The effect of anti‐Xa monitoring on the safety and efficacy of low‐molecular‐weight heparin anticoagulation therapy: A systematic review and meta‐analysis

Wang, Tingting; Xia, Xiaotong; Fu, Jinglan; Zhang, Jinhua

doi:10.1111/jcpt.13169

Cited by 25 publications

(29 citation statements)

References 9 publications

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“…In a very recent review, Wu et al concluded that anti-Xa monitoring could be beneficial for preventing VTE. 58 In contrast to this review, the vast majority of study population (>90%) in the review by Wu et al was either male or nonpregnant female. Wu et al included only one study investigating pregnant women, 24 which did not contribute to the meta-analysis, thus leaving the question on anti-Xa monitoring during pregnancy unanswered.…”

Section: Discussionmentioning

confidence: 68%

Anti-Xa Monitoring of Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review

Kjaergaard

Fuglsang

Hvas

2021

Semin Thromb Hemost

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Low-molecular-weight heparin (LMWH) is commonly used for preventing or treating venous thromboembolic disease (VTE) during pregnancy. The physiological changes in maternal metabolism have led to discussions on optimal LMWH dosing strategy and possible need for monitoring. The aim of this systematic review is to summarize and discuss whether LMWH dose adjustment according to anti-Xa provides superior effectiveness and safety compared with weight adjusted or fixed dosed LMWH in pregnant women. A systematic literature search was performed in PubMed, Embase, and Scopus on September 26, 2020. The study is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Effectiveness was defined as episodes of thrombosis and safety as bleeding episodes. In total, 33 studies were included: 4 randomized controlled studies and 29 cohort studies. Prophylactic dosing strategies employing weight dosed, fixed dosed, or anti-Xa adjusted LMWH dosing performed equal in effectiveness and safety. In pregnant women with VTE or high thromboembolic risk, therapeutic weight–adjusted LMWH and weight plus anti-Xa-adjusted LMWH provided equal results in terms of effectiveness and safety. Pregnant women with mechanical heart valves (MHVs) received therapeutic anti-Xa-adjusted LMWH with four out of seven studies presenting mean peak anti-Xa within target ranges. Still, pregnant women with MHV experienced both thrombosis and bleeding with anti-Xa in target. Based on the results of this systematic review, current evidence does not support the need for anti-Xa monitoring when using LMWH as thromboprophylaxis or treatment during pregnancy. Nonetheless, the need for anti-Xa monitoring in pregnant women with MHV may need further scrutiny.

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Section: Discussionmentioning

confidence: 68%

Anti-Xa Monitoring of Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review

Kjaergaard

Fuglsang

Hvas

2021

Semin Thromb Hemost

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“…A total of 509 anti-Xa peak level measurements within the first 14 days on ICU were analyzed (median of 5 [3][4][5][6][7][8] analyses per patient). One-third of patients were female (n ¼ 30, 33%); in median, patients were 70 (58-75) years old, had a BMI of 28.4 (24.9-32.1) kg/m 2 , and an ICU LOS of 13 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) days; none of them were vaccinated and in-hospital mortality rate was 26.4% (►Table 1).…”

Section: Results (Low-molecular-weight) Heparin Resistancementioning

confidence: 99%

“…9 10 11 Importantly, 51.6% of our patients changed between the groups of below-expected, expected, and above-expected anti-Xa responses during their ICU stay. This implies that a fixed dose regimen of LMWH, as used in randomized controlled trials 7 8 and recommended by current guidelines, 15 16 can lead to an inadequately high or low anticoagulant effect associated with bleeding 13 or thrombosis, 12 respectively.…”

Section: Discussionmentioning

confidence: 99%

“…In other populations, patients below or above desirable low-molecular-weight heparin (LMWH) levels, measured by the current gold standard as anti-Xa activity, presented with increased risk of thrombosis or bleeding, respectively. 12 13 At the same time, a patient's condition will fluctuate during his intensive care unit (ICU) stay, corresponding to different stages of inflammation and organ failure and potentially interact with pharmacodynamics and -kinetics. Therefore, a fixed dose of any drug can be doomed to fail on ICU, as, for example, the need to adapt vasopressor and antibiotic doses shows.…”

mentioning

confidence: 99%

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Low-Molecular-Weight Heparin Resistance and Its Viscoelastic Assessment in Critically Ill COVID-19 Patients

Bosch

Rugg

Schäfer

et al. 2022

Semin Thromb Hemost

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Critically ill COVID-19 patients present an inflammatory and procoagulant status with a high rate of relevant macro- and microvascular thrombosis. Furthermore, high rates of heparin resistance have been described; yet, individualized anticoagulation by drug monitoring has not been sufficiently researched. We analyzed data from critically ill COVID-19 patients treated at Innsbruck Medical University Hospital with routinely adapted low-molecular-weight heparin (LMWH) doses according to anti-Xa peak levels, and regularly performed ClotPro analyses (a viscoelastic hemostatic whole blood test). A total of 509 anti-Xa peak measurements in 91 patients were categorized as below (<0.008 IU/mL/mg), within (0.008–0–012 IU/mL/mg) or above (> 0.012 IU/mL/mg) expected ranges with respect to the administered LMWH doses. Besides intergroup comparisons, correlations between anti-Xa levels and ClotPro clotting times (CTs) were performed (226 time points in 84 patients). Anti-Xa peak levels remained below the expected range in the majority of performed measurements (63.7%). Corresponding patients presented with higher C-reactive protein and D-dimer but lower antithrombin levels when compared with patients achieving or exceeding the expected range. Consequently, higher enoxaparin doses were applied in the sub-expected anti-Xa range group. Importantly, 47 (51.6%) patients switched between groups during their intensive care unit (ICU) stay. Anti-Xa levels correlated weakly with IN test CT and moderately with Russell's viper venom (RVV) test CT. Critically ill COVID-19 patients present with a high rate of LMWH resistance but with a variable LMWH response during their ICU stay. Therefore, LMWH–anti-Xa monitoring seems inevitable to achieve adequate target ranges. Furthermore, we propose the use of ClotPro's RVV test to assess the coagulation status during LMWH administration, as it correlates well with anti-Xa levels but more holistically reflects the coagulation cascade than anti-Xa activity alone.

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“…Whether anti-Xa is also suitable to guide LMWH application for thromboembolism prophylaxis is a different question, as anti-Xa levels reflecting adequate prophylaxis have yet to be defined [ 8 , 27 ] and monitoring to avoid an accumulation of the drug is not generally required unless in high-risk patients (e.g., those with severe renal injury defined by a creatinine clearance <30 mL min −1 ) [ 7 , 26 ]. Current recommendations are to determine the trough levels of anti-Xa in this situation [ 8 , 28 ]. Our finding of the trough levels revealing no accumulation of an LMWH administered for thromboembolism prophylaxis seems to obviate the need for LMWH monitoring during CRRT.…”

Section: Discussionmentioning

confidence: 99%

Monitoring of Enoxaparin during Hemodialysis Covered by Regional Citrate Anticoagulation in Acute Kidney Injury: A Prospective Cohort Study

Wiegele

Adelmann

Dibiasi

et al. 2021

JCM

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Background: Current guidelines recommend the monitoring of anti-factor Xa (anti-Xa) levels to avoid an accumulation of low-molecular-weight heparins in patients with acute kidney injury, but there is no evidence on how to proceed with such monitoring during continuous renal replacement therapy. Against this background, we investigated the potential accumulation of enoxaparin administered subcutaneously for venous thromboembolism prophylaxis in critically ill patients during continuous renal replacement therapy covered by regional citrate anticoagulation. Methods: Anti-Xa levels were measured at baseline (≤12 h before renal replacement therapy) and on three consecutive days (A to C) when enoxaparin had reached trough levels. Supplementary testing included modified assays of rotational thromboelastometry known to be highly sensitive for low-molecular-weight heparins. Results: The 16 men and 13 women included were adults comparable in age, body mass index, thromboembolism risk assessment, and clinical severity of the disease. Throughout the four examinations, the median trough levels of anti-Xa remained below the detection limit of the test (<0.1 IU mL−1), with interquartile ranges of <0.1 to 0.14 IU mL−1 at baseline and <0.1 to 0.16 IU mL−1 on days A/B/C. All rotational thromboelastometry parameters of clot initiation and clot formation dynamics did not significantly change from baseline to day C. Conclusions: Neither anti-Xa levels nor modified assays of rotational thromboelastometry revealed any accumulation of enoxaparin administered for thromboprophylaxis during continuous renal replacement therapy covered by regional citrate anticoagulation. Although generally recommended in patients with acute kidney injury, monitoring of anti-Xa levels should be questioned in this defined setting.

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The effect of anti‐Xa monitoring on the safety and efficacy of low‐molecular‐weight heparin anticoagulation therapy: A systematic review and meta‐analysis

Cited by 25 publications

References 9 publications

Anti-Xa Monitoring of Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review

Anti-Xa Monitoring of Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review

Low-Molecular-Weight Heparin Resistance and Its Viscoelastic Assessment in Critically Ill COVID-19 Patients

Monitoring of Enoxaparin during Hemodialysis Covered by Regional Citrate Anticoagulation in Acute Kidney Injury: A Prospective Cohort Study

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