Short circuit to thrombosis: Tumour vesicles in coagulation

Venous thromboembolism (VTE) affects many cancer patients, across a broad range of cancer types. Venous thrombosis occurs when blood clotting occurs inside veins and embolism occurs if the clots break free, travel to the lungs and obstruct lung arteries. In lung cancer, VTE is the second highest cause of death with only about 10% of sufferers surviving beyond one year.

Researchers:

• Associate Professor Alex McLellan
• Morad-Rèmy Muhsin (PhD candidate)
• Catrin Buchanan (BScHons student)
• Amy Dunn (Technician)
• Sarah Saunderson (PhD candidate)

The four-fold risk of VTE in cancer patients is increased to six to seven-fold with chemotherapy treatment for the cancer. To make matters worse, coagulation can enhance cancer progression to other organs.

We have recently discovered that chemotherapy stimulates the release of pro-coagulant vesicles from the surface of lung tumours. Our findings point to a previously undescribed complex of coagulation factors that contribute to the clot-inducing activity of vesicles. These vesicles cause 'abnormal or pathological' coagulation that is essentially a short circuit bypassing many aspects of normal physiological coagulation. For example, deficiencies in coagulation factor VIII or IX cause common types of haemophilia, yet people with haemophilia who have cancer do not seem to be protected from thrombosis. We have shown that tumour vesicles do not require factors VIII or IX to provoke coagulation and they may not be subject to some of the normal control processes from naturally produced anti-coagulants. Pro-coagulant vesicles released from dying tumour cells may also contribute to the growth and spread of cancer cells that survive chemotherapy treatment.

Ultimately, this study will guide the development and use of anti-coagulant drugs in cancer. It will also allow us to identify biomarkers on circulating vesicles to determine which cancer patients will need anticoagulant treatment.