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Semin Thromb Hemost 2024; 50(02): 320-324
DOI: 10.1055/s-0043-1776325
Historical Commentary

Description of an In Vitro Platelet Function Analyzer (PFA-100/PFA-200) 30 Years in the Making

Emmanuel J. Favaloro 
1   Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Wales, Australia
2   School of Dentistry and Medical Sciences, Faculty of Science and Health, Charles Sturt University, Wagga Wagga, New South Wales, Australia
3   School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia
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Comment on:

Description of an In Vitro Platelet Function Analyzer—PFA-100™Semin Thromb Hemost 2024; 50(02): 314-319
DOI: 10.1055/s-0043-1777308

Description of an In Vitro Platelet Function Analyzer—PFA-100™

Welcome to another Commentary relating to our celebration of 50 years of publishing for Seminars in Thrombosis and Hemostasis (STH). As previously noted, 2024 marks the 50th birthday of STH, which first published in 1974.[1] A half century of publishing is a landmark worthy of celebration. We started the celebrations in 2022, when we published our first 50th Year Celebratory issue.[2] A second Celebratory issue was published in 2023,[3] and a third compilation was published as the first issue of 2024.[4] All issues were rich with content of a historical nature, as related to the fields of thrombosis and hemostasis. We plan to prepare a 4th and final 50th Year Celebratory compilation later in 2024. In the interim, we plan to publish a separate tribute to the rich history of STH in each issue of STH to publish within 2024. For the first issue of 2024, we republished the first paper ever published in STH, on the molecular structure of fibrinogen,[5] together with an accompanying Commentary from Neerman-Arbez and Casini.[6] The current Commentary accompanies the historical paper entitled “Description of an in vitro platelet function analyzer–PFA-100” republished in the current issue, from the authorship team of Kundu et al, and first published in a Supplementary issue of STH in 1995 ([Fig. 1]),[7] and which was identified as the 3rd most highly cited STH paper of all time.[8]

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Fig. 1 The front cover of the 1995 Supplement that published the historical paper[7] featured in the current issue of Seminars in Thrombosis and Hemostasis (Source: Reproduced with permission from Thieme Medical Publishers).

This historical paper[7] can be seen as a landmark paper, since it provided the first complete description of the PFA-100, an instrument that was in time to prove quite successful for its manufacturer, then Dade International Inc, which over time has transitioned into Siemens Healthineers. This paper does not mark the first “report” of the PFA-100, which occurred in a 1994 published conference paper,[9] with the affiliation then attributed to “Baxter Diagnostics.” The PFA-100 was based on an earlier (and larger) instrument called the Thrombostat-4000, which itself was often described as an in vitro bleeding time.[10] [11] The first publication mentioning the Thrombostat-4000 that I could identify from PubMed was from 1993.[10] Another four papers were published on the Thrombostat-4000 in 1993 and 1994.[12] [13] [14] [15] Then, in 1995, the prior noted Supplement of STH was published,[1] containing 16 papers that mentioned work using the Thrombostat-4000.[11] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] At the end of the Supplement issue appeared two papers related to the “updated” Thrombostat-4000, namely the PFA-100.[9] [31] Indeed, it was noted by the issue Guest Editors, in the Preface to the issue[32] that: “The Thrombostat 4000, which is no longer available, was modified and redesigned by scientists at Dade International, Inc. It is now referred to as the PFA 100 system, PFA meaning “platelet function analyzer for routine use, although at present, not yet available.””

As a Supplement of STH, this issue would have been sponsored by the manufacturer of the PFA-100. Indeed, Dade also took out an ad on the back cover to the issue ([Fig. 2]). The ad suggests that the instrument was launched at the International Society on Thrombosis and Haemostasis meeting held in Jerusalem in June of 1995 and perhaps the supplement was intended for major release at that meeting. I have no idea how much this “sponsorship” deal cost “Dade Diagnostics,” but I can conclude that this was money well spent. Given that the Thrombostat-4000 was no longer in production at that time, the publications related to this instrument[11] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] did not raise many citations. However, the two papers related to the PFA-100[9] [31] did, with both appearing in the top 100 most highly cited STH papers of all time.[8] Two other papers related to the PFA-100 also made this top 100 list.[33] [34] One of these, by Eberhard Mammen was the 4th most highly cited STH paper of all time,[33] and the other paper[34] was written by me as a tribute to Eberhard Mammen in the year of his passing (2008).[35] [36]

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Fig. 2 The back cover of the 1995 Supplement that published the historical paper[7] featured in the current issue of Seminars in Thrombosis and Hemostasis. This was an ad for the PFA-100 by the then manufacturer “Dade Diagnostics, Inc.” (Source: Reproduced with permission from Thieme Medical Publishers).

The history of the PFA-100 is now long and rich, and the PFA-100, subsequently morphing into the contemporary PFA-200, has been the subject of several reviews, including several recent “tributes” in this journal.[34] [37] [38] [39] A PubMed search of “(PFA-100) OR (PFA-200) OR (PFA100) OR (PFA200) OR (“platelet function analyser”) OR (“platelet function analyzer”)” yields over 1,200 hits ([Fig. 3]). Most of these papers are related to the PFA-100 or to the modern “updated” version (the PFA-200), but a handful are not (for example, PFA is also used as an abbreviation of “pulsed field ablation” and “phosphonoformic acid”). The first mention of the PFA-200 appears to be another of my own papers, as published in 2014, as also appearing in STH.[40] Indeed, the PFA-200 has been in operation in our laboratory since 2013, but interestingly is not yet available for sale in the United States. However, we still also operate our original PFA-100, acquired by us in 1996, and having the serial number 275! So, we were among the first pioneering group of users of this instrument; we published our first PFA related paper in 1999,[41] describing its utility as a screen for von Willebrand disease (VWD).

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Fig. 3 The history of publications related to the PFA-100/PFA-200; data from PubMed.

We still, in 2024, use the PFA-100/-200 primarily to screen for VWD, with updated findings published in 2020,[42] or else to monitor desmopressin therapy in VWD.[43] The instruments may be used for a variety of different purposes in other laboratories, for example as a preoperative screen,[44] to evaluate platelet function in animals,[45] to evaluate effects of coronavirus disease 2019 spike protein on platelet function,[46] to evaluate drug effects on platelet function,[47] [48] to evaluate the effect of recombinant von Willebrand factor (VWF) on prolonged PFA closure times in extracorporeal membrane oxygenation patients with acquired von Willebrand syndrome,[49] to monitor antiplatelet therapy,[50] as a measure of platelet function in blood donors,[51] and as a potential marker of thrombosis risk,[52] just to name a few potential uses.

I do not know how many units of the PFA-100 that “Dade Diagnostics” sold following the inaugural announcements in STH,[7] [31] nor do I know how many units of the PFA-100 and PFA-200 that Siemens has sold since it acquired Dade, but I suspect that number to be quite sizable, and I also suspect that these sales have been aided greatly by publications related to these instruments, which essentially all began with the original publications in STH.[7] [31] However, the first mention of the PFA-100 appeared in a Conference paper in 1994, so it can also be noted that the PFA-100, like STH, also celebrates a milestone, with 30 years of service to the hemostasis community in 2024.[37] Happy birthday to the PFA-100!



Publication History

Article published online:
30 October 2023

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