesn’t indicate low anti-Xa activity as LMWH has linear pharmacokinetics but high between-subject variability [20,21]. On the other hand, clinical outcomes are also influenced by patients’ characteristics and not only the dosage of LMWH.…”

Section: Discussionmentioning

confidence: 64%

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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“…Previously published case series in pregnancy and solid organ transplantation have demonstrated that standard weight-based dosing regimens have often resulted in an above goal AXAL. 5,6 In addition, studies in patients with renal failure suggest that enoxaparin requires dose reduction (either once-daily dosing at 1 mg/kg or twice-daily dosing at less than 1 mg/kg/dose) to achieve goal AXAL. [7][8][9] Finally, evidence in patients with morbid obesity suggests that even a conservative dosing strategy can lead to above goal AXAL.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Enoxaparin Dose Titration at a Large, Tertiary Teaching Facility

Freer

Green

Iuppa

et al. 2014

Clin Appl Thromb Hemost

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Therapeutic drug monitoring of enoxaparin with antifactor Xa levels (AXALs) is recommended in some populations; however, the approach to dose titration is poorly described. Our study at a large, tertiary teaching facility examined the dose response to titration of enoxaparin based on AXAL. Patients from 2008 to 2012 receiving enoxaparin were included, provided 2 or more steady state AXAL were obtained within 30 days and that the enoxaparin was prescribed for treatment rather than prophylaxis. The primary outcome was the percentage of dose change required to obtain goal range AXAL following dose titration. Eighty-seven patients were available for analysis with the following key characteristics: renal dysfunction during treatment 72%, obesity 8%, and solid organ transplant 26%. Initial goal AXAL was attained in 27 (31%) patients, and ultimately 54 (62%) patients achieved goal AXAL. Of the 31 patients who had initial AXAL above goal, 13 (42%) patients reached goal with a median dose decrease of 24%. In the 29 patients who had an initial AXAL below goal, 11 (38%) achieved therapeutic AXAL with a median dose increase of 16%. The AXAL monitoring can guide enoxaparin titration with subtherapeutic or supratherapeutic AXAL and an increase or decrease of roughly 20% is suggested as an initial change.

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Supratherapeutic anticoagulation from low-molecular-weight heparin in lung transplant recipients

Cited by 10 publications

References 17 publications

Low molecular weight heparin dosing and monitoring in solid organ transplant recipients

Low molecular weight heparin dosing and monitoring in solid organ transplant recipients

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

Analysis of Enoxaparin Dose Titration at a Large, Tertiary Teaching Facility

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