The Plasma Levels of Prostanoids and Plasminogen Activator Inhibitor-1 in Primary and Secondary Thrombocytosis

Birdane, Alparslan; Haznedaroğlu, İbrahim C.; Bavbek, Nüket; Koşar, Ali; Büyükaşık, Yahya; Özcebe, Osman; Dündar, Semra; Kirazlı, Şerafettin

doi:10.1177/107602960501100209

Cited by 8 publications

(3 citation statements)

References 39 publications

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“…Specifically, hypofibrinolysis is driven by elevated levels of plasminogen activator inhibitor-1 (PAI-1) and platelet factor 4 (PF4). These proteins are associated with excessive platelet reactivity, not with the platelet count, which is in line with our results confirming the relationship between lower platelet count and thrombosis risk (Pósán et al 1998 ; Birdane et al 2005 ; Malecki et al 2016 ). It should be stressed that activated platelets and leukocytes in ET patients were found to be the main source of tissue factor (TF) and that reduced activity of the TF pathway inhibitor additionally increases the prothrombotic risk in JAK2 V617F positive ET patients (Gadomska et al 2016 ).…”

Section: Discussionsupporting

confidence: 93%

JAK2V617F variant allele frequency, non-driver mutations, single-nucleotide variants and polycythemia vera outcome

Kanduła

Janowski

Więckowska

et al. 2022

J Cancer Res Clin Oncol

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Introduction Despite comparatively favourable prognosis in polycythemia vera (PV) patients (pts), the overall survival is shorter compared to the age-matched general population. The aim of the study was to evaluate the impact of chosen laboratory and genetic factors on the individual disease outcome, i.e. risk of thrombosis, myelofibrosis/blastic transformation and death. Materials and methods The study group consisted of 151 pts and 57 healthy donors (HD). Results JAK2V617F mutation was found in 96.7% (146/151) of the studied pts. JAK2 exon 12 mutations were identified in 2 individuals. The coexistence of JAK2V617F and JAK2 exon 12 mutation was confirmed in 2 other pts. In one case, neither JAK2V617F nor JAK2 exon 12 mutation was found. The presence of ten different non-driver mutations (ASXL1, SRSF2, U2AF1, IDH2) in eight of the analyzed pts (5.3%) was confirmed. The overall frequency of thrombotic events (TE) in the studied PV group was 23.8% (36/151). In patients with TE, median platelet count was lower than in pts without TE. Thrombotic risk did not depend on JAK2 rs12343867, TERT rs2736100, OBFC1 rs9420907 SNV, however, we found a novel strong tendency towards statistical significance between the CC genotype miR-146a rs2431697 and thrombosis. The disease progression to fibrotic phase was confirmed in 9% of the pts. Fibrotic transformation in PV pts was affected mainly by JAK2V617F variant allele frequency (VAF) and the presence of coexisting non-driver variants. The high JAK2V617F VAF and elevated white blood cell (WBC) count at the time of diagnosis were associated with an increased risk of death. Conclusion Therefore, in our opinion, complex, laboratory and genetic PV pts evaluation at the time of diagnosis should be incorporated into a new prognostic scoring system to more precisely define the PV prognosis and to optimize the therapeutic decision-making process.

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Section: Discussionsupporting

confidence: 93%

JAK2V617F variant allele frequency, non-driver mutations, single-nucleotide variants and polycythemia vera outcome

Kanduła

Janowski

Więckowska

et al. 2022

J Cancer Res Clin Oncol

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“…28 Nevertheless, the platelet contribution to PAI-1 plasma levels is controversial, because the majority of PAI-1 in platelets has been reported to be inactive compared with plasma PAI-1, which is mainly active. However, this observation could be due to preparation artifacts, and the majority of platelet PAI-1 may be active.…”

Section: Mechanisms Regulation and Sources Of Pai-1mentioning

confidence: 99%

Plasminogen Activator Inhibitor-1 and Thrombotic Cerebrovascular Diseases

Tjärnlund-Wolf

Brogren²,

Lo³

et al. 2012

Stroke

106

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“…About 90% of the total PAI-1 in blood derived from platelet α-granules and platelet count were correlated with plasma PAI-1 concentrations [ 80 ]. Recent findings showed that more than 50% of platelet PAI-1 is in the active configuration, contrary to preliminary studies where the majority of PAI-1 stored in platelets has been considered to be inactive [ 81 ].…”

Section: Molecular Connections Between Platelets and Components Of Pl...mentioning

confidence: 99%

Role of Plasminogen Activation System in Platelet Pathophysiology: Emerging Concepts for Translational Applications

Napolitano

Montuori

2022

IJMS

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Traditionally, platelets have been exclusively considered for their procoagulant and antifibrinolytic effects during normal activation of hemostasis. Effectively, activated platelets secrete coagulation factors, expose phosphatidylserine, and promote thrombin and fibrin production. In addition to procoagulant activities, platelets confer resistance of thrombi to fibrinolysis by inducing clot retraction of the fibrin network and release of huge amounts of plasminogen activator inhibitor-1, which is the major physiologic inhibitor of the fibrinolytic cascade. However, the discovery of multiple relations with the fibrinolytic system, also termed Plasminogen Activation System (PAS), has introduced new perspectives on the platelet role in fibrinolysis. Indeed, the activated membrane surface of platelets provides binding sites on which fibrinolytic enzymes can be activated. This review discusses the evidence of the profibrinolytic properties of platelets through the description of PAS components and related proteins that are contained in or bind to platelets. Our analyses of literature data lead to the conclusion that in the initial phase of the hemostatic process, antifibrinolytic effects prevail over profibrinolytic activity, but at later stages, platelets might enhance fibrinolysis through the engagement of PAS components. A better understanding of spatial and temporal characteristics of platelet-mediated fibrinolysis during normal hemostasis could improve therapeutic options for bleeding and thrombotic disorders.

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The Plasma Levels of Prostanoids and Plasminogen Activator Inhibitor-1 in Primary and Secondary Thrombocytosis

Cited by 8 publications

References 39 publications

JAK2V617F variant allele frequency, non-driver mutations, single-nucleotide variants and polycythemia vera outcome

JAK2V617F variant allele frequency, non-driver mutations, single-nucleotide variants and polycythemia vera outcome

Plasminogen Activator Inhibitor-1 and Thrombotic Cerebrovascular Diseases

Role of Plasminogen Activation System in Platelet Pathophysiology: Emerging Concepts for Translational Applications

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