Pathogenetic Analysis of Five Cases with a Platelet Disorder Characterized by the Absence of Thromboxane A2(TXA2)-Induced Platelet Aggregation in Spite of Normal TXA2 Binding Activity

Fuse, Ichiro; Hattori, Akira; Mito, M; Higuchi, Wataru; Yahata, Kazuaki; Shibata, Akira; Aizawa, Yoshifusa

doi:10.1055/s-0038-1650709

Cited by 28 publications

(17 citation statements)

References 24 publications

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“…The inhibition of an AA modifying enzyme, cyclooxygenase, by aspirin continues to be the single most successful therapy at preventing thrombotic disease (5). Thromboxane (TX)A 2 has been most clearly linked to function with the reports of genetic defects causing bleeding tendencies (6)(7)(8). There are potentially multiple classes of phospholipase A 2 (PLA 2 ) that may be involved in AA release: group IIA (IIA) secretory PLA 2 (sPLA 2 ), cytosolic PLA 2 s (cPLA 2 s), group V sPLA 2 , calcium-independent PLA 2 s, and group X sPLA 2 (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Discrete Role for Cytosolic Phospholipase A2α in Platelets

Wong

Kita

Uozumi

et al. 2002

The Journal of Experimental Medicine

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Among several different types of phospholipase A2 (PLA2), cytosolic PLA2 (cPLA2)α and group IIA (IIA) secretory PLA2 (sPLA2) have been studied intensively. To determine the discrete roles of cPLA2α in platelets, we generated two sets of genetically engineered mice (cPLA2α−/−/sPLA2-IIA−/− and cPLA2α−/−/sPLA2-IIA+/+) and compared their platelet function with their respective wild-type C57BL/6J mice (cPLA2α+/+/sPLA2-IIA−/−) and C3H/HeN (cPLA2α+/+/sPLA2-IIA+/+). We found that cPLA2α is needed for the production of the vast majority of thromboxane (TX)A2 with collagen stimulation of platelets. In cPLA2α-deficient mice, however, platelet aggregation in vitro is only fractionally decreased because small amounts of TX produced by redundant phospholipase enzymes sufficiently preserve aggregation. In comparison, adenosine triphosphate activation of platelets appears wholly independent of cPLA2α and sPLA2-IIA for aggregation or the production of TX, indicating that these phospholipases are specifically linked to collagen receptors. However, the lack of high levels of TX limiting vasoconstriction explains the in vivo effects seen: increased bleeding times and protection from thromboembolism. Thus, cPLA2α plays a discrete role in the collagen-stimulated production of TX and its inhibition has a therapeutic potential against thromboembolism, with potentially limited bleeding expected.

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Section: Introductionmentioning

confidence: 99%

Discrete Role for Cytosolic Phospholipase A2α in Platelets

Wong

Kita

Uozumi

et al. 2002

The Journal of Experimental Medicine

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“…22 The only other reported mutation in the TxA 2 receptor, Arg60Leu, 23 may be a rare single nucleotide polymorphism because there is no clear defect in function of the receptor in cell line studies. 24,25 We have not identified participants with mutations in the PAR-1 and PAR-4 thrombin receptors or the collagen receptor GPVI. There are no reported participants with mutations in the PAR-1 and PAR-4 receptors, possibly because they are incompatible with life, and only 2 patients with mutations in GPVI have been reported.…”

mentioning

confidence: 99%

Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel

Dawood

Lowe

Lordkipanidzé

et al. 2012

Blood

174

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“…Mutations involving TXA 2 R lead to reduced receptor coupling with its effector G protein and with phospholipase C. An autosomal inheritance has been described for these diseases [98][99][100].…”

Section: Agonist Platelet Receptor Defectsmentioning

confidence: 99%

Laboratory diagnostics of inherited platelet disorders

Carubbi

Masselli

Nouvenne

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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Inherited platelet disorders (IPDs) are the general and common denomination of a broad number of different rare and congenital pathologies affecting platelets. Even if these disorders are characterized by widely heterogeneous clinical presentations, all of them are commonly present as defects in hemostasis. Platelet number and/or function are affected by a wide spectrum of severity. IPDs might be associated with defects in bone marrow megakaryocytopoiesis and, rarely, with somatic defects. Although in the last few years new insights in the genetic bases and pathophysiology of IPDs have greatly improved our knowledge of these disorders, much effort still needs to be made in the field of laboratory diagnosis. This review discusses the laboratory approach for the differential diagnosis of the most common IPDs, suggesting a common multistep flowchart model which starts from the simpler test (platelet count) ending with the more selective and sophisticated analyses.

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Pathogenetic Analysis of Five Cases with a Platelet Disorder Characterized by the Absence of Thromboxane A2(TXA2)-Induced Platelet Aggregation in Spite of Normal TXA2 Binding Activity

Cited by 28 publications

References 24 publications

Discrete Role for Cytosolic Phospholipase A2α in Platelets

Discrete Role for Cytosolic Phospholipase A2α in Platelets

Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel

Laboratory diagnostics of inherited platelet disorders

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