Of platelets and aggregometers: personal reminiscences of Gus Born (1921-2018).

This paper recounts the author's personal reminiscences of the late Gustav Born and details some of his major influences on the field of platelet biology and mechanisms of hemostasis. In particular, it focuses on his development of the 'Born aggregometer' and the differences that are seen in the aggregation response to certain stimuli when aggregation is recorded using other techniques such as the impedance method.

Gustav Born: pioneer in imaging platelet and leukocyte biology.

Gustav Born achieved scientific fame for his application of light transmission aggregometry to the study of platelet function, but also led interdisciplinary research teams in pioneering quantitative in vivo imaging studies of platelet aggregation and leukocyte adhesion, and in conducting the first research into the biomechanical factors underlying atherosclerotic plaque rupture. Gus Born also communicated both current research findings and an integrated understanding of cardiovascular biology to a wide audience through acting as scientific advisor on several television productions. Using footage from two of these films, we discuss Gustav Born's scientific achievements and legacy.

An interview with Professor Gus Born.

This article is taken from an interview with Professor Gustav Victor Rudolf Born (known as Gus), and focuses on his personal reflections and his distinguished career. Professor Born's innovative research led to the development of a pioneering device, the aggregometer, which opened up the field of platelet research. In this article, Professor Born gives his modest insight into the early stages of his career and the impact Hiroshima had on his decision to work on thrombosis and hemostasis. He details the key events that led to development of a machine which had a revolutionary effect on diagnosing platelet-related diseases and the development of antiplatelet agents, thereby making it a world-wide success and saving so many lives.

Gus Born: Scientific Reflections of Later Years, Inspiring the Next Generation of Blood Researchers.

I am delighted to have been be asked by Steve Watson to write a short piece for this series in Platelets, on my friendship with Prof Gus Born which began in 2011, when he came to Cardiff to present at our UK Platelets meeting. Gus was an insipiration, his story resonates today and it is an honour to have the opportunity to record a summary of our meetings here.

Historical observations on the discovery of platelets, platelet function testing and the first antiplatelet agent.

An understanding of the historical paths that have lead to our current state of knowledge in the field of platelet studies can be both illuminating and inspiring. Considering that the existence and function of platelets were initially described just barely over 100 years ago it is exciting to recognize how far our knowledge has advanced in such a relatively short period of time. Within 20 years of Giulio Bizzozero's definitive description of blood platelets investigators began to develop tests that could quantitate the relationship between platelets, hemostasis and bleeding, and these tests have continued to be refined ever since. At the same time, and well before the role of platelets and antiplatelet agents in cardiovascular disease was appreciated, several clinicians started using aspirin for the prevention of heart attacks. All three of these paths of research - platelet biology, platelet function testing and antiplatelet therapies - all converge on what is arguably one of the most important questions in clinical medicine today: how to best prevent arterial thrombosis. For the current and future pioneers of platelet research an understanding of how we got to where we are today will hopefully allow for a clearer and inspired vision of where we will go next.

Currently available methods for platelet function analysis: advantages and disadvantages.

Platelets play a pivotal role in normal hemostasis, and derangement of their function can lead to hemorrhage or thrombosis. While progress has been made in elucidating the molecular mechanisms leading to platelet adhesion, aggregation, shape change and secretion, clinically useful tests of platelet function have lagged. A number of dedicated platelet function instruments that are much simpler to use and are now utilized as point-of-care (POC) instruments have now become available. Some instruments have been incorporated into routine clinical use and can be utilized not only as general screening tests of platelet function but as monitors of antiplatelet therapy and to potentially assess both risk of bleeding and/or thrombosis. Some of the factors that differentiate these tests are sample volume requirements, the use of whole blood, the presence of shear, POC status, need for a technician and expense. The following is a review of some of the commonly used tests of platelet function, along with their advantages and disadvantages. The tests and pertinent instruments described are based on aggregation, shear stress platelet contribution to clot strength, flow cytometry and serum and urinary thromboxane metabolites.

2B or not to be--the 45-year saga of the Montreal Platelet Syndrome.

Over 45 years ago, Montreal Platelet Syndrome was first described as a rare inherited platelet disorder characterised by macrothrombocytopenia with spontaneous platelet clumping, abnormal platelet shape change upon stimulation and a defect in platelet calpain. This syndrome has now been reclassified as type 2B von Willebrand disease with the V1316M VWF mutation in the only kindred ever reported. We herein revisit the historical platelet characteristics originally described in Montreal Platelet Syndrome in light of the new diagnosis. This paper will review the 45-year saga of Montreal Platelet Syndrome, a story that highlights the value of revisiting a rare diagnosis to look for a more common explanation.

Historical account of tests of hemostasis.

Although the fact that blood clotted when it was released from the body was well known to Hippocrates, Plato, Aristotle, Celsus, and Galen, it was not believed to have any physiologic or pathologic significance. Petit, a surgeon, recognized in the 1730s that clotting was hemostatically important in amputations. Finally, the mechanism of clotting began to be studied by Buchanan (1838), who recognized thrombin; Hammarsten (1875), who purified fibrinogen; and Arthus (1890), who discovered the need for calcium. The fact that platelets existed and had a hemostatic function was developed in the 1800s. Not until the late 1940s did the explosion in the discovery of new clotting factors begin; they now number up to Factor XIII, plus many more that have no Roman numeral designation. Discovery of clotting factors led to their assays. The use of whole blood clotting times was improved by measuring the clotting times of plasma. This was followed by the partial thromboplastin time (PTT) and the activated partial thromboplastin time (APTT). The prothrombin time became an important laboratory test. Specific factors were assayed by progressively more specific tests. These included elements of the fibrinolytic and inhibitory systems. Platelets were counted and their functions measured by bleeding times, clot retraction, adhesion, and aggregation. The diagnosis of hemostatic disorders has improved in parallel with the discoveries of new factors and the development of their precise assays.