Prevention, diagnosis, and management of PE and DVT in pregnant women

Abstract

Venous thromboembolism (VTE) is a leading cause of maternal morbidity and mortality worldwide. Despite the impact of VTE on pregnant and postpartum people and on society, guidelines addressing prevention, diagnosis, and management of VTE in pregnant and postpartum people frequently are based on recommendations from expert opinion and are extrapolated from data in nonpregnant populations. Pregnant individuals are frequently excluded from clinical trials, which is a barrier to providing safe, effective care. Anchoring to a case discussion, this review provides an update on recently published and ongoing randomized clinical trials (RCTs), prospective clinical management studies, and other research in this area. It highlights, in particular, the results of the Highlow RCT, which addresses optimal prevention of recurrence during pregnancy in people with prior VTE. Finally, we raise awareness of the impact of national and international clinical trial networks on the conduct of RCTs in pregnancy. We conclude, based on these data, that academic VTE clinical trials in pregnant women can and must be done.

Graphical abstract

Figure 1.

OPTICA study (NCT 04179487) overview, outlining inclusion and exclusion criteria, CTPA protocol parameters, and settings. Inset: The scan range for the OPTICA study extends from below the humeral heads to approximately 2  cm below the lowest dome of diaphragm. C/I, contraindication; CrCl, creatinine clearance (calculated by Cockroft-Gault equation); CT, computed tomography; PE, pulmonary embolism; UFH, unfractionated heparin; US, ultrasound; VKA, vitamin K antagonist.

Figure 2.

The “YEARS” items, which were included in the Artemis study diagnostic algorithm (Netherlands Trial Register number, NL5726). In this study, pulmonary embolism was excluded in people with no YEARS items and a D-dimer level <1000  ng/mL, or ≥1 YEARS item and D-dimer <500  ng/mL. CUS was performed if there were clinical signs of DVT.

Figure 3.

European Society of Cardiology (ESC) algorithm for diagnostic workup and management of suspected pulmonary embolism during pregnancy and up to 6 weeks postpartum. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). https://doi.org/10.1093/eurheartj/ehz405. (a) If chest X-ray is abnormal, consider also alternative cause of chest symptoms. (b) DVT in pelvic veins may not be ruled out by CUS. If the entire leg is swollen, or there is buttock pain or other symptoms suggestive of pelvic thrombosis, consider magnetic resonance venography to rule out DVT. (c) CTPA technique must ensure very low fetal radiation exposure (see Table 1). (d) Perform full blood count (to measure hemoglobin and platelet count) and calculate creatinine clearance before administration. Assess bleeding risk and ensure absence of contraindications. (e) See Konstantinides and Meyer. High, intermediate, and low PE pretest probability as defined in Konstantinides and Meyer. CTPA, computed tomography pulmonary angiography; CUS, compression ultrasonography; PE, pulmonary embolism. Reproduced with permission from Konstantinides and Meyer.

Figure 4.

Proposed definition of bleeding events in studies evaluating antithrombotic therapy in pregnant (individuals) from ISTH Scientific and Standardization Subcommittee on Control of Anticoagulation (reproduced from with permission from Elsevier. License no. 5518820689792; License date 30/03/2023. Colors correspond to the criteria selected for each class of bleeding: red for major bleeding, orange for clinically relevant nonmajor bleeding, and green for minor bleeding, respectively. (A) Proposed classification for antepartum and secondary postpartum (24  h to 6 weeks after delivery) periods. (B) Proposed classification for primary postpartum (first 24  h of delivery) period.

Figure 4.

Proposed definition of bleeding events in studies evaluating antithrombotic therapy in pregnant (individuals) from ISTH Scientific and Standardization Subcommittee on Control of Anticoagulation (reproduced from with permission from Elsevier. License no. 5518820689792; License date 30/03/2023. Colors correspond to the criteria selected for each class of bleeding: red for major bleeding, orange for clinically relevant nonmajor bleeding, and green for minor bleeding, respectively. (A) Proposed classification for antepartum and secondary postpartum (24  h to 6 weeks after delivery) periods. (B) Proposed classification for primary postpartum (first 24  h of delivery) period.

Figure 5.

How we approach VTE prevention in pregnant people with a prior VTE history. “Unprovoked VTE; VTE provoked by hormonal or minor risk factors” is an abbreviated reference to those patients who should receive both antepartum and postpartum LMWH. This group is described in the inclusion criteria for the Highlow study as “Patients with previous objectively confirmed VTE, either unprovoked, in the presence of use of oral contraceptives or estrogen/progestagen use, or related to pregnancy or the postpartum period, or minor risk factors (e.g., long distance travel, minor trauma).”