Disorders of platelet function

Fuse, Ichiro

doi:10.1016/1040-8428(94)00167-7

Cited by 20 publications

(7 citation statements)

References 311 publications

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“…To detect the secretion in activated platelets the surface exposure of secretory granule markers was studied. During the SNARE-mediated fusion platelet secretory granules may fuse directly with the surface-connected open canalicular system 11 , or merge with each other (compound fusion), and then with the open canalicular system 12 . This mode of secretion is similar to homo- and heterotypic fusion of synaptic vesicles in neurons and results in translocation of membrane-bound proteins of platelet secretory granules on the plasma membrane.…”

Section: Resultsmentioning

confidence: 99%

4-Аminopyridine sequesters intracellular Ca2+ which triggers exocytosis in excitable and non-excitable cells

Kasatkina

2016

Sci Rep

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4-aminopyridine is commonly used to stimulate neurotransmitter release resulting from sustained plasma membrane depolarization and Ca2+-influx from the extracellular space. This paper elucidated unconventional mechanism of 4-aminopyridine-stimulated glutamate release from neurons and non-neuronal cells which proceeds in the absence of external Ca2+. In brain nerve terminals, primary neurons and platelets 4-aminopyridine induced the exocytotic release of glutamate that was independent of external Ca2+ and was triggered by the sequestration of Ca2+ from intracellular stores. The initial level of 4-aminopyridine-stimulated glutamate release from neurons in the absence or presence of external Ca2+ was subequal and the difference was predominantly associated with subsequent tonic release of glutamate in Ca2+-supplemented medium. The increase in [Ca2+]i and the secretion of glutamate stimulated by 4-aminopyridine in Ca2+-free conditions have resulted from Ca2+ efflux from endoplasmic reticulum and were abolished by intracellular free Ca2+ chelator BAPTA. This suggests that Ca2+ sequestration plays a profound role in the 4-aminopyridine-mediated stimulation of excitable and non-excitable cells. 4-Aminopyridine combines the properties of depolarizing agent with the ability to sequester intracellular Ca2+. The study unmasks additional mechanism of action of 4-aminopyridine, an active substance of drugs for treatment of multiple sclerosis and conditions related to reduced Ca2+ efflux from intracellular stores.

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Section: Resultsmentioning

confidence: 99%

4-Аminopyridine sequesters intracellular Ca2+ which triggers exocytosis in excitable and non-excitable cells

Kasatkina

2016

Sci Rep

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“…the combination of agonists eliciting reduced response upon stimulation). Information on the presence of medical conditions previously reported to be associated with PSD (reviewed by Fuse [1]) was retrieved as well.…”

Section: Methodsmentioning

confidence: 99%

“…Platelet primary secretion defects (PSD) are defined by reduced primary platelet granule secretion upon stimulation by different platelet aggregation agonists [1]. PSD often results in bleeding tendency, which is usually mild to moderate albeit asymptomatic patients have been described [2]–[4].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Disease and Relationships between Laboratory Phenotype and Bleeding Severity in Platelet Primary Secretion Defects

et al. 2013

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BackgroundThe prevalence of platelet primary secretion defects (PSD) among patients with bleeding diathesis is unknown. Moreover, there is paucity of data on the determinants of bleeding severity in PSD patients.ObjectiveTo determine the prevalence of PSD in patients with clinical bleeding and to study the relationships between the type of platelet defect and bleeding severity.MethodsData on patients referred for bleeding to the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan (Italy) in the years between 2008 and 2012 were retrieved to study the prevalence of PSD. Demographic, clinical and laboratory information on 32 patients with a diagnosis of PSD was used to compare patients with or without associated medical conditions and to investigate whether or not the type and extension of platelet defects were associated with the bleeding severity score (crude and age-normalized) or with the age at first bleeding requiring medical attention.ResultsThe estimated prevalence of PSD among 207 patients with bleeding diathesis and bleeding severity score above 4 was 18.8% (95% confidence interval [CI]: 14.1–24.7%). Patients without associated medical conditions had earlier age of first bleeding (18 vs 45 years; difference: -27 years; 95% CI: -46 to -9 years) and different platelet functional defect patterns (Fisher's exact test of the distribution of patterns, P = 0.007) than patients with accompanying medical conditions. The type and extension of platelet defect was not associated with the severity of bleeding.ConclusionsPSD is found in approximately one fifth of patients with clinical bleeding. In patients with PSD, the type and extension of laboratory defect was not associated with bleeding severity.

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“…There are also fibrin(ogen) degradation products, which appear in excess in liver disease, 47 are known to adsorb to the platelet surface and interfere with platelet function 86 . However, their levels may not be well correlated with reduced platelet aggregation 87 …”

Section: Platelet Functionmentioning

confidence: 99%

Review article: blood platelet number and function in chronic liver disease and cirrhosis

Witters

Freson

Verslype

et al. 2008

Aliment Pharmacol Ther

157

134

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Summary Background The liver plays a central role in coagulation and fibrinolysis but is also closely intertwined with the function and number of blood platelets. Aim To describe and integrate all literature concerning blood platelets and liver disease by performing a thorough literature research. Methods A thorough literature research on ‘blood platelets’ and ‘liver disease’ was performed. Results Thrombocytopenia is a marked feature of chronic liver disease and cirrhosis. Traditionally, this thrombocytopenia was attributed to passive platelet sequestration in the spleen. More recent insights suggest an increased platelet breakdown and to a lesser extent decreased platelet production plays a more important role. Besides the reduction in number, other studies suggest functional platelet defects. This platelet dysfunction is probably both intrinsic to the platelets and secondary to soluble plasma factors. It reflects not only a decrease in aggregability, but also an activation of the intrinsic inhibitory pathways. The net effect, finally, is a decreased platelet function in the various types of chronic liver diseases and cirrhosis. Finally, recent data suggest that platelets are not only affected by but can also contribute to the liver disease process, as for instance, in viral hepatitis and cholestatic liver disease. Conclusion Platelet research in liver disease is a growing area of investigation and could provide new pathophysiological insights.

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Disorders of platelet function

Cited by 20 publications

References 311 publications

4-Аminopyridine sequesters intracellular Ca2+ which triggers exocytosis in excitable and non-excitable cells

4-Аminopyridine sequesters intracellular Ca2+ which triggers exocytosis in excitable and non-excitable cells

Prevalence of Disease and Relationships between Laboratory Phenotype and Bleeding Severity in Platelet Primary Secretion Defects

Review article: blood platelet number and function in chronic liver disease and cirrhosis

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