Un hommage à trois étincelles, “a tribute to three glints” is the title which I have elected for this manuscript devoted to the recognition
of an intimately intertwined triad: Professor Peter Kubisz, recently deceased, the
50th anniversary of Seminars in Thrombosis and Hemostasis (STH), and the 40th anniversary of the Sticky Platelet Syndrome (SPS).
La première…
Professor Peter Kubisz was born on June 13, 1942, in Třinec, Czechoslovakia. At age
12, he was gifted a microscope, a gift that defined his future. As a result of his
interest in platelet function, he built and employed the first aggregometer in Czechoslovakia,
while working with Professor Parizkom. In 1969, he completed his internship with Professor
Jacques Caen in the Hôpital Lariboisière in Paris, France. Between 1970 and 1980,
he was responsible for the Hematology Clinic at the University of Oran (Algiers).
He later conducted and developed his research activities in Martin, and in the Jessenius
Faculty of Medicine, in current day Slovakia. After the dissolution of Czechoslovakia
in 1992, he became Chief of the Slovakian Health Ministry. He was very active in the
International Society of Hematology, the Danubian League against Thrombosis and Hemorrhagic Disorders, and the Slovakian Society of Hemostasis and Thrombosis. Professor Kubisz was also the Chief Expert in transfusions at the Ministry of Health
of the Slovak Republic, as well as Head of Hematology at the Ministry of Health of
the Slovak Republic and a member of the advisory council of the Ministry of Health.
For many years, he was also a member of the State Institute for Drug Control (ŠUKL),
a member of the Categorization Commission of the Ministry of Health of the Slovak
Republic, Vice Chairman of the Committee of the Society of Hematology and Transfusion
(HaTS), Slovenská lekárska spoločnosť (SLS) or Slovakian Center for Diagnosis, and
as of 2006, he became the President of the Slovak Society of Hemostasis and Thrombosis
(SSHT) SLS. He was also involved in the study of angiogenesis in lower limb ischemia
and the practice of autologous stem cell transplantation, having performed the first
autograft in Slovakia in 2006. Professor Kubisz sadly passed away on September 9,
2022, at age 80. He was one of the more prolific investigators and writers on SPS
and with his colleagues, he contributed three major publications to STH,[1]
[2]
[3] that defined seminal details on SPS:
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Kubisz P, Stasko J, Holly P. Sticky platelet syndrome. Semin Thromb Hemost. 2013 Sep;39(6):674–83.
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Kubisz P, Ruiz-Argüelles GJ, Stasko J, Holly P, Ruiz-Delgado GJ. Sticky platelet syndrome:
history and future perspectives. Semin Thromb Hemost. 2014 Jul;40(5):526–34.
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Kubisz P, Holly P, Stasko J. Sticky Platelet Syndrome: 35 Years of Growing Evidence.
Semin Thromb Hemost. 2019 Feb;45(1):61–68.
La deuxième…
The journal STH was founded in 1974; accordingly, the 50th anniversary of its foundation
will be celebrated in 2024. According to the Journal Citation Reports, its impact factor in 2021 was 6.398. Scientists in low- and middle-income countries
(LMICs) face multiple quandaries when attempting to publish their work in journals
published in high-income countries (HICs). This has led to what is now called “……
the lost science of the third world: Many researchers in the developing world feel
trapped in a vicious circle of neglect and - some say - prejudice by publishing barriers
they claim good science to oblivion.”[4]
STH provides a forum in which scientific data originating in LMICs can be published
in a journal originating in HICs. The editorial team have been supportive of physicians
working in underprivileged circumstances and this positioning deserves recognition.
The support that STH provided to enable the publications of Professor Kubisz, specifically
in the area of SPS, which remains an area of debate, particularly for physicians working
in HICs, is a clear example of the philosophy of STH and should be adopted by other
journals. By both promoting and supporting the publication of the salient features
of SPS in STH, all based on the pool of knowledge that originated in a LMIC such as
Mexico, STH has clearly demonstrated a role of inclusivity and now, 50 years after
its initial publication, this journal has become one of the preferred worldwide channels
to disseminate novel knowledge in the field of thrombosis and hemostasis.
La troisième…
Forty years ago, in 1983, the trio of Holiday, Mammen, and Gilroy coined, for the
first time, the term “sticky platelet syndrome” (SPS) to describe a syndrome identified
in a group of young persons with cerebral infarction and platelet hyperaggregability.[2] At the time, I had just returned to my hometown in Puebla, Mexico, after completing
a postgraduate research fellowship in hematology at the Mayo Clinic in Rochester,
MN, where I had the privilege of meeting other “giants” in the thrombosis and hemostasis
field such as Walter Bowie, William Nichols, Kenneth Mann, and David Fass, among others.
Although I did not directly work with them, our personal encounters resulted in my
increasing interest in both thrombosis and hemostasis, since my focus had initially
centered on hematological malignancies and bone marrow transplantation. Back in Mexico
in 1999, I began initial studies on thrombophilia and two years later, in 2001, I
became familiar with the SPS and decided to analyze its prevalence in Mexico. Our
findings were published a year later, in 2002. I clearly remember the reaction of
Prof. Rodger Bick, the then editor of Clinical and Applied Thrombosis and Hemostasis, when after reviewing our paper, stated that he was pleased to accept our “excellent
paper” for publication in the journal. Never in my life had I received such a positive
and encouraging comment on a potential publication. Professor Bick was a believer
in the SPS and as a pupil of Professor Eberhard Mammen, he helped promote the term
SPS. My own interest and research on the SPS persisted despite the contrary observations
of many famous experts in coagulation, so-called “clotters,” suggesting that the SPS
was only a laboratory phenomenon or artifact and not a clinical entity per se. Our
studies and those of other scientists working in this field were, have been, and are
still criticized by several of these clotters who have neglected the need to investigate
this condition in thrombophilic individuals, very frequently as a result of their
inability or disinterest in searching for the condition's phenotype in their laboratories.
In 2011, at a meeting organized by Ernesto Novoa in Montevideo, Uruguay, I met another
believer in the SPS, Professor Peter Kubisz, and in 2013 I asked him to participate
in a symposium on platelets in Cancún, Mexico; I was then able to include both endorsers
and non-endorsers of the condition in a SPS symposium. In 2015, Professor Kubisz asked
me to lecture on the SPS in Sarajevo, Bosnia-Herzegovina, during the Mediterranean
League against Thrombosis meeting, where I had the chance to meet the Editor in Chief
of STH, Prof. Emmanuel Favaloro. Subsequently, Prof. Kubisz invited me to lecture
again on the topic in Martin, Slovakia in 2018, and I again crossed paths with Prof.
Emmanuel Favaloro.
As a result of our interest in the SPS and with the assistance of various collaborators
and of the previously mentioned giant clotters, we have now pieced several features
of the SPS which can be summarized as follows[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]:
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(1) The SPS is a phenotype of platelet hyperaggregability, defined by increased in
vitro platelet aggregation after the addition of very low concentrations of adenosine
diphosphate and/or epinephrine. The concentrations and dilutions of the agents are
relatively well-standardized. An aggregometer is needed for the diagnosis of SPS,
and its availability is one of the major obstacles to establish a diagnosis.
-
(2) The genotype is currently unknown, but several genes of platelet proteins are
currently under study: platelet glycoprotein IIIa PLA1/A2; platelet glycoprotein VI,
growth arrest-specific gene 6, coagulation factor V, integrin subunit beta-3, platelet
endothelial aggregation receptor 1, serpin family C member 1, and serpin family E
member 1, among others.
-
(3) The SPS phenotype is probably the expression of more than one genetic mutation
that together, interact with other medical conditions or environmental factors such
as diabetes mellitus, hormonal therapy, pregnancy, and others.
-
(4) The SPS may cause both arterial and venous thrombosis, the latter being more frequent.
-
(5) The SPS is a hereditary autosomal dominant trait.
-
(6) The SPS is the most frequent cause of hereditary thrombophilia in Mexico and perhaps,
in other countries.
-
(7) Patients with SPS have been identified and treated in all continents of the world.
-
(8) The SPS is a frequent cause of miscarriages and obstetric complications (it would
be good to know how many are associated with the antiphospholipid antibody syndrome).
-
(9) The SPS usually needs another thrombophilic condition to be fully expressed clinically
as a thrombotic episode.
-
(10) The hyperaggregability in SPS reverts with antiplatelet drugs and the re-thrombosis
rate in persons with the syndrome is very low when actively treated. Aspirin reverts
the hyperaggregability state in most patients, but about one-quarter of cases warrant
the administration of two antiplatelet drugs. It is therefore advisable to assess
the SPS phenotype after initiating the antiplatelet drug, to define further treatment
and its duration. Treating persons with SPS with oral anticoagulants does not reduce
the re-thrombosis rate.
-
(11) Claiming that the SPS is a nonentity indicates that it is not being properly
assessed or even considered, and may be detrimental to the patients; when diagnosed,
it only requires a simple, inexpensive, and effective treatment that is tolerated
by most patients: the use of low-dose aspirin and other antiplatelet drugs. But first,
the diagnosis has to be considered and then established. There are many published
descriptions of thromboembolic events in persons with SPS who are instructed to stop
the antiplatelet treatment and in which the authors still claim that “the SPS is a myth.”
Coda
The objective of paying homage to the triad embodied by Professor Peter Kubisz, the
50th anniversary of STH, and the 40th anniversary of the SPS, all intimately connected,
is to recognize the imbrication of science, human relations, and goodwill in the generation
and dissemination of new knowledge, that in turn, may further benefit human health.
Having been offered the opportunity to pay a tribute to this triad of “étincelles”
has indeed, been a privilege.
