131 Burn-Induced Coagulopathy: Burn Patient Plasma Causes Platelet Dysfunction

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S88-S88
Author(s):  
Breanne H Gibson ◽  
Matthew T Duvernay ◽  
Stephen Gondek ◽  
Jonathan G Schoenecker
Keyword(s):  
Platelet Function ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Morbidity And Mortality ◽  
Burn Patients ◽  
Platelet Dysfunction ◽  
Markers Of Inflammation ◽  
Vitro Effect ◽  
Burn Patient

Abstract Introduction Burn-induced coagulopathy (BIC) greatly increases the risk of thrombosis, leading to organ dysfunction and death. Although BIC is attributed to a multitude of factors including hemodilution, SIRS, and excess coagulation, the exact molecular mechanisms are elusive. Determination of these mechanisms is essential to develop new strategies aimed at reducing the morbidity and mortality of BIC as commonly used anticoagulants are ineffective at preventing the consequences of BIC. Platelet dysfunction, which has been associated with bleeding, thrombosis, poor wound repair, and susceptibility to infection, occurs in BIC, but the etiology of this phenomenon is unknown. Burn injuries provoke a dramatic increase in plasma levels of inflammatory, coagulation, and fibrinolytic factors, potentially altering the physiology of blood cells and platelets. Therefore, we hypothesized that burn patient plasma pathologically alters normal platelet function. Methods In this prospective study, plasma samples were collected from 32 adult patients with burns >10% TBSA at a regional burn center. To assess the effects of burn plasma on platelet function, platelets isolated from healthy individuals were incubated with heparinized plasma from burn patients or control plasmas (N=15) for 2 hours. Following incubation, platelets were stimulated with various agonists, and markers of platelet activation (GPIIb/IIIa activation and P-selectin expression) were measured using flow cytometry. Results Platelets incubated with burn plasmas exhibited a reduction in response to stimulation compared with those incubated with control plasma. Both GPIIb/IIIa activation and P-selectin expression were affected, suggesting a defect in platelet signaling. This dysfunction did not strongly correlate with TBSA affected or modified Baux score but was significant when compared to healthy controls (P< 0.05). However, measurement of markers of inflammation, coagulation, and fibrinolysis in burn plasmas revealed a significant correlation of both plasma D-dimer (P< 0.02) and soluble P-selectin (P< 0.05) with induced platelet dysfunction. This suggests circulating factors indicative of coagulation, fibrinolysis, and endothelial dysfunction may play a role in platelet dysfunction observed in BIC. Conclusions This study demonstrates an in vitro effect of burn patient plasma on platelet function, suggesting a possible benefit for resuscitation with FFP. BIC is a principal source of morbidity and mortality in burn patients, and current thromboprophylaxis for burn patients may not address critical elements of BIC. Future studies are required to optimize resuscitation and minimize the consequences of BIC.

scholarly journals Alteration of Platelet Cyclic AMP (cAMP) by Ethanol

1977 ◽  
Author(s):  
D.H. Cowan ◽  
M. Kikta ◽  
D. Baunach
Keyword(s):  
Cyclic Amp ◽  
Platelet Function ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Platelet Dysfunction ◽  
Camp Metabolism ◽  
Subnormal Level ◽  
Camp Levels ◽  
Stimulation Of

Studies of cAMP in human platelets exposed to ethanol were done to assess one possible mechanism for ethanol-related platelet dysfunction. Ingestion of ethanol by 3 subjects produced blood ethanol levels from 65-76 mM. Thrombocytopenia occurred in 1 subject and impaired platelet function occurred in all. Platelet cAMP decreased 36,51, and 59% below control levels. Infusion of ethanol to 2 normals produced blood ethanol levels of 43 mM and decreased platelet cAMP by 15% and 22%. Incubation of normal platelets with 86 mM ethanol in vitro decreased cAMP from 13.8 ± 2.9 (1 SD) to 9.4 ± 3.5 (p<0.02). By contrast, ethanol did not impair the increase in cAMP that occurred with 1.3 μM PGE1. Further, ethanol enhanced the increase in cAMP produced by 2.0 mM papaverine (Pap) by 160-220% and that produced by Pap + PGE1 by 58%. Dopamine, 0.1 mM, caused a 23% decrease in the basal level of cAMP, a 31% decrease below the subnormal level of cAMP seen with ethanol alone, and a 41% reduction in the increased level of cAMP produced by Pap + ethanol. The effect of ethanol on platelet cAMP metabolism is complex. Ethanol reduces basal levels of cAMP, does not decrease elevated levels that result from PGE1 stimulation of adenylate cyclase, and augments the inhibitory effect of Pap on platelet phosphodiesterase (PDE). Despite causing a decrease in basal cAMP levels, ethanol may impair platelet function by potentiating the effect of agents or other conditions which increase cAMP. The effect of ethanol on Pap-stimulated PDE activity may be blocked by dopamine, a neuropharmacologic agent that is actively accumulated by platelets.

scholarly journals Superoxide Dismutase 2 is dispensable for platelet function

2017 ◽  
Vol 117 (10) ◽  
pp. 1859-1867 ◽  
Author(s):  
Trevor P. Fidler ◽  
Jesse W. Rowley ◽  
Claudia Araujo ◽  
Luc H. Boudreau ◽  
Alex Marti ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Platelet Activation ◽  
Platelet Function ◽  
Mitochondrial Function ◽  
Oxygen Species ◽  
Platelet Dysfunction ◽  
Mitochondrial Ros ◽  
Superoxide Dismutase 2

SummaryIncreased intracellular reactive oxygen species (ROS) promote platelet activation. The sources of platelet-derived ROS are diverse and whether or not mitochondrial derived ROS, modulates platelet function is incompletely understood. Studies of platelets from patients with sickle cell disease, and diabetes suggest a correlation between mitochondrial ROS and platelet dysfunction. Therefore, we generated mice with a platelet specific knockout of superoxide dismutase 2 (SOD2-KO) to determine if increased mitochondrial ROS increases platelet activation. SOD2-KO platelets demonstrated decreased SOD2 activity and increased mitochondrial ROS, however total platelet ROS was unchanged. Mitochondrial function and content were maintained in non-stimulated platelets. However SOD2-KO platelets demonstrated decreased mitochondrial function following thrombin stimulation. In vitro platelet activation and spreading was normal and in vivo, deletion of SOD2 did not change tail-bleeding or arterial thrombosis indices. In pathophysiological models mediated by platelet-dependent immune mechanisms such as sepsis and autoimmune inflammatory arthritis, SOD2-KO mice were phenotypically identical to wildtype controls. These data demonstrate that increased mitochondrial ROS does not result in platelet dysfunction.

In vitro effect of hydroxyethyl starch 130/0.42 on canine platelet function

2012 ◽  
Vol 73 (12) ◽  
pp. 1908-1912 ◽  
Author(s):  
Janine Classen ◽  
Katja N. Adamik ◽  
Karin Weber ◽  
Stephanie Rubenbauer ◽  
Katrin Hartmann
Keyword(s):  
Hydroxyethyl Starch ◽  
Platelet Function ◽  
Vitro Effect

Normal Platelet Function In Scurvy And Experimental Human Vitamin C Deficiency

1981 ◽  
Author(s):  
G J Johnson ◽  
D Holloway ◽  
S Hutton ◽  
W Duane
Keyword(s):  
Platelet Function ◽  
Control Period ◽  
Hemorrhagic Diathesis ◽  
Platelet Dysfunction ◽  
Normal Range ◽  
Deficient Diet ◽  
Healthy Human ◽  
Normal Platelet

Mucocutaneous hemorrhage is a prominent feature of human scurvy. Platelet dysfunction has been observed in scorbutic guinea pigs and some humans with scurvy, but others have found normal platelet function in human scurvy. Since it is uncertain whether platelet dysfunction contributes to the hemorrhagic diathesis of scurvy, we studied platelet function in one patient with typical perifollicular hemorrhagic manifestations of scurvy and in five healthy human ascorbic acid (AA) deficient volunteers. Volunteers were hospitalized on a metabolic ward, and fed a diet providing 3-4mg AA per day. Platelet function studies were performed at the end of a) a 30 day control period of AA supplementation; b) a 60 day period of AA deficiency; and c) a 40 day period of AA supplementation. The patient with scurvy was studied before and 10 days after AA supplementation. The following platelet studies were performed: venous count, bleeding time (Ivy method), in vitro adhesiveness (Bowie method), in vivo adhesiveness (Johnson method), aggregation in response to ADP, collagen, epinephrine, sodium arachidonate and ristocetin, and 14C-serotonin release. Plasma and leukocyte AA were found to be normal in both periods of supplementation and markedly decreased (plasma mean 0.12 ± 0.02mg/dl; WBC mean 8.9 ± 1.8μg/108 cells) following the deficient diet. Plasma AA was 0.07mg/dl and WBC AA was 4.92μg/108 cells in the scurvy patient. Platelet count and all platelet function studies were within the normal range in the patient with scurvy and all volunteers during AA supplementation. In vivo platelet adhesiveness decreased in 4 of the 5 volunteers during AA deficiency, but it remained in the normal range in all but one. All other studies were normal in both AA deficient volunteers and the patient with scurvy. We conclude that significant platelet dysfunction does not accompany subclinical AA deficiency, and that platelet dysfunction is not primarily responsible for the hemorrhagic diathesis of scurvv.

scholarly journals Activator Protein-1 Transcriptional Activity Drives Soluble Micrograft-Mediated Cell Migration and Promotes the Matrix Remodeling Machinery

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Martina Balli ◽  
Jonathan Sai-Hong Chui ◽  
Paraskevi Athanasouli ◽  
Willy Antoni Abreu de Oliveira ◽  
Youssef El Laithy ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Cell Model ◽  
Matrix Remodeling ◽  
Activator Protein 1 ◽  
Impaired Wound Healing ◽  
Beneficial Effects

Impaired wound healing and tissue regeneration have severe consequences on the patient’s quality of life. Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown. In this study, we identified the active protein-1 (AP-1) member Fos-related antigen-1 (Fra-1) to play a central role in the extracellular signal-regulated kinase- (ERK-) mediated enhanced cell migratory capacity of soluble micrograft-treated mouse adult fibroblasts and in the human keratinocyte cell model. Accordingly, we show that increased micrograft-dependent in vitro cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. Furthermore, soluble micrograft treatment leads to increased expression and posttranslational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing-associated genes mainly involved in the regulation of cell migration. Collectively, our work provides insights into the molecular mechanisms behind the cell-free micrograft treatment, which might contribute to future advances in wound repair therapies.

scholarly journals Genome Sequence of a Virulent Pseudomonas aeruginosa Strain, 12-4-4(59), Isolated from the Blood Culture of a Burn Patient

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
S. L. Rajasekhar Karna ◽  
Tsute Chen ◽  
Ping Chen ◽  
Trent J. Peacock ◽  
Johnathan J. Abercrombie ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Wound Healing ◽  
Blood Culture ◽  
Genome Sequence ◽  
Virulent Strain ◽  
Opportunistic Pathogen ◽  
Morbidity And Mortality ◽  
Burn Patients ◽  
Burn Patient

Pseudomonas aeruginosa is an opportunistic pathogen that frequently infects wounds, significantly impairs wound healing, and causes morbidity and mortality in burn patients. Here, we report the genome sequence of a virulent strain of P. aeruginosa , 12-4-4(59), isolated from the blood culture of a burn patient.

Platelet Proinflammatory and Hemostatic Function Is Differentially Regulated in Cystic Fibrosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3948-3948
Author(s):  
Alexander Sturm ◽  
Helge Hebestreit ◽  
Ralf Grossmann
Keyword(s):  
Cystic Fibrosis ◽  
Chronic Inflammation ◽  
Platelet Activation ◽  
Platelet Function ◽  
Healthy Controls ◽  
Soluble Cd40 Ligand ◽  
Integrin Αiibβ3 ◽  
Markers Of Inflammation ◽  
Activated Platelets

Abstract Introduction: Platelet function and mechanisms of platelet-leukocyte interactions have been investigated in several vascular und inflammatory disorders. In most studies, platelet activation and an increase of platelet-leukocyte-aggregates (PLA) could be observed. We investigated platelet function in clinically stable patients with cystic fibrosis (CF). Methods: In addition to routine markers of inflammation (e. g. CRP, IgG, ESR) parameters of platelet function were measured in 54 clinically stable CF patients and 55 healthy controls (age range 3 to 41 years): The percentage of P-selectin (CD62P) and PAC-1 (activated integrin αIIbβ3) positive resting and activated platelets (in-vitro activation with the thrombin receptor activating peptide 6) and the number of PLA were determined by flow cytometry. The plasma markers of platelet activation soluble P-selectin (sCD62P) and soluble CD40 ligand (sCD40L) were measured by ELISA. Furthermore, 15 CF patients and 14 healthy controls were investigated to determine CD41a-expression (integrin αIIbβ3) on resting and activated platelets as well as leukocyte expression of P-selectin-glycoprotein ligand 1 (PSGL-1, receptor of CD62P) and integrin αMβ2. Results: Chronic inflammation leads to a decrease of PAC-1-binding to resting and activated platelets. The effects were stronger in patients with higher markers of inflammation. CD41a expression was reduced on in-vitro-activated CF platelets. In contrast, proinflammatory platelet functions remained unchanged (CD62P-expression on resting and activated platelets) or increased (sCD62P, sCD40L, PLA). Leukocyte integrin αMβ2 expression was increased and PSGL-1 expression remained unchanged in CF. Discussion: Platelet function in clinically stable patients with CF is differentially regulated: Chronic inflammation leads to an upregulation of platelet proinflammatory function. In the presence of several procoagulatory mechanisms in inflammation there is a compensatory loss of platelet hemostatic function, shown by the decreased activation and exocytosis of the platelet major integrin αIIbβ3.

Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4594-4599 ◽  
Author(s):  
Rosemarie A. Reiter ◽  
Florian Mayr ◽  
Hannes Blazicek ◽  
Elisabeth Galehr ◽  
Petra Jilma-Stohlawetz ◽  
...  
Keyword(s):  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Maximum Effect ◽  
Study Group ◽  
Platelet Dysfunction ◽  
Response Curves ◽  
Double Blind ◽  
Group 2 ◽  
Group 1

AbstractWhereas bleeding is the most frequent adverse event encountered in patients receiving glycoprotein (GP) IIb/IIIa inhibitors, there are currently no recommendations for how to treat such patients. The present study tested the hypothesis that infusion of desmopressin (DDAVP) reverses the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors (+l-aspirin). Study group 1 (10 healthy volunteers) received a DDAVP infusion to establish dose-response curves for the in vitro inhibition of platelet function by eptifibatide, abciximab, and tirofiban together with l-aspirin before and after DDAVP. In a randomized, double-blind, placebo-controlled, crossover study (group 2) volunteers received l-aspirin and a standard eptifibatide infusion. Thereafter, DDAVP or a physiologic saline infusion was given over 30 minutes. In group 1, all GPIIb/IIIa inhibitors prolonged collagen-epinephrine (CEPI) and collagen-adenosine diphosphate (CADP) closure times (CTs), measured with the platelet function analyzer 100 (PFA-100). DDAVP caused a shift in the concentration response curves to the right of all 3 GPIIb/IIIa inhibitors. In group 2, DDAVP accelerated the normalization of CADP-CT and CEPI-CT after the stop of eptifibatide infusion with a maximum effect at 1.5 hours to 2 hours. In contrast, CEPI-CT remained above normal in the placebo group for more than 4 hours. In conclusion, DDAVP accelerates normalization of the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors (+l-aspirin). (Blood. 2003;102:4594-4599)

scholarly journals Influence of Imidazole Carboxamide on Platelet Function

1977 ◽  
Author(s):  
P. Kubisz ◽  
P. Klener ◽  
S. Cronberg
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Cytostatic Drug ◽  
Bleeding Tendency ◽  
Platelet Dysfunction ◽  
Freezing And Thawing ◽  
Trade Name ◽  
Coagulation And Fibrinolysis

Imidazol carboxamide (DTIC, NSC-45388) is a cytostatic drug used in the treatment of malignant melanoma under the trade name of DacarbazinR, MSD. Its influence on platelet function, blood coagulation and fibrinolysis was investigated in vitro.At a concentration of 160 µg/ml it inhibited the increase in light transmission induced in platelet-rich plasma by standardized freezing and thawing. It also retarded the retraction of reptilase clots. This therefore indicated a stabilizing effect on the platelets at this dosage.At a concentration of 40 μg/ml the drug did not significantly influence the platelet function in vitro.This concentration corresponds to therapeutic plasma levels. At current dosage of the drug any bleeding tendency due to platelet dysfunction therefore seems unlikely.

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