Interactions Between Platelets and the Coagulation System

Bouchard, Beth A.; Silveira, Jay R.; Tracy, Paula B.

doi:10.1016/b978-0-12-387837-3.00021-3

Cited by 22 publications

(27 citation statements)

References 284 publications

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“…Upon tissue injury, the central procoagulant enzyme, thrombin, is generated through the binding of coagulation proteins to phosphatidylserine (PS), a negatively charged phospholipid exposed on the platelet surface by activation. 46 Protein binding to the phospholipid surface is mediated through calcium cations associating with the gamma-carboxyglutamic (GLA) protein domain, facilitating binding to the negatively charged PS lipid surface. Calcium associating with the GLA domain of Factor Xa facilitates Xa binding to the PS surface, resulting in the formation of the prothrombinase complex in combination with factor Va.…”

Section: Discussionmentioning

confidence: 99%

Cationic PAMAM Dendrimers Disrupt Key Platelet Functions

et al. 2012

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Poly(amidoamine) (PAMAM) dendrimers have been proposed for a variety of biomedical applications and are increasingly studied as model nanomaterials for such use. The dendritic structure features both modular synthetic control of molecular size and shape and presentation of multiple equivalent terminal groups. These properties make PAMAM dendrimers highly functionalizable, versatile single-molecule nanoparticles with a high degree of consistency and low polydispersity. Recent nanotoxicological studies showed that intravenous administration of amine-terminated PAMAM dendrimers to mice was lethal, causing a disseminated intravascular coagulation-like condition. To elucidate the mechanisms underlying this coagulopathy, in vitro assessments of platelet functions in contact with PAMAM dendrimers were undertaken. This study demonstrates that cationic G7 PAMAM dendrimers activate platelets and dramatically alter their morphology. These changes to platelet morphology and activation state substantially altered platelet function, including increased aggregation and adherence to surfaces. Surprisingly, dendrimer exposure also attenuated platelet-dependent thrombin generation, indicating that not all platelet functions remained intact. These findings provide additional insight into PAMAM dendrimer effects on blood components and underscore the necessity for further research on the effects and mechanisms of PAMAM-specific and general nanoparticle toxicity in blood.

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Section: Discussionmentioning

confidence: 99%

Cationic PAMAM Dendrimers Disrupt Key Platelet Functions

et al. 2012

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“…“Traditional” prothrombotic activities that are also proinflammatory include adhesion and aggregation 14 , display of surface molecules that favor generation of thrombin 15 , binding of fibrinogen 16, 17 , and interaction with the fibrin mesh of clots 17 (Campbell R, Weyrich AS, manuscript in preparation). Thrombin and fibrinogen are key proinflammatory factors in addition to being essential components of the coagulation cascade 18, 19 .…”

Section: The Inflammatory Repertoire Of Plateletsmentioning

confidence: 99%

Platelets as Cellular Effectors of Inflammation in Vascular Diseases

Rondina

Weyrich

Zimmerman

2013

Circulation Research

259

310

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Platelets are chief effector cells in hemostasis. In addition, they are multifaceted inflammatory cells with functions that span the continuum from innate immune responses to adaptive immunity. Activated platelets have key “thromboinflammatory” activities in a variety of vascular disorders and vasculopathies. Recently-identified inflammatory and immune activities provide insights into the biology of these versatile blood cells that are directly relevant to human vascular diseases.

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“…In the absence of any stimulation, the time to clot formation (R-time) was prolonged due to the contact pathway inactivation by CTI and anti-FXI-2. Intentional platelet activation with PAR1 peptide substantially shortened the R-time consistent with the exposure of coagulation protein binding sites and release of various hemostatic proteins from α- and dense granules [35]. In addition, release of platelet polyphosphates from dense granules accelerate FXI activation and consequently thrombin generation [36].…”

Section: 3 Resultsmentioning

confidence: 99%

Platelets do not express the oxidized or reduced forms of tissue factor

Bouchard

Gissel

Whelihan

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Expression of tissue factor (TF) antigen and activity in platelets is controversial and dependent upon the laboratory and reagents used. Two forms of TF were described: an oxidized functional form and a reduced nonfunctional form that is converted to the active form through the formation of an allosteric disulfide. This study tests the hypothesis that the discrepancies regarding platelet TF expression are due to differential expression of the two forms. Methods Specific reagents that recognize both oxidized and reduced TF were used in flow cytometry of unactivated and activated platelets and western blotting of whole platelet lysates. TF-dependent activity measurements were used to confirm the results. Results Western blotting analyses of placental TF demonstrated that, in contrast to anti-TF#5, which is directed against the oxidized form of TF, a sheep anti-human TF polyclonal antibody recognizes both the reduced and oxidized forms. Flow cytometric analyses demonstrated that the sheep antibody did not react with the surface of unactivated platelets or platelets activated with thrombin receptor agonist peptide, PAR-1. This observation was confirmed using biotinylated active site-blocked factor (F)VIIa: no binding was observed. Likewise, neither form of TF was detected by western blotting of whole platelet lysates with sheep anti-hTF. Consistent with these observations, no FXa or FIXa generation by FVIIa was detected at the surface of these platelets. Similarly, no TF-related activity was observed in whole blood using thomboelastography. Conclusion and Significance Platelets from healthy donors do not express either oxidized (functional) or reduced (nonfunctional) forms of TF.

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Interactions Between Platelets and the Coagulation System

Cited by 22 publications

References 284 publications

Cationic PAMAM Dendrimers Disrupt Key Platelet Functions

Cationic PAMAM Dendrimers Disrupt Key Platelet Functions

Platelets as Cellular Effectors of Inflammation in Vascular Diseases

Platelets do not express the oxidized or reduced forms of tissue factor

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