Effect of Different Dialysis Membranes on Platelet Function. A Tool for Biocompatibility Evaluation

1996 ◽  
Vol 19 (7) ◽  
pp. 404-410 ◽  
Author(s):  
L.B. De Sanctis ◽  
S. Stefoni ◽  
G. Cianciolo ◽  
L. Colì ◽  
A. Buscaroli ◽  
...  

Intradialytic coagulative and platelet activation, one of the main consequences of blood-membrane contact, was studied in a group of 5 RDT patients with a comparative evaluation of 3 different dialytic membranes: Cuprophan (CU), Polysulfone (PS) and Cellulose Triacetate (CT). Each patient underwent 5 consecutive dialysis sessions with the above mentioned membranes. Intradialytic platelet activation was studied through a morpho-functional evaluation between the mean platelet volume (MPV) and Serotonin (S), ß-Thromboglobulin (ß-TG) and Platelet Factor 4 (PF4) serum levels. These determinations were made before HD (time 0) and after 30', 120’ and 240'. We also checked the intradialytic status of thrombogenesis and fibrinolysis determining aPTT, thrombin time, fibrinogen, antithrombin III (AT III), α-2 antiplasmin and plasminogen, at the same time intervals. All membranes tested (CU, PS, CT) caused appreciable intradialytic platelet activation, above all after 15’ and at the end of dialysis sessions, more marked for CU than PS or CT. In particular MPV showed a decrease throughout the session (-5% at 30’ and -9% at 240') while S, ßTG and PF4 peripheral blood levels showed a significant increase at the same intervals with CU membrane. Lastly coagulative and fibrinolytic parameters showed no significant differences among any of the membranes tested.

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250353
Author(s):  
Harald Haidl ◽  
Johanna Gaugler ◽  
Gerhard Cvirn ◽  
Hildegard Jasser-Nitsche ◽  
Wolfgang Schwinger ◽  
...  

Introduction Atrial fibrillation (AF) comes along with high risk of stroke. This risk continues even after re-establishing sinus rhythm with cardioversion. Aim of this study is to evaluate the contribution of electric cardioversion (EC) to platelet activation and procoagulatory tendency. Methods Extent of platelet activation before and after electric cardioversion was quantified using flow cytometry, impedance aggregation measurements with Multiplate®, and quantification of serum levels of platelet factor 4 (PF4) and ß-thromboglobulin (ß-TG) in patients with AF (N = 10). Results No significant differences were observed in any of the measured parameters comparing the values from before and after cardioversion. Geometric means of P-selectin expression and integrin αIIbβ3 activation were 0.27 (+/- 0.07) and 2.30 (+/- 2.61) before EC and 0.28 (+/- 0.17) and 1.67 (+/- 1.82) after EC. Levels of ß-TG were 110.11 ng/ml (+/- 3.78) before and 110.51 ng/ml (+/- 2.56) after EC, levels of PF4 were 35.64 ng/ml (+/- 12.94) before and 32.40 ng/ml (+/- 4.95) after EC. Platelet aggregation triggered with adenosine diphosphate (ADP), arachidonic acid, collagen, Ristocetin, or thrombin receptor activating peptide (TRAP) revealed results within the normally expected ranges without significant changes before and after EC. Discussion Electric cardioversion has no influence on platelet activation markers which is in agreement with other studies reporting electrical cardioversion to be safe.


1968 ◽  
Vol 19 (03/04) ◽  
pp. 578-583 ◽  
Author(s):  
R Farbiszewski ◽  
S Niewiarowski ◽  
K Worowski ◽  
B Lipiński

SummaryPlatelet factor 4 released from platelets into the circulating blood was determined using both the heparin thrombin time and paracoagulation methods. It has been found that thrombin injected intravenously into rabbits releases large amounts of this factor. Infusion of plasmin does not release this factor and this finding may be of importance for the differential diagnosis between disseminated intravascular clotting and primary fibrinolysis. PF4 is not released during the hyper coagulable condition induced by HgCl2 intoxication. Only small amounts of this factor are released after contact factor infusion.A significant elevation of extraplatelet PF4 was found in 23 patients with fresh coronary thrombosis and in 9 patients with thrombophlebitis and thromboembolic complications.The significance of the above findings for the pathogenesis, treatment and laboratory diagnosis of thrombotic diseases with particular reference to heparin tolerance test is discussed.


1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.


2006 ◽  
Vol 25 (5) ◽  
pp. 243-250 ◽  
Author(s):  
M S Allagui ◽  
N Hfaiedh ◽  
C Vincent ◽  
F Guermazi ◽  
J-C Murat ◽  
...  

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junkun Liu ◽  
Chengwen Bai ◽  
Binbin Li ◽  
Aijun Shan ◽  
Fei Shi ◽  
...  

AbstractEarly identification of infection severity and organ dysfunction is crucial in improving outcomes of patients with sepsis. We aimed to develop a new combination of blood-based biomarkers that can early predict 28-day mortality in patients with sepsis or septic shock. We enrolled 66 patients with sepsis or septic shock and compared 14 blood-based biomarkers in the first 24 h after ICU admission. The serum levels of interleukin-6 (IL-6) (median 217.6 vs. 4809.0 pg/ml, P = 0.001), lactate (median 2.4 vs. 6.3 mmol/L, P = 0.014), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (median 1596.5 vs. 32,905.3 ng/ml, P < 0.001), prothrombin time (PT) (median 15.6 vs. 20.1 s, P = 0.030), activated partial thrombin time (APTT) (median 45.1 vs. 59.0 s, P = 0.026), and international normalized ratio (INR) (median 1.3 vs. 1.8, P < 0.001) were significantly lower in the survivor group. IL-6, NT-proBNP, and INR provided the best individual performance in predicting 28-day mortality of patients with sepsis or septic shock. Furthermore, the combination of these three biomarkers achieved better predictive performance (AUC 0.890, P < 0.001) than conventional scoring systems. In summary, the combination of IL-6, NT-proBNP, and INR may serve as a potential predictor of 28-day mortality in critically ill patients with sepsis or septic shock.


1994 ◽  
Vol 22 (3) ◽  
pp. 171-176 ◽  
Author(s):  
N-A Ankrah ◽  
T Rikimaru ◽  
F A Ekuban ◽  
M M Addae

Cysteine, methionine, vitamin A, β-carotene and glutathione (GSH) are known to protect body tissues against oxidative damage and inflammation but their value as protection against liver inflammation in tropical areas has received little attention. Blood levels of these nutrients were measured in Ghanaian volunteers with (Group 2) or without (Group 1) increased lipid peroxidation and signs of liver inflammation, as indicated by blood malonic dialdehyde, serum α1-antitrypsin and triglyceride levels, and the α1-acid glycoprotein: pre-albumin ratio. Serum levels of cysteine and blood glutathione were significantly lower ( P < 0.02) in group 2 than in group 1 volunteers. In contrast, serum levels of methionine, vitamin A and β-carotene were similar in both groups. Deficits in cysteine and glutathione may increase the risk of liver toxicity from oxidants in Ghanaians.


2008 ◽  
Vol 294 (3) ◽  
pp. R811-R818 ◽  
Author(s):  
Chao-Hung Wang ◽  
Wen-Jin Cherng ◽  
Ning-I Yang ◽  
Chia-Ming Hsu ◽  
Chi-Hsiao Yeh ◽  
...  

Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.


2016 ◽  
Vol 115 (02) ◽  
pp. 324-332 ◽  
Author(s):  
Rabie Jouni ◽  
Heike Zöllner ◽  
Ahmad Khadour ◽  
Jan Wesche ◽  
Anne Grotevendt ◽  
...  

SummaryProtamine (PRT) is the standard drug to neutralise heparin. PRT/heparin complexes induce an immune response similar to that observed in heparin-induced thrombocytopenia (HIT). Partially desulfated heparin (ODSH) was shown to interfere with anti-platelet factor 4/heparin antibodies (Abs), which are responsible for HIT. In this study, we analyse the impact of ODSH on the interaction between anti-PRT/heparin Abs and platelets. The ability of ODSH to prevent anti-PRT/heparin Ab-induced platelet destruction in vivo was investigated using the NOD/ SCID mouse model. ODSH improved platelet survival in the presence of PRT, heparin and anti-PRT/heparin Abs (median platelet survival after 300 minutes (min) with 20 μg/ml ODSH: 75 %, range 70–81 % vs without ODSH: 49%, range 44–59%, p=0.006). Furthermore, when ODSH was applied 60 min after Ab injection platelet survival was improved (median platelet survival after 300 min with ODSH: 83 %, range 77–93 % vs without ODSH: 59 %, range 29–61 %, p=0.02). In in vitro experiments ODSH inhibited platelet activation at concentrations > 16 μg/mL (p< 0.001), as well as PRT/heparin complex binding to platelets (mean fluorescence intensity [MFI] without ODSH: 85 ± 14 vs with ODSH: 15 ± 0.6, p=0.013). ODSH also displaced pre-bound complexes from the platelet surface (MFI without ODSH: 324 ± 43 vs with 32 μg/ml ODSH: 53 ± 9, p< 0.001). While interfering with platelet activation by anti-PRT/heparin Abs, up to a concentration of 16 μg/ml, ODSH had only minimal impact on neutralisation of heparin by PRT. In conclusion, our study shows that ODSH is able to inhibit platelet activation and destruction suggesting a potential clinical use to reduce anti-PRT/heparin Ab-mediated adverse effects.


Blood ◽  
2019 ◽  
Vol 133 (9) ◽  
pp. 978-989 ◽  
Author(s):  
Krystin Krauel ◽  
Patricia Preuße ◽  
Theodore E. Warkentin ◽  
Catja Trabhardt ◽  
Sven Brandt ◽  
...  

Abstract Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating anti–platelet factor 4 (PF4)/heparin antibodies. Platelet activation assays that use “washed” platelets are more sensitive for detecting HIT antibodies than platelet-rich plasma (PRP)–based assays. Moreover, heparin-exposed patients vary considerably with respect to the risk of PF4/heparin immunization and, among antibody-positive patients, the risk of subsequent “breakthrough” of clinical HIT with manifestation of thrombocytopenia. We used washed platelets and PRP, standard laboratory HIT tests, and physicochemical methods to identify a plasma factor interfering with PF4/heparin complexes and anti-PF4/heparin antibody–platelet interaction, thus explaining differences in functional assays. To investigate a modulating risk for PF4/heparin immunization and breakthrough of HIT, we also tested 89 plasmas from 2 serosurveillance trials. Fibronectin levels were measured in 4 patient groups exhibiting different degrees of heparin-dependent immunization and expression of HIT. The heat-labile plasma protein, fibronectin, inhibited PF4 binding to platelets in a dose-dependent fashion, particularly in washed (vs PRP) systems. Fibronectin also inhibited PF4/heparin binding to platelets, anti-PF4/heparin antibody binding to PF4/heparin complexes, and anti-PF4/heparin antibody–induced platelet activation as a result of PF4/heparin complex disruption. In addition, plasma fibronectin levels increased progressively among the following 4 patient groups: enzyme-linked immunosorbent assay (ELISA)+/serotonin-release assay (SRA)+/HIT+ &lt; ELISA+/SRA+/HIT− ∼ ELISA+/SRA−/HIT− &lt; ELISA−/SRA−/HIT−. Altogether, these findings suggest that fibronectin interferes with PF4/heparin complex formation and anti-PF4/heparin antibody–induced platelet activation. Reduced fibronectin levels in washed platelet assays help to explain the greater sensitivity of washed platelet (vs PRP) assays for HIT. More importantly, lower plasma fibronectin levels could represent a risk factor for PF4/heparin immunization and clinical breakthrough of HIT.


1988 ◽  
Vol 3 (3) ◽  
pp. 193-196 ◽  
Author(s):  
S. Barni ◽  
P. Lissoni ◽  
S. Crispino ◽  
F. Rovelli ◽  
G. Esposti ◽  
...  

Melatonin secretion is often enhanced in patients with cancer. In the light of a reported correlation between melatonin levels and body size, we investigated blood levels of this pineal hormone in a group of 72 patients affected by cancer, 30 of whom had body weight within the normal range, 30 were obese and the last 12 cases had body weight below the normal range, in order to establish whether in fact melatonin blood concentrations were related to body size. Melatonin levels were high in 19/72 patients (26%). The mean levels of the pineal hormone were similar in patients with normal, low and high body weight. Finally, there was no significant correlation between melatonin values and body weight, height or surface. Melatonin secretion thus does not appear to be influenced by body size in cancer patients.


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