Introduction

Pregnancy is a known hypercoagulable state because of hormonal and cardiovascular changes; as such, pregnant women have a higher risk of venous thromboembolism (VTE). The incidence of VTE during pregnancy and the postpartum period is estimated to range from 6 to 20 per 10,000 pregnancies. Although overall uncommon, VTE can result in substantial maternal morbidity and mortality. From 2011 to 2015, pulmonary embolism (PE) was the fourth leading cause of maternal mortality accounting for 9.2% of all deaths, many of which are largely preventable with pharmacologic and mechanical prophylaxes. ^,

Previous studies have demonstrated that the risk of VTE is increased (21.5-fold to 84-fold) in women in the postpartum period compared with the nonpregnant, nonpostpartum population up to 6 weeks after delivery, the period conventionally used to assess this heightened risk. This risk is further augmented by patient factors, such as maternal age, obesity, thrombophilia, and tobacco use, and obstetrical risk factors, such as mode of delivery, pregnancy-related hypertension, intrapartum hemorrhage, and peripartum infection. Across surgical specialties, duration of surgery is associated with the risk of VTE.

Peripartum hysterectomy is typically performed for morbidly adherent placenta disorders, hemorrhage, coagulopathy, or uterine rupture and is associated with increased morbidity, including higher blood loss, transfusion, and increased postoperative complications. It occurs in roughly 10 in 10,000 deliveries overall and 70 to 83 per 10,000 cesarean deliveries. ^, Currently, there is little understanding as to how a patient’s risk of VTE may be altered after a delivery-related hysterectomy. Similarly, there is no consensus clinical guideline for VTE prophylaxis for these patients in the postpartum period. This study aimed to determine the incidence of and risk factors for VTE in patients who underwent a peripartum hysterectomy compared with patients whose deliveries were not complicated by hysterectomy. In addition, we sought to compare the risk of VTE after hysterectomy with the other known risk factors for VTE, which providers may be more familiar with estimating. We hypothesized that patients who underwent a hysterectomy would be at higher risk of VTE in the postpartum period than those whose delivery was not complicated by this procedure.

Material and Methods

We performed a cross-sectional analysis using data from the Nationwide Readmissions Database (NRD) from 2015 to 2017. The NRD is a publicly available data set obtained with permission from the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project. As of 2017, there were 28 states represented in the NRD, representing the geographic area for 60.0% of the total US resident population and 58.2% of all US hospitalizations. It includes public hospitals, community hospitals, and academic medical centers and employs a weighted design to allow for national population estimates. Survey weighting was used in the methods below to obtain population estimates.

All patients with a delivery identified between October 1, 2015, and December 31, 2017, were included in this analysis. Delivery hospitalizations were identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) and Procedure Coding System (ICD-10-PCS) codes and a previously validated approach to capture more than 95% of delivery hospitalizations. ^, Data before October 2015 were excluded to avoid potential issues with ascertainment due to the coding transition from ICD-9 to ICD-10.

The primary outcome was VTE during delivery hospitalization or during rehospitalization within 6 weeks (42 days) after discharge from delivery. VTE was defined by diagnosis codes for PE or deep VTE. The primary exposure of interest was peripartum hysterectomy.

Analysis of demographic and medical risk factors was conducted to describe differences in baseline characteristics between patients with and without a VTE after peripartum hysterectomy. These characteristics included maternal age, insurance payer at time of delivery, obesity, pregnancy-related hypertension (ie, gestational hypertension, preeclampsia, superimposed preeclampsia, or eclampsia), a primary hypercoagulable state, current tobacco use, mode of delivery, diabetes mellitus (including both pregestational and gestational), multifetal gestation, peripartum infection (including chorioamnionitis, endometritis, and puerperal sepsis), and peripartum hemorrhage (intrapartum or postpartum). Primary hypercoagulable states were defined as either primary thrombophilias (eg, prothrombin gene mutation, protein C deficiency) or acquired thrombophilias (eg, antiphospholipid antibody syndrome and lupus anticoagulant). Chi-square and Fisher’s exact tests were used to compare the groups as appropriate.

Logistic regressions were performed to compare the risk of VTE after hysterectomy with other demographic, obstetrical, and medical risk factors. The following covariates were included as they are known to be associated with peripartum VTE: advanced maternal age (>35 years), ^, insurance payer at time of delivery, obesity, ^, pregnancy-related hypertension, ^{, ,} a primary hypercoagulable state, ^, current tobacco use, ^{, , ,} diabetes mellitus, ^, peripartum infection, ^{, ,} multifetal gestation, ^{, ,} and peripartum hemorrhage. ^,

For comparison by mode of delivery, we performed the same regressions in which mode of delivery and hysterectomy were combined into a single categorical variable with the following groups: vaginal delivery without hysterectomy, cesarean delivery without hysterectomy, and hysterectomy after vaginal or cesarean delivery. Population-weighted survey data were used to estimate the unadjusted and adjusted incidences of VTE by mode of delivery (ie, vaginal vs cesarean delivery) and for women who underwent a hysterectomy.

If a diagnosis of VTE was associated with a readmission, the time from discharge from delivery to readmission was determined. Although it is not possible to identify the indication for hysterectomy for individual patients within this data set, possible indications for peripartum hysterectomy were identified among those who underwent a hysterectomy and compared between those who did and did not have VTE. These diagnoses include hemorrhage, ^, placenta accreta spectrum, ^, amniotic fluid embolism, ^, disseminated intravascular coagulation, ^, uterine rupture, and gynecologic malignancy.

All data elements were ascertained from ICD-10 codes. The list of ICD-10 codes used and their definitions can be found in the Supplemental Appendix . Analyses were performed with Stata/MP (version 16.1; StataCorp LLC, College Station, TX). P values of <.05 were considered significant. Tables with cell sizes n≤10 were suppressed per data reporting guidelines for the NRD. This study was exempted from review by the Mass General Brigham Institutional Review Board as the data are deidentified and publicly available. This study was funded by an institutional grant from the Center of Expertise in Health Policy and Management of the Mass General Brigham Office of Graduate Medical Education, who did not have oversight of the analysis or publication of the results.

Results

Of the 4,419,037 patients with deliveries, 5098 (11.5 per 10,000 deliveries) underwent a hysterectomy. Moreover, 110 patients (215.8 per 10,000 deliveries) who underwent a hysterectomy were diagnosed with VTE, and 3855 patients (8.7 per 10,000 deliveries) who did not undergo hysterectomy were diagnosed with VTE. Of the 110 patients with VTE and peripartum hysterectomy, 87 (79%) had a cesarean delivery, and the remaining 23 (21%) had a vaginal delivery. Notably, 89 of 110 VTE diagnoses (81%) occurred during the delivery admission. Of the remaining 21 cases, 50% occurred within the first 10 days after discharge from delivery, and 75% occurred within 25 days after discharge ( Figure 1 ).

Timing of VTE among patients who underwent a peripartum hysterectomy

Of 110 cases of VTE with hysterectomy, 89 (81%) occurred during delivery admission and 21 (19%) on readmission. The Kaplan-Meier curve shows the time to readmission with VTE for those patients diagnosed within 6 weeks after delivery.

VTE , venous thromboembolism.

Mauney et al. Peripartum hysterectomy and venous thromboembolism. Am J Obstet Gynecol 2022.

The characteristics among women who underwent a peripartum hysterectomy with and without VTE are compared in Table 1 . There was a higher incidence of peripartum infection in patients with VTE after hysterectomy than in those who did not have VTE (15.5% vs 3.5%; P <.001). No other significant difference was noted between those who did and did not have VTE.

For comparison with the risk of VTE after hysterectomy, the unadjusted absolute risk of VTE for all covariates included in the adjusted analyses are shown in Table 2 . Figure 2 shows the unadjusted and adjusted incidences of VTE by mode of delivery, including peripartum hysterectomy, using the survey-weighted data. The respective unadjusted and adjusted incidences of VTE were as follows: 6.9 (95% confidence interval [CI], 6.5–7.3) and 7.4 (95% CI, 6.9–7.8) per 10,000 deliveries after vaginal delivery without peripartum hysterectomy; 12.5 (95% CI, 11.8–13.1) and 11.3 (95% CI, 10.7–11.9) per 10,000 deliveries after cesarean delivery without hysterectomy; and 217.2 (95% CI, 169.1–265.2) and 96.9 (95% CI, 73.2–120.6) per 10,000 deliveries after hysterectomy, regardless of mode of delivery.

Table 2

Comparison of unadjusted absolute risk of VTE by patient and delivery characteristics

Characteristic	VTE events (n/N)	Unadjusted absolute risk per 10,000 deliveries
Peripartum hysterectomy
No hysterectomy	3855/4,413,939	8.7
Hysterectomy	110/5098	215.8
Maternal age (y)
<35	3009/3,630,809	8.3
≥35	956/785,219	12.2
Gestation
Single	3802/4,339,434	8.9
Multiple	163/79,603	20.5
Payer for delivery
Private	1804/2,321,365	7.8
Medicaid	1859/1,870,616	9.9
Other or uninsured	301/224,407	13.4
Obesity
Not obese	3199/3,958,261	8.1
Obese	766/460,779	17.0
Pregnancy-related hypertension
Not present	3189/3,962,988	8.0
Present	776/456,049	17.0
Primary hypercoagulable state
Not present	3699/4,398,932	8.4
Present	266/20,105	132.3
Tobacco use
Not a current user	3611/4,183,404	8.6
Current user	354/235,633	15.0
Diabetes mellitus
Not present	3524/4,043,461	8.7
Present	441/375,576	11.7
Peripartum infection
Not present	3614/4,283,512	8.4
Present	351/135,525	25.9
Peripartum hemorrhage
Not reported	3556/4,266,380	8.3
Reported	409/152,657	26.8

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