Changes in platelet function and reactivity induced by quinine in relation to quinine (drug) induced immune thrombocytopenia

Connellan, J.M.; Deacon, Susan L. M.; Thurlow, P. J.

doi:10.1016/0049-3848(91)90158-s

Cited by 13 publications

(3 citation statements)

References 26 publications

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“…Connellan et al 4 suggested that quinine induces widespread conformational changes in platelet membrane antigen which exposes neoantigens and may induce quinine-associated antibodies. These antibodies, in the presence of quinine, may bind a range of platelet glycoproteins by the Fab domain rather than the Fc, suggesting that platelet destruction is not complement mediated 5.…”

Section: Discussionmentioning

confidence: 99%

Quinine-mediated disseminated intravascular coagulation

Kedia¹,

Wright²

1999

Postgraduate Medical Journal

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Section: Discussionmentioning

confidence: 99%

Quinine-mediated disseminated intravascular coagulation

Kedia¹,

Wright²

1999

Postgraduate Medical Journal

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“…Data on the specificity of both compounds for Panx channels are sparse. The inhibitory effect of quinine on platelet aggregation has been proven some years ago [148] and Mfq was recently shown to inhibit human platelet aggregation and ATP release induced by collagen (Figure 5) [123]. However, the prescription of Mfq is now strongly discouraged as studies have evidenced an association between the use of this drug and severe psychiatric side effects such as anxiety, paranoia, psychosis and anterograde amnesia [149].…”

Section: “Drug-ability” Of Panx-cx Targetsmentioning

confidence: 99%

Pannexin- and Connexin-Mediated Intercellular Communication in Platelet Function

Molica

Stierlin

Fontana

et al. 2017

IJMS

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The three major blood cell types, i.e., platelets, erythrocytes and leukocytes, are all produced in the bone marrow. While red blood cells are the most numerous and white cells are the largest, platelets are small fragments and account for a minor part of blood volume. However, platelets display a crucial function by preventing bleeding. Upon vessel wall injury, platelets adhere to exposed extracellular matrix, become activated, and form a platelet plug preventing hemorrhagic events. However, when platelet activation is exacerbated, as in rupture of an atherosclerotic plaque, the same mechanism may lead to acute thrombosis causing major ischemic events such as myocardial infarction or stroke. In the past few years, major progress has been made in understanding of platelet function modulation. In this respect, membrane channels formed by connexins and/or pannexins are of particular interest. While it is still not completely understood whether connexins function as hemichannels or gap junction channels to inhibit platelet aggregation, there is clear-cut evidence for a specific implication of pannexin1 channels in collagen-induced aggregation. The focus of this review is to summarize current knowledge of the role of connexins and pannexins in platelet aggregation and to discuss possible pharmacological approaches along with their limitations and future perspectives for new potential therapies.

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“…One proposed mechanism is that the binding of the drug to platelet surface GPs results in the exposure of new antigenic epitopes to which drug-dependent antibodies bind. 13 This antibody binding leads to increased platelet clearance by the reticuloendothelial system, bringing about the frequently observed thrombocytopenia.…”

Section: Introductionmentioning

confidence: 99%

Drug-induced thrombocytopenia: localization of the binding site of GPIX-specific quinine-dependent antibodies

Asvadi

Ahmadi

Chong

2003

Blood

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Immune thrombocytopenia is a common complication of therapy with a large number of drugs. The most widely studied drug-induced immune thrombocytopenia (DIT) is caused by quinine. In most cases of DIT, antibodies bind to the platelet membrane glycoprotein (GP) Ib-IX complex in a drug-dependent fashion and bring about increased platelet clearance by the reticuloendothelial system resulting in thrombocytopenia. Here, we report the characterization of the quinine-dependent antibody activity of sera from 13 patients with quinine-induced thrombocytopenia. In our series of patients, GPIX was the most prevalent target of quininedependent antibodies. To identify the structural determinants of GPIX recognized by quinine-dependent antibodies, 4 chimeric mouse/human GPIX constructs and stable Chinese hamster ovary (CHO) cell lines that expressed the chimeras in association with GPIb␣ and GPIb␤ were produced. The analysis of 6 patient sera with the chimeric cell lines provided evidence for localization of the anti-GPIX quinine-dependent antibody binding site to the C-ext region (amino acid [aa] 64-135) of human GPIX. Further characterization of the C-ext region of the GPIX indicated that replacement of the Arg110 and Gln115 of the human GPIX with the corresponding residues from mouse (Gln and Glu, respectively) resulted in a significant reduction in the binding of GPIX antibodies in our series of patients, with Arg110Gln, giving a more pronounced effect than Gln115Glu. Hence, these 2 residues, particularly Arg110, play an important role in the structure of the antigenic site on GPIX recognized by anti-GPIX

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Changes in platelet function and reactivity induced by quinine in relation to quinine (drug) induced immune thrombocytopenia

Cited by 13 publications

References 26 publications

Quinine-mediated disseminated intravascular coagulation

Quinine-mediated disseminated intravascular coagulation

Pannexin- and Connexin-Mediated Intercellular Communication in Platelet Function

Drug-induced thrombocytopenia: localization of the binding site of GPIX-specific quinine-dependent antibodies

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