Use of XARELTO During Pregnancy and Lactation

Summary

• The limited available data on XARELTO in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. Use XARELTO with caution in pregnant patients because of the potential for pregnancy related hemorrhage and/or emergent delivery. The anticoagulant effect of XARELTO cannot be reliably monitored with standard laboratory testing. Consider the benefits and risks of XARELTO for the mother and possible risks to the fetus when prescribing XARELTO to a pregnant woman.¹
• XARELTO has been detected in human milk. There are insufficient data to determine the effects of XARELTO on the breastfed child or on milk production.¹
• A single-arm, open-label, prospective study evaluated the excretion of prophylactic-dose XARELTO (10 mg once daily) into breast milk in 20 postpartum lactating individuals. Time to peak XARELTO concentration in both breast milk and plasma was 2 hours. The calculated milk-to-plasma (M/P) ratio was 0.45 (95% confidence interval [CI], 0.16-0.86), the daily infant dose was 0.004 mg/kg/day, and the relative infant dose was 2.9%. Median XARELTO concentrations in maternal milk following the second dose were 4 ng/mL at 0 hours, 62 ng/mL at 2 hours, 47 ng/mL at 4 hours, and 34 ng/mL at 6 hours. No adverse events were reported.²
• Established physiologically based pharmacokinetic (PBPK) models were used to simulate infant exposure to maternal XARELTO during breastfeeding. During the immediate postpartum period (0-2 days), maternal exposure to XARELTO 20 mg once daily was predicted to decrease by 27%. The maximum milk concentration recorded among any of the 100 maternal individuals was 120 ng/mL for XARELTO. For 20 mg once-daily regimen, the simulated mean maternal plasma and milk maximum concentration (C_max) values were 250 ng/mL and 77 ng/mL, respectively, and area under the curve for 24 to 48 hours (AUC_24-48) values were 1772 ng/mL·h and 542 ng/mL·h, respectively. For XARELTO, the mean±standard deviation (SD) steady-state infant plasma C_max and AUC_24-48 values were 12±4.5 ng/mL and 242±107 ng/mL·h, respectively, during the immediate postpartum period and 9±3 ng/mL and 167±70 ng/mL·h, respectively, at 5 to 6 months postpartum. The relative infant daily dose (RIDD) was 7%, and relative infant exposure ranged from 8% to 19%.³
• The New Horizons clinical trial evaluated the transfer of XARELTO into breast milk at steady state in breastfeeding women within 12 weeks postpartum. Two patients received XARELTO 20 mg once daily for 3 consecutive days. Mean maternal area under the concentration-time curve (AUC_0-24) on day 1 and area under the concentration-time curve at steady-state (AUC_{0-24 steady state}) on day 3 were 3646 and 2926 ng/mL·h, respectively. Corresponding mean breast milk AUC_0-24 and steady-state AUC_{0-24 steady state} values were 749 and 583 ng/mL·h, respectively. The M/P ratio (AUC_0-24) was 0.21 on day 1 and 0.20 at steady state. No bleeding events or adverse effects related to XARELTO were reported.⁴
• An integrated, experimentally informed PBPK model was developed to characterize the transfer of XARELTO into breast milk and estimate infant systemic exposure. The mean unbound fraction in breast milk was 51.7%. Simulated mean adult plasma and milk concentration-time profiles closely overlapped with the observed plasma concentrations. Predicted M/P ratio ranged from 0.03 to 1.62. Intrinsic clearance (CL_int) resulted in approximately 2.5-fold increases in both AUC and the M/P ratio; empirical in vitro-to-in vivo scaling factor (RAF/REF) increased these parameters by approximately 1.5-fold. Increasing passive diffusion mammary clearance (CL_pd) was associated with a 25% to 40% decrease in exposure parameters. Across the C_milk,ave and C_milk,max scenarios, predicted infant C_max values remained below 1.5 ng/mL, with T_max occurring at approximately 29.4 to 47 hours during the feeding and AUC over the dosing interval ranging from 19.9 to 64.7 ng/mL·h. Infant daily doses (IDDs) were 0.004 mg/kg/day under the C_milk,ave scenario and 0.013 mg/kg/day under the C_milk,max scenario, corresponding to RIDDs of 1.4% and 4.55%, respectively.⁵
• An ex-vivo study using isolated human placental cotyledons found a rapid transfer of XARELTO across the placental barrier from maternal-to-fetal circulation and fetal-to-maternal circulation.⁶
• Sessa et al (2019)⁷ conducted a review of Vigibase^® for direct oral anticoagulants (DOACs) to evaluate adverse events (AEs) in pregnancy. XARELTO did not show a statistically significant difference in spontaneous abortion compared to warfarin when all cases were reviewed.
• Case series^8,9 and case reports^10-14 that discuss the use of XARELTO during pregnancy and lactation are summarized below.
• Additional citations identified during literature search are included under REFERENCES section for your review.^15-18

PRODUCT LABELING

Please refer to the following sections of the enclosed Full Prescribing Information that are relevant to your inquiry: WARNINGS AND PRECAUTIONS, USE IN SPECIFIC POPULATIONS, and PATIENT COUNSELING INFORMATION.¹

Use in Specific Populations

Pregnancy

The limited available data on XARELTO in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. Use XARELTO with caution in pregnant patients because of the potential for pregnancy related hemorrhage and/or emergent delivery. The anticoagulant effect of XARELTO cannot be reliably monitored with standard laboratory testing. Consider the benefits and risks of XARELTO for the mother and possible risks to the fetus when prescribing XARELTO to a pregnant woman.

Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Pregnancy is a risk factor for venous thromboembolism and that risk is increased in women with inherited or acquired thrombophilias. Pregnant women with thromboembolic disease have an increased risk of maternal complications including pre-eclampsia. Maternal thromboembolic disease increases the risk for intrauterine growth restriction, placental abruption and early and late pregnancy loss.

Fetal/Neonatal Adverse Reactions

Based on the pharmacologic activity of Factor Xa inhibitors and the potential to cross the placenta, bleeding may occur at any site in the fetus and/or neonate.

Labor or Delivery

All patients receiving anticoagulants, including pregnant women, are at risk for bleeding and this risk may be increased during labor or delivery. The risk of bleeding should be balanced with the risk of thrombotic events when considering the use of XARELTO in this setting.

Human Data

There are no adequate or well-controlled studies of XARELTO in pregnant women, and dosing for pregnant women has not been established. Post-marketing experience is currently insufficient to determine a XARELTO-associated risk for major birth defects or miscarriage. In an in vitro placenta perfusion model, unbound XARELTO was rapidly transferred across the human placenta.

Animal Data

XARELTO crosses the placenta in animals. XARELTO increased fetal toxicity (increased resorptions, decreased number of live fetuses, and decreased fetal body weight) when pregnant rabbits were given oral doses of ≥10 mg/kg XARELTO during the period of organogenesis. This dose corresponds to about 4 times the human exposure of unbound drug, based on AUC comparisons at the highest recommended human dose of 20 mg/day. Fetal body weights decreased when pregnant rats were given oral doses of 120 mg/kg during the period of organogenesis. This dose corresponds to about 14 times the human exposure of unbound drug. In rats, peripartal maternal bleeding and maternal and fetal death occurred at the XARELTO dose of 40 mg/kg (about 6 times maximum human exposure of the unbound drug at the human dose of 20 mg/day).

Lactation

XARELTO has been detected in human milk. There are insufficient data to determine the effects of XARELTO on the breastfed child or on milk production. XARELTO and/or its metabolites were present in the milk of rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XARELTO and any potential adverse effects on the breastfed infant from XARELTO or from the underlying maternal condition.

Animal Data

Following a single oral administration of 3 mg/kg of radioactive [¹⁴C]- XARELTO to lactating rats between Day 8 to 10 postpartum, the concentration of total radioactivity was determined in milk samples collected up to 32 hours post-dose. The estimated amount of radioactivity excreted with milk within 32 hours after administration was 2.1% of the maternal dose.

Females and Males of Reproductive Potential

Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician.

The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants, including XARELTO, should be assessed in females of reproductive potential and those with abnormal uterine bleeding.

PHARMACOKINETIC STUDIES

Bruno et al (2026)² conducted a single-arm, open-label, prospective study to evaluate the excretion of prophylactic-dose XARELTO into breast milk in postpartum lactating individuals. Lactating individuals aged ≥18 years received 2 doses of prophylactic-dose XARELTO (10 mg once daily). Patients were requested not to breastfeed or provide pumped milk to their neonates during the study period.

A total of 20 lactating individuals were enrolled between April and September 2024. The time from delivery to study participation ranged from 1 to 554 days. Time to peak XARELTO concentration in both breast milk and plasma samples was 2 hours. See Table: XARELTO Concentration in Maternal Milk (N=20).

The calculated M/P ratio was 0.45 (95% CI, 0.16-0.86), the daily infant dose was 0.004 mg/kg/day, and the relative infant dose was 2.9%. No adverse events were reported.

Butler et al (2026)³ used established PBPK models of XARELTO and apixaban to simulate infant exposure to maternal medication during breastfeeding. The default XARELTO model available in Simcyp Simulator (version 23; Certara) was used without modification. The model was verified against data from nonpregnant adults and integrated with postpartum physiology population models to predict drug exposure during lactation. The models were further verified using previously published clinical data.

For XARELTO, simulations in Chinese, Japanese, and Black South African populations predicted approximately 10% higher exposure. In the immediate postpartum period (0-2 days), maternal XARELTO exposure following 20 mg once daily was predicted to be reduced by 27%. AUC values began returning to control levels by 3 to 4 weeks postpartum and reached baseline levels by approximately 6 weeks postpartum. When simulations were run, enzyme activity was assumed to match that reported at the end of pregnancy. Consequently, the XARELTO AUC at 0 to 2 days postpartum was reduced to approximately 50% of the nonpregnant value (AUC, 889 ng/mL·h). See Table: Simulated Mean Maternal Plasma and Milk C_max and AUC_24-48.

The maximum milk C_max recorded among the 100 maternal individuals was 120 ng/mL for XARELTO. IDDs of 0.02 and 0.1 mg/kg/day were used for simulations and divided into 6 equal doses to represent a regular breastfeeding pattern. For XARELTO, the mean (±SD) steady-state infant plasma C_max and AUC_24-48 were 12 (±4.5) ng/mL and 242 (±107) ng/mL·h, respectively, during the immediate postpartum period. These values decreased to 9 (±3) ng/mL and 167 (±70) ng/mL·h, respectively, at 5 to 6 months postpartum.

For XARELTO, an IDD of 0.02 mg/kg/day corresponded to a RIDD of 7%. Relative infant exposure ranged from 8% to 19%, with the highest values reported in the immediate postpartum period (11%-19%). Relative infant exposure to XARELTO decreased to 9%-11% at 2 to 3 months postpartum and to 8%-9% at 5 to 6 months postpartum.

Patel et al (2026)⁴ conducted the New Horizons clinical trial to evaluate the transfer of XARELTO into breast milk at steady state in breastfeeding mothers within 12 weeks postpartum and to provide information on edoxaban transfer into breast milk. Breastfeeding volunteers who agreed to pause breastfeeding during the 6-day trial sampling period received XARELTO 20 mg once daily or edoxaban 60 mg once daily orally for 3 consecutive days within the first 12 weeks postpartum. Four women consented to participate, and all completed the trial; volunteer 4 completed the trial on day 5 rather than day 6 due to logistical constraints. Volunteers 2 and 4 received XARELTO 20 mg once daily.

Overall, the mean (SD) age of the patients was 37 (1.4) years, and the mean day post-delivery at trial initiation was 34 days (min-max: 19-42 days). No bleeding events or adverse effects related to XARELTO were reported during the trial.

For XARELTO, the reported steady-state AUC_0-24 in adults receiving 20 mg once daily ranged from 2800 to 3200 ng/mL·h/mL. Steady-state plasma AUC values in pediatric patients receiving weight-based XARELTO dosing were reported to be comparable to the adult AUC range for equivalent exposures. Table: Noncompartmental Analysis for Women Allocated to XARELTO reports the AUC_0-24 and AUC_{0-24 steady-state} parameters for mean maternal plasma and corresponding breast milk concentrations.

Yi et al (2026)⁵ developed an integrated, experimentally informed PBPK model to quantitatively characterize the transfer of apixaban and XARELTO into breast milk and estimate infant systemic exposure. The study generated in vitro measurements of passive permeability and transporter-mediated efflux across mammary epithelial cells, incorporated these mechanistic parameters together with milk protein binding into maternal PBPK models to describe drug disposition in lactating women, and linked breast milk concentrations to a pediatric PBPK model to evaluate infant exposure under clinically relevant breastfeeding scenarios.

For XARELTO, the mean unbound fraction in breast milk was 49.67% at 100 nM, 54.33% at 1 μM, and 51% at 10 μM, resulting in an overall mean unbound fraction of 51.7%. One-way ANOVA demonstrated no significant concentration-dependent differences in protein binding (P=0.6126).

Simulated mean adult plasma and breast milk concentration-time profiles for XARELTO (10 mg twice daily and 20 mg once daily) closely overlapped with the observed plasma concentrations. Across dosing regimens, observed plasma concentrations fell within the model-predicted 5^th-95^th percentile range, indicating that the adult PBPK model adequately captured XARELTO disposition across clinically relevant exposure levels. See Table: Predicted Versus Observed PK Parameters in Adult PBPK Model.

Across all evaluated dosing regimens, the adult PBPK models simulated the observed pharmacokinetic profiles of XARELTO in plasma and breast milk. Identity plots demonstrated that simulated concentrations and key pharmacokinetic parameters, including C_max, T_max, and AUC, remained consistently within the widely accepted 2-fold range, indicating quantitative agreement with clinical measurements. Additionally, observed concentration-time profiles in both plasma and breast milk were encompassed within the simulated 5^th-95^th percentile range, supporting the model’s ability to reliably characterize dose-dependent pharmacokinetics in lactating adults. Predicted M/P ratios for XARELTO ranged from 0.03 to 1.62.

Sensitivity analyses demonstrated that CL_pd, CL_int, and RAF/REF each contributed differently to the model-simulated breast milk exposure of XARELTO. For XARELTO, CL_int had the greatest impact, resulting in approximately 2.5-fold increases in AUC and the M/P ratios. RAF/REF demonstrated moderate sensitivity, with approximately 1.5-fold increases. In contrast, CL_pd was negatively associated with exposure, with parameter values decreasing by 25% to 40% as CL_pd increased. T_max exhibited only minor changes across parameter variations.

Pediatric PBPK simulations with fitted relative CYP3A4 abundance curve predicted very low infant exposure to XARELTO across all breastfeeding scenarios. For XARELTO, model verification was performed by comparing simulated pharmacokinetic parameters with published infant data at 2 dose levels. Simulations assuming maternal dosing of XARELTO 20 mg once daily generated infant plasma profiles based on a 2-hour feeding interval over 2 days.

Across the C_milk,ave and C_milk,max scenarios, predicted infant C_max values remained below 1.5 ng/mL, with T_max occurring between approximately 29.4 and 47 hours and AUC over the dosing interval ranging from 19.9 to 64.7 ng/mL·h. The C_milk,max scenario resulted in approximately 3-fold higher infant AUC and C_max values relative to C_milk,ave scenario for XARELTO. Even under this conservative assumption, predicted infant peaks remained more than one order of magnitude lower than the reported therapeutic plasma concentration range of approximately 20-660 ng/mL for XARELTO at approved doses in adults. Predicted infant plasma concentrations following breast milk exposure were substantially lower than published infant exposure data associated with therapeutic dosing and no reported safety concerns. See Table: Predicted Versus Observed PK Parameters in Pediatric PBPK Model.

Across all breastfeeding scenarios, the calculated IDDs for XARELTO remained low relative to maternal intake. See Table: IDD and RIDD for Infants in Different Scenarios.

Bapat et al (2015)⁶ conducted an ex-vivo study using isolated human placental cotyledons to determine if XARELTO passively diffuses across the placenta, the rate and extent of this migration, and to estimate fetal drug exposure. Nine cotyledons from different placentae were perfused with 250 ng/mL of XARELTO on the maternal or fetal reservoir only or simultaneously to both.

The addition of XARELTO to the maternal reservoir resulted in a rapid transfer from maternal-to-fetal circulation with a biphasic decline in XARELTO concentrations from the maternal circulation. At 3 hours after administration, the median fetal concentration of XARELTO was 69.5 ng/mL (interquartile range [IQR], 67.9-84.7) and the median fetal-to-maternal ratio was 0.69 (IQR, 0.58-0.73).

The addition of XARELTO to the fetal reservoir also resulted in a rapid transfer to the maternal side with a similar biphasic decline in XARELTO concentration from the fetal circulation. The final maternal concentration was 58.2 ng/mL and the final maternal-to-fetal ratio was 0.69 (IQR, 0.67-0.71) at 3 hours. When XARELTO 250 ng/mL was added to both the maternal and fetal sides simultaneously, the fetal-to-maternal ratio remained relatively constant over the 3-hour period. Together, this data suggests that unbound XARELTO passively diffuses across the placenta in both directions down a concentration gradient.

database review

Sessa et al (2019)⁷ conducted a review of Vigibase^® for DOACs to evaluate AEs in pregnancy.

• Vigibase^® is a global database associated with the World Health Organization and uses standardized dictionaries to code events.
• Reports were evaluated from January 01, 1967 to July 13, 2017 having DOACs as suspected/interacting drugs for which there was reported at least one AE included in the standardized MedDRA Query “Pregnancy and neonatal topics”. There were 764 individual cases that met this definition.
  • Cases were evaluated to determine temporal and biological plausibility for all drug-event pairs by looking at the clinical and demographic characteristics.
  • The role of comorbidities on AEs of interest was assessed by using both medical judgment and review of documentation.
  • Drugs were assessed for potential drug-drug interactions that could lead to a pregnancy-related outcome/teratogenic effects.
• Of the 764 cases evaluated, only 60 (7.8%) fit criteria for data extraction.
• In cases with and without alternative causes for the AE, XARELTO (reporting odds ratio [ROR], 2.7; 95% CI, 1.79-4.07) and apixaban (ROR, 6.76; 95% CI, 2.99-15.25) had an increased probability of reporting spontaneous abortion compared to other AEs in comparison to all other drugs. However, in cases without confounders, XARELTO did not show a statistically significant estimation (ROR, 1.05; 95% CI, 0.54-2.02).
• When all cases were used, XARELTO did not show a statistically significant ROR for spontaneous abortion in comparison to warfarin (ROR, 0.79; 95% CI 0.47-1.32). Similar results were observed when the analysis was restricted only to cases without reported alternative causes for spontaneous abortion (ROR, 0.86; 95% CI, 0.37-1.99).
• When only cases without confounders were reviewed, apixaban showed a statistically significant ROR for spontaneous abortion if compared to warfarin (ROR, 5.55; 95% CI, 2.11-14.63) or XARELTO (ROR, 6.45; 95% CI, 2.27-18.35).

CASE REPORTs/CASE SERIES

Yamashita et al (2024)⁸ published a case series involving 2 lactating mothers treated with XARELTO 15 mg once daily in Japan. Blood and breast milk samples were collected from the mothers at time 0 and 2 hours after XARELTO administration. The infants were breastfed 2 hours after XARELTO administration to the mothers and blood samples were taken 2 hours after breastfeeding (4 hours after maternal XARELTO administration).

• Case 1 was a 40-year-old woman with a previous history of acute deep vein thrombosis. Three days after delivery of twin children at 37 weeks, she was transitioned from unfractionated heparin to XARELTO. All blood and breast milk samples were collected 4 days after delivery. Results may be seen in the Table: XARELTO Concentrations in Maternal and Infant Blood Samples and in Breast Milk.
• Case 2 was a 34-year-old woman who developed acute deep vein thrombosis at 28 weeks of pregnancy. She was treated with unfractionated heparin and transitioned to XARELTO 3 days after giving birth at 40 weeks of gestation. Blood and breastmilk samples were taken 5 days after delivery. Results may be seen in the Table: XARELTO Concentrations in Maternal and Infant Blood Samples and in Breastmilk.

• All plasma XARELTO concentrations in the infants 2 hours after breastfeeding were below the lower limit of quantification.
• At 3 months of follow-up, breastfeeding continued with XARELTO without complications, including no bleeding events.

Muysson et al (2020)⁹ report the drug-concentration profile of XARELTO in milk samples collected from two lactating mothers consuming XARELTO 15 mg twice daily and then subsequently transitioned to 20 mg once daily following a mild stroke and bilateral pulmonary emboli.

• The first lactating mother was a 35-year-old woman weighing 58.9 kg who gave birth at 39 weeks of gestation. Three months postpartum, she was diagnosed with a mild stroke and was initiated on XARELTO 15 mg twice daily for 21 days and then 20 mg once daily thereafter for 6 months.
• The second lactating mother was a 33-year-old woman who gave birth at 39 weeks gestation. Four weeks postpartum, she was diagnosed with bilateral pulmonary emboli and was initiated on XARELTO 15 mg twice daily for 21 days and then 20 mg once daily thereafter for 6 months.
• Milk samples for the first lactating mother were collected on day 10 of treatment after taking the 15 mg dose twice daily at -0, 1, 3, 5, 8, 10, and 12 hours. Milk samples for the second lactating mother were collected on day 10 of treatment after taking the 15 mg dose twice daily at -0, 1, 2, 4, 8, 10, 12, and 24 hours.
  • Milk samples for the 20 mg dose were collected 7 days after transitioning to the higher dose at -0, 1, 2, 4, 8, 10, 12, and 24 hours (sampling for the 20 mg dose regimen was identical for both patients).
• The average concentration of XARELTO in milk observed in both patients was 0.16±0.0004 μg/mL taking the 15 mg twice daily dose. The maximum concentration was 0.3±0.02 μg/mL at 1 hour. The estimated infant dose per 12 hours was 0.01 mg/kg and the estimated relative infant dose was 5%.
• The average concentration of XARELTO in milk for the 20 mg dose was 0.07±0.02 μg/mL. The maximum concentration was 0.26±0.01 μg/mL at 2 hours. The estimated infant dose per day was 0.01 mg/kg and the estimated relative infant dose was 4%.
• Both patients were advised against breastfeeding once they began XARELTO treatment. They continued to pump to keep up their supply and to donate milk samples to the investigators.

Chi et al (2026)¹⁰ published a case report of a 28-year-old woman who presented with amenorrhea for more than 2 months, fever, and cough for 1 week. Early pregnancy with a single viable fetus was confirmed by serum human chorionic gonadotropin testing and ultrasound examination.

• The patient was initially diagnosed with a respiratory tract infection and received intravenous penicillin 4.8 million units every 8 hours. After 3 days of treatment, fever worsened, reaching 40°C, and cough progressed with hemoptysis.
• Based on multidisciplinary team discussion, the patient's chest CT findings were considered consistent with acute organizing pneumonia. Treatment was changed to intravenous ceftriaxone 2 g once daily and intravenous methylprednisolone 20 mg once daily. After 1 week of treatment, fever resolved and cough symptoms decreased with no sputum.
• Methylprednisolone was gradually tapered and discontinued after 1 week. Follow-up chest CT demonstrated a marked reduction in the left lung patchy consolidation, with most of the left pleural effusion was absorbed.
• Three days after discontinuation of methylprednisolone, fever recurred (38.5°C) with a heart rate of 119 beats/minute. Chest CT revealed an expansion of the left lung consolidation compared with the previous examination, along with a small pleural effusion in the left pleural cavity.
• Contrast-enhanced chest computed tomography subsequently revealed bilateral pulmonary artery embolism, poor perfusion in most branches of the left lower lobe pulmonary artery, and partial lung infarction of the left lung. D-dimer concentration increased to 2.97 mg/L, while echocardiography and lower-extremity vascular ultrasonography showed no obvious abnormalities.
• The patient received oral XARELTO 20 mg once daily for anticoagulation. One week later, symptoms resolved, and follow-up chest computed tomography performed 2 weeks later showed marked absorption of the lung infarction lesion.
• During 5 months of follow-up, no recurrence of symptoms was reported. The patient subsequently delivered a healthy baby boy.

Farid et al (2026)¹¹ published a case report of a 30-year-old gravida 1 para 0 woman with a history of unprovoked lower-extremity deep vein thrombosis who had been receiving XARELTO for secondary prophylaxis. At 7 weeks' gestation, XARELTO was discontinued, and anticoagulation therapy was transitioned to enoxaparin.

• Twelve days later, the patient presented with an acute posterior circulation stroke due to a mid-distal basilar artery occlusion and underwent urgent endovascular thrombectomy.
• At presentation, she was thrombocytopenic (platelets 85×10⁹/L). Testing confirmed heparin-induced thrombocytopenia, with a positive platelet factor 4 enzyme immunoassay followed by a confirmatory serotonin release assay.
• Enoxaparin was discontinued, and argatroban was initiated following endovascular thrombectomy. Anticoagulation was subsequently transitioned to subcutaneous danaparoid and later to fondaparinux for continued treatment during pregnancy.
• At 39+1 weeks' gestation, labor was induced, resulting in the delivery of a healthy female infant. The patient received intermediate dose fondaparinux for 6 weeks postpartum.

Liu et al (2025)¹² published a case report of a 40-year-old woman at 37 weeks of pregnancy who presented with chest tightness and suffocation. Based on the patient's symptoms, clinical examination findings, and evidence of fetal distress, an emergency Caesarean section was performed.

• One day after the operation, the patient reported no chest tightness or breathlessness, and oxygen saturation remained at 95%-96% without oxygen inhalation. She received two subcutaneous injections of enoxaparin 60 mg to prevent lower-limb thrombosis.
• Plasma D-dimer concentration increased to 88.68 μg/mL. Echocardiography demonstrated pulmonary artery widening with an estimated pulmonary artery systolic pressure of approximately 37 mmHg and moderate echogenicity in the right pulmonary artery. Pulmonary artery computed tomography angiography revealed multiple columnar filling defects in the lumen of pulmonary artery trunk and its branches. Analysis supported clinical diagnosis of multiple pulmonary embolism and right ventricular dysfunction.
• Following multidisciplinary consultation, the patient received critical care management, including continuous oxygen therapy, fluid balance monitoring, and anticoagulant therapy. Ultrasonography of both lower limbs demonstrated left popliteal vein thrombosis, and a lower-limb venous filter was implanted.
• The patient was transferred to the intensive care unit and received high-flow oxygen therapy, moxifloxacin, enoxaparin 7500 units subcutaneously every 12 hours, gastric protection, and treatment to improve microcirculation.
• The patient's symptoms and clinical examination findings improved following the above series of therapies in the intensive care unit (ICU), and she was transferred to the respiratory department for further treatment 5 days later. Re-examination with lower limb venous ultrasound showed a reduction in the venous lumen obstruction, and blood flow had resumed smoothly. Plasma D-dimer concentration decreased to 1.69 μg/mL.
• During hospitalization, the infant remained in good health and was fed formula milk. Both the patient and infant were discharged on hospital day 10.
• Following discharge, the patient received oral XARELTO 15 mg twice daily for 2 weeks, followed by 20 mg once daily. She was readmitted on 9 May 2024 for removal of the inferior vena cava filter and continued oral XARELTO for anticoagulation for an additional 2 months with regular follow-up.

Myers et al (2016)¹³ published a case report involving a 20-year-old female patient who presented for consideration of termination of an unplanned pregnancy while on XARELTO 20 mg once daily for VTE prevention.

• Initial ultrasound revealed the fetus was 25+ weeks gestation. XARELTO therapy was discontinued, and low molecular weight heparin was initiated.
• The patient continued regular follow-up with fetal scans which showed normal growth and no fetal abnormalities or bleeding.
• She underwent an emergency Caesarean section at 39+ weeks due to spontaneous rupture of membranes. A male baby was delivered without evidence of intracranial hemorrhage. Follow-up examinations were normal.

Konigsbrugge et al (2014)¹⁴ reported a case involving a 24-year-old female who was found to be 19 weeks gestation while on XARELTO 15 mg once daily for VTE prophylaxis.

• Upon discovery of pregnancy, XARELTO therapy was immediately discontinued and replaced with low molecular weight heparin.
• Routine follow-up was conducted without anomalies. The patient delivered a male infant at 40 weeks without any complications.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 29 July 2026.