Beside their central role in haemostasis and thrombosis platelets are crucially involved in inflammation, arteriosclerosis, angiogenesis, anti-microbial host defense and hematogenous tumour growth/metastasis. The integrity of platelet function is a prerequisite for intact haemostasis but it enables also efficient interaction with other blood and vascular cells leading to functional crosstalk of the interacting partners. Platelets bind to leukocytes und form together heterocellular conjugates in the blood circulation which present a cellular and functional link between the haemostasis and inflammation system.
Ex vivo detection of human platelet-monocyte conjugates in the peripheral blood by flow cytometry (dot plot presentation of single cells and cell-conjugates) and fluorescence microscopy.
Specific platelet function tests provide useful tools for the research of platelet biology and defects, for the clinical diagnosis of platelet-related disorders, for monitoring of haemostatic therapy and individualizing treatment. In addition to the traditional test of platelet aggregometry this platform laboratory provides modern methods to study in detail the
- Activation and functional capacity of single platelets (flow cytometry)
- Platelet-dependent thrombin generation/ coagulation (calibrated automated thrombography)
- Interaction of platelets with other blood / vascular cells, migration and dynamics of thrombus formation in real time under flow (integrated BioFlux-flow chamber system)
- Platelet protein composition and posttranslational modifications (LC-MS-based quantitative platelet proteomics and phospho-proteomics in collaboration with Leibniz – Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund).
This platform laboratory provides the feasibility for CTH-associated and external collaboration partners to apply modern ex vivo/in vitro methods for research and clinical studies in the field of human/murine platelet phenotyping and function analysis.
In addition, the platform offers methods and expertise for specialized diagnostics of platelet function disorders in collaboration with the Thrombosis Clinic and Outpatient clinic for coagulopathies of the CTH.
Projects using the method
Scientific Platform Coordinator
PD Kerstin Jurk, PhD
Position: Principal Investigator
Kathrin Groß (neé Schwierczek)
- Reiss C, Mindukshev I, Bischoff V, Subramanian H, Kehrer L, Friebe A, Stasch JP, Gambaryan S, Walter U. The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood. Br J Pharmacol. 2015 Nov;172(21):5199-210.
- Bollmann F, Jäckel S, Schmidtke L, Schrick K, Reinhardt C, Jurk K, Wu Z, Xia N, Li H, Erkel G, Walter U, Kleinert H, Pautz A. Anti-inflammatory and anti-thrombotic effects of the fungal metabolite galiellalactone in apolipoprotein e-deficient mice. PLoS One. 2015;10:e0130401.
- Jurk K. Analysis of platelet function and dysfunction. Hamostaseologie. 2015;35:60-72.
- Burkhart JM, Gambaryan S, Watson SP, Jurk K, Walter U, Sickmann A, Heemskerk JWM, Zahedi RP. What can proteomics tell us about platelets? Circulation Research. 2014;114:1204-1219.
- Beck F, Geiger J, Gambaryan S, Veit J, Vaudel M, Nollau P, Kohlbacher O, Martens L, Walter U, Sickmann A, Zahedi RP. Time-resolved characterization of camp/pkadependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways. Blood. 2014;123:e1-e1.
- de Witt SM, Swieringa F, Cavill R, Lamers MM, van Kruchten R, Mastenbroek T, Baaten C, Coort S, Pugh N, Schulz A, Scharrer I, Jurk K, Zieger B, Clemetson KJ, Farndale RW, Heemskerk JW, Cosemans JM. Identification of platelet function defects by multi-parameter assessment of thrombus formation. Nature Commun. 2014;5:425.
- Knorr M, Hausding M, Pfeffer A, Jurk K, Jansen T, Schwierczek K, Oelze M, Kröller-Schön S, Schulz E, Wenzel P, Gori T, Burgin K, Sartor D, Scherhag A, Münzel T, Daiber A. In vitro and in vivo characterization of a new organic nitrate hybrid drug covalently bound to pioglitazone. Pharmacology. 2014;93:203-21.
- Hausding M, Jurk K, Daub S, Kröller-Schön S, Stein J, Schwenk M, Oelze M, Mikhed Y, Ghaemi Kerahrodi J, Kossmann S, Jansen T, Schulz E, Wenzel P, Reske-Kunz AB, Becker C, Münzel T, Grabbe S, Daiber A. CD40L contributes to angiotensin-II induced pro-thrombotic state, vascular inflammation, oxidative stress and endothelial dysfunction. Basic Res Cardiol. 2013; 108:386.
- Burkhart JM, Vaudel M, Gambaryan S, Radau S, Walter U, Martens L, Geiger J, Sickmann A, Zahedi RP. The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways. Blood. 2012; 120:e73-e82