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Cancer and Stroke


Learning objectives

  • Cancer as a risk for stroke
  • Different mechanisms

Introduction

  • The relationship between stroke and cancer is complex
  • Cancers can cause stroke indeed Stroke may be the presenting feature
  • High risk - adenocarcinoma or those with widespread metastases
  • Cancer is 2nd leading cause of death and stroke 4th in the USA
  • Occult cancer may be an important missed diagnosis in cryptogenic stroke.

Cancers causing stroke

  • Lung cancer
  • Prostate cancer
  • primary brain tumours
  • Haematological malignancies
  • Pancreatic cancer
  • Gynaecological

Cancers with haemorrhagic metastases

  • Melanoma, Renal, thyroid cancer
  • germ cell tumours

Aetiologies

  • Tumour compression on vascular supply – arterial/venous/capillary
  • Procoagulant effect of malignancy
  • Procoagulant effect of treatments
  • Leukostasis
  • Cardioemboli from marantic endocarditis
  • Radiation vasculopathy from head and neck cancers
  • Coexisting risk factors : hypertension, hyperlipidemia, diabetes, atrial fibrillation and tobacco use

Possible mechanism: see See paper

MechanismCausal factorAssociated tumoursStroke Characteristics
HypercoagulabilityAdenocarcinomas especially; secrete mucin; tumours activate coagulation cascade; release pro-coagulant cytokinesAdenocarcinoma of breast, lung, prostate, etc. Also brain, kidney or hematologic malignanciesEmbolic appearing infarcts, end vessels
Venous-to-arterial embolismPFO, right-to-left shuntUncertain, likely similar to tumours of hypercoagulable stateEmbolic appearing
Non bacterial thrombotic endocarditisSterile vegetations, clumps of platelets and fibrin develop on aortic valveAdenocarcinoma is most commonMultiple widely distributed small and large strokes
Direct tumour compression of vesselTumour growth and resultant oedema compresses major intracranial vesselGlioblastoma multiforme, metastasis to brain Large vessel, MCA common
Tumour embolismRare- cardiac tumour causes embolization of malignant cellsAtrial or aortic valve myxoma, metastatic tumours to heartEmbolic appearing
HyperviscocityRare-“Thickened” blood causes hypoviscious obstruction of small end vesselsPolycythemia vera, multiple myeloma, Waldenstrom’s Macroglobulinemia, leptomeningeal carcinomatosisSmall end-vessels strokes
Angioinvasive/infiltrativeRare-Hematologic malignancies infiltrate blood vessel wall, causing irregularities that predispose to arterial embolismB-cell lymphomaMultiple vascular territory infarcts
Post –radiation vasculopathyRadiation after head and neck cancer causes vasculopathy leading to accelerated atherosclerosis, predisposing to vessel wall irregularities and embolismSquamous cell carcinoma, other head and neck tumoursEmbolic stroke from the affected carotid
Chemotherapy associatedUnknownAssociated with as cisplatin, methotrexate, L-aspariginase, thalidomide, lenalidomide, and bevacizumabVaried

Clinical

  • Ischaemic stroke syndromes
  • Haemorrhagic stroke syndromes
  • Strokes in cancer patients may be subclinical
  • DVT often a sign of hypercoagulability

Marantic endocarditis

  • This is a nonbacterial thrombotic endocarditis where there are found to be vegetations consisting of an amorphous mixture of fibrin and platelets onto heart valves on previously undamaged heart valves (most often aortic and mitral) in the absence of a bloodstream bacterial infection.
  • It is a rare condition often associated with hypercoagulable states or advanced malignancy such as adenocarcinomas.
  • The diagnosis is made by Echocardiography showing evidence of vegetations.
  • It may be a cause of cardioembolic stroke. Management is focused on managing the underlying cause.

Investigations

  • FBC, U&E, ESR, TFTs, CRP, ECG
  • CT scan +/- contrast
  • MRI +/- Gadolinium
  • 12 lead ECG
  • Echo and TOE if marantic endocarditis suspected
  • Tumour staging

Differentials

  • Prothrombotic conditions
  • Vasculitis

Management

  • Ensure good VTE prophylaxis as high risk with immobility + cancer
  • Close liaison with oncology and haematology with shared care planing
  • Depends very much on the state of the patient, the advancement of their malignancy and their best interest.
  • LMWH is usually the treatment with a confirmed coagulopathy or a marantic endocarditis

References and further reading


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