Postpartum Thromboprophylaxis

Sargam Kapoor, MBBS: Sargam Kapoor, MBBSThomas L. Ortel, MD, PhD: Thomas L. Ortel, MD, PhDPregnancy and the puerperium mark phases of significantly heightened prothrombotic risk. The pathophysiologic basis of this enhanced pregnancy-related thrombotic risk lies in the increased levels of procoagulant proteins (coagulation factors II, VII, VIII, X and fibrinogen), acquired resistance to activated protein C, and the decreased level of the natural anticoagulant free protein S. Pregnancy-associated deep vein thrombosis is associated with substantial morbidity, and pulmonary embolism is established as a leading cause of maternal mortality in the developed world.1 The odds of developing pregnancy-associated venous thromboembolism (VTE) are highest in the first 6 weeks after childbirth.2 This risk is even greater after cesarean delivery as opposed to vaginal delivery.1 History of personal VTE or the presence of an inherited thrombophilia are highly provocative risk factors, making decisions regarding peripartum thromboprophylaxis more straightforward when present. However, in their absence, the benefits and risks of pharmacologic thromboprophylaxis in the postpartum period are less well understood. In light of the dearth of robust data on the role of pharmacologic thromboprophylaxis in pregnancy, decisions surrounding whether or not to use low-molecular-weight or unfractionated heparins are guided by consensus guidelines published by the American College of Chest Physicians, the American College of Obstetricians and Gynecologists, the Royal College of Obstetricians and Gynaecologists (RCOG), and the American Society of Hematology.3–6 These recommendations stem from low-quality evidence that is based on data extrapolated from other settings, such as nonobstetric surgery. Moreover, the recommendations from each of these societies are markedly different, with the proportion of patients qualifying for pharmacologic prophylaxis after cesarean delivery ranging from 0.2% per the American Society of Hematology’s 2018 guideline to 73.4% per the RCOG criteria.7 Whereas the American Society of Hematology’s and American College of Obstetricians and Gynecologists’ guidelines suggest that heparin-based postpartum thromboprophylaxis be reserved predominantly for women with prior VTE or family history of VTE or thrombophilia, the American College of Chest Physicians and RCOG criteria are more expansive, with a broader focus on women with other comorbid and pregnancy- or delivery-related risk factors, such as multiple gestation, preeclampsia, postpartum hemorrhage, age older than 35 years, and obesity. Current practices, therefore, vary widely based on the guideline adopted by a specific institution, leading to a lack of a universal, evidence-based postpartum thromboprophylaxis strategy. In this month's issue of Obstetrics & Gynecology, Bruno et al (see page 265) report a multicenter retrospective study that evaluated VTE incidence within 12 weeks of delivery across four health systems in the United States between 2016 and 2019.8 Secondary outcomes included hospital readmission, bleeding, and wound complications after cesarean delivery, with and without heparin-based prophylaxis. The authors excluded individuals at highest risk of postpartum VTE, namely those with a personal history of VTE or thrombophilia and those on therapeutic anticoagulation for other indications. The postpartum pharmacologic thromboprophylaxis utilization rate during delivery hospitalization in this cohort of patients with 64,886 deliveries was 13.8% (95% CI, 13.5–14.1%), with a VTE incidence of 0.11% (95% CI, 0.09–0.14%). Of individuals who received pharmacologic prophylaxis, 62.7% delivered by cesarean, reflecting practice patterns favoring heparin prophylaxis in this scenario. It was also noted that pharmacologic prophylaxis utilization was higher in older individuals, those with obesity, and those with other comorbidities. To eliminate the risk of confounding, a logistic propensity score regression model was used, and the average treatment effect among treated patients was determined to assess the association of prophylaxis with outcomes. The authors report that there was no association between prophylaxis and the incidence of VTE. Interestingly, of the 72 VTE occurrences in this cohort, 0.31% occurred in individuals receiving prophylaxis and 0.08% in those without prophylaxis. Although these counterintuitive findings could be a result of confounding, they beg the question whether our current thromboprophylaxis practice patterns, including anticoagulant choice, dosing, or duration, are suboptimal for individuals at increased VTE risk. Additionally, 43.1% and 56.9% of the VTE events in this study were in the postcesarean delivery and vaginal delivery groups, respectively, indicating a noteworthy incidence of VTE after vaginal delivery. As for the secondary outcomes, the causal effect of prophylaxis on hospital readmission and wound complications was noted to be −1.36% (95% CI, −2.51 to −0.14%) and −1.45% (95% CI, −2.35 to −0.65%), respectively, indicating potential harm. A key strength of this study is rooted in the inclusion of four different hospital systems across the United States, with prophylaxis utilization rates varying from 1.6% to 34%, thereby increasing the generalizability of the results. The lack of benefit in VTE rate with postpartum pharmacologic prophylaxis noted in this study is consistent with the findings of a systematic review and meta-analysis by Oakes et al.9 The remarkable VTE incidence rate noted after vaginal delivery in this cohort has been reported previously as well10 and emphasizes the urgent need for development of risk-assessment tools for postpartum VTE for all modes of delivery. Alternatively, these data raise curiosity regarding whether thromboprophylaxis should in fact be offered to all individuals postpartum, regardless of their VTE risk, and whether any plausible benefit would outweigh the accompanying risks. However, recent observational data published by Champion et al11 show that adopting a more clinically selective thromboprophylaxis approach was associated with a decrease in wound hematomas without an increase in VTE rates. Future directions should include large, multicenter, prospective studies that are adequately powered to assess the efficacy and safety of postpartum pharmacologic prophylaxis. This is particularly challenging given the low absolute rate of postpartum VTE, despite the markedly increased relative risk of VTE. With the paucity of good-quality data, this study by Bruno et al highlights the lack of an effect of heparin-based prophylaxis on VTE risk reduction in individuals perceived to be at higher risk for postpartum VTE, which can vary widely based on institutional protocols. It also brings attention to the elephant in the room that more prophylaxis may not equate to less VTE, but, in fact, may be associated with greater wound-related and bleeding complications.