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Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion
Linköping University, Department of Medicine and Health Sciences, Pharmacology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Health Sciences, Pharmacology . Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0003-3184-0427
Linköping University, Department of Medicine and Health Sciences, Pharmacology . Linköping University, Faculty of Health Sciences.
2006 (English)In: Blood Coagulation and Fibrinolysis, ISSN 0957-5235 (print), 1473-5733 (online), Vol. 17, no 5, 359-368 p.Article in journal (Refereed) Published
Abstract [en]

Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the α2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against αIIbβ3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase αIIbβ3-mediated platelet adhesion to albumin, dependent on α2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent.

Place, publisher, year, edition, pages
2006. Vol. 17, no 5, 359-368 p.
Keyword [en]
adrenaline, albumin, lysophosphatidic acid, platelet adhesion, synergism
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-13247DOI: 10.1097/01.mbc.0000233366.18605.b2OAI: diva2:18136
Available from: 2008-05-21 Created: 2008-05-21 Last updated: 2013-09-03
In thesis
1. Platelet Adhesion to Proteins in Microplates: Applications in Experimental and Clinical Research
Open this publication in new window or tab >>Platelet Adhesion to Proteins in Microplates: Applications in Experimental and Clinical Research
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Platelets are crucial for prevention of blood loss after vessel injury. Platelet adhesion to disrupted vessel walls is mediated by receptors such as the GPIb-IX-V complex that binds von Willebrand factor and the collagen-binding integrin α2β1. Also cross-linking of platelets, mediated by αIIbβ3 that binds to fibrinogen, results in platelet aggregation that further contributes to hemostasis. Platelets are also important pathophysiologically because of their role in thrombus formation following atherosclerotic plaque rupture. Pharmacological treatments aimed to prevent such events include use of platelet inhibitors such as acetylsalicylic acid (ASA) and clopidogrel. Despite the presence of several different platelet function assays, no one has so far been considered useful for clinical evaluation of the effect of anti-platelet treatment. The aim of this thesis was to evaluate possible applications in experimental as well as in clinical research for a platelet adhesion assay performed during static conditions. In principle, platelets in plasma are allowed to attach to protein coated microplates. Adhered platelets are then detected by induction of an enzymatic reaction followed by spectrophotometric measurements of the developed product. Our results show that the platelet adhesion assay is able to detect experimentally induced activation as well as inhibition of platelets. The assay also seems useful for investigation of synergistically induced platelet activation, especially when the coated surface consists of albumin. This is exemplified by the combination of lysophosphatidic acid and adrenaline, which induced a synergistically increased platelet adhesion to albumin that was dependent on αIIbβ3-receptors and on the secretion of ADP. Furthermore, secretion of ADP as well as TXA2 seems to contribute to several adhesive reactions investigated with this assay. The dependence on secretion, together with results showing that adhesion to collagen and fibrinogen is dependent on α2β1- and αIIbβ3-receptors respectively, indicate that the adhesive interactions occurring in the assay is in accordance with the general knowledge about platelet function. Regarding clinical applications, we found that platelet adhesion was increased for patients with essential thrombocythemia (ET) compared to controls. This is in line with the in vivo function of ET-platelets since a common complication for ET-patients is thrombosis. Furthermore, the assay was able to detect effects of treatment with clopidogrel in patients with unstable angina. To some extent it also measured the effects of ASA-treatment. In conclusion, our results suggest that the assay is suitable for experimental research and that further studies should be performed aimed at developing the assay into a clinically useful device.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. 67 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1068
platelets, platelet adhesion, platelet assay, synergistic activation, thrombosis, anti-platelet treatment
National Category
Pharmacology and Toxicology
urn:nbn:se:liu:diva-11733 (URN)978-91-7393-863-1 (ISBN)
Public defence
2008-06-03, Aulan, Hälsans Hus 240, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Available from: 2008-05-21 Created: 2008-05-21 Last updated: 2013-09-03Bibliographically approved

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