17-alpha hydroxyprogesterone caproate and risk for venous thromboembolism during pregnancy.

INTRODUCTION: 17-alpha hydroxyprogesterone caproate (17 P) is a progestin commonly used during pregnancy to reduce risk of recurrent preterm birth. History of thromboembolism is a contraindication to 17 P and the package insert for 17 P recommends discontinuation in the setting of an acute VTE event. The objective of this study was to determine whether 17 P is associated with increased risk of VTE. STUDY DESIGN: The MarketScan claims database was used to perform a retrospective cohort of women who underwent delivery from 4/2008 to 1/2015. We identified women who received 17 P during pregnancy based on pharmacy benefits. Risk for VTE including deep vein thrombosis, pulmonary embolism, or both was stratified based on the presence or absence of 17 P pharmacy receipt. Both antenatal and delivery hospitalization VTE events were asceratined and these periods were analyzed individually. Relative risk (RR) was determined based on 17 P receipt. RESULTS: Among 4,775,667 delivery hospitalizations, 18,745 women received 17 P. Among women who did not receive 17 P, 0.52% of women (n = 24,529) had a VTE diagnosis compared to 0.61% (n = 114) receiving 17 P (RR 1.18, 95% CI 0.98-1.42). Comparing VTE events (i) during the antenatal period and (ii) during delivery hospitalizations, risks did not differ significantly for patients receiving 17 P. When risk was restricted to the cohort of patients without a diagnosis of a prior VTE event, 0.30% of women (n = 56) receiving 17 P were diagnosed with an event versus 0.28% of women (n = 13,427) not receiving 17 P (RR 1.07, 95% 0.82-1.39). DISCUSSION: No significant increased risk for VTE was noted with 17 P receipt. While new research has led to reconsideration of clinical use of 17 P for preterm birth prevention based on efficacy, findings from this analysis do not support major risk for thrombosis.

Receipt of anticoagulation after venous thromboembolism diagnoses during delivery hospitalizations.

INTRODUCTION: Obstetric venous thromboembolism (VTE) is a leading cause of maternal mortality. While hospital discharge data provide a readily accessible means of studying this relatively rare outcome, diagnosis codes are of limited validity. Prior studies have demonstrated that VTE billing codes may be subject to misclassification and false positives and overestimate obstetric VTE risk. Given the public health significance of accurately estimating obstetric VTE, the purpose of this study was to determine to what degree patients received anticoagulants after discharge from a delivery hospitalization associated with an acute VTE diagnosis as pharmacy claims may more accurately assess the incidence of obstetric VTE. STUDY DESIGN: A retrospective cohort study using the MarketScan database was performed using 2008-2014 claims data. We identified women 15-54 years of age diagnosed with acute VTE during a delivery hospitalization. We determined the proportion of women with VTE that received anticoagulants within 60 days of delivery discharge. Only women with ≥60 days of pharmacy benefits after discharge were included. Receipt of low molecular weight and unfractionated heparin, warfarin, and Xa inhibitors was ascertained. Receipt of anticoagulants was analyzed individually based on diagnoses for deep vein thrombosis (DVT), pulmonary embolism (PE), or both. The Chi-square test was performed for categorical comparisons. RESULTS: Of 2,664,951 delivery hospitalizations, 2112 women had a diagnosis of VTE (0.08%) including 236 women with PE alone, 1760 women with DVT alone, and 116 women with both DVT and PE. Of these women, 51.3% (95% CI 49.2-53.4%) received an anticoagulant including 49.5% of women with DVT (95% CI 47.2-51.8%), 50.0% of women with PE (95% CI 43.7-56.3%), and 81.9% of women with both DVT and PE (95% CI 73.9-87.9%). CONCLUSION: This analysis of pharmacy claims found that estimates for the proportion of deliveries with acute VTE diagnoses that subsequently received anticoagulants was similar to chart-confirmed VTE, albeit in a large population. In addition to previous studies comparing database claims to chart review that showed that the prevalence of VTE was grossly overestimated, these findings support that the proportion of cases with VTE during delivery hospitalization may be approximately half that ascertained with billing codes.

Leveraging resources for obstetric venous thromboembolism prevention in a state safety collaborative.

In recent years, state obstetric quality and maternal safety initiatives have led efforts to reduce maternal risk and improve maternal safety. A priority of many of these collaboratives has been to disseminate and implement safety bundles focusing on leading causes of maternal mortality including venous thromboembolism. In 2013, the Safe Motherhood Initiative (SMI), a quality improvement effort led by ACOG District II in New York State, began developing a VTE bundle reviewed available clinical evidence, practice guidelines, and protocols and assessed how hospitals with varying resources could implement standardized approaches to obstetric thromboembolism prophylaxis. This bundle was subsequently released for implementation in New York State's hospitals with support from SMI. The purpose of this review is to characterize, from the perspective of a state safety leadership collaborative, the resources that were most critical in assisting individual hospitals in (i) determining which VTE prophylaxis strategies would be adopted, and (ii) operationalizing implementation.

Optimizing obstetric venous thromboembolism protocol adherence: The experience of a hospital system.

The purpose of this review is to explore the role of hospital systems in reliably providing high quality obstetric venous thromboembolism (VTE) prophylaxis focusing on the example of the Kaiser Permanente Southern California hospital system. While providers ultimately administer thromboprophylaxis on a patient-by-patient basis, hospital-level protocols, practices, and resources may be the most important determinants of whether a patient receives appropriate care. In comparison to the complex maternal and fetal emergencies that obstetricians are routinely called on to manage, VTE prophylaxis can often be simplified and integrated into the workflow, making decision-making time efficient and straightforward for the provider. Not having protocols (i.e. the provider being on their own) is associated with desired management occurring in only 40% of cases. Enhanced VTE protocols with complementary strategies to encourage use and identification of oversights addressed in real time can result in appropriate care in >90% of cases.

Outcomes research on obstetric venous thromboembolism.

Outcomes research on obstetric venous thromboembolism (VTE) involves a number of major challenges. While obstetric VTE, including deep vein thrombosis and pulmonary embolism, is relatively common on a population basis, diagnoses during pregnancy are relatively rare in comparison to high-risk scenarios such as orthopedic surgery. This review characterizes outcomes research on obstetric VTE with a focus on strengths, limitations, and appropriate inferences from existing research. It is divided into four sections. First, evidence regarding validity of diagnosis codes for VTE in administrative data is reviewed. Second, limitations of both clinical research and administrative-data study models are analyzed. Third, examples of high-quality obstetric VTE research from the literature and opportunities for improved research in the future are reviewed. Fourth, future directions for research are explored.

Introduction: Obstetric venous thromboembolism.

How to best reduce maternal risk from obstetric venous thromboembolism (VTE) is a relatively controversial topic. In comparison, for other leading causes of maternal mortality and severe morbidity such as obstetric hemorrhage and hypertension, there is general agreement on recommendations. While obstetric VTE poses a unique epidemiological and public health challenge, a number of recommendations related to care improvement and patient safety can be made. This edition of Seminars in Perinatology focuses on (i) overview of clinical research and epidemiology that can serve as a basis for informed decision making regarding VTE prophylaxis strategies, (ii) VTE prophylaxis implementation from a leadership perspective, (iii) future directions for research on obstetric VTE, and (iv) critical care management of obstetric VTE.

Utilization of venous thromboembolism prophylaxis in American hospitalized pregnant women undergoing cesarean section.

Background Pregnancy-related venous thromboembolism (VTE) is a leading preventable cause of maternal mortality in the United States; however, American guidelines for pharmacologic VTE prophylaxis remain less aggressive than other developed countries. The Safe Motherhood Initiative (SMI) combines aspects of American and international guidelines to increase utilization of prophylaxis and thereby decrease incidence of pregnancy-related VTE. Objectives To evaluate the prescribing and administration rates of pharmacologic VTE prophylaxis for women undergoing cesarean section (c-section) when retrospectively applying the SMI recommendations. Setting Large academic medical center in Sacramento, California, USA. Method This was a single-center retrospective cohort study of pregnant women undergoing c-section who would have met criteria for pharmacologic prophylaxis according to the SMI. Main outcome measures Prescribing and administration rates of mechanical and pharmacologic VTE prophylaxis. Secondary outcomes included incidence of thromboembolism within 6 weeks after c-section and thromboembolic associated mortality. Results A total of 616 charts were analyzed. When applying the SMI guidelines for VTE prophylaxis, the prescribing rates for mechanical and pharmacologic prophylaxis were 94.3% and 4.71% of patients, respectively, and 94.9% of ordered pharmacologic prophylaxis doses were administered. The incidence of 6-week post-partum VTE was 0.49%. There were no cases of VTE-associated mortality. Conclusion This study demonstrated that a large population of c-section patients fit the SMI criteria for pharmacologic VTE prophylaxis but did not receive it. We observed a 0.49% rate of VTE, which was slightly higher than the nationally reported average rate of 0.3%. With growing rates of pregnancy-associated VTE in the United States, perhaps a more aggressive guideline is warranted.

Postpartum venous thromboembolism readmissions in the United States.

BACKGROUND: There are limited data on when postpartum readmissions for thromboembolism occur after delivery hospitalizations on a population basis in the United States. OBJECTIVE: We sought to characterize risk factors for and timing of postpartum venous thromboembolism readmission after delivery hospitalization discharge. STUDY DESIGN: The Healthcare Cost and Utilization Project Nationwide Readmissions Database for calendar years 2013 and 2014 was used to perform a retrospective cohort study evaluating risk for readmission for venous thromboembolism within 60 days of discharge from a delivery hospitalization. Risks for deep vein thrombosis and pulmonary embolism were individually assessed. Obstetric, medical, demographic, and hospital factors associated with postpartum readmission for venous thromboembolism were analyzed. Risk was characterized as odds ratios with 95% confidence intervals. Both unadjusted and adjusted analyses were performed. Adjusted analyses included relevant obstetric, medical, demographic, and hospital factors within logistic regression models. RESULTS: From Jan. 1 through Oct. 31 in 2013 and 2014, 6,269,641 delivery hospitalizations were included in the analysis. In all, 2975 cases of readmission for any venous thromboembolism were identified (4.7 per 10,000 delivery hospitalizations) including 1170 cases of deep vein thrombosis and 1805 cases of pulmonary embolism. In all, 69.6% of readmissions for any venous thromboembolism occurred within the first 20 days of discharge vs 22.3% and 8.0% at 21-40 and 41-60 days after discharge. Median times to readmission were 12.7, 14.0, and 11.7 days for venous thromboembolism, deep vein thrombosis, and pulmonary embolism, respectively. Women readmitted for any venous thromboembolism were more likely to have a history of venous thromboembolism (4.2% vs 0.3%, P < .01), to have had a cesarean delivery (54.4% vs 32.4%, P < .01), to have a thrombophilia (1.8% vs 0.4%, P < .01), to have had a longer delivery hospitalization of >3 days for vaginal delivery and >4 days for cesarean (18.0% vs 6.6%, P < .01), to have been diagnosed with gestational hypertension or preeclampsia (19.7% vs 8.2%, P < .01), and to have had postpartum hemorrhage with transfusion (2.6% vs 0.5%, P < .01). These factors retained significance in adjusted models. History of venous thromboembolism and hemorrhage with transfusion were associated with the largest odds of readmission (odds ratio, 9.5; 95% confidence interval, 6.6-13.6, and odds ratio, 3.6; 95% confidence interval, 2.4-5.5, respectively). Other factors associated with increased odds included thrombophilia (odds ratio, 2.0; 95% confidence interval, 1.2-3.5), cesarean delivery (odds ratio, 2.0; 95% confidence interval, 1.8-2.3), longer delivery hospitalization (odds ratio, 1.8; 95% confidence interval, 1.5-2.2), and preeclampsia or gestational hypertension (odds ratio, 2.0; 95% confidence interval, 1.6-2.4). CONCLUSION: While the majority of events occurred within 20 days of discharge, risk factors other than thrombophilia and prior venous thromboembolism were generally associated with modestly increased odds of events, and only a small proportion of readmissions occurred among women with thrombophilia and prior events. Our data demonstrate both the challenging nature and urgent need for further research to determine which clinical practices and interventions may reduce risk for venous thromboembolism readmissions on a population basis.

A comparison of recommendations for pharmacologic thromboembolism prophylaxis after caesarean delivery from three major guidelines.

OBJECTIVE: Guidelines for pharmacologic obstetric venous thromboembolism (VTE) prophylaxis from the American Congress of Obstetricians (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG), and the American College of Chest Physicians (Chest) vary significantly. The objective of this study was to determine the practical implications of these recommendations in terms of prophylaxis rates for a tertiary obstetric population. STUDY DESIGN: Cross-sectional. SETTING: Tertiary referral hospital. POPULATION: Patients post-operative day 1 after caesarean delivery. METHODS: This cross-sectional study evaluated rates of pharmacologic prophylaxis for women based on RCOG, ACOG, and Chest recommendations. Medical, obstetric, and demographic risk factors for thromboembolism were reviewed for individual patients. Rates of prophylaxis based on each of the guidelines with 95% confidence intervals were calculated. OUTCOME MEASURE: Recommended pharmacologic prophylaxis. RESULTS: About 293 patients were included in the analysis. Under RCOG guidelines, 85.0% of patients would receive post-caesarean pharmacologic prophylaxis [95% confidence interval (CI) 80.5-88.6%] compared with 1.0% of patients under ACOG guidelines (95% CI 0.3-3.0%) and 34.8% of patients under Chest guidelines (95% CI 29.6-40.4%). Caesarean during labour, obesity, advanced maternal age, pre-eclampsia, and multiple gestation were among the most commonrisk factors. CONCLUSION: Recommended prophylaxis differed significantly. Under ACOG recommendations a small minority of patients would receive prophylaxis, whereas under RCOG recommendations a large majority of patients would receive low-molecular-weight heparin. Given the large differences in prophylaxis rates for post-caesarean thromboprophylaxis based on different guidelines, further research is urgently needed to compare the risks and benefits of recommendations. TWEETABLE ABSTRACT: Recommendations from major society guidelines for post-caesarean thromboprophylaxis differ greatly.

Compliance with mechanical venous thromboproembolism prophylaxis after cesarean delivery.

OBJECTIVE: Universal perioperative mechanical thromboprophylaxis is recommended for patients undergoing cesarean delivery because of increased risk for venous thromboembolism (VTE) associated with this mode of delivery. While research supports clinical benefits from this approach, other specialties have demonstrated suboptimal compliance with prophylaxis device use. The objective of this study was to review patient compliance with sequential compression devices (SCDs). METHODS: This cross-sectional observational study utilized data from a prospective quality assurance analysis to evaluate demographic, medical and obstetrical factors associated with postoperative SCD compliance after cesarean delivery. Observations were performed before 7 a.m. on the first postoperative day, a time point when patients were unlikely to be fully ambulatory and would most benefit from device use. The reason for failure was documented in cases where the device was not being properly used. RESULTS: Two hundred and ninety-three patients underwent cesarean delivery, had SCD compliance assessed and were included in the analysis. Twenty one percent of patients (n=60) were non-compliant with SCD use. Reasons for noncompliance included patient discomfort, machine malfunction and incorrect device use. Patients who were non-compliant had similar risk factors for thromboembolism compared to women who were compliant. CONCLUSION: Although SCD's are effective in preventing thromboembolism, device use was suboptimal in this cohort of post-cesarean patients. These findings are similar to those from other fields. For institutions that rely primarily on mechanical thromboprophylaxis for obstetric patients, quality assurance and auditing of use may be necessary to ensure patients are receiving adequate prophylaxis. For post-cesarean patients with additional VTE risk factors, pharmacologic prophylaxis may be beneficial.

Thromboembolism incidence and prophylaxis during vaginal delivery hospitalizations.

OBJECTIVE: Although major international guidelines recommend venous thromboembolism (VTE) prophylaxis during vaginal delivery hospitalization for women with additional risk factors, US guidelines recommend prophylaxis for a very small number of women who are at particularly high risk for an event. The purpose of this study was to characterize practice patterns of VTE prophylaxis in the United States during vaginal delivery hospitalizations and to determine VTE incidence in this population. STUDY DESIGN: A population-level database was used to analyze VTE incidence and use of VTE prophylaxis during vaginal delivery hospitalizations in the United States between 2006 and 2012 (n = 2,673,986). We evaluated whether patients received either pharmacologic or mechanical prophylaxis. Hospital-level factors and patient characteristics were included in multivariable regression analysis that evaluated prophylaxis administration. RESULTS: We identified 2,673,986 women who underwent vaginal delivery. Incidence of VTE increased during the study period from 15.6-29.8 events per 100,000 delivery hospitalizations. Within the cohort, 2.6% of patients (n = 68,835) received VTE prophylaxis. Pharmacologic prophylaxis was rare; <1% of women received unfractionated or low-molecular-weight heparin. Although patients with thrombophilia or a previous VTE event were likely to receive prophylaxis (60.8% and 72.8%, respectively), patients with risk factors for VTE such as obesity, smoking, and heart disease were unlikely to receive prophylaxis (rates of 5.9%, 3.3%, and 6.2%, respectively). CONCLUSION: Our findings demonstrate that the administration of VTE prophylaxis outside a small group of women at extremely high risk for VTE is rare during vaginal delivery hospitalization. Given that VTE incidence is rising in this population, further research to determine whether broadening prophylaxis for VTE may reduce severe maternal morbidity and death is indicated.