ParaneoplasticHypercoagulableICD-10 I82.81
Trousseau sign of malignancy
Trousseau syndrome; migratory superficial thrombophlebitis of malignancy; thrombophlebitis migrans
The Trousseau sign of malignancy is unprovoked recurrent, migratory superficial thrombophlebitis (or recurrent venous thromboembolism) as a manifestation of cancer-associated hypercoagulability. Described by Armand Trousseau in 1865 β who later developed the same syndrome himself and died of pancreatic cancer. Strongest association is with pancreatic adenocarcinoma, but also gastric, lung, ovarian, colorectal, prostate and haematological malignancies. Pathogenesis involves tumour-induced expression of tissue factor, cancer procoagulant, mucin shedding, and platelet activation. Management is anticoagulation β LMWH first-line β alongside investigation for and treatment of the underlying cancer.
CurrentLast reviewed 15 May 2026
Clinical features
- Recurrent painful, palpable, red-tender cord along a superficial vein.
- Migratory β affects multiple anatomical sites at different times.
- Often involves veins in unusual anatomical sites (upper extremity, anterior chest, abdominal wall) β not just the leg.
- Frequently unprovoked β no trauma, no IV catheter, no obvious cause.
- May co-exist with deep venous thrombosis, pulmonary embolism, arterial thromboembolism, non-bacterial thrombotic endocarditis (marantic endocarditis), disseminated intravascular coagulation.
- Differential diagnosis β infection (suppurative phlebitis), BehΓ§et syndrome, antiphospholipid syndrome, hypercoagulable inherited disorders.
Cancer associations
- Pancreatic adenocarcinoma β the classical and strongest association; ~ 50% of cancer-associated Trousseau syndrome.
- Gastric adenocarcinoma, particularly mucinous.
- Lung adenocarcinoma.
- Ovarian, colorectal, prostate, breast, brain malignancies.
- Haematological malignancies β myeloproliferative neoplasms, lymphoma, multiple myeloma.
- Approximately 5β15% of patients with idiopathic VTE will be diagnosed with an underlying malignancy within 12 months.
Pathogenesis
- Tumour cells express tissue factor (TF / CD142), the key initiator of the extrinsic coagulation pathway.
- Cancer procoagulant β a cysteine protease produced by tumour cells that directly activates factor X.
- Tumour-derived microparticles carrying TF circulate and propagate coagulation systemically.
- Adenocarcinomas (particularly mucin-producing) β released mucins activate platelets and the coagulation cascade.
- Cytokine release (TNF-Ξ±, IL-1) damages endothelium and creates a prothrombotic state.
- The overall effect is a clinically significant systemic hypercoagulable state β Trousseau syndrome is one manifestation.
Workup for occult malignancy
- Detailed history β weight loss, anorexia, night sweats, GI symptoms, smoking, family history.
- Physical examination β abdominal masses, hepatosplenomegaly, lymphadenopathy, weight, breast / testicular examination.
- Initial bloods β FBC, U&E, LFT, calcium, CRP, faecal occult blood, urinalysis.
- Imaging β chest X-ray; consider CT NCAP; FDG-PET-CT.
- Targeted onward investigation β upper / lower GI endoscopy, mammography in women, cervical / pelvic imaging, prostate examination + PSA in men.
- Modest yield (~ 5β10%) of cancer detection in unprovoked VTE in real-world UK cohorts β but the diagnosis when made can substantially change management.
Management
- Anticoagulation β low-molecular-weight heparin (LMWH; dalteparin, tinzaparin, enoxaparin) first-line for cancer-associated thrombosis:
- Originated with CLOT trial (Lee, NEJM 2003) β dalteparin superior to warfarin for cancer-associated thrombosis.
- CATCH trial (Lee, JAMA 2015) β tinzaparin similarly effective.
- Direct oral anticoagulants (DOACs β edoxaban, apixaban, rivaroxaban) β non-inferior to LMWH per SELECT-D, ADAM-VTE, CARAVAGGIO, HOKUSAI-VTE-Cancer; UK NICE NG158 now positions DOACs as alternatives to LMWH for cancer-associated VTE, with consideration of bleeding risk (avoid in upper GI cancer).
- Treatment duration β at least 3β6 months; lifelong while active cancer present and tolerated.
- Treatment of the underlying malignancy β surgical, chemotherapy, radiotherapy β often improves coagulation status alongside anticoagulation.
- Inferior vena cava filter β reserve for short-term contraindication to anticoagulation; not preventive.
- Severe / refractory cases β therapeutic-dose continuous LMWH (rather than DOAC); aspirin alone is insufficient.
References
- Trousseau A. Phlegmasia alba dolens β clinique mΓ©dicale de l'Hotel-Dieu de Paris. 1865.
- Lee AY et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer (CLOT). N Engl J Med; 2003.
- Lee AY et al. Tinzaparin vs warfarin for treatment of acute VTE in patients with active cancer (CATCH). JAMA; 2015.
- NICE NG158. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. London: NICE; 2020 (last updated 2 August 2023; reviewed 1 May 2026).
- Khorana AA et al. Cancer-associated venous thromboembolism. Nat Rev Dis Primers; 2022.
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