scholarly journals Ultraviolet C light pathogen inactivation treatment of platelet concentrates preserves integrin activation but affects thrombus formation kinetics on collagen in vitro

Transfusion ◽  
2015 ◽  
Vol 55 (10) ◽  
pp. 2404-2414 ◽  
Author(s):  
Britt Van Aelst ◽  
Rosalie Devloo ◽  
Philippe Vandekerckhove ◽  
Veerle Compernolle ◽  
Hendrik B. Feys
Keyword(s):  
Thrombus Formation ◽  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Integrin Activation ◽  
Formation Kinetics ◽  
Ultraviolet C

Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets

2001 ◽  
Vol 20 (10) ◽  
pp. 533-550 ◽  
Author(s):  
V Ciaravino ◽  
T McCullough ◽  
A D Dayan
Keyword(s):  
Ex Vivo ◽  
Reproductive Toxicity ◽  
In Vivo Studies ◽  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Baxter Healthcare ◽  
Safety Margins ◽  
Toxicology Assessment

The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations-compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53- mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000 fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of in vitro and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system.

CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates

2016 ◽  
Vol 115 (01) ◽  
pp. 99-108 ◽  
Author(s):  
Kousi Alzoubi ◽  
Madhumita Chatterjee ◽  
Britta Walker ◽  
Patrick Münzer ◽  
Dong Luo ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
Protein Abundance ◽  
Integrin Activation ◽  
Platelet Surface ◽  
Shear Rates ◽  
Occlusive Vascular Disease ◽  
Phosphatidylserine Exposure

SummaryCD44 is required for signalling of macrophage migration inhibitory factor (MIF), an anti-apoptotic pro-inflammatory cytokine. MIF is expressed and released from blood platelets, key players in the orchestration of occlusive vascular disease. Nothing is known about a role of CD44 in the regulation of platelet function. The present study thus explored whether CD44 modifies degranulation (P-selectin exposure), integrin activation, caspase activity, phosphatidylserine exposure on the platelet surface, platelet volume, Orai1 protein abundance and cytosolic Ca2+-activity ([Ca2+]i). Platelets from mice lacking CD44 (cd44-/- ) were compared to platelets from corresponding wild-type mice (cd44+/+ ). In resting platelets, P-selectin abundance, αllbβ3 inte-grin activation, caspase-3 activity and phosphatidylserine exposure were negligible in both genotypes and Orai1 protein abundance, [Ca2+]i, and volume were similar in cd44-/- and cd44+/+ platelets. Platelet degranulation and αllbβ3 integrin activation were significantly increased by thrombin (0.02 U/ml), collagen related peptide (CRP, 2 µg/ml and Ca2+-store depletion with thapsigargin (1 µM), effects more pronounced in cd44-/- than in cd44+/+ platelets. Thrombin (0.02 U/ml) increased platelet [Ca2+]i, caspase-3 activity, phosphatidylserine exposure and Orai1 surface abundance, effects again significantly stronger in cd44-/- than in cd44+/+ platelets. Thrombin further decreased forward scatter in cd44-/- and cd44+/+ platelets, an effect which tended to be again more pronounced in cd44-/- than in cd44+/+ platelets. Platelet adhesion and in vitro thrombus formation under high arterial shear rates (1,700 s-1) were significantly augmented in cd44-/- mice. In conclusion, genetic deficiency of CD44 augments activation, apoptosis and prothrombotic potential of platelets.

scholarly journals In vitro Quality of Platelets with Low Plasma Carryover Treated with Ultraviolet C Light for Pathogen Inactivation

2015 ◽  
Vol 43 (3) ◽  
pp. 190-197 ◽  
Author(s):  
Lacey Johnson ◽  
Ryan Hyland ◽  
Shereen Tan ◽  
Frank Tolksdorf ◽  
Chryslain Sumian ◽  
...  
Keyword(s):  
Pathogen Inactivation ◽  
Ultraviolet C

scholarly journals Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo

2007 ◽  
Vol 179 (7) ◽  
pp. i19-i19
Author(s):  
Bernhard Nieswandt ◽  
Markus Moser ◽  
Irina Pleines ◽  
David Varga-Szabo ◽  
Sue Monkley ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Thrombus Formation ◽  
Integrin Activation

Pathogen inactivation of platelets using ultraviolet C light: effect on in vitro function and recovery and survival of platelets

Transfusion ◽  
2012 ◽  
Vol 53 (5) ◽  
pp. 990-1000 ◽  
Author(s):  
Saber Bashir ◽  
Philip Cookson ◽  
Michael Wiltshire ◽  
Louise Hawkins ◽  
Luke Sonoda ◽  
...  
Keyword(s):  
Pathogen Inactivation ◽  
Light Effect ◽  
Ultraviolet C
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