Side Effect: Stroke (thrombotic and hemorrhagic)

A stroke is a medical emergency that occurs when blood flow to a part of the brain is interrupted, leading to brain cell damage or death.
Strokes are usually caused by either:

• a blockage in the blood vessels supplying the brain (ischemic stroke), often from a blood clot
• or bleeding in the brain (hemorrhagic stroke), either spontaneously or after trauma or surgery

The symptoms of a stroke can vary depending on which part of the brain is affected, but they often include:

• sudden weakness or numbness on one side of the body
• facial drooping
• difficulty speaking or understanding speech
• sudden vision changes
• dizziness
• severe headache (sometimes described as the worst of a person’s life)

Patients with cancer have an increased risk of developing a blood clot, known as a thrombotic event. Blood clots may include those in the legs or lungs, but if a blood clot travels from these areas to the brain, it may cause a stroke. Some patients with cancer develop blood clots more easily due to the cancer itself, or due to certain types of chemotherapy. When someone develops blood clots more easily, this is often referred to as having a hypercoagulable state.

This risk of having a stroke may be further increased in patients with other risk factors such as:

• immobility (spending much of the day in a chair or in bed)
• having surgery (which may cause a person to lay down for longer periods than normal, and because surgery can sirut normal blood flow that increases the risk of developing a blood clot
• atrial fibrillation (causes blood to pool in the atrium of the heart where it then moves slower than normal. This slower moving blood may clot more easily)
• Smoking (increases risk of clotting and stroke by causing narrowing of blood vessels, known as vasoconstriction)

Certain cancer treatments can increase risk of stroke such as:

• Immunomodulatory agents:
  • lenalidomide (Revlimid®)
  • pomalidomide (Pomalyst®)
  • thalidomide (Thalomid®)
• Asparaginase:
  • pegaspargase (Oncaspar®)
  • asparaginase (Rylaze®)
• Tamoxifen (Nolvadex®)
• VEGF inhibitors:
  • bevacizumab (Avastin®, Mvasi®, Zirabev®)
  • lenvatinib (Lenvima®)
  • regorafenib (Stivarga®)
  • cabozantinib (Cabometyx®, Cometriq®)
  • ramucirumab (Cyramza®)
  • sunitinib (Sutent®)
  • sorafenib (Nexavar®)

Patients with cancer can also have an increased risk of hemorrhagic stroke, particularly those with:

• primary brain tumors
• brain metastases
• low platelet count (thrombocytopenia)
• an increased amount of activity of clotting factors, known as a coagulopathy
• medications that increase the risk of bleeding:
  • Anticoagulants: apixaban (Eliquis), rivaroxaban (Xarelto), edoxaban (Savaysa), warfarin
  • NSAIDS: ibuprofen, naproxen, meloxicam
  • Antiplatelet: clopidogrel (Plavix), aspirin

Controlling blood pressure, stopping smoking, and maintaining adequate physical activity can help reduce the risk of thrombotic stroke (blood clot in the brain).

• Certain patients with a heart condition known as atrial fibrillation (fast heart beat) may benefit from taking anticoagulation medication to reduce the risk of developing a blood clot. The risks and benefits of this must be balanced with the risk of bleeding as well.
• Patients with a history of a blood clot in the brain may take antiplatelet or anticoagulant medication to prevent them from having a second stroke

Prevention of hemorrhagic stroke (bleeding in the brain) in patients with cancer involves managing underlying risk factors such as high blood pressure and avoiding the use of anticoagulants and antiplatelet drugs when possible, or holding these medications during of periods of time when the platelet count is very low, such as after a cycle of chemotherapy.

The use of anticoagulant therapy in patients with cancer should be carefully considered and individualized based on the patient's risk of thrombosis and bleeding.

Treatment of thrombotic stroke

• Treatment of thrombotic stroke may involve emergent interventions to remove the clot such as administration of intravenous tissue plasminogen activator, or “tPA” (a “clot-busting medication”) or mechanical thrombectomy (surgical removal of the clot).
• Anticoagulant therapy such as enoxaparin (Lovenox®), apixaban (Eliquis®), rivaroxaban (Xarelto®), or warfarin (Coumadin®) may also be used to prevent further clot formation, or antiplatelet medications such as aspirin or clopidogrel (Plavix) or ticagrelor (Brilinta) may be recommended to reduce the risk of having another stroke.

Treatment of hemorrhagic stroke

• Treatment of hemorrhagic stroke in patients with cancer involves controlling bleeding and managing any underlying coagulopathy or low platelet count (thrombocytopenia).
• Interventions to remove the pooled blood may be indicated.
  • This is typically done by a neurosurgery team when the increased amount of blood in the brain creates too much pressure for the brain to handle.
• If bleeding is caused by a tumor, chemotherapy, radiation, or surgery can be used.
  • If there is swelling around the affected area, corticosteroids such as dexamethasone (Decadron®) and methylprednisolone (Solu-Medrol®) may be used to decrease the pressure inside the head.