Venous thromboembolism prophylaxis in pregnant women with inflammatory bowel disease: evidence gaps and future directions from the KASID Guidelines Task Force Team

1. Baseline Risk of VTE in Patients with IBD

Patients with IBD have a higher risk of VTE than non-IBD patients. The risk of VTE in patients with IBD is most pronounced during hospitalization and episodes of active disease, and is further modulated by well-established risk factors including surgery, pregnancy, obesity, and advanced age [12-15]. Population-based cohort studies and meta-analyses consistently demonstrate a 2- to 3-fold increased risk of VTE in patients with IBD compared with the general population [6,14,16]. This elevated risk has been observed across different healthcare settings, including ambulatory, hospitalized, and postdischarge phases, although the absolute risk varies substantially by clinical context [13,15].

The prothrombotic tendency in IBD is multifactorial and closely related to chronic systemic inflammation. Intestinal inflammation promotes a hypercoagulable state through endothelial dysfunction, platelet activation, upregulation of procoagulant factors, and impaired fibrinolysis [17-19]. Disease activity plays a key role in thrombosis of IBD; patients experiencing persistent active disease or disease flares carry a substantially higher risk of VTE than those in remission [20]. In previous studies, the risk of VTE was reported to be the highest during periods of active disease, hospitalization, surgery, and use of corticosteroids [13,21]. Notably, hospitalization further amplifies the risk of VTE, with up to a 6-fold increase in patients hospitalized for active IBD compared with that in non-hospitalized patients, reflecting the combined effects of inflammation, immobility, and acute illness [13,20]. Although the risk of IBD-associated VTE was evaluated mostly in Western populations [6,16,22], emerging evidence from Asia indicates a similar relative risk (RR) [8,9,14,15,23]. A recent systematic review and meta-analysis incorporating 5 nationwide population-based cohort studies from Asia reported a pooled RR for VTE of approximately 2.1 in patients with IBD compared with the non-IBD controls (pooled RR, 2.065; 95% confidence interval [CI], 1.905–2.238), indicating that IBD confers an intrinsic thrombotic risk independent of ethnicity [12]. However, in terms of absolute incidence, studies from Asian countries have consistently reported substantially lower VTE rates than those observed in Western populations. In the general non-IBD population, the incidence of VTE is approximately 0.2–0.6 per 1,000 person-years in Asian populations, compared with 1.0–1.5 per 1,000 person- years in Western populations. Similarly, among patients with IBD, the absolute incidence of VTE is lower in Asian populations (approximately 1–1.2 per 1,000 person-years) than in Western populations (approximately 2–3 per 1,000 person-years); however, during hospitalization or periods of active disease, VTE incidence increases markedly in Asian populations as well [8,9,12,14,15,23]. A Japanese prospective multicenter study reported VTE in 16.7% of hospitalized IBD patients versus 2.3% in those with other digestive diseases (P=0.0296), a rate comparable to that reported in Western countries [23]. A Taiwanese nationwide cohort study further demonstrated that IBD patients with 2 or more annual hospitalizations exhibited a significantly higher risk of DVT and PE [15]. In a Korean nationwide cohort study, VTE incidence reached 9.83 per 1,000 person-years during hospitalization without flares and 15.26 per 1,000 person-years when hospitalization coincided with active disease flares [9].

Collectively, the available evidence establishes IBD as a chronic prothrombotic condition, with the baseline VTE risk substantially exceeding that of the general population. This heightened baseline risk provides a critical framework for understanding the additive or potentially synergistic effects of pregnancy and postpartum state on VTE risk in women with IBD. However, the relatively lower absolute incidence of VTE observed in East Asian populations suggests that risk assessment and thromboprophylaxis strategies may need to be tailored rather than directly extrapolated from Western guidelines.

2. Risk of VTE during Pregnancy in Women with IBD

Pregnancy is a well-recognized hypercoagulable state, associated with a 4- to 6-fold rise in the risk of VTE compared with the non-pregnant state [24,25]. In addition, IBD independently increases the risk of VTE, raising concerns for synergistic effect when these conditions coexist. Moreover, pregnant women with IBD are more liable to experience immobilization and undergo surgical interventions including cesarean section, which are established risk factors for VTE [26,27]. Supporting this, a large-scale nationwide Danish cohort study encompassing nearly 2 million deliveries reported an incidence rate of 4.20 per 1,000 person-years (95% CI, 2.83–5.58) for VTE during pregnancy among women with IBD, compared with 2.41 per 1,000 person-years (95% CI, 2.33–2.50) in non-IBD pregnancies. After adjustment for maternal age and smoking status, IBD remained an independent risk factor for VTE during pregnancy (adjusted RR, 1.67; 95% CI, 1.15–2.41) [28]. Similarly, a meta-analysis demonstrated that pregnant women with IBD have a significantly higher risk of VTE than pregnant women without IBD, with a pooled RR of 2.13 (95% CI, 1.78–2.66; P<0.001) [29]. Notably, the risk of VTE among pregnant women with IBD is heterogeneous and strongly influenced by additional factors, including disease activity and IBD subtype. In particular, this risk is further amplified by active disease during pregnancy, and women experiencing an IBD flare exhibit more than a two-fold increase in the risk of VTE than those in remission [28,29]. Considerable heterogeneity in thromboembolic risk has also been observed according to IBD subtype. Population-based analyses have consistently reported a higher incidence of VTE in women with UC than in those with CD during pregnancy and postpartum period [28-30]. Registry-based studies from Denmark, Sweden, and the United States demonstrated a 2- to 3-fold rise in the risk of VTE among pregnant women with UC, whereas the corresponding risk increase in those with CD was modest, typically ranging from 1- to 2-fold [28,30,31], and in some studies, reaching statistical significance only during pregnancy but not during postpartum. Overall, pregnancy in women with IBD confers a moderately increased RR and a clinically relevant absolute risk of VTE, especially in the presence of active disease, highlighting the need for optimal disease control and individualized risk stratification for VTE prevention during pregnancy.

3. Risk of VTE during Postpartum Period in Women with IBD

The postpartum period represents the phase of the highest VTE risk, driven by persistent pregnancy-related hypercoagulability, delivery-associated vascular injury, and transient immobilization [32,33]. Even in the general population, the absolute risk of VTE rises sharply after delivery, particularly within the first 3–6 weeks postpartum, before gradually declining toward baseline by approximately 12 weeks [34,35].

IBD further amplifies the risk of VTE during this postpartum period. In patients with IBD, the prolonged prothrombotic state may overlap with postpartum disease flares, anemia, infection, surgical delivery, and delayed mobilization, thereby increasing the thrombotic risk. Furthermore, disease flares in late pregnancy or the early postpartum period are associated with a persistently elevated risk of VTE in patients with IBD [28,29].

This synergistic risk of VTE in women with IBD in the postpartum period was consistently demonstrated in previous studies [28-30]. In a Danish nationwide cohort study, the incidence rate of postpartum VTE within the first 12 weeks after delivery was 7.03 per 1,000 person-years among women with IBD, more than double that observed in women without IBD (2.88 per 1,000 person-years). After adjustment for key obstetric factors, including cesarean section and postpartum hemorrhage (PPH), IBD remained independently associated with postpartum VTE (adjusted RR 2.10; 95% CI, 1.33–3.30) [28]. These findings are further supported by a recent comprehensive meta-analysis, which reported that women with IBD had a 2.6-fold higher risk of postpartum VTE than women without IBD (pooled RR, 2.61; 95% CI, 1.84–3.69) [29]. Notably, subgroup analyses of this study suggested a higher postpartum VTE risk in patients with UC than in those with CD; however, the relatively small number of patients with CD limits definitive conclusions.

Collectively, the available evidence indicates that IBD is a clinically meaningful risk modifier for postpartum VTE, with the highest absolute risk concentrated in the early postpartum period. These findings highlight the importance of increased clinical vigilance and individualized thromboprophylaxis strategies for women with IBD after delivery, particularly in the presence of additional obstetric or disease-related risk factors.

4. Current Recommendations for VTE Prophylaxis in Guidelines and Expert Opinion

Current guidelines consistently highlight the importance of VTE risk assessment and selective thromboprophylaxis in pregnant women with IBD (Table 1). The Toronto Consensus Statement recommends anticoagulant thromboprophylaxis with low-molecular-weight heparin (LMWH) in patients with IBD who undergo cesarean delivery or who are hospitalized for an IBD flare [36]. Similarly, the European Crohn’s and Colitis Organisation (ECCO) guideline recommends the risk assessment of VTE before conception and during pregnancy, particularly in women with active disease, and advises LMWH thromboprophylaxis in high-risk patients, including those undergoing cesarean section, those hospitalized for disease flares, or those with additional VTE risk factors [37]. The 2025 Global Consensus Statement on the Management of Pregnancy in IBD does not specify a particular thromboprophylaxis regimen but recommends counseling women with IBD about the increased risk of VTE during pregnancy and postpartum period and suggests considering thromboprophylaxis in patients with risk factors such as active disease or cesarean delivery [11]. Similarly, the American Gastroenterological Association (AGA) IBD Parenthood Project recommends LMWH prophylaxis for pregnant women hospitalized for IBD, mechanical prophylaxis and early ambulation after cesarean delivery, and extension of postpartum pharmacologic prophylaxis for up to 3–6 weeks in women with prior VTE or additional risk factors [38]. The 2023 Australian IBD Consensus Statements similarly recommend both pharmacologic and mechanical VTE prophylaxis in hospitalized patients with IBD, with particular emphasis on those undergoing cesarean delivery or presenting with additional thrombotic risk factors [39]. Overall, these guidelines and expert opinion consensus support individualized VTE risk assessment and targeted use of LMWH prophylaxis in high-risk pregnant women with IBD rather than routine prophylaxis for all patients.

Table 1.

Guideline Comparison for VTE Prophylaxis in Pregnant Patients with IBD

Obstetric and gynecologic guidelines also recognize chronic immune-mediated inflammatory diseases, including IBD, as important risk factors for VTE. In the thromboprophylaxis guideline of the Royal College of Obstetricians and Gynaecologists (RCOG), active inflammatory IBD is identified as a significant pre-existing risk factor for thromboembolism, comparable to a previous VTE provoked by major surgery or the presence of a known high-risk thrombophilia. Although routine thromboprophylaxis is not recommended for all pregnant women with IBD, LMWH prophylaxis is recommended in patients with active IBD who have additional risk factors, such as cesarean delivery, obesity, or advanced maternal age in this guideline [40]. In the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin, IBD is recognized as a medical risk factor for pregnancy-associated VTE; however, routine thromboprophylaxis is not recommended solely on the basis of IBD and they recommend prophylactic anticoagulation according to the presence of additional risk factors [41].

5. Choice of Anticoagulant, Dosing and Timing for Thromboprophylaxis in Pregnant Women with IBD

The specific choice of anticoagulant, dose, and timing of thromboprophylaxis in pregnant women with IBD have not been clearly defined in existing Western guidelines. The Toronto and ECCO guidelines favor LMWH for thromboprophylaxis in high-risk patients with IBD [36,37]. Although the duration of thromboprophylaxis varies across guidelines, it is generally continued for at least 10 days postpartum, with extension up to 6 weeks in women at particularly high risk, based on other obstetric and thrombosis guideline recommendations [41,42].

Given the complexity of balancing thrombotic and bleeding risks, a multidisciplinary approach involving gastroenterologists, obstetricians, and hematologists is essential. In patients with low thrombotic risk, mechanical thromboprophylaxis alone may be sufficient. Intermittent pneumatic compression devices and graduated compression stockings enhance venous return and reduce venous stasis, and are recommended in women undergoing cesarean delivery or those with additional risk factors such as prolonged immobilization or hospitalization [41-47]. Mechanical prophylaxis is particularly valuable during the perioperative period, when pharmacologic anticoagulation may be temporarily withheld due to bleeding risk, and may serve as a safe adjunctive strategy in high-risk clinical settings such as cesarean delivery, hospitalization for disease flares, or prolonged immobilization.

When pharmacologic prophylaxis is indicated, LMWH is regarded as the anticoagulant of choice in pregnant women with IBD, given its well-established maternal and fetal safety profile [43,45]. Neither unfractionated heparin (UFH) nor LMWH crosses the placenta, and both are considered safe for use during pregnancy [41,45,48]. However, LMWH is generally preferred in clinical practice due to its more predictable pharmacokinetics, lower risk of heparin-induced thrombocytopenia (HIT), and lower risk of osteoporotic fractures with long-term use. In previous studies, LMWH has not been associated with teratogenicity, fetal bleeding, congenital anomalies, or adverse neurodevelopmental outcomes. Large observational studies and guideline-based reviews consistently support the safety of LMWH throughout all trimesters of pregnancy. In contrast, vitamin K antagonists, and direct oral anticoagulants are contraindicated or not recommended because of placental transfer and insufficient safety data [41,42].

Physiological changes during pregnancy, including increased maternal blood volume, enhanced renal clearance, and alterations in heparin-binding proteins, can substantially influence the pharmacokinetics of anticoagulants [27,45]. However, no large randomized controlled trials have defined the optimal dosing regimen during pregnancy, and current recommendations are largely based on observational data and expert consensus. Nevertheless, available evidence does not support routine dose reduction relative to the non-pregnant state, and standard therapeutic doses are generally required when anticoagulation is indicated. Therapeutic-dose anticoagulation (enoxaparin 1 mg/kg every 12 hours) is recommended for pregnant patients with acute VTE and for those at a very high risk of thrombosis, such as women with recurrent VTE or with mechanical heart valves [41,45]. In such cases, UFH dosing is titrated according to the level of activated partial thromboplastin time, whereas LMWH is administered using weight-adjusted therapeutic dosing based on maternal body weight.

For dosing of thromboprophylaxis, fixed-dose regimens are generally preferred. According to the ACOG [41], standard prophylactic dosing consists of 40 mg of enoxaparin administered subcutaneously once daily, with intermediate-dose prophylaxis (enoxaparin 40 mg twice daily) reserved for women at elevated thrombotic risk. The RCOG adopts a weight-based approach, recommending enoxaparin 40 mg once daily for women weighing 50–90 kg, with stepwise escalation to 60 mg daily for 91–130 kg, 80 mg daily for 131–170 kg, and 0.6 mg/kg/day for those exceeding 170 kg [42].

The timing of antenatal thromboprophylaxis should be individualized according to risk stratification. The RCOG recommends prophylactic LMWH throughout pregnancy in women with a prior history of VTE (with limited exceptions), initiation from 28 weeks’ gestation in those with multiple concurrent risk factors, and routine prophylaxis during any antenatal hospitalization unless contraindicated [42]. Careful peripartum management is essential for minimizing bleeding and neuraxial complications. Both the RCOG and ACOG recommend that appropriate time intervals be observed between the last LMWH dose and delivery or neuraxial anesthesia, with cautious and timely resumption of anticoagulation in the postpartum period [41,42].

6. Bleeding and Other Complication Risks Associated with Thromboprophylaxis in Pregnant Women with IBD

Evidence on the bleeding risk associated with antenatal and postnatal anticoagulation remains heterogeneous and somewhat controversial. In a systematic review, major bleeding events, predominantly related to obstetric causes, were reported in 1.98% of women receiving anticoagulation during pregnancy or postpartum period (95% CI, 1.50–2.57) [48]. Notably, this analysis included women receiving both therapeutic-and prophylactic-dose heparin, suggesting that the true bleeding risk associated with prophylactic-dose LMWH alone is likely to be below 2%.

Regarding local postoperative complications after cesarean delivery, several observational studies and systematic reviews have reported an approximately 2% absolute increase in the risk of wound hematoma among women receiving LMWH thromboprophylaxis [48,49]. Data regarding the association between anticoagulation and PPH are less consistent. While some studies have suggested an increased risk of PPH in women receiving antenatal or postnatal anticoagulation [50], others have failed to demonstrate a significant association [51-53], highlighting ongoing uncertainty in this area. Furthermore, a Cochrane systematic review comparing thromboprophylaxis with UFH or LMWH with no pharmacologic prophylaxis after cesarean section reported a higher incidence of bleeding or bruising in women receiving heparin; however, no clear increase in life-threatening or severe bleeding events was observed [54]. Beyond bleeding-related outcomes, LMWH is associated with a favorable non-hemorrhagic safety profile during pregnancy. The risk of HIT is substantially lower with LMWH than with UFH [48,55]. In a systematic review of 2,777 pregnancies exposed to LMWH, no cases of HIT were reported, supporting the safety of LMWH with respect to immune-mediated thrombocytopenia [48]. Prolonged use of UFH during pregnancy has been associated with osteoporosis and fragility fractures; however, this risk appears to be very low with LMWH. In the same systematic review, the incidence of osteoporotic fractures was 0.04% (95% CI, 0.01–0.20), and allergic skin reactions occurred in 1.8% (95% CI, 1.34–2.37) of women receiving LMWH [48].

Collectively, these findings suggest that LMWH thromboprophylaxis during pregnancy and the postpartum period may be associated with a modest increase in minor bleeding complications, while the risks of clinically significant or life-threatening hemorrhage as well as other non-hemorrhagic complications remain low when appropriate dosing and peripartum management strategies are employed.

7. ART and Its Impact on Thromboprophylactic Strategies in Women with IBD

Recent Korean population-based studies have reported a rising incidence of pregnancy-associated VTE despite an overall decline in total birth rates, identifying advanced maternal age, cesarean delivery, multiparity, and multifetal pregnancy as significant independent risk factors [56,57]. Of these, multifetal gestation represents a particularly strong predictor, likely through exacerbation of venous stasis and pregnancy-related hemodynamic alterations. Assisted reproductive technology (ART), increasingly utilized among women with chronic immune-mediated diseases including IBD, may further amplify thrombotic risk via supraphysiological hormonal stimulation, ovarian hyperstimulation syndrome (OHSS), and periods of reduced mobility during early pregnancy. In particular, OHSS may contribute substantially to thrombotic risk through severe hemoconcentration and a rapid rise in supraphysiological estrogen levels.

Given the additional prothrombotic burden imposed by chronic IBD-related systemic inflammation, ART-associated risk factors are likely to exert additive effects on VTE risk. In this context, 2 mitigation strategies warrant particular consideration in women with IBD undergoing ART: elective single embryo transfer to minimize multifetal pregnancy, and elective frozen embryo transfer to reduce the risk of OHSS [42,46,58]. Collectively, these considerations highlight the importance of multidisciplinary counseling, including gastroenterologists, obstetricians, and reproductive specialists throughout the preconception period in women with IBD.

8. Evidence Gap and Possible Future Directions for VTE Prophylaxis during Pregnancy in Women with IBD: Asian Perspective

Despite growing recognition of an elevated risk of VTE during pregnancy and the postpartum period in women with IBD, evidence specific to Asian populations remains markedly limited. Ethical and practical constraints on enrolling pregnant women in clinical trials have resulted in a scarcity of high-quality, pregnancy-specific data, particularly across Asian countries.

Nevertheless, available evidence suggests that compared with non-IBD controls, the overall risk of VTE is clearly increased in pregnant women with IBD, supporting consideration of pharmacologic thromboprophylaxis with LMWH in selected high-risk patients [28-30]. However, studies from multiple Asian cohorts–including multinational East Asian data,8 and nationwide studies from Taiwan [15], Korea [9], and Japan [23],–consistently indicated a substantially lower absolute incidence of VTE than those observed in Western population, with approximately 1–1.2 per 1,000 person-years in Asian populations compared with 2–3 per 1,000 person-years in Western populations [6,8,9,12,14,15,23,59]. This discrepancy raises uncertainty regarding the uniform application of Western guideline recommendations to Asian patients (Table 2).

Table 2.

Risk of Venous Thromboembolism in Patients with IBD: Comparison between Asian and Western Studies

This issue is relevant in the context of cesarean delivery, which is also a major trigger for thromboprophylaxis in many Western guidelines [36,37]. In some East Asian countries, including South Korea, cesarean section rates are substantially higher than those reported in Western populations, even among the general obstetric population. Betran et al. [60] reported a 44.9-percentage-point increase in the cesarean section rate in East Asian countries over the last three decades. According to national health insurance claims data, the cesarean delivery rate in South Korea has risen steadily, exceeding 60% in 2022 and approaching approximately 67% in 2024, placing South Korea among the highest-ranking OECD (Organisation for Economic Co-operation and Development) nations in cesarean delivery rates [61,62]. In contrast, a recent Canadian population-based study analyzing data up to 2020 reported a cesarean section rate of 35.4%, highlighting a substantial difference in obstetric practice patterns between the 2 countries [63]. Considering relatively low absolute incidence rate of VTE and risk of bleeding, the routine application of LMWH prophylaxis to all women with IBD undergoing cesarean delivery may not be directly transferable to Asian clinical practice [36,37].

Notably, several Asian studies demonstrate that absolute risk of VTE rises substantially during hospitalization and active disease, approaching levels observed in Western cohorts when these conditions coexist [9,14,15]. Data from a Korean population-based cohort study illustrate this risk gradient clearly: the incidence of VTE was 2.81 per 1,000 person-years during disease flares compared with 0.92 per 1,000 person-years during inactive disease, rising further to 9.83 per 1,000 personyears during hospitalization without flares, and reaching its peak at 15.26 per 1,000 person-years when hospitalization coincided with active disease flares. Similarly, elevated risks were observed following IBD-related surgery (13.13 per 1,000 person-years) and major surgery (12.77 per 1,000 person-years) [9]. These findings suggest that despite a lower baseline risk, pregnant women with IBD in Asia who experience active disease flares or require hospitalization may warrant anticoagulant thromboprophylaxis.

Anticoagulant selection, dosing, and duration should be individualized based on a comprehensive assessment of VTE risk, incorporating disease activity, cesarean delivery status, immobilization, obesity, obstetric complications, thrombophilia, and personal or family history of VTE. Pregnant women with IBD presenting with multiple concurrent risk factors–including cesarean delivery, ART, preterm birth, preeclampsia, obstetric hemorrhage, or postpartum infection–represent a particularly high-risk subgroup in whom more aggressive thromboprophylaxis should be strongly considered (Table 3). Despite the lower absolute incidence of VTE in Asian populations, the coexistence of pregnancy and IBD represents a clinically meaningful prothrombotic state, and clinicians should remain vigilant against underutilization of thromboprophylaxis in high-risk patients, particularly in the setting of active disease, hospitalization, cesarean delivery, or ART. Future research should focus on developing risk-adapted, population-specific strategies for VTE prevention in pregnant women with IBD in Asia [64].

Table 3.

Scenario-Based VTE Prophylaxis in Hospitalized IBD Patients according to Guidelines^a

Rather than applying uniform Western recommendations, it may be more appropriate to present an expert-informed, risk-adapted multidisciplinary clinical approach that reflects the unique epidemiologic and obstetric characteristics of Asian populations [65]. Drawing on the available Asian cohort data and real-world clinical experience, this framework emphasizes a stepwise and collaborative process led by a multidisciplinary team–comprising gastroenterologists, obstetricians, hematologists, cardiologists, and colorectal surgeons where indicated–encompassing the following elements: (1) assessment of baseline and disease-related VTE risk; (2) identification of situational risk modifiers including hospitalization, active disease, and surgery; (3) individualized consideration of pharmacologic thromboprophylaxis; and (4) determination of appropriate prophylaxis duration.

This framework does not aim to replace existing Western guidelines, but rather to contextualize them within Asian clinical practice, where the absolute VTE risk is lower, cesarean delivery rates are higher, and disease activity and hospitalization appear to be the dominant drivers of thrombotic risk. It should be acknowledged that pregnancy-specific VTE epidemiologic data from Asia are currently derived predominantly from Korean nationwide studies; while hospital-based data from Japan and China are emerging, large-scale population-based studies from additional Asian countries are urgently needed to establish a more comprehensive and representative regional evidence base.