scholarly journals Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

2020 ◽  
Vol 40 (12) ◽  
pp. 2975-2989 ◽  
Author(s):  
Francesco Taus ◽  
Gianluca Salvagno ◽  
Stefania Canè ◽  
Cristiano Fava ◽  
Fulvia Mazzaferri ◽  
...  

Objective: Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia. Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism. Approach and Results: Overall, 37 patients and 28 healthy subjects were studied. Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry. The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay. The contribution of platelets to coagulation factor activity was selectively measured. Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P <0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P <0.0001) were detected in patients. Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P =nonsignificant). The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients ( P <0.0001 versus controls). Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2 [monocyte chemoattractant protein 1]), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets. Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients. Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P <0.001), showed accelerated factor XII–dependent coagulation. Conclusions: Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1995 ◽  
Author(s):  
Mariarita Caroleo ◽  
Elvira Anna Carbone ◽  
Marta Greco ◽  
Domenica Maria Corigliano ◽  
Biagio Arcidiacono ◽  
...  

Alterations of the immune system are known in eating disorders (EDs), however the importance of cytokine balance in this context has not been clarified. We compared cytokines and growth factors at opposite ends of BMI ranges, in 90 patients classified in relation to BMI, depressive and EDs comorbidities. Serum concentrations of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were determined by a biochip analyzer (Randox Labs). Differences were calculated through ANOVA. Possible predictors of higher cytokine levels were evaluated through regression analysis. IL-1α, IL-10, EGF, and IFN-γ were altered individuals with anorexia nervosa (AN) and binge eating disorder (BED). Night-eating was associated with IL-8 and EGF levels, IL-10 concentrations with post-dinner eating and negatively with sweet-eating, long fasting with higher IFN-γ levels. IL-2 increase was not linked to EDs, but to the interaction of depression and BMI. Altogether, for the first time, IL-1α, IL-10, EGF, and IFN-γ were shown to differ between AN and HCs, and between AN and individuals with obesity with or without BED. Only IL-2 was influenced by depression. Dysfunctional eating behaviors predicted abnormal concentrations of IL-10, EGF, IL-8 and IFN-γ.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4080-4080
Author(s):  
Seung Yeon Kwon ◽  
Jung Woo Han ◽  
Sung Chul Won ◽  
Jaewoo Song ◽  
Chuhl Joo Lyu

Abstract Prothrombine time (PT) and activated prothrombine time (aPTT) are common tests used for screening of coagulation function before surgical procedures. We analyzed underlying causes of abnormal coagulation test results which were incidentally found during pre-surgical evaluation in healthy patients without definite bleeding history. Total 58 children referred to pediatric hematoloy service for abnormal PT and aPTT results in pre-surgical evaluation between June 2006 and May 2008 were analyzed retrospectively by review of medical records. 50 patients showed aPTT prolongation, 5 patients PT prolongation, 2 patients PT and aPTT prolongation and another three patients showed normal PT and aPTT. Among 55 patients with abnormal results, 25 patients (43%) were recovered spontaneously during their follow up tests, 17 patients (29%) showed lower level of certain coagulation factor than reference range and the other 13 patients were lost during follow up despite of recommendation for further evaluation. Mean value of international normalized ratio (INR) for PT and aPTT of the patients recovered spontaneously were 1.05±0.11, 44.53±5.01seconds(s), and 1.12±0.11, 47.0±5.36s in patients with lower level of coagulation factor, showing significant increase of PTT in patients with lower factor levels (p&lt;0.05). Median time required for spontaneous recovery was four weeks and 18 patients (72%) were recovered within this time. Among 17 patients with lower level of certain coagulation factor then reference level, there were 11 patients with low factor XII level, three patients with low factor VIII level, three patients with low von Willebrand factor, two patients each for low factor VII and factor XI and one patient with low factor V level. Among them three patients with low level in von Willebrand factor, one patient with low factor VII and two patients with low factor XI showed deficient level of coagulation factors requiring factor replacement for the surgical procedures. From this analysis of patients with incidentally found PT or aPTT prolongation, 43% of patients were spontaneously recovered during follow up period within 4 weeks in median. However, we also found that 29% of patients had relatively lower level of coagulation factor than reference range. Even though most of them were factor XII decrease which is not closely related with bleeding tendency, six patients had significant deficiencies of coagulation factors requiring factor replacement during surgical procedures. These results suggest that we should keep following up and undergo adequate evaluation for underlying coagulation factor deficiencies in patients who have sustaining PT and aPTT prolongation abnormalities despite of absence of any bleeding history.


2010 ◽  
Vol 30 (03) ◽  
pp. 150-155 ◽  
Author(s):  
J. W. Wang ◽  
J. Eikenboom

SummaryVon Willebrand factor (VWF) is a pivotal haemostatic protein mediating platelet adhesion to injured endothelium and carrying coagulation factor VIII (FVIII) in the circulation to protect it from premature clearance. Apart from the roles in haemostasis, VWF drives the formation of the endothelial cell specific Weibel-Palade bodies (WPBs), which serve as a regulated storage of VWF and other thrombotic and inflammatory factors. Defects in VWF could lead to the bleeding disorder von Willebrand disease (VWD).Extensive studies have shown that several mutations identified in VWD patients cause an intracellular retention of VWF. However, the effects of such mutations on the formation and function of its storage organelle are largely unknown. This review gives an overview on the role of VWF in WPB biogenesis and summarizes the limited data on the WPBs formed by VWD-causing mutant VWF.


1991 ◽  
Vol 65 (05) ◽  
pp. 608-617 ◽  
Author(s):  
Joseph A Chinn ◽  
Thomas A Horbett ◽  
Buddy D Ratner

SummaryThe role of fibrinogen in mediating platelet adhesion to polymers exposed to blood plasma was studied by comparison of the effect of plasma dilution on fibrinogen adsorption and platelet adhesion, and by the use of coagulation factor deficient plasmas. Polyetherurethane substrates were first preadsorbed with dilute plasma, then contacted with washed platelets suspended in a modified, apyrase containing Tyrode’s buffer. Platelet adhesion was studied under static conditions in Multiwell dishes, and also under shearing conditions using a parallel plate perfusion chamber. Fibrinogen adsorption and platelet adhesion were measured using 125I radiolabeled baboon fibrinogen and min radiolabeled baboon platelets, respectively. Surfaces were characterized by electron spectroscopy for chemical analysis (ESCA).When fibrinogen adsorption to Biomer was measured after 2 h contact with a series of dilute plasma solutions under static conditions, a peak in adsorption was observed from 0.26% plasma, i.e., adsorption was greater from 0.26% plasma than from either more or less dilute plasma. A peak in subsequent platelet adhesion to the plasma preadsorbed surfaces, measured after 2 h static incubation with washed platelets, was also observed but occurred on Biomer preadsorbed with 1.0% plasma.When fibrinogen adsorption was measured after 5 min contact under shearing conditions, the fibrinogen adsorption peak occurred on surfaces that had been exposed to 1.0% plasma. A peak in platelet adhesion to these preadsorbed surfaces, measured after 5 min contact with the platelet suspensions under shearing conditions, was observed on Biomer preadsorbed with 0.1% plasma. Shifts between the positions of the peaks in protein adsorption and platelet adhesion occurred on other polymers tested as well.Platelet adhesion was almost completely inhibited when baboon and human plasmas lacking fibrinogen (i. e., serum, heat defibrinogenated plasma, and congenitally afibrinogénémie plasma) were used. Platelet adhesion was restored to near normal when exogenous fibrinogen was added to fibrinogen deficient plasmas. Adhesion was also inhibited completely when a monoclonal antibody directed against the glycoprotein IIb/IIIa complex was added to the platelet suspension. Platelet adhesion to surfaces preadsorbed to von Willebrand factor deficient plasma was the same as to surfaces preadsorbed with normal plasma.While it appears that surface bound fibrinogen does mediate the initial attachment of platelets to Biomer, the observation that the fibrinogen adsorption and platelet adhesion maxima do not coincide exactly also suggests that the degree of subsequent platelet adhesion is dictated not only by the amount of surface bound fibrinogen but also by its conformation.


1986 ◽  
Vol 55 (01) ◽  
pp. 108-111 ◽  
Author(s):  
M Köhler ◽  
P Hellstern ◽  
C Miyashita ◽  
G von Blohn ◽  
E Wenzel

SummaryThis study was performed to evaluate the influence of different routes of administration on the efficacy of DDAVP treatment. Ten healthy volunteers received DDAVP intranasally (i.n.), subcutaneously (s.c.) and intravenously (i.v.) in a randomized cross-over trial. Factor XII and high molecular weight (HMW)-kininogen levels increased only slightly after DDAVP administration. The mean increase of factor VIII: C was 3.1 (i. v.), 2.3 (s. c.), and 1.3 (i.n.) - fold over baseline. Ristocetin cofactor (von Willebrand factor antigen) increased 3.1 (2.5), 2.0 (2.3) and 1.2 (1.2) - fold over baseline mean values after i.v., s.c. and i.n. DDAVP, respectively. The half-disappearance time of factor VIII and von Willebrand factor (vWF) after DDAVP ranged from five (factor VIII: C) to eight hours (vWF). The mean increase of fibrinolytic activity was more pronounced after i.v. DDAVP. The antidiuretic effect was moderate with no apparent differences between the routes of application. This study provides further evidence that both i.v. and s.c. DDAVP administration result in an appropriate and reliable stimulation of haemostasis. An additional advantage of s. c. administration is its suitability for home treatment.


Diabetes ◽  
1984 ◽  
Vol 33 (2) ◽  
pp. 125-129 ◽  
Author(s):  
R. P. Lamberton ◽  
A. D. Goodman ◽  
A. Kassoff ◽  
C. L. Rubin ◽  
D. H. Treble ◽  
...  

2021 ◽  
Vol 147 (2) ◽  
pp. AB23
Author(s):  
Natasha Ferraroni ◽  
Gabriela Yoshimoto ◽  
Camila Veronez ◽  
Luiza Silva ◽  
Marina Batista ◽  
...  

2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Irina A. Shurygina ◽  
Мichael G. Shurygin ◽  
Lubov V. Rodionova ◽  
Nataliya I. Ayushinova

AbstractObjectivesTo study the expression of growth factors in the regulation of tissue repair after peritoneal damage tissue response to peritoneal damage.MethodsExperimental study in 35 male Wistar rats determining the evolution over time of the tissue response to aseptic peritoneal damage. A standardized bowel and peritoneal lesions were created in the right lower quadrant by laparotomy. Then, tissular expression of growth factors was evaluated by multiplex polymerase chain reaction at seven timepoints between 6 h and 30 days, postoperatively.ResultsTissular responses of granulocyte-stimulating factors (Csf2, Csf3), connective tissue growth factor (Ctgf), epidermal growth factors and receptor (Egf, Egfr), fibroblast growth factors (Fgf2, 7 and 10), heparin binding EGF-like growth factor (Hbegf), hepatocyte growth factor (Hgf), insulin-like growth factor-1 (Igf1), mitogenic transforming growth factors (Tgfa, Tgfb1, Tgfbr3), and vascular endothelial growth factor A (Vegfa) were biphasic with a first expression peak at day 3, followed by a more pronounced peak at day 14.ConclusionsWe observed a long-lasting, widespread response of tissular growth factors for at least two weeks after peritoneal damage. To be clinically effective, the prophylaxis of postoperative adhesions might be needed for an extended period of time.


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