Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: In the Highlow study (NCT01828697), 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. RESULTS: 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%). CONCLUSION: 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.

Noninvasive diagnostic work-up for suspected acute pulmonary embolism during pregnancy: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Use of the National Early Warning Score for predicting deterioration of patients with acute pulmonary embolism: a post-hoc analysis of the YEARS Study.

BACKGROUND: The Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning Score (NEWS) is a general prognostic risk score for multiple clinical settings. We investigated whether the NEWS had a comparable performance with the PESI and sPESI, for predicting intensive care unit (ICU) admission and death in patients with acute PE. METHODS: In haemodynamically stable patients with confirmed PE from the YEARS Study (2013-2015), we evaluated the performance of the NEWS, PESI and sPESI for predicting 7-day ICU admission and 30-day mortality. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. RESULTS: Of 352 patients, 12 (3.4%) were admitted to the ICU and 5 (1.4%) died. The AUC of the NEWS for ICU admission was 0.80 (95% CI 0.66 to 0.94) and 0.92 (95% CI 0.82 to 1.00) for 30-day mortality. At a threshold of 3 points, NEWS yielded a sensitivity and specificity of 92% and 53% for ICU admission and 100% and 52% for 30-day mortality. The AUC of the PESI was 0.64 (95% CI 0.48 to 0.79) for ICU admission and 0.94 (95% CI 0.87 to 1.00) for mortality. At a threshold of 66 points, PESI yielded a sensitivity of 75% and a specificity of 38% for ICU admission. For mortality, these were 100% and 37%, respectively. The performance of the sPESI was similar to that of PESI. CONCLUSION: In comparison with PESI and sPESI, NEWS adequately predicted 7-day ICU admission as well as 30-day mortality, supporting its potential relevance for clinical practice.

Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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]). INTERPRETATION: 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. FUNDING: French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer.

Inferior vena cava filters in pregnancy: Safe or sorry?

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.

Postthrombotic syndrome and quality of life after deep vein thrombosis in patients treated with edoxaban versus warfarin.

Background: Postthrombotic syndrome (PTS) is a long-term complication after deep vein thrombosis (DVT) and can affect quality of life (QoL). Pathogenesis is not fully understood but inadequate anticoagulant therapy with vitamin K antagonists is a known risk factor for the development of PTS. Objectives: To compare the prevalence of PTS after acute DVT and the long-term QoL following DVT between patients treated with edoxaban or warfarin. Methods: We performed a long-term follow-up study in a subset of patients with DVT who participated in the Hokusai-VTE trial between 2010 and 2012 (NCT00986154). Primary outcome was the prevalence of PTS, defined by the Villalta score. The secondary outcome was QoL, assessed by validated disease-specific (VEINES-QOL) and generic health-related (SF-36) questionnaires. Results: Between 2017 and 2020, 316 patients were enrolled in 26 centers in eight countries, of which 168 (53%) patients had been assigned to edoxaban and 148 (47%) to warfarin during the Hokusai-VTE trial. Clinical, demographic, and thrombus-specific characteristics were comparable for both groups. Mean (SD) time since randomization in the Hokusai-VTE trial was 7.0 (1.0) years. PTS was diagnosed in 85 (51%) patients treated with edoxaban and 62 (42%) patients treated with warfarin (adjusted odds ratio 1.6, 95% CI 1.0-2.6). Mean differences in QoL scores between treatment groups were not clinically relevant. Conclusion: Contrary to our hypothesis, the prevalence of PTS tended to be higher in patients treated with edoxaban compared with warfarin. No differences in QoL were observed. Further research is warranted to unravel the role of anticoagulant therapy on development of PTS.

Effect of polypharmacy on bleeding with rivaroxaban versus vitamin K antagonist for treatment of venous thromboembolism.

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.

Home Treatment Compared to Initial Hospitalization in Normotensive Patients with Acute Pulmonary Embolism in the Netherlands: A Cost Analysis.

BACKGROUND: Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home treatment of pulmonary embolism (PE) is associated with a cost reduction. An accurate estimation of cost savings per patient treated at home is currently lacking. AIM: The aim of this study was to compare health care utilization and costs during the first 3 months after a PE diagnosis in patients who are treated at home versus those who are initially hospitalized. METHODS: Patient-level data of the YEARS cohort study, including 383 normotensive patients diagnosed with PE, were used to estimate the proportion of patients treated at home, mean hospitalization duration in those who were hospitalized, and rates of PE-related readmissions and complications. To correct for baseline differences within the two groups, regression analyses was performed. The primary outcome was the average total health care costs during a 3-month follow-up period for patients initially treated at home or in hospital. RESULTS: Mean hospitalization duration for the initial treatment was 0.69 days for those treated initially at home (n = 181) and 4.3 days for those initially treated in hospital (n = 202). Total average costs per hospitalized patient were €3,209 and €1,512 per patient treated at home. The adjusted mean difference was €1,483 (95% confidence interval: €1,181-1,784). CONCLUSION: Home treatment of hemodynamically stable patients with acute PE was associated with an estimated net cost reduction of €1,483 per patient. This difference underlines the advantage of triage-based home treatment of these patients.

Pregnancy in women with an inferior vena cava filter: a tertiary center experience and overview of the literature.

Patients with an inferior vena cava (IVC) filter that remains in situ encounter a lifelong increased risk of deep vein thrombosis and IVC filter complications including fracture, perforation, and IVC filter thrombotic occlusion. Data on the safety of becoming pregnant with an in situ IVC filter are scarce. The objective was to evaluate the risk of complications of in situ IVC filters during pregnancy. We performed a retrospective cohort study of pregnant patients with an in situ IVC filter from a tertiary center between 2000 and 2020. We collected data on complications of IVC filters and pregnancy outcomes. Additionally, we performed a systematic literature search in MEDLINE, Embase, and gray literature. We identified 7 pregnancies in 4 patients with in situ IVC filters with a mean time since IVC filter insertion of 3 years (range, 1-8). No complications of IVC filter occurred during pregnancy. Review of literature yielded five studies including 13 pregnancies in 9 patients. In 1 pregnancy a pre-existent, until then asymptomatic, chronic perforation of the vena cava wall by the IVC filter caused major bleeding and uterine trauma with fetal loss. Overall, the complication rate was 5%. It seems safe to become pregnant with an indwelling IVC filter that is intact and does not show signs of perforation, but because of the low number of cases, no firm conclusions about safety of in situ IVC filters during pregnancy can be drawn. We suggest imaging before pregnancy to reveal asymptomatic IVC filter complications.

Quality of life in patients with pulmonary embolism treated with edoxaban versus warfarin.

BACKGROUND: Long-term sequelae of acute pulmonary embolism (PE) include decreased quality of life (QoL). Evidence suggests that adequacy of initial anticoagulant treatment in the acute phase of venous thrombosis has a key impact on late postthrombotic complications. We hypothesize that patients with acute PE treated with edoxaban for acute PE experience have improved QoL compared to those treated with warfarin. METHODS: Patients with PE who participated in the Hokusai-VTE trial were contacted between June 2017 and September 2020 for a single long-term follow-up visit. Main outcomes were the generic and disease-specific QoL measured by the 36-Item Short Form Health Survey (SF-36) and Pulmonary Embolism Quality of Life questionnaire. RESULTS: We included 251 patients from 26 centers in eight countries, of which 129 (51%) had been assigned to edoxaban and 122 (49%) to warfarin. Patient- and thrombus-specific characteristics were similar in both groups. Mean time since randomization in the Hokusai-VTE trial was 7.0 years (standard deviation, 1.0). No relevant or statistical differences were observed in the QoL for patients treated with edoxaban compared to patients treated with warfarin. The mean difference between patients treated with edoxaban and patients with PE treated with warfarin was 0.8 (95% confidence interval [CI]. -1.6 to 3.2) for the SF-36 summary mental score and 1.6 (95% CI, -0.9 to 4.1) for summary physical score. CONCLUSION: Our findings indicate that patients with an index PE treated with edoxaban or warfarin have a similar long-term QoL. Since our study was a follow-up study from a well-controlled clinical trial setting, future studies should be designed in a daily clinical practice setting. We suggest a longitudinal design for investigation of changes in QoL over time.

Safety of direct oral anticoagulant exposure during pregnancy: a retrospective cohort study.

BACKGROUND: Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in many indications for anticoagulation. Prescribed to millions of patients, including women of reproductive age, exposure to DOACs in early pregnancy is not uncommon, but data on the embryotoxic risks are scarce. We aimed to assess the risk of DOAC embryotoxicity in a large sample of reported cases. METHODS: In this retrospective cohort study, we collected individual case reports of DOAC exposure in pregnancy from gynaecologists, haematologists, and vascular specialists starting from May, 2015. We obtained exports in April and October, 2017, August, 2018, and December, 2019, from the pharmacovigilance databases of the DOAC manufacturers, the European Medicines Agency (EMA), the German drug authority, and searched the homepage of the US Food and Drug Administration (FDA) for pregnancy exposure reports. Data from the International Society of Thrombosis and Haemostasis (ISTH) registry were obtained in August, 2018, and on July 21, 2020; data from the Teratology Information Service in Ulm, Germany, were received July 22, 2020. We also ran a systematic literature search on July 22, 2020, for cases of DOAC exposure. These data were compiled with those from our 2016 risk assessment and duplicate reports were excluded. Fetal or neonatal abnormalities were classified as a major birth defect according to the European Concerted Action on Congenital Anomalies and Twins (EUROCAT) classification and adjudicated into four categories: relation to DOAC exposure likely, possible, unlikely, or unrelated. FINDINGS: We identified 1193 reports of DOAC exposure during pregnancy: 49 from physicians, 48 from the ISTH registry, 29 from the Teratology Information Service, 62 from the German drug authority, 536 from Bayer (extracted from the Bayer pharmacovigilance system, the WHO VigiBase, and from the FDA Adverse Event Reporting System), 87 from Boehringer Ingelheim, 16 from Daiichi Sankyo, 98 from the literature search, two from the FDA homepage search, ten from the Risk Evaluation and Mitigation Strategy Review, and 256 from the EMA reports. After excluding potential duplicates, we identified 614 unique cases of DOAC exposure in pregnancy occurring between Feb 1, 2007, and July 9, 2020, that consisted of rivaroxaban in 505 (82%) pregnancies, dabigatran in 36 (6%), apixaban in 50 (8%), and edoxaban in 23 (4%). The median duration of DOAC exposure was 5·3 weeks (IQR 4·0-7·0) into pregnancy. Information on pregnancy outcome was available in 336 (55%) of 614 pregnancies: 188 (56%) livebirths, 74 (22%) miscarriages, and 74 (22%) elective pregnancy terminations. 21 (6%; 95% CI 4-9) of 336 showed fetal abnormalities, of which 12 (4%; 2-6) were adjudicated as major birth defects potentially related to DOAC exposure. INTERPRETATION: Although reports of pregnancy outcomes after DOAC exposure are missing important details and predominantly describe rivaroxaban exposures, the available data do not suggest that DOAC exposure in pregnancy carries a high risk of embryopathy. The 2016 ISTH guidance against elective pregnancy termination for fear of DOAC embryotoxicity and the recommendation in favour of close pregnancy surveillance is still valid. Pregnancy outcome data are inconsistently captured in pharmacovigilance databases, indicating a strong need for a more robust system of reporting. FUNDING: None.

Current practice patterns of outpatient management of acute pulmonary embolism: A post-hoc analysis of the YEARS study.

BACKGROUND: Studies have shown the safety of home treatment of patients with pulmonary embolism (PE) at low risk of adverse events. Management studies focusing on home treatment have suggested that 30% to 55% of acute PE patients could be treated at home, based on the HESTIA criteria, but data from day-to-day clinical practice are largely unavailable. AIM: To determine current practice patterns of home treatment of acute PE in the Netherlands. METHOD: We performed a post-hoc analysis of the YEARS study. The main outcomes were the proportion of patients who were discharged <24 h and reasons for admission if treated in hospital. Further, we compared the 3-month incidence of PE-related unscheduled readmissions between patients treated at home and in hospital. RESULTS: Of the 404 outpatients with PE included in this post-hoc analysis of the YEARS study, 184 (46%) were treated at home. The median duration of admission of the hospitalized patients was 3.0 days. The rate of PE-related readmissions of patients treated at home was 9.7% versus 8.6% for hospitalized patients (crude hazard ratio 1.1 (95% CI 0.57-2.1)). The 3-month incidence of any adverse event was 3.8% in those treated at home (2 recurrent VTE, 3 major bleedings and two deaths) compared to 10% in the hospitalized patients (3 recurrent VTE, 6 major bleedings and fourteen deaths). CONCLUSIONS: In the YEARS study, 46% of patients with PE were treated at home with low incidence of adverse events. PE-related readmission rates were not different between patients treated at home or in hospital.

Thrombosis and hemostasis health in pregnancy: Registries from the International Society on Thrombosis and Haemostasis.

Online patient registries are used to collect data on clinical conditions with rare occurrence or unclear diagnostic and management practices. The success of these registries depends on clear definition of goals, correct identification of patient population/inclusion criteria, availability of appropriate setup and maintenance tools, and the quality of dissemination. The Scientific and Standardization Committee (SSC) for Women's Health Issues in Thrombosis and Hemostasis, one of 20 committees of the International Society on Thrombosis and Haemostasis (ISTH) has developed 6 registries for women's bleeding and thrombotic conditions over the past 2 years and are currently in various stages of progress. Here, we provide information about these registries, including rationale, objectives, and methods for data collection. The aim is to enhance worldwide participation and thus promote the success of these registries. We used ISTH REDCap, a mature and secure Web application for building and managing online surveys and databases, and the ISTH advertising platform to maximize participation. Registries (links and project details available on ISTH and Women's SSC Web sites) include: (1) WiTEAM, project on thrombophilia and placenta-mediated obstetric complications; (2) a registry for disseminated intravascular coagulation in pregnancy; (3) severe congenital protein C deficiency-an obstetric study; (4) obstetric and gynecologic outcomes of women with platelet function disorders; (5) thrombolysis and invasive treatments for massive pregnancy-related pulmonary embolism; (6) pregnancy and exposure to direct oral anticoagulants. The ISTH promotes online registries on women's issues to enhance understanding of current practices, identify knowledge gaps, promote research, and ultimately improve patient safety and quality of life.

Sex matters: Practice 5P's when treating young women with venous thromboembolism.

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-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Everything the clinician needs to know about evidence-based anticoagulation in pregnancy.

Pregnancy is a hemostatic challenge: women are prone to thromboembolism during their pregnancy and at the same time, especially during delivery, there is substantial risk of bleeding. Pregnant women are often excluded from randomized controlled trials, and high quality evidence regarding optimal anticoagulant management is thus lacking. Anticoagulants are being used in pregnancy for prevention and treatment of various pregnancy complications such as thrombotic events, preeclampsia and pregnancy loss. When anticoagulant therapy is necessary, special attention should be given to both woman and unborn child. In this review, we aim to 1) provide an overview of safe anticoagulant use in pregnancy, 2) discuss treatment goals in pregnancy, and 3) summarize the evidence available to guide decision making for frequently encountered clinical dilemmas in this field.