Trousseau syndrome presenting with recurrent multi-territory infarctions: a case report of two patients highlighting divergent outcomes and dynamic hypercoagulability under direct oral anticoagulants and low-molecular-weight heparin

Background Trousseau syndrome is a cancer-associated hypercoagulable state characterized by recurrent thromboembolic events, including ischemic stroke. Optimal anticoagulation strategies remain controversial, particularly regarding the effectiveness of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin (LMWH). Case presentation We report two patients with Trousseau syndrome who presented with recurrent multi-territory cerebral infarctions despite ongoing DOAC therapy. Case 1 was a 66-year-old man with active intrahepatic cholangiocarcinoma who developed repeated ischemic strokes and deep vein thrombosis while receiving rivaroxaban. After switching to LMWH, D-dimer levels decreased markedly. However, anticoagulation was de-escalated in the context of apparent normalization of D-dimer, followed by recurrent stroke, subsequent discontinuation of anticoagulation, and a rapid surge in D-dimer levels, ultimately resulting in death. Case 2 was a 74-year-old man with suspected recurrent metastatic gastric adenocarcinoma who developed ischemic stroke while on rivaroxaban. Following transition to LMWH, D-dimer levels progressively declined, and the patient remained clinically stable without recurrence during follow-up. A longitudinal timeline analysis integrating biomarker dynamics, treatment transitions, and clinical events demonstrated distinct patterns between the two cases, suggesting a potential discordance between D-dimer levels and underlying hypercoagulable activity. Conclusion These cases highlight the dynamic nature of hypercoagulability in Trousseau syndrome. Normalization of D-dimer alone may not reliably indicate sustained control of malignancy-associated hypercoagulability and should not be used in isolation to guide anticoagulation de-escalation. LMWH may provide more consistent control in selected high-risk patients, although causal inference cannot be established from this report.