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Targeting procoagulant platelets in cardiovascular disease

ANZAC Research Institute

  • Early-Mid Career Fellowship
Organ System:
  • Cardiovascular
Date Funded:
  • 31 May, 2018
Chief Investigator/s:
  • Dr. Hai Po Helena Liang

Blood clots blocking the blood supply to the heart and the brain, known as arterial thrombosis, cause heart attack and stroke – the leading cause of death and disability in the Australia. Platelets are the cells that form these blood clot, thus drugs targeting platelets such as aspirin are the mainstay of heart attack and stroke prevention. Yet current treatment has limited effectiveness with optimal therapy – up to 30 per cent of patients will have a recurrent event within three years, and more effective therapies often lead to bleeding side effects.

Our work has identified a particular sub-set of platelets within people with cardiovascular disease that increase blood clots, but are not turned-off by aspirin. These are called procoagulant platelets. Measurement of procoagulant platelets in patients has initially been very difficult due to the lack of sensitive and specific tests. We have recently developed a way to measure procoagulant platelets in people at risk of heart attack and stroke, and have shown that more procoagulant platelets are indeed formed during stroke and heart attacks. It is therefore this sub-set of platelets in people with cardiovascular disease that we would like to target more specifically when designing new drugs, in order to increase the beneficial effect and at the same time reduce the bleeding side effect when treating patients.

Interestingly, a simple non-invasive process called remote ischaemic preconditioning (RIPC), which is performed by inflating and deflating a blood pressure cuff three times, was able to reduce procoagulant platelets in people with heart disease when aspirin and other anti-platelet drugs could not. Others have previously shown that RIPC can protect the heart muscle and brain from damage during heart attack and stroke, but the mechanism by which it does this is unknown.

My studies indicate that RIPC affects procoagulant platelets by affecting the platelet mitochondria. Mitochondria are organelles inside the platelet that converts glucose to energy. My project investigates the link between procoagulant platelets, platelet mitochondrial function and cardiovascular disease. In addition to providing the rationale for RIPC, these studies aim to identify platelet mitochondrial pathways as a novel target for cardiovascular disease that will work in addition to existing cardiovascular drugs without causing bleeding. Ultimately, our work would be able to provide more tailored therapies for patients, reduce our patients’ waiting time, pain and risk of receiving treatments, improve their disease outcome, and reduce medical cost for the NSW health system.