Patient Information

A 53-year-old multiparous Vietnamese woman (gravida 2, para 2; G2P2) was referred for evaluation of acute right lower-extremity pain that began one week after completing a long-distance journey. The pain progressively worsened, radiating along the medial thigh into the right groin. She self-administered acetaminophen and diclofenac without relief. The patient had been diagnosed with adenomyosis in January 2024 and had been receiving combined oral hormonal therapy consisting of ethinylestradiol 0.03 mg plus drospirenone 3 mg daily since June 2024. She also reported chronic menorrhagia and anemia. No relevant family history or previous thrombotic events was documented.

She initially presented to a private clinic, where Doppler ultrasonography of the lower extremities confirmed a right iliofemoral vein thrombosis. Rivaroxaban 15 mg twice daily was prescribed as an induction dose. Two hours after the first dose, the patient developed profuse vaginal bleeding accompanied by dizziness, necessitating admission to Thong Nhat Hospital, a tertiary-care teaching hospital in Viet Nam.

Clinical Findings

Upon presentation, the patient’s vital signs were as follows: blood pressure 120/70 mmHg, heart rate 110 beats per minute (bpm), respiratory rate 20 breaths per minute, and temperature 37.0 °C. Physical examination demonstrated swelling of the right lower extremity with calf and inguinal tenderness. There was no evidence of respiratory distress or neurologic deficits.

Timeline

Diagnostic Assessment

Initial laboratory investigations at a private clinic demonstrated a hemoglobin (Hb) concentration of 8.6 g/dL, an elevated D-dimer level of 6.36 μg/mL (reference interval 0.27–1.09 μg/mL), and a markedly raised cancer antigen-125 (CA-125) concentration of 2,539.1 U/mL (reference ≤ 35 U/mL); CA 19-9 remained within the normal range. Doppler ultrasonography performed with a Siemens ACUSON SC2000 PRIME system (Siemens Medical Solutions USA, Inc.) identified thrombosis of the right iliofemoral vein. Subsequent testing at Thong Nhat Hospital recorded a hemoglobin level of 7.0 g/dL and a D-dimer level of 3,180 ng/mL, with otherwise normal coagulation profiles as well as hepatic and renal function tests. A comprehensive evaluation for inherited or acquired thrombophilia (factor V Leiden, prothrombin G20210A, antithrombin, protein C/S, and antiphospholipid antibodies) was not performed during the index admission because of limited test availability. Electrocardiography showed no S1Q3T3 pattern, and transthoracic echocardiography demonstrated no evidence of right ventricular dysfunction.

Therapeutic Intervention

Initial anticoagulation with rivaroxaban 15 mg twice daily resulted in profuse vaginal hemorrhage. The patient required transfusion of four units of packed red blood cells. Because systemic anticoagulation was temporarily contraindicated, an optional inferior vena cava (IVC) filter (ALN, ALN Implants Chirurgicaux, France) was inserted. Definitive surgical management comprised a total hysterectomy with bilateral salpingo-oophorectomy performed at Hung Vuong Obstetrics and Gynecology Hospital. Postoperatively, anticoagulation was reinitiated with enoxaparin 6,000 IU subcutaneously every 12 h for three days, after which therapy was transitioned to rivaroxaban 15 mg once daily for maintenance.

Follow-up and Outcomes

The patient was discharged in a stable condition and scheduled for outpatient follow-up. She subsequently reported a complete resolution of symptoms. At three months post-operatively, the CA-125 concentration had fallen to < 35 U/mL (baseline 2,539.1 U/mL), and Doppler ultrasonography confirmed full resolution of the right iliofemoral deep-vein thrombosis without residual thrombus. Retrieval of an inferior vena cava (IVC) filter is typically recommended within 1–3 months. Owing to the temporary unavailability of retrieval equipment at our institution, the patient will be reassessed for filter removal at the earliest feasible opportunity.

Discussion

We conducted a targeted literature search of PubMed/MEDLINE, Embase, Scopus, and Web of Science from database inception to 31 August 2025, employing the search strategy: “adenomyosis” AND (“deep vein thrombosis” OR “venous thromboembolism” OR “pulmonary embolism” OR “cerebral venous thrombosis”). We also manually reviewed the reference lists of all pertinent publications. Following title-, abstract-, and full-text screening, we identified only case reports and small case series; no randomized controlled trials or large observational cohort studies were retrieved. These observations underscore the rarity of adenomyosis-associated VTE, corroborating previous estimates of fewer than 40 documented cases. A concise summary of reported DVT cases is presented in Table 2.

Our case report describes a 53-year-old woman with a history of adenomyosis who had received estrogen–progesterone hormone replacement therapy for two months. She was admitted with pain in the right calf, thigh, and groin after a long-distance trip. Duplex ultrasonography confirmed right iliofemoral deep-vein thrombosis (DVT). Thrombogenesis results from an imbalance between pro-thrombotic and anti-thrombotic pathways, classically summarized in Virchow’s triad of hypercoagulability, venous stasis, and endothelial injury 11. In this patient, the main predisposing factors were estrogen exposure and prolonged travel-related immobility. According to the 2019 European Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, oral contraceptives or hormone replacement therapy constitute a moderate-risk factor (odds ratio 2–9), whereas prolonged sitting or travel is considered a weak-risk factor (odds ratio <2) for venous thromboembolism 12. She had no history of trauma, surgery, heart failure, atrial fibrillation, or recent myocardial infarction. Could these two risk factors alone have precipitated thrombosis in this case? A cross-sectional study conducted between July and September 2020 in a Shanghai hospital demonstrated that patients with adenomyosis and menorrhagia exhibited a higher degree of hypercoagulability than those without menorrhagia 13. Moreover, previous studies have documented VTE complications in adenomyosis, including lower-limb DVT, pulmonary embolism, cerebral venous thrombosis, and multisite thrombosis 5,6,7,8.

In our patient, venous stasis may have constituted an additional pathogenic factor, because she presented with diffuse adenomyosis and a uterus enlarged to approximately a 16-week gestational size. A markedly large uterus can compress the right common iliac vein, impeding venous return and facilitating thrombus formation. Recent European Society of Cardiology guidelines have identified adenomyosis as a risk factor for future cardiovascular disease, including stroke and acute myocardial infarction 14. Previous case reports have documented cerebral venous thrombosis, ischemic stroke, pulmonary embolism (PE), and multisite thrombosis involving the brain, kidney, and spleen in patients with adenomyosis 5. Xiaolong Zong et al. demonstrated that patients with CA-125 levels greater than 1000 U/mL have a higher risk of PE, venous thrombo-embolism (VTE), and multisite thrombosis; moreover, those with CA-125 exceeding 1000 U/mL were significantly more likely to experience recurrent thrombosis than patients with CA-125 below 1000 U/mL 5. Our patient presented with a completely occlusive deep-vein thrombosis (DVT) in the right lower extremity and an initial CA-125 level of 2539.1 U/mL, substantially higher than the threshold reported by Xiaolong Zong et al. This finding implies a more severe thrombotic burden than that described in Xiaolong Zong’s report, where the thrombus was limited to the distal veins of the right leg and the CA-125 level was 687 U/mL 6. Nevertheless, she reported no chest pain, dyspnea, headache, visual disturbances, or abdominal pain, and supplementary investigations—including electrocardiography (ECG), transthoracic echocardiography, and abdominal ultrasonography—revealed no evidence of thrombosis at other sites.

Therapeutic approaches for adenomyosis-associated VTE or PE are primarily derived from individual case reports. In most descriptions, initial therapy consists of intravenous unfractionated heparin, subsequently replaced by a novel oral anticoagulant (NOAC) or aspirin as maintenance therapy 15,16. Control of adenomyosis itself involves surgical intervention—typically total hysterectomy—or medical management with non-steroidal anti-inflammatory drugs (NSAIDs), hormone replacement with estrogen plus progesterone, or gonadotropin-releasing hormone (GnRH) agonists 17. Because individuals with concurrent adenomyosis and thrombosis generally respond poorly to NSAIDs and must avoid exogenous estrogen owing to the heightened thrombotic risk, most published cases have been treated with either GnRH agonists or definitive hysterectomy after the VTE event.

Our patient could not receive systemic anticoagulation secondary to profound vaginal hemorrhage; therefore, an inferior vena cava (IVC) filter was placed to mitigate the risk of PE. Given the unavailability of GnRH agonists and their delayed onset of action, a total hysterectomy was performed at Hung Vuong Hospital. Anticoagulation was re-initiated on postoperative day 1 with enoxaparin 6,000 IU subcutaneously every 12 h for three days, after which the regimen was switched to rivaroxaban 15 mg/day at discharge. Expert opinion supports extended anticoagulation in patients with CA-125 concentrations > 1,000 U/mL or those with a history of recurrent VTE 5. Although no consensus exists regarding the optimum timing or dosage of anticoagulation following surgery for iliofemoral DVT secondary to adenomyosis, the literature documents heterogeneous strategies ranging from antiplatelet agents to vitamin K antagonists and NOACs. In light of the absence of evidence-based guidelines and the patient’s high bleeding risk, we elected to resume rivaroxaban at the reduced dose of 15 mg once daily, aiming to balance hemorrhagic and thrombotic hazards. The intended duration of therapy was ≥ 3 months, after which Doppler ultrasonography would be performed to evaluate thrombus resolution. If the CA-125 level fell below 1,000 U/mL and no residual thrombosis was detected, discontinuation of anticoagulation would be considered. Retrieval of the IVC filter is generally advocated within three months of placement.