Preise und Stipendien

Gewinner der Preise und Stipendien 2024

Lernen Sie die Preis- und Stipendiatsträger sowie Ihre Arbeiten näher kennen:

Die Vergabe der GTH Preise und Stipendien fand auch in diesem Jahr wieder während der Opening Ceremony statt (Foto: T. Ecke, Berlin)

Alexander-Schmidt-Preis

Für die Arbeit:
Platelet ACKR3/CXCR7 favors antiplatelet lipids over an atherothrombotic lipidome and regulates thromboinflammation

Alexander-Schmidt-Preis
Dr. (PhD) Madhumita Chatterjee, Tübingen

Rudolf-Marx-Stipendium

Für das Projekt:
Immunophenotyping of platelet subsets in health and disease 

am Center for Platelet Research Studies, Boston Children’s Hospital, Harvard Medical School 

Rudolf-Marx-Stipendium
Muataz Ali Hamad, Freiburg

Nachwuchsförderpreis Thromboseforschung / vaskuläre Medizin

Für die Arbeit:
Mechanosensing via a GpIIb/Src/14-3-3ζ axis critically 2regulates platelet migration in vascular inflammation

Nachwuchsförderpreis Thromboseforschung / vaskuläre Medizin
Dr. med Rainer Kaiser, München

Nachwuchsförderpreis Blutungskrankheiten

Für die Arbeit:
Immune tolerance against infused FVIII in hemophilia A is mediated by PD-L1+ Tregs

Nachwuchsförderpreis Blutungskrankheiten
Dr. rer. nat. Janine Becker-Gotot, Bonn

Gewinner der Preise und Stipendien 2023

Lernen Sie die Preis- und Stipendiatsträger sowie Ihre Arbeiten näher kennen:

Die Vergabe der GTH Preise und Stipendien fand auch in diesem Jahr wieder während der Opening Ceremony statt (Foto: T. Ecke, Berlin)

Alexander Schmidt-Preis

Für die Arbeit:
The interaction between anti-PF4 antibodies and anticoagulants in vaccine-induced thrombotic thrombocytopenia

Alexander Schmidt-Preis
Prof. Dr. Tamam Bakchoul, Tübingen

Nachwuchsförderpreis Thromboseforschung / vaskuläre Medizin

Für die Arbeit:
Hereditary thrombotic thrombocytopenic purpura and COVID-19: Impacts of vaccination and infection in this rare disease

 

Nachwuchsförderpreis Thromboseforschung / vaskuläre Medizin
Erica Tarasco, Bern

Nachwuchsförderpreis Blutungskrankheiten

Für die Arbeit:
GGCX mutations show different responses to vitamin K thereby determining the severity of the hemorrhagic phenotype in VKCFD1 patients

 

Nachwuchsförderpreis Blutungskrankheiten
Dr. Suvoshree Gosh, Bonn

Rudolf-Marx-Stipendium

Für das Projekt:
Analyzing the different conformational states of full-length coagulation Factor VIII by a combination of computational modeling, atomic force microscopy (AFM) and AFM assembly pipeline

Rudolf-Marx-Stipendium
Samhitha Urs Ramaraje Urs, Bonn

Rudolf-Marx-Stipendium

Für das Projekt:
Beyond coagulation: the role of VKORC1 in vascular calcification

Rudolf-Marx-Stipendium
Francesco Forin, Zürich

Die GTH Early Career Research Grants

Prof. Johannes Oldenburg, Präsident des ISTH Jahreskongresses in Berlin 2017, entschied 2019, seinen ISTH President´s Legacy Fund der GTH zur Verfügung zu stellen. Mit dem überwältigenden Rücklauf und der enormen Zahl von hochwertigen Bewerbungen für die daraufhin ausgeschriebenen Early Career Research Grants war kaum zu rechnen. Alle Bewerbungen durchliefen einen mehrstufigen Reviewprozess  und wurden schließlich von der Grant Jury der GTH beurteilt.

Neben der fachlichen Qualifikation der Antragsteller*innen und dem lokalen Forschungsumfeld waren die  Aktualität und die Umsetzbarkeit des Projektantrags wichtige Entscheidungskriterien. Die Early Career  Research Grants sollten die geförderten Nachwuchswissenschaftler*innen unterstützen, sich in einem kompetitiven Umfeld als unabhängige Projektleiter zu etablieren. Bei der Begutachtung und Auswahl der Anträge wurden Kooperationen mit anderen Forschergruppen aus den GTH Ländern Deutschland, Österreich  und Schweiz in besonderem Maße gewürdigt.

Lernen Sie die Preisträger 2021, 2022 und 2023 sowie Ihre Arbeiten näher kennen:

(Fotos: online Preisverleihung, T. Ecke, Berlin)

Dr. Stephan Nopp, Wien

Prediction of bleeding risk, assessment of patient-centered outcomes, and impact of rehabilitation on physical and mental health in patients with venous thromboembolism.

Dr. Stephan Nopp, Wien

Dr. Stephan Nopp, Wien

Aims of this project:

1) to investigate the predictive ability of biomarkers, e.g., Growth differentiation factor-15 (GDF-15), a promising cardiovascular marker,13,14 for bleeding risk prediction in VTE  patients to improve the risk-benefit assessment of anticoagulation. We hypothesize that  GDF-15 adds predictive value to current bleeding risk assessment tools (e.g., HAS-BLED, VTE-BLEED score), as it did in the setting of anticoagulation for atrial fibrillation.

2) to investigate the long-term impact of VTE on overall well-being, to characterize patients at high risk for physical and/or psychological sequelae, and to advance understanding of  functional limitations after VTE.

3) to provide evidence from a randomized-controlled study on the efficacy of pulmonary  rehabilitation in PE patients with long-term sequelae (i.e., post-PE syndrome). We  hypothesize that a 6-week ambulatory rehabilitation improves functional capacity as well as  quality of life in selected patients with post-PE symptoms.

Dr. Stephan Nopp, Wien

M. Sc. Sandra Konrath, Hamburg-Eppendorf

Mechanism and therapy of the fat embolism syndrome

M. Sc. Sandra Konrath, Hamburg-Eppendorf

M. Sc. Sandra Konrath, Hamburg-Eppendorf

Aims of project
Include specific hypotheses to be tested.

Our preliminary data suggest that BM-derived fat contributes to FES by activating FXII that in turn drives procoagulant and proinflammatory disease mechanisms via the intrinsic  pathway of coagulation and the BK forming kallikrein-kinin system. The following three aims will be pursued:

1. To analyze the mechanism of FES in human plasma and endothelial cells

2. To explore procoagulant and proinflammatory FES-associated reactions in mouse thrombosis models and human lungs

3. To develop a proof-of-concept therapeutic approach for interference with FES

M. Sc. Sandra Konrath, Hamburg-Eppendorf

Dr. Leo Nicolai, München

Mechanisms and therapeutic potential of platelet migration

Dr. Leo Nicolai, München

Dr. Leo Nicolai, München

Aims of project
Include specific hypotheses to be tested.

We hypothesize and provide first data that SFKs play a critical role in platelet migration and thromboinflammation and could make immune responsive platelets amenable to therapy with approved SFK inhibitors like Dasatinib. We now strive to better understand the  molecular regulation of platelet migration via SFKs, confirm the effect in patients treated  with Dasatinib, and investigate its efficacy in two mouse models of sepsis and  hyperinflammation.

– Aim 1: Clarify the signaling cascade via c-Src that mediates platelet migration

– Aim 2: Elucidate the platelet phenotype of patients treated with Dasatinib

– Aim 3: Evaluate SFK inhibition and its effects on platelets in clinically relevant models of  sepsis

This project will therefore contribute importantly to understanding the molecular regulation of this novel, important platelet function in thrombosis, hemostasis and inflammation, and  will potentially pave a way to clinical trials with the goal to specifically target platelets in  thrombo-inflammation.

Dr. Leo Nicolai, München

Dr. rer. Nat. Marie-Therese Hopp, Bonn

Exploring the molecular basis of labile heme as a prothrombotic modulator in hemolytic disorders

Dr. rer. Nat. Marie-Therese Hopp, Bonn

Dr. rer. Nat. Marie-Therese Hopp, Bonn

The aim of this project is to provide knowledge about the molecular basis of heme-driven effects on factors of the blood coagulation system in the context of prothrombotic  complications in patients suffering from hemolytic disorders. More specifically FVIII(a) and  VWF will be analyzed thoroughly concerning their direct interaction with heme.

Dr. rer. Nat. Marie-Therese Hopp, Bonn

Dr. med. Lennart Beckmann, Hamburg

Factor XI inhibition in cancer-associated thrombosis

Dr. med. Lennart Beckmann, Hamburg

Dr. med. Lennart Beckmann, Hamburg

Hypothesis
We hypothesize that pharmacological FXI inhibition will not sufficiently mitigate tumor cell-induced coagulation activation in all cancer subtypes. Particularly in cancers with abundant TF expression, FXI inhibition will be inferior to the LMWH tinzaparin and the direct oral FXa inhibitor rivaroxaban.
We also hypothesize that at least some cancer cells show aberrant production of FXI, which may render pharmacological FXI inhibition less efficacious in the context of CAT treatment.
Aims
1. To investigate the anticoagulant effect of FXI inhibition in comparison to tinzaparin and rivaroxaban in an ex vivo model of tumor-cell induced coagulation activation.
2. To investigate the effects of FXI inhibitors, tinzaparin, and rivaroxaban on thrombin generation in platelet-free plasma from cancer patients.
3. To screen several cancer cells for endogenous FXI production, and to characterize the effect of FXI inhibition on coagulation activation in FXI producing vs non-producing cell lines.

Dr. med. Lennart Beckmann, Hamburg

Martina Wolff, Greifswald

Platelet tether formation in health and disease – From danger-signal to immuno-thrombosis

Martina Wolff, Greifswald

Martina Wolff, Greifswald

The Aim of the project is to clarify the role of platelet tethers in bacterial/viral infection and disease (Fig. 4). The hypothesis I would like to address under the guidance of Prof. Nieswandt and Prof. Greinacher within the SFB TR240 is, that these tethers also act in human platelets physiologically as a “danger- label” to attract leucocytes to sites of infection. Subsequent, these tether labels facilitate opsonization of bacterial or viral components by leucocytes and interaction with endothelial cells. Our contribution beyond the mouse model data is, that certain diseases (e.g. dis-turbance of bone marrow blood production, multiple sclerosis treatment) lead to pre-activation of platelets. In both situations, subsequently, tethers are generated at lower threshold, resulting in misdirected and overshooting thrombo-inflammation. As a consequence, the risk for thrombosis is enhanced. In this project I will systematically assess 1.) conditions leading to GPIIbIIIa tether formation in-vitro, 2.) circumstances and risk factors that cause en-hanced GPIIbIIIa tether formation in patients. Taking ma-jor advantage of the findings in mouse models shared with us within the SFB TR240. This may lead to new concepts of prevention and treatment of thrombosis in patients.

Martina Wolff, Greifswald

Olga Oleshko aus Hannover

Immune Complexes in Acquired Hemophilia A: Is Hemostasis More Severely Disturbed than in Congenital Hemophilia A?

Olga Oleshko aus Hannover

Olga Oleshko aus Hannover

The aim of our proposed study is to learn, why patients with acquired hemophilia A bleed differently from patients with congenital hemophilia. In both disorders, coagulation FVIII is missing or defective but the  functional consequences appear to be different given the different bleeding phenotype. Our work will help to  better understand the true reasons for bleeding and open new possibilities for individualized treatment.

Olga Oleshko aus Hannover

Florian Moik aus Wien

The Inflamed Endothelium and Risk of Cancer-Associated Thrombotic Events – The ERA Project

Florian Moik aus Wien

Florian Moik aus Wien

Blood clots, either in the veins (leading to thrombosis and occlusion of the blood vessels in the lungs), or in the  arteries (leading to heart attacks and strokes), is a frequently occurring and serious problem in patients with  cancer. In this research project, markers that can easily be measured in the blood and indicate activation and inflammation of the inner layer of blood vessels before and during cancer therapy are investigated to show whether they can be used to foresee the risk of blood clots in patients with cancer. This can help to guide medical therapy to prevent blood clots in high-risk patients with cancer and may eventually improve the overall-prognosis of these patients.

Florian Moik aus Wien

Sneha Singh aus Bonn

Detection and Characterization of molecular Interfaces of FXIII-Fibrinogen Complex by employing integrative  Hybrid Approaches

Sneha Singh aus Bonn

Sneha Singh aus Bonn

We propose to structurally and functionally characterize the FXIII: Fibrinogen association observed in plasma.  Our findings will help determine the pathomolecular mechanisms underlying qualitative defects that impact the  stability, assembly or dissociation of the FXIII: Fibrinogen macromolecular complex and result in coagulopathies  or thrombotic. The structural resolution of this complex will also lay the groundwork for designing future pharmacological drugs and inhibitors against this complex.

Sneha Singh aus Bonn

Gewinner der Preise und Stipendien 2022

Lernen Sie die Preis- und Stipendiatsträger sowie Ihre Arbeiten näher kennen:

Die meisten Preisträgerinnen und Preisträger konnten präsent in Leipzig ihre Urkunden entgegennehmen, andere wurden virtuell geehrt. Eine Besonderheit in 2022: Die fünf  Bewerbungen für das Rudolf-Marx-Stipendium waren besonders qualifiziert und förderungswürdig,  so dass die Entscheidung des GTH Vorstands positiv für Alle ausfiel. Erstmals wurden also fünf Stipendien in einem Jahr vergeben. (Foto: T. Ecke, Berlin)

Gewinner_GTH22

Alexander Schmidt-Preis

Für die Arbeit:
Annual incidence and severity of acute episodes in hereditary thrombotic thrombocytopenic purpura

Prof. Dr. med. Johanna Kremer Hovinga
Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor, Bern

Nachwuchsförderpreis Thromboseforschung / vaskuläre Medizin

Für die Arbeit:
Acquired platelet GPVI receptor dysfunction in critically ill patients with sepsis

Lukas Johannes Weiss
Universitätsklinikum Würzburg

Nachwuchsförderpreis Blutungskrankheiten

Für die Arbeit:
Elevated levels of tissue factor pathway inhibitor in patients with mild to moderate  bleeding tendency

Dr. Dino Mehic
Medizinische Universität Wien

Rudolf-Marx-Stipendium

Für das Projekt:
In vitro flow-based assay to study platelet procoagulant activity and thrombus formation

Dr. Alessandro Aliotta
CHUV Centre Hospitalier Universitaire Vaudois, Lausanne

Rudolf-Marx-Stipendium

Für das Projekt:
The Role of Factors VIII, IX, XI and D-Dimers in Paediatric Non-Central Venous Catheter- Related Thrombosis and their Clinical Outcome

Alessandra Bosch-Spiteri
Universitäts Kinderspital Zürich

Rudolf-Marx-Stipendium

Für das Projekt:
Improved Coagulation Diagnostics using Antibody-activated Partial Thromboplastin Time

M. Sc. Sandra Konrath
Universitätsklinikum Hamburg- Eppendorf (UKE)

Rudolf-Marx-Stipendium

Für das Projekt:
Die Rolle endothelialer und granulozytärer PAD4 bei der NLRP3 Inflammasom Aktivierung  und NETose im myokardialen Ischämie-/Reperfusionsschaden

Nicolas Schommer
Universitätsklinkum Freiburg

Rudolf-Marx-Stipendium

Für das Projekt:
The distinct role of platelet subpopulations in thrombosis and bleeding: A focus on  antibody-mediated procoagulant platelets

Jan Zlamal
Institut für klinische und experimentelle Transfusionsmedizin, Tübingen

Gewinner der Preise und Stipendien 2021

Lernen Sie die Preis- und Stipendiatsträger sowie Ihre Arbeiten näher kennen:

(Fotos: online Preisverleihung)

Nachwuchsförderpreis Thromboseforschung/vaskuläre Medizin

Der Preis geht an Dr. rer. nat. Shrey Kohli aus Leipzig für die Arbeit:

Placental thrombo-inflammation impairs embryonic survival by
reducing placental thrombomodulin expression

Nachwuchsförderpreis Thromboseforschung/vaskuläre Medizin

Placental thrombo-inflammation impairs embryonic survival by reducing placental thrombomodulin expression

Abstract:

Excess platelet activation by extracellular vesicles (EVs) results in trophoblast inflammaQ: 6 some  activation, interleukin 1b (IL-1b) activation, preeclampsia (PE), and partial embryonic lethality.  Embryonic thrombomodulin (TM) deficiency, which causes embryonic lethality hallmarked by  impaired trophoblast proliferation, has been linked with maternal platelet activation. We  hypothesized that placental TM loss, platelet activation, and embryonic lethality are mechanistically  linked to trophoblast inflammasome activation. Here, we uncover unidirectional interaction of  placental inflammasome activation and reduced placental TM expression: although inflammasome  inhibition did not rescue TM-null embryos from lethality, the inflammasome-dependent cytokine  IL-1b reduced trophoblast TM expression and impaired pregnancy outcome. EVs, known to induce  placental inflammasome activation, reduced trophoblast TM expression and proliferation.  Trophoblast TM expression correlated negatively with IL-1b expression and positively with platelet numbers and trophoblast proliferation in human PE placentae, implying translational relevance.  Soluble TM treatment or placental TM restoration ameliorated the EV-induced PE-like phenotype in  mice, preventing placental thromboinflammation and embryonic Q:7 death. The lethality of TM-null  embryos is not a consequence of placental NLRP3 inflammasome activation. Conversely, EV- induced placental inflammasome activation reduces placental TM expression, promoting placental  and embryonic demise. These data identify a new function of placental TM in PE and suggest that  soluble TM limits thromboinQ: 8 flammatory pregnancy complications. (Blood. 2020;00(00):1-6)

Alexander-Schmidt-Preis

Der Preis geht an Prof. Dr. Christoph Male aus Wien für die Arbeit:

Inhibitor incidence in an unselected cohort of previously untreated
patients with severe hemophilia B: a PedNet study

Hermann Adolf Alexander Schmidt (* 15. Mai 1831, † 10. April 1894) war ein deutschbaltischer Physiologe, der durch seine Arbeit über die Verdickung von Blut weltweit bekannt geworden war.
Alexander Schmidt studierte ab 1850 an der Kaiserlichen Universität zu Dorpat Geschichte, wechselte aber bald zur Medizin. Nach seiner Promotion in Dorpat 1858 setzte er seine Studien an der Universität Wien und der Berliner Universität fort.
Unter Felix Hoppe-Seyler unternahm er in Berlin seine erste eigene Untersuchung über die Ausflockung von Muskelfasern. Von 1866 bis 1867 arbeitete er mit Carl Friedrich Wilhelm Ludwig in Leipzig. Nach der Emeritierung seines alten Lehrers Friedrich Heinrich Bidder folgte er ihm auf den Lehrstuhl in Dorpat nach. Schmidt lehrte bis zu seinem Tod 1894 an der Universität Dorpat, der er 1885 bis 1889 als Rektor vorstand. Im Jahr 1884 wurde er zum Mitglied der Leopoldina gewählt.

Quelle: wikipedia

Alexander-Schmidt-Preis

Inhibitor incidence in an unselected cohort of previously untreated patients with severe hemophilia B: a PedNet study

Abstract:

The incidence of FIX inhibitors in severe hemophilia B (SHB) is not well defined. Frequencies of 3-5% have been reported but most studies to date were small, including patients with different severities, and without prospective follow-up for inhibitor incidence. Study objective was to investigate inhibitor incidence in patients with SHB followed up to 500 exposure days (ED), the frequency of allergic reactions, and the relationship with genotypes. Consecutive previously untreated patients
(PUPs) with SHB enrolled into the PedNet cohort were included. Detailed
data was collected for the first 50 ED, followed by annual collection of
inhibitor status and allergic reactions. Presence of inhibitors was defined
by at least two consecutive positive samples. Additionally, data on factor
IX gene mutation was collected. 154 PUPs with SHB were included; 75%
were followed until 75 ED, and 43% until 500 ED. Inhibitors developed in
14 patients (7 high-titre). Median number of ED at inhibitor manifestation
was 11 (IQR 6.5-36.5). Cumulative inhibitor incidence was 9.3% (95%CI
4.4-14.1) at 75 ED, and 10.2% (5.1-15.3) at 500 ED. Allergic reactions
occurred in 4 (28.6%) inhibitor patients. Missense mutations were most
frequent (46.8%) overall but not associated with inhibitors. Nonsense
mutations and deletions with large structural changes comprised all
mutations among inhibitor patients and were associated with an inhibitor
risk of 26.9% and 33.3%, respectively. In an unselected, well-defined
cohort of PUPs with SHB, cumulative inhibitor incidence was 10.2% at 500
ED. Nonsense mutations and large deletions were strongly associated with
the risk of inhibitor development.

The ‘PedNet Registry’ is registered at clinicaltrials.gov; identifier:
NCT02979119

Nachwuchsförderpreis Blutungskrankheiten

Der Preis geht an MSc. Ing. Alessandro Aliotta aus Lausanne für die Arbeit:

Sodium–Calcium Exchanger Reverse Mode Sustains Dichotomous Ion Fluxes Required for Procoagulant COAT Platelet Formation

Nachwuchsförderpreis Blutungskrankheiten

Sodium–Calcium Exchanger Reverse Mode Sustains Dichotomous Ion Fluxes Required for Procoagulant COAT Platelet Formation

Abstract:

Procoagulant collagen-and-thrombin (COAT)-activated platelets represent a  subpopulation of activated platelets, which retain a coat of prohemostatic  proteins and express phosphatidylserine on their surface.  Dichotomous intracellular signaling generating procoagulant platelet activity  instead of traditional aggregating endpoints is still not fully  elucidated. It has been demonstrated that secondary messengers such as  calcium and sodium play a critical role in platelet activation. Therefore, we  developed a flow cytometric analysis to investigate intracellular ion fluxes  simultaneously during generation of aggregating and procoagulant  platelets. Human platelets were activated by convulxin-plus-thrombin.  Cytosolic calcium, sodium, and potassium ion fluxes were visualized by  specific ion probes and analyzed by flow cytometry.We observed high and prolonged intracellular calcium concentration, transient sodium increase,  and fast potassium efflux in COAT platelets, whereas aggregating non- COAT platelets rapidly decreased their calcium content, maintaining higher  cytosolic sodium, and experiencing lower and slower potassium depletion.  Considering these antithetical patterns, we investigated the role of the  sodium–calcium exchanger (NCX) during convulxin-plusthrombin activation. NCX inhibitors, CBDMB and ORM-10103, dose-dependently reduced the global calcium mobilization induced by convulxin-plus-thrombin  activation and dose-dependently prevented formation of  procoagulant COAT platelets. Our data demonstrate that both NCX modes  are used after convulxin-plus-thrombininduced platelet activation. Non- COAT platelets use forward-mode NCX, thus pumping calcium out and  moving sodium in, while COAT platelets rely on reverse NCX function,  which pumps additional calcium into the cytosol, by extruding sodium. In  conclusion, we described for the first time the critical and dichotomous role  of NCX function during convulxin-plus-thrombin-induced platelet activation.

Gewinner der Preise und Stipendien 2020

v. l.: Dr. S. Barco, Mainz; Dr. V. Luca, Mainz; M.Sc. S. Singh, Bonn; Dr. M. Bender, Würzburg; Dr. Dino Mehic, Wien; Foto: T. Ecke, Berlin

Preisverleihung auf der GTH Mitgliederversammlung 2020 in Bremen

v. l.: Dr. S. Barco, Mainz; Dr. V. Luca, Mainz; M.Sc. S. Singh, Bonn; Dr. M. Bender, Würzburg; Dr. Dino Mehic, Wien; Foto: T. Ecke, Berlin

Lernen Sie die Preis- und Stipendiatsträger sowie Ihre Arbeiten näher kennen:

Alexander-Schmidt-Preis

Der Preis geht an Dr. Markus Bender aus Würzburg für die Arbeit:

Platelet lamellipodia formation is not required for thrombus formation and stability

Hermann Adolf Alexander Schmidt (* 15. Mai 1831, † 10. April 1894) war ein deutschbaltischer Physiologe, der durch seine Arbeit über die Verdickung von Blut weltweit bekannt geworden war.
Alexander Schmidt studierte ab 1850 an der Kaiserlichen Universität zu Dorpat Geschichte, wechselte aber bald zur Medizin. Nach seiner Promotion in Dorpat 1858 setzte er seine Studien an der Universität Wien und der Berliner Universität fort.
Unter Felix Hoppe-Seyler unternahm er in Berlin seine erste eigene Untersuchung über die Ausflockung von Muskelfasern. Von 1866 bis 1867 arbeitete er mit Carl Friedrich Wilhelm Ludwig in Leipzig. Nach der Emeritierung seines alten Lehrers Friedrich Heinrich Bidder folgter er ihm auf den Lehrstuhl in Dorpat nach. Schmidt lehrte bis zu seinem Tod 1894 an der Universität Dorpat, der er 1885 bis 1889 als Rektor vorstand. Im Jahr 1884 wurde er zum Mitglied der Leopoldina gewählt.

Quelle: wikipedia

Alexander-Schmidt-Preis

Platelet lamellipodia formation is not required for thrombus formation and stability

Abstract:

During platelet spreading, the actin cytoskeleton undergoes rapid rearrangement, forming filopodia and lamellipodia. Controversial data have been published on the role of lamellipodia in thrombus formation and stability. The WAVE regulatory complex, which has been shown in other cells to drive lamellipodia formation by enhancing actin nucleation via the Arp2/3 complex, is activated by Rac1 interaction with the WAVE complex  subunit Cyfip1. We analyzed Cyfip1flox/flox Pf4-Cre mice to investigate the role of Cyfip1 in platelet function. These mice displayed normal platelet counts and a slight reduction in platelet volume. Activation of mutant platelets was only moderately reduced to all tested agonists as measured by αIIbβ3 integrin activation and P-Selectin surface exposure. However, lamellipodia formation of mutant platelets was completely abolished on different matrices. Nevertheless, Cyfip1- deficient platelets formed stable thrombi on collagen fibers ex vivo and in two models of occlusive arterial thrombosis in vivo. Similarly, the hemostatic function and maintenance of vascular integrity during inflammation of the skin and lung were unaltered in the mutant mice. Investigation of platelet morphology in an induced thrombus under flow revealed that platelets rather form filopodia in the thrombus shell, and are flattened with filopodia-like structures when in direct contact to collagen fibers at the bottom of the thrombus. We provide for the first time direct evidence that platelet lamellipodia formation is not required for stable thrombus formation, and that morphological changes of platelets differ between a static spreading assay and thrombus formation under flow.

GTH-Nachwuchsförderpreis: Thrombose

Der Nachwuchsförderpreis Thrombose ging an

Dr. Stefano Barco aus Mainz

Für die Arbeit:

Trends in mortality related to pulmonary embolism in the European Region, 2000–15: analysis of vital registration data from the WHO Mortality Database (Stefano Barco*, Seyed Hamidreza Mahmoudpour*, Luca Valerio*, Frederikus A Klok, Thomas Münzel, Saskia Middeldorp, Walter Ageno, Alexander T Cohen, Beverley J Hunt, Stavros V Konstantinides)

GTH-Nachwuchsförderpreis: Thrombose

Summary:

Background: European estimates of the burden imposed by pulmonary embolism are not available to this date. We aimed to assess pulmonary embolism-related mortality and time trends in the WHO European Region.

Methods: We analysed vital registration data from the WHO Mortality Database (2000–15) covering subregions of the WHO European Region: Eastern Europe, Northern Europe, Southern Europe, Western Europe, and Central Asia. Deaths were considered pulmonary embolism-related if International Classification of Disease-10 code for acute pulmonary embolism (I26) or any code for deep or superficial vein thrombosis was listed as the primary cause of death. We used locally estimated scatterplot smoothing weighted by size of the Member State population to calculate proportionate mortality and time trends in age-standardised mortality.
Findings: In the 3-year period between 2013 and 2015, an average of 38 929 pulmonary embolism-related deaths occurred annually in the 41 Member States with available data and a population of 650 950 921; among individuals aged 15–55 years, pulmonary embolism accounted for 8–13 per 1000 deaths in women and 2–7 per 1000 deaths in men. Between 2000 and 2015, age-standardised annual pulmonary embolism-related mortality rates decreased linearly from 12·8 (95% CI 11·4–14·2) to 6·5 (5·3–7·7) deaths per 100 000 population without substantial sex-specific differences.
Interpretation: The observed decreasing trends in pulmonary embolism-related mortality might reflect improved management of the disease, in line with case fatality data from cohort studies. Additional, or alternative, explanations might include the absence of a uniform case definition and changes in coding practices and performing autopsy. Pulmonary embolism still imposes a relevant medical and societal burden. Continuing efforts are warranted to improve awareness and implement effective preventive and therapeutic measures.
Funding: German Federal Ministry of Education and Research.
Copyright: © 2019 Elsevier Ltd. All rights reserved.

GTH-Nachwuchsförderpreis: Blutung

Der Nachwuchsförderpreis Thrombose ging an

M.Sc. Sneha Singh aus Bonn

Für die Arbeit:

The Plasma Factor XIII Heterotetrameric Complex Structure: Unexpected Unequal Pairing within a Symmetric Complex (Sneha Singh, Alexis Nazabal, Senthilvelrajan Kaniyappan, Jean-Luc Pellequer, Alisa S. Wolberg, Diana Imhof, Johannes Oldenburg and Arijit Biswas)

GTH-Nachwuchsförderpreis: Blutung

Abstract:

Factor XIII (FXIII) is a predominant determinant of clot stability, strength, and composition. Plasma FXIII circulates as a pro-transglutaminase with two catalytic A subunits and two carrier-protective B subunits in a heteroatetramer (FXIII-A2B2). FXIII-A2 and -B2 subunits are synthesized separately and then assembled in plasma. Following proteolytic activation by thrombin and calcium-mediated dissociation of the B subunits, activated FXIII (FXIIIa) covalently cross links fibrin, promoting clot stability. The zymogen and active states of the FXIII-A subunits have been structurally characterized; however, the structure of FXIII-B subunits and the FXIII-A2B2 complex have remained elusive. Using integrative hybrid approaches including atomic force microscopy, cross-linking mass spectrometry, and computational approaches, we have constructed the first all-atom model of the FXIII-A2B2 complex. We also used molecular dynamics simulations in combination with isothermal titration calorimetry to characterize FXIII-A2B2 assembly, activation, and dissociation. Our data reveal unequal pairing of individual subunit monomers in an otherwise symmetric complex, and suggest this unusual structure is critical for both assembly and activation of this complex. Our findings enhance understanding of mechanisms associating FXIII-A2B2 mutations with disease and have important implications for the rational design of molecules to alter FXIII assembly or activity to reduce bleeding and thrombotic complications.

Hans-Egli-Forschungsstipendium

Das Hans-Egli-Forschungsstipendium ging an

Dr. Dino Mehic aus Wien

Für das Forschungsprojekt:

Hyperfibrinolysis as a possible mechanism of bleeding of unknown cause: Linking impaired levels of fibrinolytic factors to genetic information 

Publikationsliste (relevante Publikationen)
Bitte beachten Sie, dass diese Publikationen von meiner PhD-Betreuerin Priv. Doz. Dr. Johanna Gebhart, PhD sind. Sie wird mich bei der Durchführung des Projekts fachlich unterstützen.

Gebhart, J. et al. Fibrinolysis in patients with a mild-to-moderate bleeding tendency of unknown cause. Ann Hematol. 2017 Mar;96(3):489-495.
DOI: 10.1007/s00277-016-2893-6

Gebhart J, et al. High proportion of patients with bleeding of unknown cause in persons with a mild-to-moderate bleeding tendency: Results from the Vienna Bleeding Biobank (VIBB). Haemophilia. 2018 May;24(3):405-413
DOI: 10.1111/hae.13422

Hofer S, et al. Gebhart J. Thrombin generating potential, plasma clot formation and clot lysis are impaired in patients with bleeding of unknown cause. J Thromb Haemost. 2019 Sep;17(9):1478-1488.
DOI: 10.1111/jth.14529

Das Stipendium wird ermöglicht durch eine Spende der Bayer Vital GmbH in Höhe von 30.000 €.

Hans-Egli-Forschungsstipendium

Aims (Ziele, Hypothesen):

This project aims to confirm our findings on an altered pattern of fibrinolysis in a larger group of patients with BUC. In detail, we will investigate tPA antigen and activity, tPA-PAI-1 complexes, PAI-1 antigen, TAFI activity, alpha2-antiplasmin activity, fibrinogen, plasminogen activity and D-dimer. Furthermore we will investigate fibrinolysis based on viscoelastic changes using thromboelastrometry (ROTEM) as well as plasma clot lysis upon addition of tPA in a turbidimetric test. Data will be compared to a group of 187 patients with a diagnosis of a mild bleeding disorder (e.g. VWD, PFD) as well as a group of 100 age- and sex-matched healthy controls. Furthermore, as a completely novel approach, results will be linked to genetic data available from whole exome sequencing of the genes encoding for the investigated parameters.
Primary objectives of the study are (1) to investigate differences in the measured parameters of fibrinolysis between patients with BUC, with an established diagnosis of a bleeding disorder and healthy controls, and (2) to identify new genetic mutations and alterations (e.g. single nuclear polymorphisms, SNPs) associated with altered levels of the investigated fibrinolytic factors.
Secondary objectives are to evaluate the impact of altered fibrinolysis on (a) the clinical bleeding phenotype, assessed by 2 standardized bleeding assessment tools and (b) ROTEM results, and (c) plasma clot lysis.

Marco-Brockhaus-Wissenschaftspreis für Thromboseforschung im Kindesalter

Der Marco-Brockhaus-Wissenschaftspreis für Thromboseforschung im Kindesalter ging an

Dr. Valerio Luca aus Mainz

Für die Arbeit:

Clinical presentation, treatment and course of Lemierre syndrome and bacterial-associated venous thromboembolism in children and adolescents. (Luca Valerio, MD; Stefano Barco, MD, PhD)

Der Preis wird ermöglicht durch eine Spende von Herrn Brockhaus in Höhe von 10.000 €.

Marco-Brockhaus-Wissenschaftspreis für Thromboseforschung im Kindesalter

Summary:

Das Lemierre-Syndrom betrifft normalerweise gesunde Jugendliche oder junge Erwachsene und tritt mit einer Gesamttodesrate von 1 bis 10 Fällen pro Million Personenjahre mit einer geschätzten Sterblichkeitsrate von 4 bis 9% auf. Diagnostische Kriterien bleiben umstritten und umfassen akute Kopf-Hals-Bakterieninfektionen (häufig Tonsillitis durch Anaerobier mit hohem Sepsis-und Gefäßinvasionspotenzial, insbesondere Fusobacterium necrophorum), kompliziert durch lokale Venenthrombose, die gewöhnlich die Vena jugularis interna involviert, und systemische septische Embolie. Die medizinische Behandlung basiert auf einer Antibiotikatherapie mit anaerober Abdeckung, Antikoagulanzien, und unterstützender Behandlung bei Sepsis. Chirurgische Maßnahmen können erforderlich sein, einschließlich der Drainage der Abszesse, Gewebedebridement und Jugularvenenligatur. Die Evidenz für das klinische Management ist in Ermangelung einer ausreichend bemessenen Studie mit klinischen Ergebnissen äußerst schlecht. In diesem Artikel illustrieren wir zwei Fälle von Lemierre- Syndrom, die nicht durch Fusobacterium necrophorum verursacht wurden und bieten eine klinisch orientierte Diskussion über die Hauptprobleme der Epidemiologie, Pathophysiologie und Managementstrategien dieser Erkrankung. Abschließend fassen wir das Studienprotokoll einer vorgeschlagenen systematischen Übersichtsarbeit und einer individuellen Patientendaten-Metaanalyse der Literatur zusammen. Unsere laufende Arbeit zielt darauf ab, das Risiko neuer thromboembolischer Ereignisse, schwerer Blutungen oder Todesfälle bei Patienten mit Lemierre-Syndrom zu untersuchen und die Rolle der Antikoagulanzien-Therapie in diesem Zusammenhang besser zu klären. Diese Bemühungen bilden den Ausgangspunkt für eine evidenzbasierte Behandlung des Lemierre-Syndroms, welche auf multinationalen interdisziplinären kollaborativen Studien aufbaut.

Gewinner der Preise und Stipendien 2019 in Berlin

v. l.: PD Dr. J. Koscielny, Dr. J. Gebhart, Dr. A. Schmidt, Dr. E. Grilz, PD Dr. R. Klamroth, Foto: T.Ecke, Berlin

Preisverleihung auf der GTH Mitgliederversammlung 2019 in Berlin

v. l.: PD Dr. J. Koscielny, Dr. J. Gebhart, Dr. A. Schmidt, Dr. E. Grilz, PD Dr. R. Klamroth, Foto: T.Ecke, Berlin

Rudolf-Marx-Stipendium 2019

Für maximal 25.000€ wird im Rahmen dieses Stipendiums ein umrissenes Forschungsprojekt aus dem Bereich der Hämostaseologie oder der vaskulären Biologie und Medizin an einer externen Forschungseinrichtung im In- oder Ausland gefördert. Das Stipendium geht an:

Dr. Johanna Gebhart aus Wien für das Projekt:

Autoantibodies in primary ITP: Ability for platelet desialylation and not glycoproteinspecificity alters responsiveness to different treatment strategies and the bleeding phenotype

Rudolf-Marx-Stipendium 2019

Alexander-Schmidt-Preis

Für hervorragende Arbeiten auf dem Gebiet der Hämostaseologie vergibt die GTH jährlich diesen mit 15.000€ dotierten Preis. Bewerben können sich GTH Mitglieder mit hochrangigen Arbeiten aus dem Gebiet der Hämostaseologie / vaskulären Medizin, die von einem Gutachtergremium für die Veröffentlichung in einer wissenschaftlichen Zeitschrift angenommen oder bereits veröffentlicht wurden.

Prämiert wurde die folgende Arbeit von Dr. Katrin Czogalla-Nitsche aus Bonn:

Warfarin and vitamin K compete for binding to Phe55 in human VKOR

Alexander-Schmidt-Preis

GTH-Nachwuchsförderpreise: Thrombose

Der Nachwuchsförderpreis Thrombose ging an

Dr. Ella Grilz aus Wien

Für die Arbeit:

Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer

GTH-Nachwuchsförderpreise: Thrombose

Hans-Egli Forschungsstipendium

Das mit 30.000€ ausgestattete Stipendium soll jungen Wissenschaftlern ermöglichen, sich für ein halbes Jahr intensiv der Forschung eines Projektes auf dem Gebiet der angeborenen Blutungskrankheiten zu widmen. Das Stipendium geht an:

Dr. Anja Schmidt aus Oberursel

für das Projekt:

Zytokinprofile nach FVIII- und FIX-Stimulation – Relevanz für die unterschiedlichen Immunantworten?

Hans-Egli Forschungsstipendium

Gewinner der Preise und Stipendien 2018

204-2018-02-21-gth-kongress

Lernen Sie die Preis- und Stipendiatsträger sowie Ihre Arbeiten näher kennen:

Hans-Egli-Stipendium

Der Preis geht an Dr. Johanna Gebhart aus Wien für die Arbeit:

Parameters Influencing the Phenotype of Non-Severe Haemophilia A and B

Prof. Dr. med. Hans Egli zählt zu den Pionieren der Hämostaseologie in Deutschland. Sein Wirken beeinflusste ganz entscheidend die Möglichkeiten der Behandlung von Patienten mit angeborenen Blutungserkrankungen. Insbesondere die Einführung der Heimselbstbehandlung in Deutschland Anfang der 1970er Jahre hat er maßgeblich vorangetrieben. Damit eröffnete er den Patienten völlig neue Perspektiven für ein weitgehend selbstbestimmtes Leben. Hans Egli war unter anderem Gründungsdirektor des jetzigen Instituts für Experimentelle Hämatologie und Transfusionsmedizin der Universität Bonn und Gründungsmitglied der Deutschen Arbeitsgemeinschaft für Blutgerinnungsforschung (DAB), aus der 1982 die GTH hervorging. Besondere Verdienste hat sich Hans Egli in der Förderung und Ausbildung von Nachwuchswissenschaftlern im Bereich der Hämostaseologie und Transfusionsmedizin erworben.

Hans-Egli-Stipendium
Dr. Johanna Gebhart aus Wien

Parameters Influencing the Phenotype of Non-Severe Haemophilia A and B

1. Current status of research (Stand der Forschung)
Haemophilia is classified as severe, moderate and mild, according to the basal factor VIII/ IX (FVIII/ IX) activity levels.1 This classification to a certain extent indicates the bleeding phenotype. However, there is a big heterogeneity of the phenotype amongst patients with similar or even with the same factor levels as e.g.10–? 15% of the patients with severe haemophilia have a milder presentation of the disease than expected.2,3 On the other hand, Den Uijl et al. found that more than 25% of patients with moderate haemophilia have a phenotype similar to the severe form and also in patients with moderate and mild haemophilia a wide variation of the bleeding phenotype was seen.4,5 Beyond the underlying gene–?mutations and the FVIII/ IX levels, different mechanisms of haemostasis, like alterations of the fibrinolytic system or thrombophilic mutations (F V Leiden G1691A Mutation, Prothrombin c.*97G>A Variation), have been inconsistently described as disease–?modifying factors in patients with haemophilia.6,7 Further, clinical characteristics, anamnestic data and bleeding assessment tools are useful for definition of the clinical severity and these tools enable a more precise evaluation of the bleeding phenotype than the baseline factor activity alone. 4–6

2. Own preparatory work (Eigene Vorarbeiten)

My PhD project focused on the investigation of plasma clot properties and fibrinolytic parameters in patients with a mild–?to–?moderate bleeding tendency of unknown cause (BUC). We found alterations in the plasma clot formation rate in presence of tissue plasminogen activator (tPA) in our patients with BUC in comparison to age–? and sex–?matched healthy controls.8 Still, assessed plasma clot properties did not correlate with the bleeding severity of our patients with BUC. Within this project we have also investigated plasma clot characteristics in 25 patients with mild, moderate, or severe deficiencies of FVIII and found similar trends in respect to lower clot formation rates correlating with lower FVIII activity. In another project, we used the thrombin generation assay (TGA) as a measure of the overall hemostatic potential and could not identify a difference between patients with BUC and healthy controls.9 In the investigation of fibrinolytic parameters, higher tPA activity, lower levels of tPA–?PAI–?1 complexes and paradoxically increased TAFI and alpha2–?antiplasmin were independently associated with BUC in sex–?adjusted logistic regression analyses, indicating an etiological role of the fibrinolytic system in these patients.10

3. Aims, Hypothesis, work programme (Ziele, Hypothesen, Arbeitsprogramm)

With the proposed project we aim to identify alterations in the global clotting tests (thrombin generation assay and plasma clot characteristics) and in the fibrinolytic system, and we will investigate the role of thrombophilic mutations as disease–?modifying factors in patients with non–?severe hemophilia A or B. We hypothesize that the additional evaluation of the above–?mentioned hemostatic parameters enables a more accurate estimation of the individual bleeding phenotype than the residual FVIII/FIX activity. The primary endpoint of the study is the score of the ISTH–?BAT treated as a metric score. The secondary endpoints are the joint status (WFH–?score), the annualised bleeding rate, data on the FVIII/ IX consumption, and the age at the first manifestation of bleeding symptoms. Sample size estimation has been performed using the formulas and software by Dupont and Plummer. Assuming a mean ISTH–?BAT score of 10 (SD 2) and a mean time–?to–?peak clot formation8 of 30 min (SD 3) in non–?severe haemophilia patients, the assumed regression equation has a slope of 0.2, concluding a necessary sample size of 89 patients to reach a power of 80% at the 0.05 alpha level.

GTH-Nachwuchsförderpreise: Thrombose

Der Nachwuchsförderpreis Thrombose ging an

Julia Riedl aus Wien

Für die Arbeit:

Podoplanin Expression in Primary Brain Tumors Induces Platelet Aggregation and Increases Risk of Venous Thromboembolism (Riedl J, Preusser M, Nazari PM, Posch F, Panzer S, Marosi C, Birner P, Thaler J, Brostjan C, Lötsch D, Berger W, Hainfellner JA, Pabinger I, Ay C. Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism. Blood. 2017;129(13):1831–1839.)

GTH-Nachwuchsförderpreise: Thrombose

Alexander-Schmidt-Preis

Für hervorragende Arbeiten auf dem Gebiet der Hämostaseologie vergibt die GTH jährlich diesen mit 15.000€ dotierten Preis. Bewerben können sich GTH Mitglieder mit hochrangigen Arbeiten aus dem Gebiet der Hämostaseologie / vaskulären Medizin, die von einem Gutachtergremium für die Veröffentlichung in einer wissenschaftlichen Zeitschrift angenommen oder bereits veröffentlicht wurden.

Prämiert wurde die folgende Arbeit von Prof. Dr. Tobias Fuchs:

Host DNAses Prevent Vascular Occlusion by Neutrophil Extracellular Traps

Alexander-Schmidt-Preis

GTH-Nachwuchsförderpreise: Blutung

Der Nachwuchsförderpreis Blutungskrankheiten ging an

Dr. Nadine Vollack aus Hannover

Für die Arbeit:

CD32 Inhibition and High Dose Factor VIII Suppress Murine FVIII-Specific Recall Response by Distinct Mechanisms in Vitro (Vollack N, Friese J, Bergmann S, Tiede A, Werwitzke S. CD32 inhibition and high dose of rhFVIII suppress murine FVIII-specific recall response by distinct mechanisms in vitro. Thromb Haemost. 2017;117(9):1679–1687.)

GTH-Nachwuchsförderpreise: Blutung

Rudolf-Marx-Stipendium 2018

Für maximal 25.000€ wird im Rahmen dieses Stipendiums ein umrissenes Forschungsprojekt aus dem Bereich der Hämostaseologie oder der vaskulären Biologie und Medizin an einer externen Forschungseinrichtung im In- oder Ausland gefördert. Das Stipendium geht an:

Martina Bucsaiova aus Wien für das Projekt:

Do Bacterial Infections Infl uence the Interaction of Platelets with Dendritic Cells?

Rudolf-Marx-Stipendium 2018
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