Platelets and their response to acute changes in blood flow

L-R: Ms Nurul Abidin Zainal, Dr Warwick Nesbitt and Dr Crispin Szydzik
are authors on the paper

In world-first research to combine computational models of blood flow with single platelet signalling studies, a Monash collaborative study has found that platelets are able to sense acute changes in blood flow found within diseased vessels or blood-contacting devices through a unique mechano-sensor. 

The team includes Australian Centre for Blood Diseases (ACBD) researchers, in collaboration with Alfred Health, University of Melbourne (Engineering & Medicine) and RMIT University (Engineering).

Rapid measurement of platelet function moves closer to fruition

2017 Nandurkar group, three of whom are authors on the article
describing their device for measuring platelet function.

by Anne Crawford

Monash and RMIT scientists have edged closer to refining a device that will rapidly measure platelet function in the blood of people with von Willebrand's disease (vWD), the most common inherited bleeding disorder in Western populations. The device will also act as a high-throughput screening tool for other blood platelet disorders and new drug discovery.

Blood clot study points to new drug target

Shauna French and Dr Justin Hamilton analysing results

by Anne Crawford

Arterial thrombosis – blood clot in an artery – can lead to several serious conditions including heart attack and stroke, and is the most common cause of death and disability in Australia. A Monash PhD student at the Australian Centre for Blood Diseases (ACBD) has conducted research demonstrating a potential new solution to the clotting that causes the problem.

Existing drugs aiming to prevent arterial thrombosis by acting on the platelets that form blood clots have limitations in efficacy and/or safety, some causing excessive bleeding.

Congratulations to Justin Hamilton & co-authors for selection of Plenary Paper

Congratulations to Dr Justin Hamilton and his co-authors on their recent publication for selection as the Plenary Paper in the latest edition of the journal Platelets. If you would like to share the reference, use the Platelet links:

• https://twitter.com/plateletjournal/status/755298258579230720
• https://www.facebook.com/plateletsjournal/posts/1017882728303175

Reference: Petitjean C, Setiabakti NM, Mountford JK, Arthur JF, Ellis S, Hamilton JR. (2016) Combined deficiency of PI3KC2α and PI3KC2β reveals a nonredundant role for PI3KC2α in regulating mouse platelet structure and thrombus stability. Platelets, 27:5, 402-409, DOI: 10.3109/09537104.2016.1145202

Anti-AIDS drug can affect platelet activation

By Dr Jodie Abramovitch

Abacavir is an anti-retroviral medication that is commonly used to treat HIV infection to prevent or control the development of AIDS. Abacavir use has been associated with an increased risk for cardiovascular disease (CVD). However, it is unknown how abacavir leads to this increased risk of CVD.

Dr Janine Trevillyan - HIV researcher and
lead author of this study

Monash researchers from the Department of Infectious Diseases and the Australian Centre for Blood Diseases (ACBD) theorised that abacavir could be affecting platelet activation thus leading to the development of CVD. Therefore the aim of their study was to determine if platelet reactivity was altered with abacavir administration.

Patients with well controlled HIV infection on non-abacavir treatments were recruited from the Infectious Diseases clinic at the Alfred Hospital. Twenty selected patients were given abacavir alongside their non-abacavir treatments for 15 days and had blood samples taken at day 0, 15 (treatment ceased) and 28. Platelet reactivity (as measured by VASP-index) was significantly decreased during abacavir treatment (at day 15 compared to day 0). A measurable decrease in soluble glycoprotein VI levels (sGPVI) was also indicative of lower platelet reactivity. Platelet surface protein integrin-β3 was also observed to be lower which may suggest a change in platelet structure. At day 28 following clearance of abacavir from the body, measurements were similar to those taken at day 0.

The findings in this study show that abacavir does have an effect on platelet reactivity, though this is reversible following cessation of treatment. The link between platelets and CVD needs to be explored further and the clinical implications of these results requires more research in a larger group of patients. This study has identified possible markers of disease in sGPVI and integrin- β3.

Reference: Trevillyan JM, Arthur JF, Jing J, Andrews RK, Gardiner EE, Hoy JF. Effects of abacavir administration on structural and functional markers of platelet activation. AIDS. 2015 Nov: 29;2309-13. 

doi: 10.1097/QAD.0000000000000848

New gene mutation identified in Bernard-Soulier syndrome patient

By Dr Jodie Abramovitch

Bernard-Soulier syndrome (BSS) is a rare condition in which blood does not clot properly leading to increased bleeding. The underlying cause of this condition is due to a defect or deficiency in a specific receptor found on platelets (component of blood that aids blood clot formation) called GPIb-IX-V. This particular receptor controls platelet adhesion, allowing them to ultimately form a clot and thereby prevent excessive bleeding.

Dr Elizabeth Gardiner and A/Prof Robert Andrews

Monash researchers from the Australian Centre of Blood Diseases in the Systems Haematology group, led by Associate Professor Robert Andrews and Dr Elizabeth Gardiner, and collaborators from the Alfred Hospital and the Kolling Institute of Medical Research (Sydney) have identified a new gene mutation in platelet receptor component GPIbβ in a patient with BSS. The patient had a greatly reduced number of platelets in the blood and a clinical history of mild bleeding.

Upon closer analysis of the patient’s platelets, a number of important platelet molecules were found to only be expressed at very low levels or were undetectable. Another molecule that assists with receptor organisation, called CD9, was also found to be reduced.

They discovered that this patient had a previously undescribed genetic mutation in GPIbβ that was interrupting the formation of important platelet receptors. This led to platelets that were unable to clot together properly, resulting in a longer bleeding time.

The link between mutated GPIbβ and reduced CD9 is unclear though has been previously reported in other BSS patients. As such, CD9 may be a new marker to help definitively diagnose BSS patients.

Reference: Qiao J, Davis AK, Morel-Kopp MC, Ward CM, Gardiner EE, Andrews R. Low levels of CD9 coincidental with a novel nonsense mutation in glycoprotein Ibβ in a patient with Bernard-Soulier syndrome.  Ann Hematol. 2015; 94(12): 2069-71

doi: 10.1007/s00277-015-2473-1

New blood clot buster discovered

Dr Justin Hamilton with one of his students,
Natasha Setiabakti (BMedSc(Hons)).

Researchers have made a discovery that could lead to new therapies for treating heart attack and stroke patients.

Published in Nature Communications, the study led by Monash researchers has uncovered a unique approach to prevent platelet function, responsible for forming blood clots.

Blood clots are the cause of heart attacks and most strokes, which are the most common cause of death and disability in the world.

Dr Justin Hamilton,  Head of the Platelet & Megakaryocyte Cell Biology Lab in the Australian Centre for Blood Diseases (ACBD) at Monash University, said drugs that prevented platelet function were the leading approach for heart attack and stroke prevention. However, many patients do not respond to current therapies.