Low molecular weight heparin for the prophylaxis of thromboembolism in women with prosthetic mechanical heart valves during pregnancy

SummaryIncreased thromboembolic events occur in women with mechanical prosthetic valves during pregnancy, and selecting an effective and safe anticoagulant is still a challenge. Low molecular weight heparin (LMWH) is a promising alternative, but a recent warning and label change about its use in patients with mechanical prosthetic valves has caused confusion among physicians. The aim of the present study was to review the risks of maternal and fetal complications with mechanical heart valves treated with LMWH during pregnancy. We performed a review of the current medical literature through MEDLINE and EMBASE (1989 to 2004). Additional data sources included abstract proceedings, and reference lists of selected articles. Among 81 pregnancies in 75 women, the proportion of valve thrombosis was 8.64% (7/81; 95% CI, 2.52%–14.76%). The frequency of overall thromboembolic complication (TEC) was 12.35% (10/81; 95% CI, 5.19%–19.51%). Nine of ten patients with TEC received a fixed dose of LMWH and two of these received a fixed low dose of LMWH. Among 51 pregnancies whose anti-factor Xa levels were monitored, only one patient was reported to have a thromboembolic complication. The frequency of live births with LMWH was 87.65% (95%CI, 80.49%94.81%). In pregnant women with mechanical heart valves, LMWH appears to be a suitable option to a vitamin K antagonist. The use of LMWH warrants monitoring and appropriate dose adjustments to maintain a 4–6 hr post-injection anti-factor Xa level at a minimum of 1.0 U/ml to decrease the incidence of TEC.

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Efficacy and safety of low molecular weight heparin in patients with mechanical heart valves: systematic review and meta-analysis

Journal of Thrombosis and Haemostasis ◽

10.1111/jth.12544 ◽

2014 ◽

Vol 12 (5) ◽

pp. 650-659 ◽

Cited By ~ 10

Author(s):

D. Caldeira ◽

C. David ◽

A. T. Santos ◽

J. Costa ◽

F. J. Pinto ◽

...

Keyword(s):

Systematic Review ◽

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Heart Valves ◽

Meta Analysis ◽

Mechanical Heart Valves ◽

Low Molecular Weight ◽

Efficacy And Safety

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Early Anti-Xa Assay-Guided Low Molecular Weight Heparin Chemoprophylaxis is Safe in Adult Patients with Acute Traumatic Brain Injury

The American Surgeon ◽

10.1177/000313482008600434 ◽

2020 ◽

Vol 86 (4) ◽

pp. 369-376

Author(s):

Simon G. Rodier ◽

Mirhee Kim ◽

Samantha Moore ◽

Spiros G. Frangos ◽

Manish Tandon ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Molecular Weight ◽

Quality Improvement ◽

Venous Thromboembolism ◽

Low Molecular Weight Heparin ◽

Dose Group ◽

Factor Xa ◽

Fixed Dose ◽

Low Molecular Weight ◽

Improvement Project

This study evaluated the safety of early anti-factor Xa assay–guided enoxaparin dosing for chemoprophylaxis in patients with TBI. We hypothesized that assay-guided chemoprophylaxis would be comparable in the risk of intracranial hemorrhage (ICH) progression to fixed dosing. An observational analysis of adult patients with blunt traumatic brain injury (TBI) was performed at a Level I trauma center from August 2016 to September 2017. Patients in the assay-guided group were treated with an initial enoxaparin dose of 0.5 mg/kg, with peak anti-factor Xa activity measured four hours after the third dose. Prophylactic range was defined as 0.2 to 0.5 IU/mL with a dose adjustment of ± 10 mg based on the assay result. The assay-guided group was compared with historical fixed-dose controls and to a TBI cohort from the most recent Trauma Quality Improvement Project dataset. Of 179 patients included in the study, 85 were in the assay-guided group and 94 were in the fixed-dose group. Compared with the fixed-dose group, the assay-guided group had a lower Glasgow Coma Score and higher Injury Severity Score. The proportion of severe (Abbreviated Injury Score, head ≥3) TBI, ICH progression, and venous thromboembolism rates were similar between all groups. The assay-guided and fixed-dose groups had chemoprophylaxis initiated earlier than the Trauma Quality Improvement Project group. The assay-guided group had the highest percentage of low molecular weight heparin use. Early initiation of enoxaparin anti-factor Xa assay–guided venous thromboembolism chemoprophylaxis has a comparable risk of ICH progression to fixed dosing in patients with TBI. These findings should be validated prospectively in a multicenter study.

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Low-molecular-weight heparin or warfarin for anticoagulation in pregnant women with mechanical heart valves: what are the risks? A retrospective observational study

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/j.1471-0528.2012.03359.x ◽

2012 ◽

Vol 119 (8) ◽

pp. 1008-1013 ◽

Cited By ~ 48

Author(s):

S Basude ◽

C Hein ◽

SL Curtis ◽

A Clark ◽

J Trinder

Keyword(s):

Molecular Weight ◽

Observational Study ◽

Pregnant Women ◽

Low Molecular Weight Heparin ◽

Heart Valves ◽

Mechanical Heart Valves ◽

Retrospective Observational Study ◽

Low Molecular Weight

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Biological Activity of Low-Molecular-Weight Heparin Increases Over 9 Days in Patients Treated for Acute Venous Thromboembolism.

Blood ◽

10.1182/blood.v114.22.4176.4176 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4176-4176

Author(s):

Job Harenberg ◽

Kai Bauer ◽

Claudia Abletshauser

Keyword(s):

Molecular Weight ◽

Body Weight ◽

Venous Thromboembolism ◽

Low Molecular Weight Heparin ◽

Factor Xa ◽

The Body ◽

Bleeding Complications ◽

Fixed Dose ◽

Low Molecular Weight ◽

Acute Venous Thromboembolism

Abstract Abstract 4176 Subcutaneous (s.c.) body-weight adjusted as well as fixed dose low-molecular-weight heparin (LMWH) for treatment of acute venous thromboembolism (VTE) has been proven to be at least as effective and safe as intravenous unfractionated heparin (UFH). We hypothesized that the anticoagulant effects of LMWH may accumulate during a 9 days fixed dose therapy in patients with acute VTE. Ten patients received 8,000 IU LMWH certoparin bid s.c. for 9±1 days after having given written informed consent. The local ethics committee accepted the study protocol. Serial blood and urine were collected at days 2 and 9 and daily before and after the morning administration of the anticoagulant. The pharmacodynamic parameters were analysed on the anti-factor Xa S2222 method (aXa), heptest, thrombin generation inhibition assay (TGIA), and tissue factor pathway inhibitor activity (TFPI). The area under the activity time curves (AUC) of the parameters was compared at days 2 and 9. LMWH reached steady state levels of the S2222 and heptest assay within 24 hrs. aXa, heptest, TGIA and TFPI were 22%, 38%, 13% and 22% higher at day 9 compared to day 2. The elimination half-lives of aXa and heptest and the aXa excreted into the urine did not differ between days 2 and 9, respectively. The AUC of the aXa did not correlate with the body weight of the patients. Fixed dose, body weight-independent subcutaneous LMWH accumulated to some extend after 9 days of treatment in patients with acute VTE. However, the results of the clinical trials with the LMWH certoparin did not show more bleeding complications compared to UFH. Therapy with LMWH for more than 10 days may require dose reduction. Disclosures: Harenberg: Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Consultancy, Honoraria; Roche Diagnostics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bayer Health Care: Consultancy, Honoraria. Abletshauser:Novartis: Employment.

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