Anticoagulation In Women Research Articles

CT venography for the diagnosis of postpartum venous thromboembolism: a prospective multi-center cohort study.

To assess the role of CT venography (CTV) in the diagnosis of venous thromboembolism (VTE) during the postpartum period. This multicenter prospective cohort study was conducted between April 2016 and April 2020 in 14 university hospitals. All women referred for CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE) within the first 6 weeks postpartum were eligible. All CTPAs were performed on multidetector CT machines with the usual parameters and followed by CTV of the abdomen, pelvis, and proximal lower limbs. On-site reports were compared to expert consensus reading, and the added value of CTV was assessed for both. The final study population consisted of 123 women. On-site CTPA reports mentioned PE in seven women (7/123, 5.7%), all confirmed following expert consensus reading, three involving proximal pulmonary arteries and four limited to distal arteries. Positive CTV was reported on-site in nine women, five of whom had negative and two indeterminate CTPAs, bringing the VTE detection rate to 11.4% (14/123) (95%CI: 6.4-18.4, p = 0.03). Expert consensus reading confirmed all positive on-site CTV results, but detected a periuterine vein thrombosis in an additional woman who had a negative CTPA, increasing the VTE detection rate to 12.2% (15/123) (95%CI: 7.0-19.3, p = 0.008). Follow-up at 3 months revealed no adverse events in this woman, who was left untreated. Median Dose-Length-Product was 117 mGy.cm for CTPA and 675 mGy.cm for CTPA + CTV. Performing CTV in women suspected of postpartum PE doubles the detection of venous thromboembolism, at the cost of increased radiation exposure. CTV can help in the decision-making process concerning curative anticoagulation in women with suspected postpartum PE, particularly those whose CTPA results are indeterminate or whose PE is limited to the subsegmental level. Postpartum women are at risk of pulmonary embolism, and CT pulmonary angiography can give equivocal results. CT venography (CTV) positivity increased the venous thromboembolism detection rate from 5.7 to 11.4%. CTV may help clinical decision-making, especially in women with indeterminate CTPA results or subsegmental emboli.

Double bad luck: pulmonary embolism and vaginal bleeding - a case report

BackgroundPulmonary embolism is a common and potentially fatal condition. Exogenous estrogens in contraceptives are associated with an increased risk of venous thrombo-embolism. However, discontinuation of a combined oral contraceptive can lead to severe withdrawal bleeding in an anticoagulated patient.Case presentationWe report a case of a 47-year-old female who presented to the emergency room with a two-day history of worsening shortness of breath and chest pain. Her chronic medication included a combined oral contraceptive pill. Transthoracic echocardiogram showed pulmonary hypertension and right ventricular dilatation. Computerized tomography scan revealed bilateral pulmonary embolism. She received thrombolysis with alteplase and was started on rivaroxaban. Five days after discharge, however, she was readmitted with severe vaginal bleeding.Discussion and conclusionWe describe a case of submassive pulmonary embolism, treated with thrombolysis and anticoagulation, who developed severe vaginal bleeding after stopping the contraceptive pill. This case highlights the importance of detailed menstrual history taking when initiating anticoagulation in women. Discontinuation of oral contraceptives, while important in reducing the risk of recurrent thrombosis, could be postponed until the end of the recommended course of anticoagulation and until a safe alternative form of contraception has been established, if required.

Trends of use and factors that determine the choice of oral anticoagulants in women and men with atrial fibrillation.

The aim was to identify sex-specific factors linked with oral anticoagulant initiation in a cohort of patients with atrial fibrillation using administrative data from Quebec (Canada) between 2014 and 2017. Cohort entry defined as new users, that is, no claims in last 12 months, a cohort of 32 050 patients was stratified in two groups, that is, women and men. Multivariable regression models were used to identify factors of initiations for low- and standard-dose direct oral anticoagulants (DOACs) versus warfarin, and low- versus standard-dose DOACs. In both sexes, warfarin initiation decreased and DOAC initiation increased, with year of initiation as major factors of DOACs use. In 2017, the increase was of 2- to 4-fold and 3- to 8-fold for low- and standard-dose DOACs (vs. warfarin), respectively. The proportion of patients starting on a low-dose DOAC was higher in women than men. Older age for both sexes and CHADS2 score ≥2 (only women) were major factors of low-dose dabigatran and rivaroxaban versus warfarin use. The only significant factor of standard-dose DOAC versus warfarin use was age of 65-79 for women or men treated with apixaban by 1.8- and 1.4-fold, respectively. Factors that made women and men less likely to receive a standard-dose DOAC versus warfarin were higher CHADS2 (for dabigatran and rivaroxaban), HAS-BLED and frailty scores, prior coronary disease, major bleeding, and chronic kidney disease (CKD) status. The choice of a low- versus standard-dose DOAC was mainly driven by age and CKD, and higher CHADS2 score (for dabigatran and apixaban) for both sexes.

Recurrence after stopping anticoagulants in women with combined oral contraceptive-associated venous thromboembolism: A systematic review and meta-analysis.

The risk of recurrence after discontinuation of anticoagulation for a combined oral contraceptive (COC)-associated venous thromboembolism (VTE) is unclear. Therefore, we conducted a systematic review and meta-analysis to estimate the incidence of recurrent VTE among women with COC-associated VTE, unprovoked VTE and to compare the incidence of recurrent VTE between the two groups. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase Classic +Embase and Medline ALL to July 2020 and citations from included studies were searched. Randomized controlled trials, prospective cohort studies and meta-analyses of these study types were selected. The analysis was conducted by random-effects model. Nineteen studies were identified including 1537 women [5828 person-years (PY)] with COC-associated VTE and 1974 women (7798 PY) with unprovoked VTE. Studies were at low risk of bias. The incidence rate of VTE recurrence was 1.22/100 PY [95% confidence interval (CI) 0.92-1.62, I2 =6%] in women with COC-associated VTE, 3.89/100 PY (95% CI 2.93-5.17, I2 =74%) in women with unprovoked VTE and the unadjusted incidence rate ratio was 0.34 (95% CI 0.26-0.46, I2 =3%). The recurrence risk in women after COC-associated VTE is low and lower than after an unprovoked VTE.

Risk of Recurrence after Stopping Anticoagulants in Women with Combined Oral Contraceptive-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

BackgroundAlthough combined oral contraceptives (COC) are considered a transient risk factor for venous thromboembolism (VTE), the risk of recurrence after discontinuation of anticoagulation is unclear. Few studies have focused on the risk of recurrence in this group; studies report variable results and are limited by small sample size. The risk of recurrence appears to be low, but this could relate to the young age of affected women. Deciphering the absolute VTE recurrence risk after a COC-associated VTE is crucial in helping clinicians and patients decide if anticoagulation could be discontinued after the initial treatment period.ObjectivesThe objectives of this systematic review and meta-analysis are to estimate the incidence of recurrent VTE among women with COC-associated VTE, compared with women with unprovoked VTE.MethodsWe searched the following databases: Cochrane Central Register of Controlled Trial, Cochrane Database of Systematic Reviews, Embase Classic +Embase, and Medline ALL, all from the OvidSP platform, from the database's inception to July 2020. Additional studies were identified by screening citations from included studies.Prospective cohort studies, randomized controlled trials (RCTs), and meta-analyses of prospective cohort studies or RCTs were reviewed by two authors for study inclusion (Figure 1). Studies were included if women had objectively confirmed COC-associated VTE, received a minimum of three months of anticoagulation, discontinued COC prior to or at time of discontinuation of anticoagulation, time of follow-up began after anticoagulation was stopped, and recurrent VTE data was available. Studies were excluded if patients were systematically treated with an alternative pharmacologic agent intended to reduce the risk of recurrent VTE such as aspirin. Authors of identified papers were contacted for additional data on critical variables. If there were multiple publications from a cohort, the study with the longest follow up was included.Two authors extracted study data and assessed included studies for risk of bias using the Newcastle Ottawa Scale. Meta-analysis was done using a random effects Poisson regression model. Heterogeneity was assessed using the I-squared measure.ResultsOur systematic review included 19 studies with a total of 1,537 women (5,828 patient years of follow up) with an index COC-associated VTE, and 1,974 women (7,798 patient years of follow up) with an index unprovoked VTE. Authors contributed additional unpublished data in 16 of the 19 studies. Overall, studies were at low risk of bias, with a mean of 7 stars (out of a possible 9) in the Newcastle Ottawa Scale.Among the 19 studies, the incidence rate of VTE recurrence in women with COC-associated VTE was 1.22 per patient year (95% confidence interval (CI) 0.94 to 1.59, I 2 = 6.4%, 95% prediction interval (PI) 0.81 to 1.85) (Figure 2). The incidence rate of VTE recurrence in women with an index unprovoked VTE not associated with COC was 3.89 per patient year (95% CI 2.98 to 5.07, I 2 =74.2%, 95% PI 1.37 to 11.03).The unadjusted incidence rate ratio of recurrent VTE comparing women with COC-associated events to women with unprovoked events was 0.34 (95% CI 0.26 to 0.45, I 2 = 2.6%, 95% PI 0.26 to 0.46). Only three studies had age-adjusted comparisons, but each with a different effect measure so they could not be combined, with a relative risk ratio 0.4 (95% CI 0.2 to 0.8) (also adjusted for site of VTE and congenital thrombophilia) (Eischer 2014), a hazard ratio of 0.11 (95% CI 0.01 to 0.85) (Kearon 2019), and an incidence rate ratio of 1 (95% CI 0.3 to 3.2) (Le Moigne 2013).ConclusionsThe estimated risk of VTE recurrence after a COC-associated VTE is low, and is lower compared to women with unprovoked VTE, however this comparison may be confounded by age. With only a minority of studies providing age adjusted analyses, the true difference remains unknown. Our meta-analysis is strengthened by the substantial contribution of unpublished data from individual study authors. This can help to guide clinicians and patient shared decision-making on the duration of anticoagulation. [Display omitted] DisclosuresLe Gal: LEO Pharma: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; Aspen: Honoraria; Sanofi: Honoraria. Schulman: Boehringer-Ingelheim: Research Funding; Octapharma: Research Funding. Skeith: CSL Behring: Research Funding; Leo Pharma: Honoraria; Sanofi: Honoraria.

Stroke risk factors and outcomes among hospitalized women with atrial fibrillation.

Observational cohort analyses suggest that women with atrial fibrillation (AF) endure a greater burden of stroke. We conducted an analysis of an observational cohort study completed at our tertiary care medical center to assess sex-related differences in cardiovascular risk factors, prescription of antithrombotic therapy, and 90-day outcomes. We analyzed 5000 hospitalized patients with AF: 1888 women and 3112 men. Clinical characteristics of AF, risk of stroke and bleeding, prescription of antithrombotic therapy, and 90-day clinical outcomes, including stroke and all-cause mortality, were compared. We observed a 50% higher relative frequency of stroke in hospitalized women with AF compared with men. While the frequencies of prescription of antithrombotic therapy at discharge were similar, anticoagulation was omitted in 40% of women with AF. The 90-day frequencies of major adverse events and mortality were increased in hospitalized women with AF not prescribed antithrombotic therapy at discharge. Prescription of anticoagulation in women with AF at hospital discharge was associated with a 60% and 40% relative reduction in the odds of mortality and major adverse events at 90days. In conclusion, women hospitalized with AF have a higher risk of stroke at 90days compared with men. Anticoagulation at hospital discharge was omitted in 40% of women with AF, but when prescribed, was associated with a reduction in mortality and major adverse events at 90days, respectively. We analyzed 5000 hospitalized patients with atrial fibrillation (AF) (1888 women and 3112 men) in an observational cohort study completed at our tertiary care medical center to assess sex-related differences in cardiovascular risk factors, prescription of antithrombotic therapy, and 90-day outcomes. We observed a 50% higher relative frequency of stroke in hospitalized women with AF compared with men. The 90-day frequencies of major adverse events and mortality were increased in hospitalized women with AF not prescribed antithrombotic therapy at discharge. Prescription of anticoagulation in women with AF at hospital discharge was associated with a 60% and 40% relative reduction in the odds of mortality and major adverse events at 90days.

Prophylactic anticoagulation for preterm premature rupture of membranes: a decision analysis

The current standard of care in the setting of preterm premature rupture of membranes involves antenatal hospitalization until delivery. The reduced physical activity during this time compounds the heightened risk for venous thromboembolism in pregnancy. Prophylactic anticoagulation can decrease this risk of venous thromboembolism; however, this benefit must be balanced against the risks of precluding neuraxial analgesia or increasing the risk of postpartum hemorrhage. The objective of this study was to determine the optimal modality for venous thromboembolism prophylaxis during hospitalization for preterm premature rupture of membranes using a decision analysis model. A decision-analytical Markov model was constructed using the TreeAge software comparing the use of unfractionated heparin, low-molecular-weight heparin or no anticoagulation in women with a singleton pregnancy who were hospitalized for preterm premature rupture of membranes after 24 weeks and remained hospitalized until delivery. Maternal outcomes examined included attainment of neuraxial analgesia (vs no analgesia for vaginal delivery or general anesthesia for cesarean delivery), venous thromboembolism, postpartum hemorrhage, and maternal death. Probabilities and utilities were derived from existing literature. Sensitivity analyses were performed to interrogate model assumptions, and a Monte Carlo probabilistic sensitivity analysis was performed to examine the robustness of the model. In this decision-analytical model, no prophylactic anticoagulation maximized maternal utilities. Clinical outcomes among a theoretical cohort of 100,000 women are shown in the Table. The 1- and 2-way sensitivity analyses supported this conclusion. Monte Carlo probabilistic sensitivity analysis indicated that no prophylaxis was the preferred choice in 56% of simulations, unfractionated heparin in 34% of simulations, and low-molecular-weight heparin in 10% of simulations. Our results do not support the routine use of prophylactic anticoagulation in women admitted to the hospital for preterm premature rupture of membranes. These findings can be used to inform clinical decisions when admitting low-risk singleton pregnancies to the hospital in the setting of preterm premature rupture of membranes.

Prophylactic Anticoagulation While Hospitalized for Premature Prelabor Rupture of Membranes: A Decision Analysis [31L

INTRODUCTION: Premature prelabor rupture of membranes (PPROM) necessitates hospital admission thus limiting activity and theoretically increasing the risk for venous thromboembolism (VTE). While prophylactic anticoagulation decreases the risk of VTE, it may increase the risk for postpartum hemorrhage (PPH) and affect the ability to obtain neuraxial analgesia. This study analyzed the use of prophylactic anticoagulation during hospitalization for PPROM with a decision analysis model. METHODS: The designed decision-analytic model compared the use of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or no anticoagulation in women with a singleton pregnancy admitted to the hospital for PPROM after 24 weeks who remained hospitalized until delivery. Assumptions included: induction of labor at 34 weeks or earlier spontaneous labor; therapeutic use of LMWH in the setting of new onset VTE; and universal desire for neuraxial analgesia. The outcomes of VTE, PPH, spontaneous labor, route of delivery, and type of anesthesia attained were assessed. One and two way sensitivity analyses were performed to interrogate model assumptions and a Monte Carlo probabilistic sensitivity analysis was performed using uniform distributions. RESULTS: No prophylactic anticoagulation is the chosen strategy based on the highest expected value and sensitivity analyses. No prophylaxis was the preferred choice 78% of the time, UFH 20% of the time, and LMWH 2% of the time. CONCLUSION: Our results do not support the routine use of prophylactic anticoagulation in women admitted to the hospital for PPROM. These findings can be used to inform clinical decisions when admitting low risk singleton pregnancies with PPROM.

Postpartum anticoagulation in women with mechanical heart valves.

BackgroundWomen with mechanical heart valves (MHV) requiring anticoagulation (AC) are at high risk for hemorrhagic complications. Despite guidelines to manage antenatal and peripartum AC, there are few evidence-based recommendations to guide the initiation of postpartum AC. We reviewed our institutional experience of pregnant women with MHV to lay the groundwork for recommendations of immediate postpartum AC therapy.Study designThis descriptive retrospective cohort used ICD-9 and -10 codes to identify pregnant women with MHV on AC at the Yale-New Haven Hospital from 2007 to 2018. All identified patients were confirmed by chart review. Delivery hospitalization and the immediate postpartum AC management were reviewed. Maternal complications recorded were postpartum hemorrhage, transfusion, wound hematoma, intra-abdominal bleeding, stroke, valve thrombosis, and death. Further, immediate neonatal outcomes were detailed.ResultsForty-two pregnant women with nonnative heart valves were identified during the study period. From those pregnant women, nine had an MHV and were anticoagulated throughout gestation. Of 19 total pregnancies, 14 met the inclusion criteria. The median gestational age of the delivered pregnancies was early term (37w2d). Nine deliveries were via cesarean (64%). The median time to restart AC after birth was 6 hours. After six deliveries (43%), AC was initiated ≤6 hours postpartum. Hemorrhagic complications occurred in six cases (43%), including wound and intra-abdominal hematomas. Four cases (29%) required blood transfusion. No maternal strokes, thrombotic events, or deaths were recorded. Five (38.5%) neonates required admission to the neonatal intensive care unit.ConclusionMHV in pregnancy was rare but was associated with significant maternal morbidity, particularly postpartum hemorrhagic complications. We noted significant variability in the timing of restarting postpartum AC and in the selected agents. Pooled institutional data and an interdisciplinary approach are recommended to minimize competing risks and sequelae of valve thrombosis and obstetrical hemorrhage and, thereby, to optimize maternal outcomes and develop evidence-based guidelines for postpartum AC management.

P254“HERDOO2” clinical decision rule to guide duration of anticoagulation in women with unprovoked venous thromboembolism: D-Dimer inter-assay concordance

P254“HERDOO2” clinical decision rule to guide duration of anticoagulation in women with unprovoked venous thromboembolism: D-Dimer inter-assay concordance

“HERDOO2” clinical decision rule to guide duration of anticoagulation in women with unprovoked venous thromboembolism. Can I use any d-Dimer?

BackgroundThe “HERDOO2 rule” is a prospectively validated clinical decision rule used to identify low-risk women who can safely discontinue anticoagulants after completing 5–12 months of anticoagulant treatment for unprovoked venous thromboembolism. The VIDAS®d-Dimer (DD) assay, a component of the rule, was used in the derivation and validation of the rule at half the usual diagnostic cut-point for exclusion of venous thrombosis. It is unknown if other commercial DD assays used at a corresponding cut-point will categorize patients at high concordance with the VIDAS® DD. ObjectiveTo determine if other available automated quantitative DD assays have high enough concordance with the VIDAS® DD assay to allow their use within the “HERDOO2” clinical decision rule. MethodsFrozen plasma samples from a sub-set (n = 248) of female participants in the “HERDOO2” validation study were tested using five DD assays: VIDAS®, Innovance®, HemosIL®, Tina-quant® and Liatest®, with duplicate testing for 50 samples. First, using the mean DD for 50 samples with duplicate results, we determined the optimal cut-point values for each test that corresponded with a VIDAS® DD result of 250 μg/L using linear regression analysis. Next, kappa analysis was conducted on the DD results of the remaining 198 samples to determine concordance between each tested DD at the respective optimal cut-point and the VIDAS® DD at 250 μg/L. In a separate analysis we determined the concordance at half the usual venous thrombosis exclusion cut-point. ResultsRegression analysis of the DD results in 50 samples identified the optimal cut-point for each DD assay to match a VIDAS® DD cut-point of 250 μg/L: Innovance® 177 μg/L, Liatest® 233 μg/L, Tina-quant® 48 μg/L and HemosIL® 56 μg/L. Next, in 198 different samples, the concordance of VIDAS® DD (≥250 μg/L or <250 μg/L) was explored at the optimal cut-point of the other DD assays. The concordance was poor for all DD assays: Innovance® (kappa 0.38 (95% CI, 0.26–0.51)), Liatest® (kappa 0.38 (95% CI, 0.25–0.50)), HemosIL® (kappa 0.36 (95% CI, 0.23–0.49)) and Tina-quant® (kappa 0.30 (95% CI, 0.16–0.43)). Similar poor concordance was identified using half of the diagnostic DD cut-point for each tested assay: Innovance® (kappa 0.44 (95% CI, 0.32–0.56)), Liatest® (kappa 0.38 (95% CI, 0.25–0.51)), HemosIL® (kappa 0.04 (95% CI, −0.01—0.08)) and Tina-quant® (kappa 0.04 (95% CI, −0.004–0.07)). ConclusionThe “HERDOO2 rule” is the only prospectively validated clinical decision rule that can be used to identify low-risk women with unprovoked venous thrombosis who can safely discontinue anticoagulants. An important implementation issue is whether any commercial DD assay can be used in the HERDOO2 rule, and at what cut-point. Our analysis shows that the HemosIL®, Innovance®, Liatest® and Tina-quant® DD assays should not be used in the “HERDOO2” rule due to poor concordance with the VIDAS® DD assay and unacceptable misclassification of women at high and low risk of recurrent venous thrombosis.

Uterine bleeding during anticoagulation in women with venous thromboembolism

Women presenting with uterine bleeding during the course of anticoagulant therapy for venous thromboembolism (VTE) present a difficult therapeutic dilemma due to the absence of evidence-based recommendations. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics of women presenting with uterine bleeding during anticoagulation for VTE, its frequency, time course, management and 30-day outcomes. As of October 2016, 31,951 women with VTE were recruited in RIETE. During the course of anticoagulant therapy, 53 (0.17%) developed major uterine bleeding, 118 (0.37%) non-major uterine bleeding and 948 (2.97%) had major bleeding in other sites. Median time elapsed from VTE to bleeding was: 32, 71 and 22 days, respectively. Mean age was: 56±17, 52±20 and 75±14 years, respectively. Women with major uterine bleeding more likely had cancer (51%), anemia (72%), raised platelet count (19%) or recent major bleeding (11%) at VTE presentation than those in the other subgroups. During the first 30 days after bleeding, 17%, 1.7% and 31% of women died, respectively. Of 11 women with uterine bleeding who died, 9 (82%) had cancer, two (18%) died of bleeding and one (9.1%) died of pulmonary embolism after discontinuing anticoagulation. Uterine bleeding during the course of anticoagulation for VTE is not uncommon and mostly affects young women. Those with cancer, anaemia, raised platelet count or recent bleeding at baseline are at an increased risk for uterine bleeding during anticoagulation.

Valvular heart disease and pregnancy part II: management of prosthetic valves

### Learning objectives Prosthetic heart valves (PHV) have been used to treat patients with both congenital and acquired valve lesions since the first surgical replacement in 1960.1 The two principal...

Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia.

Since hypercoagulability might result in recurrent miscarriage, anticoagulant agents could potentially increase the chance of live birth in subsequent pregnancies in women with unexplained recurrent miscarriage, with or without inherited thrombophilia. To evaluate the efficacy and safety of anticoagulant agents, such as aspirin and heparin, in women with a history of at least two unexplained miscarriages with or without inherited thrombophilia. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 October 2013) and scanned bibliographies of all located articles for any unidentified articles. Randomised and quasi-randomised controlled trials that assessed the effect of anticoagulant treatment on live birth in women with a history of at least two unexplained miscarriages with or without inherited thrombophilia were eligible. Interventions included aspirin, unfractionated heparin (UFH), and low molecular weight heparin (LMWH) for the prevention of miscarriage. One treatment could be compared with another or with no-treatment (or placebo). Two review authors (PJ and SK) assessed the studies for inclusion in the review and extracted the data. If necessary they contacted study authors for more information. We double checked the data. Nine studies, including data of 1228 women, were included in the review evaluating the effect of either LMWH (enoxaparin or nadroparin in varying doses) or aspirin or a combination of both, on the chance of live birth in women with recurrent miscarriage, with or without inherited thrombophilia. Studies were heterogeneous with regard to study design and treatment regimen and three studies were considered to be at high risk of bias. Two of these three studies at high risk of bias showed a benefit of one treatment over the other, but in sensitivity analyses (in which studies at high risk of bias were excluded) anticoagulants did not have a beneficial effect on live birth, regardless of which anticoagulant was evaluated (risk ratio (RR) for live birth in women who received aspirin compared to placebo 0.94, (95% confidence interval (CI) 0.80 to 1.11, n = 256), in women who received LMWH compared to aspirin RR 1.08 (95% CI 0.93 to 1.26, n = 239), and in women who received LMWH and aspirin compared to no-treatment RR 1.01 (95% CI 0.87 to 1.16) n = 322).Obstetric complications such as preterm delivery, pre-eclampsia, intrauterine growth restriction and congenital malformations were not significantly affected by any treatment regimen. In included studies, aspirin did not increase the risk of bleeding, but treatment with LWMH and aspirin increased the risk of bleeding significantly in one study. Local skin reactions (pain, itching, swelling) to injection of LMWH were reported in almost 40% of patients in the same study. There is a limited number of studies on the efficacy and safety of aspirin and heparin in women with a history of at least two unexplained miscarriages with or without inherited thrombophilia. Of the nine reviewed studies quality varied, different treatments were studied and of the studies at low risk of bias only one was placebo-controlled. No beneficial effect of anticoagulants in studies at low risk of bias was found. Therefore, this review does not support the use of anticoagulants in women with unexplained recurrent miscarriage. The effect of anticoagulants in women with unexplained recurrent miscarriage and inherited thrombophilia needs to be assessed in further randomised controlled trials; at present there is no evidence of a beneficial effect.

Thromboembolism in pregnancy: Challenges and controversies in the prevention of pregnancy-associated venous thromboembolism and management of anticoagulation in women with mechanical prosthetic heart valves

Thromboembolism in pregnancy is an important clinical issue. Despite identification of maternal and pregnancy-specific risk factors for development of pregnancy-associated venous thromboembolism, limited data are available to inform on optimal approaches for prevention. The relatively low overall prevalence of pregnancy-associated venous thromboembolism has prompted debate about the validity of recommendations, which are mainly based on expert opinion, and have resulted in an increased use of pharmacological thromboprophylaxis in pregnancy and postpartum. A pragmatic approach is required in the absence of more robust data. Anticoagulation management of pregnant women with mechanical prosthetic heart valves is particularly challenging. Continuation of therapeutic anticoagulation during pregnancy is essential to prevent valve thrombosis. Warfarin, the most effective anticoagulant, is associated with adverse fetal outcomes, including embryopathy and stillbirth. Fetal outcome is improved with therapeutic-dose low-molecular-weight heparin, but there may be more thromboembolic complications. More intensive anticoagulation, targeting higher trough anti-Xa levels, may reduce the risk of valve thrombosis.

Inherited and Acquired Thrombophilias

Thrombophilias represent an evolving story that continues to stir controversy for care providers and obstetrical patients. The predominant thrombophilic mutations include the factor V Leiden mutation, prothrombin gene mutation G20210A, methylene tetrahydrafolate reductase C667T, and deficiencies of the natural anticoagulants proteins C and S, and antithrombin. Prospective cohort studies have provided an accurate assessment of the risk of placenta-mediated complications posed by common inherited thrombophilic conditions. Acquired thrombophilic conditions consist of the antiphospholipid antibody syndrome (APAS) and hyperhomocysteinemia. Well-conducted, placebo-controlled, randomized trials have demonstrated no benefit of anticoagulation in women with recurrent pregnancy loss and inherited thrombophilia. The routine use of anticoagulation to prevent other placenta-mediated complications in the setting of inherited thrombophilia should be considered experimental until the results of adequate clinical trials are available. Heparin anticoagulation and antiplatelet therapies are the cornerstone of treatment of APAS in pregnancy.

Thrombophilia and Recurrent Pregnancy Loss : Is Heparin Still the Drug of Choice ? = أهبة التخثر و فقدان الحمل المتكرر : هل الهيبارين لايزال العلاج المفضل ؟

The association between thrombophilia and recurrent pregnancy loss (RPL) has become an undisputed fact. Thorombophilia creates a hypercoaguable state which leads to arterial and/or venous thrombosis at the site of implantation or in the placental blood vessels. Anticoagulants are an effective treatment against RPL in women with acquired thrombophilia due to antiphospholipid syndrome. The results of the use of anticoagulants for treating RPL in women with inherited thrombophilia (IT) are encouraging, but recently four major multicentre studies have shown that fetal outcomes (determined by live birth rates) may not be as favourable as previously suggested. Although the reported side-effects for anticoagulants are rare and usually reversible, the current recommendation is not to use anticoagulants in women with RPL and IT, or for those with unexplained losses. This review examines the strength of the association between thrombophilia and RPL and whether the use of anticoagulants can improve fetal outcomes.

The Risk Of Recurrence In Women With Venous Thromboembolism While Using Estrogens: A Prospective Observational Cohort Study

▪ ObjectiveBecause of the high recurrence risk, guidelines recommend indefinite anticoagulation in women with a first unprovoked proximal deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). The optimal duration of anticoagulation in women who had venous thromboembolism (VTE) while using estrogens is unknown. We therefore compared the risk of recurrent VTE between women who used estrogens at the time of first VTE and women who did not. MethodsThis analysis was performed within the frame of the Austrian Study on Recurrent Venous Thromboembolism (AUREC), an on-going prospective observational study. Patients with a first objectively confirmed DVT of the leg and/or PE who had received anticoagulants for 3 to 18 months were included. Exclusion criteria were: age < 18 years; VTE associated with surgery, trauma, cancer or pregnancy; long-term anticoagulation; natural inhibitor deficiency; lupus anticoagulant; homozygosity or double heterozygosity for factor V Leiden and/or the prothrombin mutation. Women were advised to refrain from further estrogen use and were excluded in case of non-adherence. The study end point was recurrent symptomatic DVT and/or PE verified by imaging. The local ethics committee approved the study and all patients gave written informed consent. ResultsWe followed 630 women (mean age 46 +/- 17 years) who had been treated with oral anticoagulants for 7 (+/- 3) months for an average of 69 (+/- 52) months. Recurrent VTE was recorded in 71 patients (11%). Recurrent VTE occurred in 22 (7%) of 333 estrogen users and in 49 (17%) of 297 non-users. After 1, 2 and 5 years, the cumulative probability of recurrence was 1% (95% CI 0-2), 1% (95% CI 0-2) and 6% (95% CI 3-9) among estrogen users and 5% (95% CI 2-7), 9% (95% CI 6-13) and 17% (95% CI 12-22) among non-users, respectively (p < 0.001, Figure). Compared to non-users, estrogen users had a relative risk (RR) of recurrent VTE of 0.4 (95% CI 0.2-0.8) after adjustment for age, site of first VTE and factor V Leiden carrier status. Compared to non-users in the respective age groups, the RR of recurrent VTE was 0.4 (95% CI 0.2-0.8) among estrogen containing contraceptive users and was 0.7 (95% CI 0.3-1.5) among women using estrogen containing hormone replacement therapy. [Display omitted] ConclusionWomen who had their first VTE while using estrogens have a low risk of recurrent VTE. The recurrence risk is particularly low in estrogen containing contraceptive users. We therefore propose that these women should receive anticoagulant therapy for no longer than 3 months. Disclosures:No relevant conflicts of interest to declare.

PF.59 What is the Optimal Dose of Low Molecular Weight Heparin in Pregnant Women with Raised BMI?

IntroductionObesity is a risk factor for thromboembolism in pregnancy. Recent RCOG guidelines suggested a non-evidence based weight-dependent protocol in which monitoring of anti-Xa levels was not required. This contrasted with...

Can Factor V Leiden and Prothrombin G20210A Testing in Women With Recurrent Pregnancy Loss Result in Improved Pregnancy Outcomes? Results From a Targeted Evidence-Based Review

Women with recurrent pregnancy loss are offered Factor V Leiden (F5) and/or prothrombin G20210A (F2) testing to identify candidates for anticoagulation to improve outcomes. A systematic literature review was performed to estimate test performance, effect sizes, and treatment effectiveness. Electronic searches were performed through April 2011, with review of references from included articles. English-language studies addressed analytic validity, clinical validity, and/or clinical utility and satisfied predefined inclusion criteria. Adequate evidence showed high analytic sensitivity and specificity for F5 and F2 testing. Evidence for clinical validity was adequate. The summary odds ratio for association of recurrent pregnancy loss with F5 in case-controlled studies was 2.02 (95% confidence interval, 1.60-2.55), with moderate heterogeneity and suggestion of publication bias. Longitudinal studies in women with recurrent pregnancy loss or unselected cohorts showed F5 carriers were more likely to have a subsequent loss than noncarriers (odds ratios: 1.93 and 2.03, respectively). Results for F2 testing were similar. For clinical utility, evidence was adequate that anticoagulation treatments were ineffective (except in antiphospholipid antibody syndrome) and had treatment-associated harms. The certainty of evidence is moderate (high, moderate, and low) that anticoagulation of women with recurrent pregnancy loss and F5/F2 variants would currently lead to net harms.