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Projects / Programmes source: ARRS

Reversibility of transient thrombocytopenia induced by a snake venom component offers a safe antithrombotic prevention in interventional angiology and cardiology

Research activity

Code Science Field Subfield
3.06.00  Medical sciences  Cardiovascular system   

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
Transient thrombocytopenia; Functional platelets; Snaclec; Antiplatelet drug; Antiaggregants, Hemorrhage
Evaluation (rules)
source: COBISS
Points
4,409.08
A''
451.18
A'
2,070.02
A1/2
2,606.61
CI10
5,977
CImax
745
h10
33
A1
15.15
A3
1.94
Data for the last 5 years (citations for the last 10 years) on March 29, 2023; A3 for period 2017-2021
Data for ARRS tenders ( 04.04.2019 – Programme tender, archive )
Database Linked records Citations Pure citations Average pure citations
WoS  523  10,338  8,140  15.56 
Scopus  509  11,481  9,164  18 
Researchers (19)
no. Code Name and surname Research area Role Period No. of publications
1.  15595  Katarina Babnik    Technician  2020 - 2023 
2.  24927  PhD Miran Brvar  Neurobiology  Principal Researcher  2020 - 2023  549 
3.  38536  Mojca Dobaja  Public health (occupational safety)  Researcher  2020 - 2023  36 
4.  18122  Boštjan Drolc  Veterinarian medicine  Technician  2020 - 2023  10 
5.  12449  PhD Robert Frangež  Veterinarian medicine  Researcher  2020 - 2023  269 
6.  37918  Damjan Grenc  Neurobiology  Researcher  2020 - 2023  124 
7.  50498  Adrijan Ivanušec  Biochemistry and molecular biology  Researcher  2021 - 2023  23 
8.  55063  Špela Koren  Biochemistry and molecular biology  Junior researcher  2021 - 2023  14 
9.  00412  PhD Igor Križaj  Biochemistry and molecular biology  Researcher  2020 - 2023  696 
10.  18802  PhD Adrijana Leonardi  Biochemistry and molecular biology  Researcher  2020 - 2023  139 
11.  56248  Leja Perne    Technician  2022 - 2023 
12.  20213  PhD Toni Petan  Biochemistry and molecular biology  Researcher  2020 - 2023  161 
13.  04570  PhD Jože Pungerčar  Biochemistry and molecular biology  Researcher  2020 - 2023  318 
14.  18125  Jasna Šporar    Technician  2020 - 2023 
15.  21553  PhD Jernej Šribar  Biochemistry and molecular biology  Researcher  2020 - 2023  106 
16.  07002  PhD Dušan Šuput  Neurobiology  Researcher  2020 - 2023  423 
17.  13334  PhD Milka Vrecl Fazarinc  Veterinarian medicine  Researcher  2020 - 2023  253 
18.  56000  Mia Žganjar  Biochemistry and molecular biology  Researcher  2021 - 2023 
19.  22588  PhD Monika Cecilija Žužek  Veterinarian medicine  Researcher  2020 - 2023  62 
Organisations (4)
no. Code Research organisation City Registration number No. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  85,623 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  73,429 
3.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  44,841 
4.  0406  University of Ljubljana, Veterinary Faculty  Ljubljana  1627139  9,759 
Abstract
In thromboembolic diseases, such as myocardial infarction and ischemic stroke, platelets play a pivotal role. Currently used antiplatelet drugs have one common side effect – a decreased count of platelets with inhibited function. Such condition represents a high risk of life-threatening hemorrhage especially in interventional cardiology and angiology employing antithrombotic approach. Recently, we reported an interesting observation of a profound and transient thrombocytopenia of functional platelets in patients bitten by the nose-horned viper (Vipera ammodytes ammodytes, Vaa), revealing that the Vaa venom contains component(s) that can transiently decrease platelets count without affecting their function. In this project, we will comprehensively describe this antithrombotic substance(s) and its mode of action thus paving the way to development of a new group of antiplatelet agents, which will minimize the risk of life-threatening bleeding in antithrombotic approach in interventional cardiology and angiology, and increase the effectiveness of vessel dilatation and emboli aspiration. Based on our preliminary data, we suggest that snake C-type lectin-like proteins (snaclecs) induce transient and reversible thrombocytopenia in the Vaa venom-poisoned patients by binding to GPIb receptors on platelets. The Vaa snaclecs are proteins of 25–50 kDa. They apper as heterodimers formed from an ? subunit of 14–15 kDa and a ß subunit of 13–14 kDa held together by an inter-chain disulphide bond, and their dimeric form – (?ß)2. The scientific challenge that the proposed project is tackling requires a multidisciplinary approach, clinical, pharmacological, pathophysiological, biochemical and immunological, at the clinical, preclinical as well as basic research levels. Project team gathers experts with required complementary skills and equipment from the University Medical Centre Ljubljana, Jožef Stefan Institute, Veterinary and Medical faculties of the University of Ljubljanaand University of Zagreb - an external partner, which all successfully collaborated in the past, with a strictly defined role in the project. The four main goals that we are pursuing in the proposed project are: (1) to identify whether the Vaa snaclecs induce thrombocytopenia in patients envenomed by the Vaa venom by reversibly attaching platelets to the blood vessel wall or by reversible aggregation of platelets; (2) to purify snaclecs from the Vaa venom and biochemically characterize them in depth; (3) to define the molecular basis of the interaction of the Vaa snaclecs with platelets, a process behind a transient and reversible thrombocytopenia of functional platelets observed in vivo; and (4) to evaluate clinical potential of snaclecs in preventing arterial thrombosis in a mouse model. To efficiently reach our goals the project’s implementation work plan is divided into 6 workpackages (WPs). Besides WP1, which is aimed at stimulating a strong and efficient interaction amongst WPs and all five partner groups, and WP6, which is devoted to dissemination of our achievements, the experimental part of the work is concentrated in WP2 to WP5, each relating to one of the above stated four main project goals. The two main deliverables of the proposed project are: (1) a thorough characterization of the Vaa venom component(s) responsible for inducing profound and transient thrombocytopenia in patients and (2) a description of the mechanism of its action on the molecular level. Both results are essential for the further development of a novel group of antiplatelet agents. According to the ample experience and high competence of all partners, availability of all research equipment necessary to conduct the planned experiments, numerous international collaborations, and a track of very successful collaborations of the implicated research groups in the past, we are certain that the goals are realistically set and achievable within the three-year period.
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