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Platelet Surface Expression (platelet + surface_expression)
Selected AbstractsDiversity of Glanzmann thrombasthenia in southern India: 10 novel mutations identified among 15 unrelated patientsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2006E. J. R. NELSON Summary.,Background: Glanzmann thrombasthenia (GT) is a congenital bleeding disorder caused by either a lack or dysfunction of the platelet integrin ,IIb,3. Objectives: To determine the molecular basis of GT in patients from southern India. Patients: Fifteen unrelated patients whose diagnosis was consistent with GT were evaluated. Results: Platelet surface expression of ,IIb,3 was < 10%, 10%,50%, and > 50% of controls in five, nine, and one patient(s), respectively. Immunoblotting of the platelet lysates showed no ,IIb in 14 patients, and no ,3 in 10 patients, although severely reduced in four patients. Platelet fibrinogen was undetectable in 13 patients, and severely reduced in one patient. One patient showed normal surface ,IIb,3 expression, and normal ,IIb, ,3 and fibrinogen levels in the lysate. Ten novel candidate disease-causing mutations were identified in 11 patients. The missense mutations included Gly128Ser, Ser287Leu, Gly357Ser, Arg520Trp, Leu799Arg in ,IIb, and Cys575Gly in ,3. We have already shown that Gly128Ser, Ser287Leu, and Gly357Ser mutations variably affect ,IIb,3 surface expression. The Cys575Gly mutation may disrupt the disulphide link with Cys586 to cause the GT phenotype. The molecular pathology of the other missense mutations is not clear. Two nonsense mutations, Trp-16Stop and Glu715Stop in ,IIb, and a 7-bp deletion (330-336TCCCCAG) in ,3 are predicted to result in truncated proteins. An IVS15(,1)G , A mutation in ,IIb induced a cryptic splice site as confirmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Thirteen polymorphisms were also identified (five in ,IIb and eight in ,3), among which five were novel. Conclusions: While identifying a significant number of novel mutations causing GT, this study confirms the genetic heterogeneity of the disorder in southern India. [source] Enhanced Prothrombin Formation and Platelet Activation in Chinese Patients After Transcatheter Closure of Atrial Septal DefectCLINICAL CARDIOLOGY, Issue 7 2010Xiao-Chun Zeng MD Background The objective of this study was to investigate changes in coagulation activation and platelet activation after transcatheter closure of atrial septal defect (ASD) by determining the levels of specific markers over time to provide insight into preventing postprocedural embolism. Hypothesis We hypothesis that the activation status of coagulation and the platelet would be changed after the closure of ASD. Methods Forty consecutive patients who underwent transcatheter closure of ASD with the Lifetech ASD occluder (Lifetech Scientific, Shenzhen, China) were included in this prospective study. The serum level of prothrombin fragment 1 + 2 (F1 + 2) and expressions of P-selectin (CD62P) and platelet glycoprotein IIb/IIIa receptor (CD41a) on the surface of platelets were evaluated at baseline and at 1 day, 1 month, and 3 months after the closure. Results The median F1 + 2 level was 0.96 nmol/L. This increased to a maximal value of 1.43 nmol/L at 1 day after closure, but gradually returned to the baseline level at 1 month after closure and remained there at 3 months after closure (medians were 0.98 nmol/L and 1.08 nmol/L, respectively). Platelet surface expression of CD62P and CD41a decreased at 1 day, 1 month, and 3 months after closure. For CD62P, average expressions were 8.21% ± 2.11%, 6.28% ± 1.72%, 5.29% ± 1.52%, and 4.41% ± 1.11%, respectively, for baseline and 1 day, 1 month, and 3 months after closure. For CD41a, average expressions were 79.37% ± 14.14%, 71.98% ± 13.77, 56.69% ± 13.05%, and 54.88% ± 11.62%, respectively. Conclusions Transcatheter closure of ASD with the Lifetech ASD occluder was associated with significantly increased coagulation activation and decreased platelet activation. No evidence supporting the use of aspirin to prevent thrombus formation after closure was found. Copyright © 2008 Wiley Periodicals, Inc. This work was supported by Guangxi Key Technologies R&D Programme, 0472002-30, China. The authors have no other funding, financial relationships, or conflicts of interest to disclose. [source] A 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet functionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000De Miguel Background The thrombotic process is a multicellular phenomenon in which not only platelets but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal, a 4-trifluoromethyl derivative of salicylate, reduced platelet aggregation not only by inhibiting thromboxane A2 production but also by stimulating nitric oxide (NO) generation by neutrophils. The aim of the present study was to evaluate whether oral treatment of healthy volunteers with triflusal could modify the ability of their neutrophils to produce NO and to test the role of the NO released by neutrophils in the modulation of ADP-induced platelet aggregation and ,-granule secretion. Methods The study was performed in 12 healthy volunteers who were orally treated with triflusal (600 mg day,1) for 5 days. Flow cytometric detection of platelet surface expression of P-selectin was used as a measure of the ability of platelets to release the contents of their ,-granules. Results After treatment with triflusal, there was an increase in NO production by neutrophils and an increase in endothelial nitric oxide synthase (eNOS) protein expression in neutrophils. A potentiation of the inhibition of platelet aggregation by neutrophils was reversed by incubating neutrophils with both an l -arginine antagonist, NG -nitro- l -arginine methyl ester ( l -NAME) and an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). A slight decrease in P-selectin surface expression on platelets was found which was not modified by the presence of neutrophils and therefore by the neutrophil-derived NO. Exogenous NO released by sodium nitroprusside dose-dependently inhibited both ADP-stimulated ,-granule secretion and platelet aggregation. Therefore, platelet aggregation showed a greater sensitivity to be inhibited by exogenous NO than P-selectin expression. Conclusion Oral treatment of healthy volunteers with triflusal stimulated NO production and eNOS protein expression in their neutrophils. After triflusal treatment, the neutrophils demonstrated a higher ability to prevent ADP-induced platelet aggregation. However, the neutrophils and the endogenous NO generated by them failed to modify P-selectin expression in ADP-activated platelets. [source] Effects of Helicobacter pylori Eradication on Platelet Activation and Disease Recurrence in Patients with Acute Coronary SyndromesHELICOBACTER, Issue 6 2004J. Ignasi Elizalde ABSTRACT Background., Platelet activation is consistently observed in animal models of Helicobacter pylori infection and could help to explain the alleged epidemiological association between H. pylori and coronary heart disease. Materials and Methods., Ninety-two patients with recent acute coronary syndromes were enrolled. Helicobacter pylori -positive patients were randomized to receive a 7-day course of omeprazole, amoxycillin and metronidazole or placebos. Two months later, H. pylori status was reassessed and baseline parameters, including soluble P-selectin and platelet surface expression of CD62P, CD63 and CD41, were measured again. Patients were followed-up for 1 year or until death or readmission. Results., No baseline differences were observed between H. pylori -positive and -negative cases. Among H. pylori -positive patients, 18 received placebo and 31 received active medication resulting in eradication in 21 cases. No differences were observed in inflammatory parameters or platelet activation markers between patients with persistent or resolved H. pylori infection. However, coronary events recurred at 6 and 12 months, respectively, in 35% and 55% of patients with persisting H. pylori infection compared with 10% and 25% of patients in whom H. pylori was either absent or eradicated (p = .01). Only final H. pylori status [RR 3.07 (95% CI 1.35,98)] and number of coronary risk factors [RR 2.58 (95% CI 1.51,4.41)] were independent predictors of recurrence. Conclusions., Infection with H. pylori does not induce significant platelet activation in patients treated for coronary disease. Helicobacter pylori -infected patients, however, may have an increased risk of recurrence of coronary events. [source] | ||||||||||