Factor Xa Inhibition: Correlation between the Plasma Levels of Anti-Xa Activity and Occurrence of Thrombosis and Haemorrhage

Leizorovicz, Alain; Bara, L.; Samama, M; Haugh, Margaret

doi:10.1159/000216915

Cited by 47 publications

(39 citation statements)

References 13 publications

(18 reference statements)

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“…15 However, another study has shown that most major bleeds occurred in those patients receiving the highest doses of LMWH 16 and those with mean antiXa levels greater than 0.8 IU/mL. Other studies have shown that the pharmacokinetics of LMWH are altered during pregnancy.…”

Section: Resultsmentioning

confidence: 98%

Use of high intensity adjusted dose low molecular weight heparin in women with mechanical heart valves during pregnancy: a single-center experience

Quinn¹,

Klemperer²,

Brooks³

et al. 2009

Haematologica

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Brief Report IntroductionProvision of safe and effective anticoagulation for pregnant women with mechanical heart valves is a challenging management problem. All current anticoagulation regimens are associated with maternal thromboembolism (TE) and/or bleeding. Vitamin K antagonist (VKA) therapy throughout pregnancy results in the lowest observed risk of TE (3.9%). However, VKA use is associated with fetal anomaly rates of 6.4%, fetal death of 12% and neurodevelopmental problems.1,2 The rate of TE with unfractionated heparin (UFH) is high at 25% if used throughout pregnancy and 9% if used for the first trimester. 1 Therapeutic dose LMWH is an attractive alternative to VKAs and UFH. However, in the HIP-CAT study which compared enoxaparin with sequential UFH and warfarin in pregnant women with mechanical valves, 2/7 women receiving therapeutic dose enoxaparin 1 mg/kg 12 hourly developed fatal valve thrombosis. 3 The incidence of TE using LMWH in this setting is not known because of the limited data available, but James et al. found an overall TE rate of 22% and a maternal mortality of 4%. 4 In another review, Oran et al. found an overall incidence of valve thrombosis of 8.64% (8/81) and the overall TE rate 12.35% (10/81).5 However, 9 of these 10 patients received a fixed dose of LMWH, and in 2 of these a low fixed dose was used. Among 51 pregnancies where antiXa levels were monitored, only one patient was reported to have had TE. The American College of Chest Physicians (ACCP) advises that there are insufficient data for definitive recommendations on how best to anticoagulate women with mechanical valves in pregnancy, in view of concerns for fetal well-being with warfarin therapy and the possible poorer efficacy of subcutaneous UFH and LMWH in preventing maternal TE. 6 Recommendations have included adjusted dose LMWH throughout pregnancy to keep a 4 h post-dose anti-Xa level of 1.0-1.2 IU/mL although updated ACCP guidelines recommend adjusted dose LMWH to achieve the manufacturer's peak anti-Xa level 4 h post subcutaneous injection (approximately 1.0 IU/mL) with consideration of LDA in women with prosthetic heart valves at particularly high risk of thrombosis. 7Against this background, we conducted a prospective audit of our experience with the use of our dose-adjusted regimen of high intensity LMWH in pregnant women with mechanical heart valves, and documented TE and bleeding complications, pregnancy outcome, as well as anti-Xa levels throughout their pregnancies. Design and MethodsAll pregnancies in women with mechanical heart valves between 2001 and 2007 who received LMWH were included. The use of standard dose low molecular weight heparin (LMWH) to anticoagulate women with mechanical valves in pregnancy is associated with morbidity and mortality. We conducted a prospective audit of the use of adjusted dose high intensity LMWH in 12 pregnancies in 11 women with prosthetic heart valves. LMWH ± low-dose aspirin was started at therapeutic-dose with monitoring of anti-Xa levels to achieve a target level of 1.0-1.2 ...

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Section: Resultsmentioning

confidence: 98%

Use of high intensity adjusted dose low molecular weight heparin in women with mechanical heart valves during pregnancy: a single-center experience

Quinn¹,

Klemperer²,

Brooks³

et al. 2009

Haematologica

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“…Levine et al [24] reported a highly significant association between anti-Xa levels and rates of venographically confirmed deep vein thrombosis and wound hematomas with LMWH prophylaxis following total hip arthroplasty. Other investigators have noted weaker associations between anti-Xa levels and deep vein thrombosis rates with LMWH prophylaxis following general surgery [19,22], but not for major orthopedic procedures [16,21,23,26].…”

Section: Discussionmentioning

confidence: 94%

Effect of Patient Weight on the Anticoagulant Response to Adjusted Therapeutic Dosage of Low-Molecular- Weight Heparin for the Treatment ofVenous Thromboembolism

Wilson

Wilbur

Burton

et al. 2001

Pathophysiol Haemos Thromb

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Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in obese patients are limited. Some manufacturers have recommended a maximum daily dose of LMWH not to be exceeded. The purpose of this study was to determine if body weight influenced the anticoagulant response to a weight-based dose of LMWH for the treatment of venous thromboembolism. Patients with serum creatinine levels <150 µmol/l receiving the LMWH , dalteparin 200 anti-Xa IU/kg based on actual body weight subcutaneously once daily for the treatment of deep vein thrombosis or pulmonary embolism, were eligible for the study. Patients received a minimum of 5 days LMWH treatment. Patients had peak anti-Xa levels (IL Test Chromogenic assay) measured 3–4 h following their day 3 injection and trough anti-Xa levels measured immediately prior to injections on day 3 and 5. No dose adjustments were made on the basis of the anti-Xa levels. Patients were a priori stratified into three weight classes: (A) within 20% of ideal body weight (IBW) (n = 13); (B) 20–40% of IBW (n = 14), and (C) greater than 40% of IBW (n = 10). The largest patient weighed 190 kg and had a body mass index of 58. Mean daily LMWH doses were 14,030, 17,646 and 23, 565 IU for groups A, B and C, respectively. Mean (SD) trough anti-Xa levels on day 3 were 0.12 (0.05) anti-Xa IU/ml for group A, 0.11 (0.03) anti-Xa IU/ml for group B and 0.11 (0.03) anti-Xa IU/ml for group C (p > 0.2). Similar trough anti-Xa levels were observed on day 5. Mean (SD) peak anti-Xa levels on day 3 were 1.01 (0.20) anti-Xa IU/ml, 0.97 (0.21) anti-Xa IU/ml and 1.12 (0.22) anti-Xa IU/ml for groups A, B and C, respectively (p > 0.2). No thromboembolic or bleeding complications occurred during LMWH therapy in any patients. These findings suggest that body mass does not appear to have an important effect on the response to LMWH up to a weight of 190 kg in patients with normal or near normal renal function.

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“…In this context it needs to be born in mind that target ranges are different for different LMWHs, and that it is still unknown if targets derived from pharmacological studies in healthy volunteers are indeed applicable to the critically ill population with major, heterogeneous and unpredictable modifications in pharmacokinetics and pharmacodynamics, as well as changes in haemostatic competence. Another problem is the only weak relationship between anti-Xa activity and clinical occurrence of symptomatic and asymptomatic VTE [18][19][20]. However, determination of anti-Xa activity is recommended if renal elimination of LMWH is impaired [2].…”

Section: Discussionmentioning

confidence: 99%

Coagulation Day 2010: an Austrian survey on the routine of thromboprophylaxis in intensive care

et al. 2012

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Purpose: Venous thromboembolism (VTE) is a common but often overlooked lifethreatening complication of critical illness. The aim of this cross-sectional survey was to assess current practice of thromboprophylaxis as well as adherence to international guidelines. Methods: After ethics committee approval, all intensive care units in Austrian hospitals treating adult patients were invited to participate in this web-based survey. Anonymized data on each patient treated at the participating intensive care units on Coagulation Day 2010 were collected using an electronic case report form. Risk assessment, choice and monitoring of anticoagulants, means of mechanical prophylaxis, and demographic data were recorded. Results: Data from 325 critically ill patients were collected. Patients had a median of four risk factors for thrombosis and 6 % suffered from VTE. Of the 325 patients, 80 % received low molecular weight heparins subcutaneously, 10 % received unfractionated heparin intravenously, 1 % received alternative anticoagulants and 9 % received no pharmacological prophylaxis. Mechanical prophylaxis was used in 49 % with a predominant use of graduated compression stockings. In 39 % a combination of pharmacological and mechanical prophylaxis was applied and 5 % received no prophylaxis at all. Overall guideline adherence was 40 % on Coagulation Day 2010. Conclusion: Current practice of thromboprophylaxis is predominantly based on the administration of low molecular weight heparins prescribed at rather arbitrary doses without a discernible relationship to drug monitoring, thromboembolic risk factors, vasopressor use or fluid balance. The use of mechanical prophylaxis, evaluation of risk scores and overall guideline adherence must be further encouraged by education, training and communication.

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Factor Xa Inhibition: Correlation between the Plasma Levels of Anti-Xa Activity and Occurrence of Thrombosis and Haemorrhage

Cited by 47 publications

References 13 publications

Use of high intensity adjusted dose low molecular weight heparin in women with mechanical heart valves during pregnancy: a single-center experience

Use of high intensity adjusted dose low molecular weight heparin in women with mechanical heart valves during pregnancy: a single-center experience

Effect of Patient Weight on the Anticoagulant Response to Adjusted Therapeutic Dosage of Low-Molecular- Weight Heparin for the Treatment ofVenous Thromboembolism

Coagulation Day 2010: an Austrian survey on the routine of thromboprophylaxis in intensive care

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