Article
Biochemistry & Molecular Biology
Karolina Siewiera, Magdalena Labieniec-Watala, Nina Wolska, Hassan Kassassir, Cezary Watala
Summary: Various factors, such as blood anticoagulants, platelet suspension media, and ADP stimulation, have been found to affect platelet mitochondrial respiration significantly. The method of platelet preparation may have a greater impact on mitochondrial respiration than platelet activation itself.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Brian Schnoor, Anne-Laure Papa
Summary: Lyophilized platelets, as a potential hemostatic agent, have long-term ambient storage capabilities and high biocompatibility, which make them a promising platform for drug delivery. The interactions between lyophilized platelets and fresh platelets have paradoxical effects on platelet adhesion and aggregation, which could have an impact for clinical applications.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Immunology
Isaclaudia Gomes de Azevedo-Quintanilha, Mariana Macedo Campos, Ana Paula Teixeira Monteiro, Alessandra Dantas do Nascimento, Andrea Surrage Calheiros, Douglas Mathias Oliveira, Suelen Silva Gomes Dias, Vinicius Cardoso Soares, Julia da Cunha Santos, Isabel Tavares, Thiago Moreno Lopes Souza, Eugenio D. Hottz, Fernando A. Bozza, Patricia T. Bozza
Summary: Chikungunya fever, transmitted by mosquitoes, is a viral disease characterized by symptoms such as fever and joint pain. This study found that the infection leads to platelet activation, suggesting their involvement in immune processes and inflammatory amplification.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vera Sovkova, Karolina Vocetkova, Vera Hedvicakova, Veronika Hefka Blahnova, Matej Buzgo, Evzen Amler, Eva Filova
Summary: The study found that different components of platelet concentrates have varying effects on cells: groups containing plasma had higher levels of growth factors, while groups containing platelet proteins had higher levels of chemokines and growth factors. The synergic effect of plasma and platelet proteins plays a crucial role in cell proliferation and viability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Layla Van Doren, Nga Nguyen, Christopher Garzia, Elizabeth K. Fletcher, Ryan Stevenson, David Jaramillo, Athan Kuliopulos, Lidija Covic
Summary: 12-LOX-derived 12(S)-HETE stimulates GPR31-Gi signaling pathways to enhance platelet activation and arterial thrombosis. Inhibition of this pathway with GPR310 provides protective effects against platelet aggregation and thrombosis without affecting hemostasis.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Karolina Siewiera, Magdalena Labieniec-Watala, Hassan Kassassir, Nina Wolska, Dawid Polak, Cezary Watala
Summary: The study found that prolonged exposure of blood platelets to high concentrations of glucose in diabetes can lead to increased mitochondrial respiration, but this is not the main reason for abnormal platelet functioning. Additionally, metformin was not able to inhibit platelet activation under in vitro conditions, indicating that its beneficial effect on the coagulation system in vivo may be related to other mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Manuella Caux, Rana Mansour, Jean-Marie Xuereb, Gaetan Chicanne, Julien Viaud, Alicia Vauclard, Frederic Boal, Bernard Payrastre, Helene Tronchere, Sonia Severin
Summary: This study demonstrates that PIKfyve and its lipid products PtdIns5P and PtdIns(3,5)P-2 play crucial roles in regulating granule integrity in both megakaryocytes and platelets. Inhibition of PIKfyve leads to impaired granule integrity, affecting platelet aggregation and thrombus formation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Jianfeng Shi, Renyang Tong, Meng Zhou, Yu Gao, Yichao Zhao, Yifan Chen, Wenhua Liu, Gaoxiang Li, Dong Lu, Guofeng Meng, Liuhua Hu, Ancai Yuan, Xiyuan Lu, Jun Pu
Summary: The study revealed that the circadian protein Rev-erb alpha is functionally expressed in platelets and enhances platelet activation and thrombus formation. This suggests that Rev-erb alpha could be a promising therapeutic target for managing thrombosis-related cardiovascular diseases.
EUROPEAN HEART JOURNAL
(2022)
Article
Pharmacology & Pharmacy
Kate L. Arkless, Dingxin Pan, Manu Shankar-Hari, Richard T. Amison, Clive P. Page, Khondaker Miraz Rahman, Simon C. Pitchford
Summary: This study compared the effects of ADP, Ap3A, NAD(+), ADP-ribose, and Up4A on platelet functions, and found that these endogenous nucleotides can modulate platelet's inflammatory functions through activating P2Y(1) receptors, but have different effects on thrombotic functions. Molecular docking analysis revealed distinct differences in amino acid interactions and depth of fit within the binding pocket between these nucleotides and ADP.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Lacey Johnson, Pearl Lei, Lauren Waters, Matthew P. Padula, Denese C. Marks
Summary: The aim of this study was to define the phenotype of in vitro generated platelet subpopulations and identify the subpopulations present in cryopreserved components. The study found that cryopreserved platelets contained procoagulant platelets and a novel population that did not align with the phenotype of aggregatory or apoptotic subpopulations.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Oncology
Edna Cukierman
Summary: The study demonstrates the protu-morigenic role of pancreatic stellate cell-derived cancer-associated fibroblasts in pancreatic cancer.
Review
Pharmacology & Pharmacy
Dingxin Pan, Graham Ladds, Khondaker Miraz Rahman, Simon C. Pitchford
Summary: Platelets are essential for maintaining haemostasis and are also important for promoting inflammation during the immune response. Their activation can lead to inappropriate inflammation in various disease conditions. The pathways of platelet activation differ between inflammation and haemostasis.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Hematology
Suelyn Van Den Helm, Conor Mccafferty, Natasha Letunica, Ka Ying Chau, Paul Monagle, Vera Ignjatovic
Summary: Platelets play a major role in regulating hemostasis and coagulation. However, research on platelet phenotype and function in neonates and children has been limited. Recent advances in more sensitive platelet function testing methods have allowed for further investigation of platelet characteristics and function in this population. This review provides an overview of the latest developments in platelets and their role in developmental hemostasis and neonatal pediatric disease over the past five years.
THROMBOSIS RESEARCH
(2023)
Article
Hematology
Georges Jourdi, Sofia Ramstrom, Ruchika Sharma, Tamam Bakchoul, FC-PFT TP Study Grp
Summary: The aim of this study was to provide expert consensus guidance on the use of flow cytometry for the evaluation of platelet function in patients with low platelet counts. Through literature review and focus group discussions, consensus recommendations were made on sample collection, preanalytical variables, sample type, and results expression. These recommendations would allow standardization of protocols in future clinical studies.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Cardiac & Cardiovascular Systems
Zhiyong Qi, Liang Hu, Jianjun Zhang, Wenlong Yang, Xin Liu, Daile Jia, Zhifeng Yao, Lin Chang, Guanxing Pan, Haoxuan Zhong, Xinping Luo, Kang Yao, Aijun Sun, Juying Qian, Zhongren Ding, Junbo Ge
Summary: PCSK9 in plasma directly enhances platelet activation and in vivo thrombosis by binding to platelet CD36 and activating downstream signaling pathways. PCSK9 inhibitors or aspirin can abolish the enhancing effects of PCSK9.
Editorial Material
Hematology
James H. Morrissey, David Lillicrap
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Divyani Paul, James H. Morrissey
Summary: This study demonstrated that in Nanodiscs containing 10% PS, 60% PE, and 30% phosphatidylcholine, each factor X molecule requires approximately 1.05 PS molecules for stable binding, indicating a truly PS-specific binding site per Gla domain.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Editorial Material
Hematology
David Lillicrap, James H. Morrissey
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Editorial Material
Hematology
David Lillicrap, James H. Morrissey
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Medicine, Research & Experimental
Srinivas Abbina, Chanel C. La, Sreeparna Vappala, Manu Thomas Kalathottukaren, Usama Abbasi, Arshdeep Gill, Stephanie A. Smith, Charles A. Haynes, James H. Morrissey, Jayachandran N. Kizhakkedathu
Summary: Designing polyP inhibitors with good biocompatibility is a major challenge, but by modifying the steric shield design, highly biocompatible inhibitors can be achieved.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Melanie P. Muller, James H. Morrissey, Emad Tajkhorshid
Summary: Factor VII plays a critical role in the initiation of the coagulation cascade. Its membrane binding with the Gla domain is essential for its activity, and it has been found to preferentially bind to phosphatidic acid (PA) rather than phosphatidylserine (PS) like other clotting factors. Researchers have developed models to study the binding modes of the Factor VII Gla domain to different lipids and identified potential PA-specific binding sites.
Editorial Material
Hematology
David Lillicrap, James H. Morrissey
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Critical Care Medicine
Julie Goswami, Taleen A. MacArthur, Cillian Mahony, Jayachandran N. Kizhakkedathu, Sreeparna Vappala, Stephanie Smith, James H. Morrissey, Grant M. Spears, Kent R. Bailey, Jing-Fei Dong, Rosemary A. Kozar, Nathan Hall, Andrea Johnstone, Myung S. Park
Summary: This study demonstrates that DNase treatment accelerates thrombin generation kinetics in trauma patient samples, suggesting that NETs may contribute to the hypercoagulable state observed in trauma patients.
Article
Hematology
Sreeparna Vappala, Stephanie A. A. Smith, Jayachandran N. N. Kizhakkedathu, James H. H. Morrissey
Summary: The contact pathway of blood clotting has drawn attention in recent years due to its links to thrombosis, inflammation, and innate immunity. This pathway has emerged as a potential target for safer thromboprotection, and research has identified polyphosphate, DNA, and RNA as important triggers of the contact pathway. This review focuses on the roles of extracellular polyphosphate and nucleic acids in thrombosis, with an emphasis on novel agents under development that target the prothrombotic activities of polyphosphate and NETs.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2023)
Article
Multidisciplinary Sciences
Chanel C. La, Stephanie A. Smith, Sreeparna Vappala, Reheman Adili, Catherine E. Luke, Srinivas Abbina, Haiming D. Luo, Irina Chafeeva, Matthew Drayton, Louise A. A. Creagh, Maria de Guadalupe Jaraquemada-Pelaez, Nicole Rhoads, Manu Thomas Kalathottukaren, Peter K. Henke, Suzana K. Straus, Caigan Du, Edward M. Conway, Michael Holinstat, Charles A. Haynes, James H. Morrissey, Jayachandran N. Kizhakkedathu
Summary: Current treatments for thrombosis prevention are complicated by the risk of bleeding. This study proposes a design concept called macromolecular polyanion inhibitors (MPI) to inhibit polyphosphate (polyP) and reduce bleeding risk. The lead MPI candidates exhibit antithrombotic activity in mouse models without causing bleeding and are well tolerated. This inhibitor has the potential to improve thrombosis prevention without increasing the risk of bleeding.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Kevin J. Cheng, Ashley M. De Lio, Riya Jain, Divyani Paul, James H. Morrissey, Taras V. Pogorelov
Summary: This study reveals the multimodal binding of lactadherin and provides insights into the binding mechanisms of its C domain homologs, factor V and factor VIII. Molecular dynamics simulations show that lactadherin primarily binds to membranes through inserted and side-lying states, offering new therapeutic opportunities for diseases related to blood coagulation.
Article
Hematology
Aleksandr Shamanaev, Maxim Litvak, Qiufang Cheng, Michal Ponczek, S. Kent Dickeson, Stephanie A. Smith, James H. Morrissey, David Gailani
Summary: The aim of this study was to identify the amino acids in the FXII EGF1 domain that are required for polyphosphate-dependent FXII functions. The results showed that Lys73, Lys74, Lys76, and Lys81 form a binding site for polyanionic substances, such as polyphosphate, which is crucial for surface-dependent FXII function.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Meeting Abstract
Hematology
Taleen A. MacArthur, Julie Goswami, Sreeparna Vappala, John Zietlow, Stephanie A. Smith, James H. Morrissey, Scott P. Zietlow, Grant M. Spears, Kent R. Bailey, Jing-fei Dong, Rosemary A. Kozar, Jayachandran N. Kizhakkedathu, Myung S. Park
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Immunology
Edward M. Conway, Nigel Mackman, Ronald Q. Warren, Alisa S. Wolberg, Laurent O. Mosnier, Robert A. Campbell, Lisa E. Gralinski, Matthew T. Rondina, Frank L. van de Veerdonk, Karin M. Hoffmeister, John H. Griffin, Diane Nugent, Kyung Moon, James H. Morrissey
Summary: In this article, the authors discuss the emerging understanding of COVID-19-associated coagulopathy and the need to comprehend its cellular and molecular mechanisms. They categorize the current understanding into three main pathological mechanisms and address key questions and research gaps in order to improve diagnosis and treatment. The suitability of animal models for studying this condition is also considered.
NATURE REVIEWS IMMUNOLOGY
(2022)