In a rare and clinically complex case highlighting the hidden dangers of cancer-associated coagulopathy, medical specialists at Padua University Hospital in Italy successfully diagnosed and treated a 21-year-old woman who developed a large, asymptomatic right atrial thrombus prior to initiating any systemic chemotherapy for classical Hodgkin lymphoma (cHL).
Thrombotic complications are a well-documented hazard for individuals battling hematologic malignancies. However, these events overwhelmingly manifest during active chemotherapy regimens or as a direct mechanical complication of central venous access device (CVAD) placements, such as peripherally inserted central catheters (PICCs). Discovering a significant intracardiac blood clot during the pre-treatment diagnostic window—and prior to the start of disease-fighting drugs—is an extraordinary medical rarity.
The case, detailed in Frontiers in Hematology, emphasizes the absolute necessity of deploying advanced, multimodality imaging techniques during oncology staging. By swiftly distinguishing between true cardiac neoplasm infiltration and an acute thrombus, multidisciplinary medical teams can initiate prompt, tailored anticoagulation therapy. This intervention protects patients from catastrophic pulmonary embolisms or systemic strokes, ensuring they can proceed safely through curative cancer treatments without interruption or life-threatening bleeding.
Detailed Chronology: From First Symptoms to Complete Metabolic Response
Presentation and Initial Work-Up
The clinical journey began when a 21-year-old woman visited the Hematology Unit complaining of a self-detected, painful laterocervical lymphadenopathy (swollen lymph nodes in the neck). She reported classic, systemic B-symptoms of lymphoma: profuse night sweats, generalized pruritus (severe itching), and an unintentional, rapid weight loss of 8 kilograms (roughly 17.6 pounds) over the span of just one month.
Initial laboratory blood panels exposed a concerning systemic inflammatory and hematologic profile:
- White Blood Cell (WBC) Count: $15.95 times 10^9/textL$ (showing marked neutrophilic leukocytosis at $11.50 times 10^9/textL$)
- Hemoglobin (Hb): $104text g/L$ (indicating mild anemia)
- Platelet Count (PLTs): $548 times 10^9/textL$ (demonstrating reactive thrombocytosis)
- Erythrocyte Sedimentation Rate (ESR): $92text mm/h$ (signifying high systemic inflammation)
- Lactate Dehydrogenase (LDH): $185text U/L$
A subsequent head and neck ultrasound revealed multiple enlarged, hypoechoic lymph nodes measuring between 2 to 3 centimeters in diameter, some of which displayed irregular vascularization patterns. Suspecting a lymphoproliferative disorder, physicians performed an excisional lymph node biopsy. Pathology confirmed a definitive diagnosis of classical Hodgkin lymphoma, nodular sclerosis subtype (Grade 1 according to British National Lymphoma Investigation criteria).
Staging and Incidental Discovery
To map the extent of the disease, a staging positron emission tomography-computed tomography (PET-CT) scan was conducted. It highlighted hypermetabolism in multiple supradiaphragmatic lymph nodes, formally staging her disease as Stage IIB. Intriguingly, the PET scan also flagged increased fluorodeoxyglucose (FDG) uptake in the right pericardiac region, initially raising red flags for possible direct cardiac or pericardial tumor involvement.
In preparation for systemic chemotherapy, clinicians placed a peripherally inserted central catheter (PICC) to facilitate drug delivery. A total-body CT scan confirmed the lymphoma’s stage.
However, exactly 13 days post-PICC placement—and still prior to the administration of any chemotherapy drugs—a routine pre-treatment transthoracic echocardiography (TTE) delivered a shocking surprise. The ultrasound revealed a multilobulated, isoechoic mass measuring $3.5 times 2.4text cm$ firmly adherent to the lateral wall of the right atrium. The mass extended toward the tricuspid valve plane, though thankfully without causing vena cava inflow obstruction or acute hemodynamic compromise.
Resolving the Diagnostic Dilemma
Faced with a mysterious right atrial mass in a newly diagnosed lymphoma patient, the medical team confronted two major clinical puzzles:
- Was the mass a malignant cardiac infiltration of the Hodgkin lymphoma or an independent blood clot (thrombus)?
- Did the abnormal FDG uptake in the pericardiac region seen on the PET scan represent actual heart muscle disease involvement?
To solve this, advanced diagnostics were deployed. Cardiac magnetic resonance imaging (CMR) was performed. CMR provided critical tissue characterization, demonstrating that the right atrial mass shared an isointense signal on cine, T1-weighted, and T2-weighted sequences. It displayed internal signal heterogeneity with a complete absence of first-pass perfusion and late gadolinium enhancement. These classical imaging signatures proved the lesion was completely avascular—confirming it was a benign thrombus rather than a malignant lymphomatous tumor infiltration. Furthermore, a rigorous re-evaluation of the PET-CT scan confirmed that the localized FDG uptake did not anatomically align with the interatrial mass observed on the echocardiogram.
Anticoagulation Strategy and Cancer Treatment
Recognizing the acute thrombotic risk, the medical team initiated a carefully calibrated anticoagulation protocol. Treatment began with low-molecular-weight heparin (LMWH) at 6,000 IU daily, which was swiftly escalated to a full therapeutic dose of 8,000 IU twice daily after the CMR confirmation.
Because active cancer therapies can cause complex drug-drug interactions—for instance, chemotherapeutic agents like doxorubicin can reduce the area under the curve (AUC) of direct oral anticoagulants like apixaban, thereby lowering systemic drug exposure—clinicians managed the transition with extreme caution. Following specialist consultation, the patient was successfully transitioned to oral apixaban (5 mg twice daily).
With the thrombotic risk successfully mitigated, the patient was cleared for oncological therapy. She underwent the rigorous HD17 treatment regimen, consisting of two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by two cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine).
She completed the grueling chemotherapy regimen without encountering any thromboembolic or hemorrhagic complications. An end-of-treatment PET-CT scan confirmed a complete metabolic response (achieving a stellar Deauville score of 2). A follow-up TTE performed one month post-treatment demonstrated a dramatic, progressive reduction in the size of the right atrial mass, shrinking down to $1.7 times 1.2text cm$ with zero venous inflow obstruction. The patient remains in stable remission under active clinical surveillance.
Supporting Context & Metrics
The Mechanics of Cancer-Associated Thrombosis
Venous thromboembolism (VTE) is a notorious complication in oncology, occurring through a triad of factors known as Virchow’s triad: hypercoagulability (driven by systemic factors released by the tumor), endothelial injury, and circulatory stasis. While overall VTE rates in lymphoma patients range from 4% to 10% (and up to 13% in broader hematologic malignancy cohorts), instances of pre-treatment thrombosis remain exceptionally scarce.
[Malignant Hypercoagulability] + [Endothelial Injury via PICC] + [Flow Disturbance]
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[Atypical Intracardiac Thrombus Formation]When central venous access devices like PICC lines are introduced into patients with baseline cancer-related hypercoagulability, the risk profile multiplies. The foreign-body surface of the catheter activates the coagulation cascade, while minor mechanical trauma during insertion injures the delicate endothelial lining of blood vessels. In this patient, the 13-day window between PICC insertion and the detection of the right atrial mass strongly points toward a catheter-contributed or catheter-induced etiology, though the absence of baseline pre-PICC cardiac imaging leaves a minor window of uncertainty regarding pre-existing micro-thrombi.
Comparative Intracardiac Thrombosis in Hodgkin Lymphoma
Intracardiac thrombosis involving the right atrium is a life-threatening pathology that carries high mortality if ignored. A review of existing medical literature underscores how rare this presentation is within classical Hodgkin lymphoma:
| Author & Year | Patient Age/Sex | Type of VTE | Timing | Treatment Strategy | Anticoagulation Protocol | Clinical Outcome |
|---|---|---|---|---|---|---|
| Bangolo A. et al. | 31, Female | Right atrial thrombosis | 7 years post-treatment | Thrombectomy + Anticoagulation | Apixaban | Full Recovery |
| Ren S. et al. | 29, Female | Right atrial thrombosis | During chemotherapy | Medical Anticoagulation | LMWH, Apixaban | Full Recovery |
| Chan T.S. et al. | 33, Female | Left ventricular thrombosis | During chemotherapy | Mitral valve replacement | Not Available | Full Recovery |
| Chan A. et al. | 56, Male | Right atrial thrombosis | Post-chemotherapy | Anticoagulation / Thrombectomy eval | Unspecified Heparin | Mortality |
| Giordano A. et al. (Current) | 21, Female | Right atrial thrombosis | At initial diagnosis | Medical Anticoagulation | LMWH, Apixaban | Full Recovery |
As demonstrated, the Padua University Hospital case is unique because the right atrial thrombus was identified prior to the initiation of any systemic chemotherapy—underscoring that life-threatening clotting events can brew before cancer treatments even begin.
Official Statements and Institutional Support
This breakthrough clinical report was made possible through a collaborative effort by researchers from the Hematology Unit at Padua University Hospital. The investigative team was spearheaded by Andrea Giordano, Valentina Bodanza, Francesca Angotzi, Alice Cellini, Anna Bevilacqua, Marta D’Antiga, Marta De Ferrari, Valentina Pergola, Elisa Campello, Livio Trentin, and Andrea Visentin.
Financial backing and research grants instrumental to this case study were provided by:
- The Italian Association for Cancer Research (AIRC) via grant IG-25024 (awarded to L. Trentin).
- Progetti di Rilevanza Nazionale PRIN PNRR (grant P2022PSMX4, awarded to A. Visentin).
- The Padua-based non-profit organization ONLUS “Ricerca per Credere nella Vita” (RCV).
- The Supporting Talent in ReSearch@University of Padua Starting Grant (Be_CL3VER, awarded to A. Visentin).
The authors formally declared that the research was conducted in the complete absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Written informed consent was explicitly obtained from the patient for the publication of all associated clinical data and imaging figures.
Future Outlook
The successful management of this complex case establishes an important clinical precedent for oncologists and hematologists worldwide. It delivers several critical takeaways for future medical practice:
- Mandatory High Index of Suspicion: Clinicians must remain vigilant for atypical thrombotic manifestations—including rare intracardiac masses—during the baseline staging work-up of newly diagnosed lymphoma patients, even before chemotherapy commences.
- The Power of Multimodality Imaging: Relying on a single imaging modality can lead to dangerous misdiagnoses. The combination of echocardiography (TTE) for structural visualization, PET-CT for metabolic staging, and cardiac magnetic resonance (CMR) for definitive tissue characterization is indispensable for separating benign thrombi from malignant tumors.
- Optimized Anticoagulation Pathways: Safely navigating cancer-associated thrombosis requires a dynamic pharmaceutical strategy. Bridging patients from low-molecular-weight heparin to direct oral anticoagulants (such as apixaban), while carefully factoring in the pharmacokinetic impacts of chemotherapeutic agents like doxorubicin, prevents catastrophic bleeding or clotting events.
Ultimately, early recognition and interdisciplinary teamwork can successfully resolve even the most terrifying thrombotic complications, allowing young, vulnerable cancer patients to focus entirely on winning their battle against malignant disease.