Learning objectives
- Learning
- Understand
- Integrate
- Reflect
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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
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Possible mechanism: see See paper
| Mechanism | Causal factor | Associated tumours | Stroke Characteristics |
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| Hypercoagulability | Adenocarcinomas especially; secrete mucin; tumours activate coagulation cascade; release pro-coagulant cytokines | Adenocarcinoma of breast, lung, prostate, etc. Also brain, kidney or hematologic malignancies | Embolic appearing infarcts, end vessels |
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| Venous-to-arterial embolism | PFO, right-to-left shunt | Uncertain, likely similar to tumours of hypercoagulable state | Embolic appearing |
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| Non bacterial thrombotic endocarditis | Sterile vegetations, clumps of platelets and fibrin develop on aortic valve | Adenocarcinoma is most common | Multiple widely distributed small and large strokes |
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| Direct tumour compression of vessel | Tumour growth and resultant oedema compresses major intracranial vessel | Glioblastoma multiforme, metastasis to brain |
Large vessel, MCA common |
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| Tumour embolism | Rare- cardiac tumour causes embolization of malignant cells | Atrial or aortic valve myxoma, metastatic tumours to heart | Embolic appearing |
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| Hyperviscocity | Rare-“Thickened” blood causes hypoviscious obstruction of small end vessels | Polycythemia vera, multiple myeloma, Waldenstrom’s Macroglobulinemia, leptomeningeal carcinomatosis | Small end-vessels strokes |
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| Angioinvasive/infiltrative | Rare-Hematologic malignancies infiltrate blood vessel wall, causing irregularities that predispose to arterial embolism | B-cell lymphoma | Multiple vascular territory infarcts |
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| Post –radiation vasculopathy | Radiation after head and neck cancer causes vasculopathy leading to accelerated atherosclerosis, predisposing to vessel wall irregularities and embolism | Squamous cell carcinoma, other head and neck tumours | Embolic stroke from the affected carotid |
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| Chemotherapy associated | Unknown | Associated with as cisplatin, methotrexate, L-aspariginase, thalidomide, lenalidomide, and bevacizumab | Varied |
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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