Effect of toxins from different periodontitis-associated bacteria on human platelet function.

Background: Periodontitis is caused by a dysbiosis of oral bacteria resulting in alveolar bone destruction and teeth loss. The role of platelets in pathogenesis of periodontitis is a subject of research. The release of toxins from periodontitis-associated bacteria may influence platelet function and contribute to the modulation of hemostatic or inflammatory responses.

Influence of short-term refrigeration on collagen-dependent signalling mechanisms in stored platelets.

Platelet concentrates (PC) are used to treat patients with thrombocytopenia and hemorrhage, but there is still the demand to find the optimal strategy for temperature-dependent storage of PC. Recently, we could show that cold storage for 1 h (short-term refrigeration) is sufficient to induce enhanced platelet responsiveness. The aim of this study was to investigate effects of cold storage on collagen-dependent activating signalling pathways in platelets from apheresis-derived PC (APC).

Increased Responsiveness of Stored Platelets after Short-Term Refrigeration.

Introduction: Refrigeration of platelets is considered to provide advantages in therapy of acute hemorrhage due to increased platelet responsiveness. The alleviation of inhibitory signaling caused by cold temperature (CT) has been identified as an important mechanism contributing to enhanced platelet reactivity, detectable in freshly prepared platelets within 1 h of cold storage. The aim of this study was to confirm the effects of short-term refrigeration in platelets from apheresis-derived platelet concentrates (APC).

The effect of short-term refrigeration on platelet responsiveness.

Storage of platelet concentrates (PC) at cold temperature (CT) is discussed as an alternative to the current standard of storage at room temperature (RT). Recently, we could show that cold-induced attenuation of inhibitory signaling is an important mechanism promoting platelet reactivity. For developing strategies in blood banking, it is required to elucidate the time-dependent onset of facilitated platelet activation.

Platelet Toll-Like-Receptor-2 and -4 Mediate Different Immune-Related Responses to Bacterial Ligands.

 Like immune cells, platelets express toll-like receptors (TLRs) on their surface membrane. TLR2 and TLR4 are able to recognize bacterial antigens and have the potential to influence hemostatic functions and classical intracellular signaling pathways. This study investigated the role of TLR2 and TLR4 for immune-related functions in human platelets.

Composition of plasma in apheresis-derived platelet concentrates under cold storage.

Background: Compared to room temperature (RT, 22-24°C) storage, refrigeration of platelet concentrates (PC) may provide advantages due to lower risks of bacterial growth and increased responsiveness of platelets. However, storage at cold temperature (CT, 2-6°C) may also strongly influence the plasmatic composition of PC. This study analysed the content of plasma in apheresis-derived platelet concentrates (APC).

Profile of the single-use, multiple-pass protein A adsorber column in immunoadsorption.

Background And Objectives: Immunoadsorptions (IA) are used to remove autoantibodies from the plasma in autoimmune disorders. In this study, we evaluated the effects of a single-use, recombinant staphylococcal protein A-based immunoadsorber on blood composition of the patient.

Materials And Methods: In a cohort of patients with myasthenia gravis or stiff-person syndrome, essential parameters of blood cell count, coagulation, clinical chemistry or plasma proteins and immunoglobulins (Ig) were measured before and after IA (n = 11).

Influence of long-term proteasome inhibition on platelet responsiveness mediated by bortezomib.

Introduction: Although platelets contain a full proteasome system, its role in platelet function is not completely understood yet. Since the proteasome system may be involved in time-delayed processes, platelet responsiveness was investigated after long-term, bortezomib-mediated proteasome inhibition.

Materials And Methods: Citrate-anticoagulated whole blood was stored with 5 nM and 1 μM bortezomib for 24 h.

The involvement of toll-like receptors 2 and 4 in human platelet signalling pathways.

In addition to haemostasis, platelets play an essential role in mechanisms of inflammation and in immunological reactions. Platelets express various toll-like receptors (TLR) on their surface, among them TLR2 and TLR4, which are important for the recognition of bacterial patterns. This study compared TLR2- and TLR4-dependent platelet signalling and their effect on platelet function.

The Impact of Cold Storage on Adenosine Diphosphate-Mediated Platelet Responsiveness.

 Cold storage of platelets is considered to contribute to lower risk of bacterial growth and to more efficient hemostatic capacity. For the optimization of storage strategies, it is required to further elucidate the influence of refrigeration on platelet integrity. This study focused on adenosine diphosphate (ADP)-related platelet responsiveness.

The role of proteasome activity for activating and inhibitory signalling in human platelets.

Platelets express key proteins of the proteasome system, but its functional role in the regulation of platelet integrity, however, is not fully understood yet. Therefore, this study evaluated activating and inhibitory platelet signalling pathways using the potent and selective proteasome inhibitor bortezomib. In washed platelets, the effect of bortezomib on viability and on aggregation was assessed.

The Role of Human Platelet Preparation for Toll-Like Receptors 2 and 4 Related Platelet Responsiveness.

 Like immune cells, platelets express the repertoire of toll-like receptors (TLR), among them TLR2 and TLR4, which are important for the recognition of bacterial patterns. Receptor-mediated functional effects in platelets have been investigated, but reliable conclusions are tampered due to heterogeneous study designs with variable platelet preparation methods. This study compares TLR2- and TLR4-dependent platelet responsiveness in platelet-rich plasma (PRP) and in washed platelets (WPs).

The role of agonist-induced activation and inhibition for the regulation of purinergic receptor expression in human platelets.

Introduction: Adenosine diphosphate (ADP) as physiological activator of human platelets mediates its effects via three purinergic receptors: P2Y1, P2Y12 and P2X1. The inhibition of P2Y12 is used pharmacologically to suppress aggregation underlining the physiological significance of this receptor. Since the regulation of purinergic receptor expression has not thoroughly been investigated yet, this study analyzed the content of purinergic receptors on the platelet surface membrane upon activation and inhibition.

The role of adenosine diphosphate mediated platelet responsiveness for the stability of platelet integrity in citrated whole blood under ex vivo conditions.

Background: Platelets are important for effective hemostasis and considered to be involved in pathophysiological processes, e.g. in cardiovascular diseases.

Evaluation of dose-dependent effects of the proteasome inhibitor bortezomib in human platelets.

Platelets express key proteins of the proteasome system and contain protein ubiquitination pathways. The functional role of the proteasome system in platelets, however, is still subject of studies. In addition to its role as anticancer drug, the potent and selective proteasome inhibitor bortezomib can be used for experimental proteasome research.

Role of Purinergic Receptor Expression and Function for Reduced Responsiveness to Adenosine Diphosphate in Washed Human Platelets.

Background: Washing of platelets is an important procedure commonly used for experimental studies, e.g. in cardiovascular research.

Expression and function of purinergic receptors in platelets from apheresis-derived platelet concentrates.

Background: The storage of platelets affects platelet integrity and functionality, a process named platelet storage lesion (PSL). Reduced adenosine diphosphate (ADP)-induced platelet aggregation is a typical manifestation of PSL. However, the role of ADP receptors in this context has not been evaluated yet.

Specific inhibitory effects of the NO donor MAHMA/NONOate on human platelets.

Nitric oxide (NO) is a physiological inhibitor of platelet function and has vaso-dilating effects. Therefore, synthesized NO releasing agents are used e.g.

Increasing susceptibility of nitric oxide-mediated inhibitory platelet signaling during storage of apheresis-derived platelet concentrates.

Background: Storage of platelets (PLTs) affects PLT integrity and functionality, a process named the PLT storage lesion. Normal PLT function essentially depends on the balanced interaction of activating and inhibitory signaling pathways. As there are poor data on the alterations of inhibitory signaling during storage of PLT concentrates, this study investigates the modulation capability of the cyclic nucleotide-mediated inhibitory pathways by use of the nitric oxide donor diethylamine diazenium diolate (DEA/NO).

Decreasing phosphodiesterase 5A activity contributes to platelet cGMP accumulation during storage of apheresis-derived platelet concentrates.

Background: Platelet storage lesion (PSL) considerably decreases the quality of platelets (PLTs) in concentrates characterized by a loss of signaling responses to agonists and impaired PLT activation, secretion, and aggregation. To understand the role of inhibitory signaling pathways in the mechanism of PSL, the basal state of the cyclic nucleotide (CN)-dependent signaling systems in stored PLTs was investigated.

Study Design And Methods: Whole blood samples (WB) and apheresis-derived PLT concentrates (APCs) were obtained from healthy volunteers.

The thrombin inhibitors hirudin and Refludan(®) activate the soluble guanylyl cyclase and the cGMP pathway in washed human platelets.

A number of direct thrombin inhibitors are successfully used clinically and experimentally as novel antithrombotics and specific anticoagulants. They are also used as anticoagulants in certain blood collection tubes for the analysis of platelet function. A series of platelet function tests have emerged to measure adequate responses to antiplatelet therapy.

Evaluation of the new INNOVANCE® PFA P2Y cartridge in patients with impaired primary haemostasis.

Recently, the INNOVANCE® PFA P2Y (P2Y) cartridge of the PFA-100® system (Siemens Healthcare Diagnostics, Marburg, Germany) has been developed for the monitoring of adenosine diphosphate (ADP) P2Y(12) receptor inhibition in patients under dual antiplatelet therapy. The aim of this study was to evaluate the influence of pre-existing defects in primary haemostasis on the P2Y cartridge independent from specific antiplatelet medication. Therefore, the closure time (CT) of the P2Y cartridge was measured in a cohort of 176 patients with assumed bleeding disorders and compared with the results of established methods for the assessment of primary haemostasis.