Background
Potential hazards of vena cava filters include migration, tilt, perforation, fracture, and in-filter thrombosis. Due to physiological changes during pregnancy, the incidence of these ...complications might be different in pregnant women.
Aim
To evaluate the use and safety of inferior vena cava filters in both women who had an inferior vena cava filter inserted during pregnancy, and in women who became pregnant with an inferior vena cava filter
in situ
.
Methods
We performed two searches in the literature using the keywords “vena cava filter”, “pregnancy” and “obstetrics”.
Results
The literature search on women who had a filter inserted during pregnancy yielded 11 articles compiling data on 199 women. At least one filter complication was reported in 33/177 (19%) women and included in-filter thrombosis (
n
= 14), tilt (
n
= 6), migration (
n
= 5), perforation (
n
= 2), fracture (
n
= 3), misplacement (
n
= 1), air embolism (
n
= 1) and allergic reaction (
n
= 1). Two (1%) filter complications led to maternal deaths, of which at least one was directly associated with a filter insertion. Filter retrieval failed in 9/149 (6%) women. The search on women who became pregnant with a filter
in situ
resulted in data on 21 pregnancies in 14 women, of which one (6%) was complicated by uterine trauma, intraperitoneal hemorrhage and fetal death caused by perforation of the inferior vena cava filter.
Conclusion
The risks of filter complications in pregnancy are comparable to the nonpregnant population, but could lead to fetal or maternal death. Therefore, only in limited situations such as extensive thrombosis with a contraindication for anticoagulants, inferior vena filters should be considered in pregnant women.
Sex matters when it comes to venous thromboembolism (VTE). We defined 5P's – period, pill, prognosis, pregnancy, and postthrombotic syndrome – that should be discussed with young women with VTE. ...Menstrual blood loss (Period) can be aggravated by anticoagulant therapy. This seems particularly true for direct oral anticoagulants. Abnormal uterine bleeding can be managed by hormonal therapy, tranexamic acid, or modification of treatment. The use of combined oral contraceptives (Pill) is a risk factor for VTE. The magnitude of the risk depends on progestagen types and estrogen doses used. In women using therapeutic anticoagulation, concomitant hormonal therapy does not increase the risk of recurrent VTE. Levonorgestrel‐releasing intrauterine devices and low‐dose progestin‐only pills do not increase the risk of VTE. In young women VTE is often provoked by transient hormonal risk factors that affects prognosis. Sex is incorporated as predictor in recurrent VTE risk assessment models. However, current guidelines do not propose using these to guide treatment duration. Pregnancy increases the risk of VTE by 4‐fold to 5‐fold. Thrombophilia and obstetric risk factors further increase the risk of pregnancy‐related VTE. In women with a history of VTE, the risk of recurrence during pregnancy or post partum appears to be influenced by risk factors present during the first VTE. In most women with a history of VTE, antepartum and postpartum thromboprophylaxis with low‐molecular‐weight heparin is indicated. Women generally are affected by VTE at a younger age then men, and they have to deal with long‐term complications (Post‐thrombotic syndrome) of deep vein thrombosis early in life.
Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous ...thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain.
In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete.
Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk RR 0·69 95% CI 0·32–1·47; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 95% CI 0·65–2·09).
In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism.
French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer.
Thus far, the association between residual vein occlusion and immediate compression therapy and postthrombotic syndrome is undetermined. Therefore, we investigated whether compression therapy ...immediately after diagnosis of deep vein thrombosis affects the occurrence of residual vein obstruction (RVO), and whether the presence of RVO is associated with postthrombotic syndrome and recurrent venous thromboembolism. In a prespecified substudy within the IDEAL (individualized duration of elastic compression therapy against long-term duration of therapy for prevention of postthrombotic syndrome) deep vein thrombosis (DVT) study, 592 adult patients from 10 academic and nonacademic centers across The Netherlands, with objectively confirmed proximal DVT of the leg, received no compression or acute compression within 24 hours of diagnosis of DVT with either multilayer bandaging or compression hosiery (pressure, 35 mm Hg). Presence of RVO and recurrent venous thromboembolism was confirmed with compression ultrasonography and incidence of postthrombotic syndrome as a Villalta score of at least 5 at 6 and 24 months. The average time from diagnosis until assessment of RVO was 5.3 (standard deviation, 1.9) months. A significantly lower percentage of patients who did receive compression therapy immediately after DVT had RVO (46.3% vs 66.7%; odds ratio, 0.46; 95% confidence interval, 0.27-0.80; P = .005). Postthrombotic syndrome was less prevalent in patients without RVO (46.0% vs 54.0%; odds ratio, 0.65; 95% confidence interval, 0.46-0.92; P = .013). Recurrent venous thrombosis showed no significant association with RVO. Immediate compression should therefore be offered to all patients with acute DVT of the leg, irrespective of severity of complaints. This study was registered at ClinicalTrials.gov (NCT01429714) and the Dutch Trial registry in November 2010 (NTR2597).
•Immediate compression therapy after DVT is associated with a 20% absolute reduction of RVO.•The reduction of residual thrombosis is associated with an 8% absolute reduction of postthrombotic syndrome at 24 months.
Background
Polypharmacy, including use of inhibitors of CYP3A4 and P‐glycoprotein (P‐gp), is common in patients with venous thromboembolism (VTE) and is associated with increased bleeding.
Methods
In ...8246 patients included in the EINSTEIN‐VTE studies for acute VTE, we evaluated the effect of polypharmacy on bleeding and on the relative differences between rivaroxaban and enoxaparin/vitamin K antagonist (VKA). We assessed the incidence of clinically relevant bleeding (major and clinically relevant nonmajor bleeding) by number of comedications (none, 1–3, ≥4) at baseline, and by use of CYP3A4 and/or P‐gp inhibitors. Interaction between rivaroxaban versus enoxaparin/VKA and comedication was assessed by Cox regression analysis with pinteraction estimates.
Results
With increasing number of comedications, the incidence of clinically relevant bleeding rose from 5.7% to 13.3% in rivaroxaban recipients and from 9.1% to 11.1% in enoxaparin/VKA recipients. Whereas rivaroxaban was associated with a reduced bleeding risk compared with enoxaparin/VKA in patients without comedication (hazard ratio HR 0.6, 95% confidence interval CI 0.4–0.9), the risk was similar in patients with ≥4 comedications (HR 1.2, 95% CI 0.97–1.5, pinteraction .002). Use of CYP3A4 and/or P‐gp inhibitors was associated with a doubled bleeding risk compared with no use, without a difference between rivaroxaban and enoxaparin/VKA.
Conclusion
We conclude that fixed‐dose rivaroxaban as compared with enoxaparin followed by dose‐adjusted VKA is not associated with an increased bleeding risk in patients with VTE administered polypharmacy in general and CYP3A4 and/or P‐gp inhibitors specifically. This implies that the observed increased bleeding risks with polypharmacy and use of CYP3A4 and/or P‐gp inhibitors are likely explained by comorbidities and frailty, and not by pharmacokinetic interactions.
Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women.
The aim of this study was to establish the safety and ...efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis.
We performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided.
We identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127).
This study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis.
•Few studies evaluated diagnostic strategies in pregnant women with suspected pulmonary embolism.•We performed an individual patient data meta-analysis to evaluate these strategies in pregnancy.•Both the Wells rule as the YEARS algorithm could safely rule out pulmonary embolism in pregnancy.•However, efficiency improved considerably when applying adapted (higher) D-dimer thresholds.•The efficiency of bilateral ultrasonography in patients without signs of deep-vein thrombosis was very low.
Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary ...embolism undergo computed tomographic (CT) pulmonary angiography or ventilation-perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown.
In a prospective study involving pregnant women with suspected pulmonary embolism, we assessed three criteria from the YEARS algorithm (clinical signs of deep-vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the d-dimer level. Pulmonary embolism was ruled out if none of the three criteria were met and the d-dimer level was less than 1000 ng per milliliter or if one or more of the three criteria were met and the d-dimer level was less than 500 ng per milliliter. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep-vein thrombosis; if the results were positive (i.e., a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism.
A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep-vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval CI, 0.04 to 1.2); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% CI, 35 to 44). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester.
Pulmonary embolism was safely ruled out by the pregnancy-adapted YEARS diagnostic algorithm across all trimesters of pregnancy. CT pulmonary angiography was avoided in 32 to 65% of patients. (Funded by Leiden University Medical Center and 17 other participating hospitals; Artemis Netherlands Trial Register number, NL5726.).
Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose.
...The objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH.
In the Highlow study (NCT 01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH.
In total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference −11%, 95% CI −20% to −2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference −13%, 95% CI −18% to −8%).
With spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection.
•Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely.•In the Highlow study, women were randomized to intermediate or low-dose LMWH.•Onset of labor was spontaneous in 39% of women on intermediate and 49% on low-dose LMWH.•Fewer women on intermediate than on low-dose LMWH were eligible for neuraxial procedures.
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