Microparticles and Fibrinolysis

Vallier, Ludovic; Cointe, Sylvie; Lacroix, Romaric; Bonifay, Amandine; Judicone, Coralie; Dignat-George, Françoise; Kwaan, Hau C.

doi:10.1055/s-0036-1592301

Cited by 36 publications

(42 citation statements)

References 44 publications

(60 reference statements)

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“…72 Many components of the fibrinolytic system have also been found to be increased in microparticles/microvesicles derived from APL promyelocytes as well as NB4 cells. 52,[73][74][75] These are subcellular particles, 0.1 to 1.0 μ in size, consisting of cell membrane vesicles, with increased amounts of tPA, uPA, annexin A2, and PAI-1 as well as tPA-PAI-1 complex and uPA-PAI-1 complex. As a result, enhanced plasmin generation occurs in these microparticles/microvesicles.…”

Section: Increased Fibrinolysismentioning

confidence: 99%

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Kwaan

Weiss

Tallman

2019

Semin Thromb Hemost

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Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality. Perturbed hemostatic dysfunction is present as the result of abnormalities in both the coagulation and the fibrinolytic systems. The activation of coagulation is distinct from the classical disseminated intravascular coagulation. Multiple abnormalities in the fibrinolytic system have recently been identified. The most significant change is increased production of tissue plasminogen activator (tPA) and its receptor annexin A2 by the APL promyelocytes. Among the hemorrhagic complications, intracranial hemorrhage predominates. The pathogenesis of this catastrophic event is elucidated by new evidence of adverse effect of tissue plasminogen activator (tPA) on the brain, including both the plasmin-dependent and plasmin-independent pathways. In order to address the hemorrhagic complications, a thorough understanding of the hemostatic dysfunction is essential. In this article, our current concept of the abnormal hemostasis in APL is reviewed. The failure to reduce the early death rate, despite the introduction of effective therapy, will also be discussed.

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Section: Increased Fibrinolysismentioning

confidence: 99%

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Kwaan

Weiss

Tallman

2019

Semin Thromb Hemost

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“…However, anticoagulant proteins are also present on the surface of LMVs, including thrombomodulin [20], endothelial protein C receptor [21] and TF pathway inhibitor (TFPI) [22]. Moreover, LMVs have been more recently described to have plasmin generation capacity (MV-PGC) [6,23]. …”

Section: Introductionmentioning

confidence: 99%

A new assay to evaluate microvesicle plasmin generation capacity: validation in disease with fibrinolysis imbalance

Cointe

Souab

Bouriche³

et al. 2018

J of Extracellular Vesicle

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Among extracellular vesicles, leukocyte-derived microvesicles (LMVs) have emerged as complex vesicular structures. Primarily identified as procoagulant entities, they were more recently ascribed to plasmin generation capacity (MV-PGC). The objectives of this work were (1) to develop a new hybrid bio-assay combining the specific isolation of LMVs and measurement of their PGC, and compare its performance to the original method based on centrifugation, (2) to validate MV-PGC in septic shock, combining increased levels of LMVs and fibrinolytic imbalance. Using plasma sample spiked with LMVs featuring different levels of PGC, we demonstrated that CD15-beads specifically extracted LMVs. The MV dependency of the test was demonstrated using electron microscopy, high speed centrifugation, nanofiltration and detergent-mediated solubilization and the MV-PGC specificity using plasmin-specific inhibitors, or antibodies blocking elastase or uPA. Thanks to a reaction booster (ε-ACA), we showed that the assay was more sensitive and reproducible than the original method. Moreover, it exhibited a good repeatability, inter-operator and inter-experiment reproducibility. The new immunomagnetic bio-assay was further validated in patients with septic shock. As a result, we showed that MV-PGC values were significantly lower in septic shock patients who died compared to patients who survived, both at inclusion and 24 h later (1.4 [0.8–3.0] vs 3.1 [1.7–18] A405 × 10−3/min, p = 0.02; 1.4 [1–1.6] vs 5.2 [2.2–16] A405 × 10−3/min, p = 0.004). Interestingly, combining both MV-PGC and PAI-1 in a ratio significantly improved the predictive value of PAI-1. This strategy, a hybrid capture bioassay to specifically measure LMV-PGC using for the first time, opens new perspectives for measuring subcellular fibrinolytic potential in clinical settings with fibrinolytic imbalance.

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“…22,23 Plasmin, the chief fibrinolytic enzyme, is generated by the cleavage of plasminogen by the activators, tissue plasminogen activator (tPA) and the urokinase plasminogen activator. The rate of activation is exceedingly slow but is greatly accelerated by the presence of plasminogen receptors on the surface of cells.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the thrombotic and fibrinolytic activities of tumor cell–derived extracellular vesicles

Durrieu¹,

Bharadwaj²,

Waisman

2018

Blood Advances

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Key Points• Microvesicles, but not exosomes, from tumor cells have thrombotic activity.• Tumor derivedexosomes can confer increased plasmingenerating capacity to a recipient cell.Exosomes and microvesicles (MVs) are small extracellular vesicles secreted by tumor cells and are suggested to contribute to the thrombotic events that commonly occur in patients with advanced malignancies. Paradoxically, these vesicles have been reported to also possess fibrinolytic activity. To determine whether thrombotic or fibrinolytic activity is a predominant characteristic of these extracellular vesicles, we prepared exosomes andMVs from 2 breast cancer cell lines (MDA-MB-231 and MCF7), a lung cancer cell line (A549), and a leukemia cell line (NB4) and assayed their thrombotic and fibrinolytic activities.We observed that thrombotic activity was a common feature of MVs but not exosomes.

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Microparticles and Fibrinolysis

Cited by 36 publications

References 44 publications

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

A new assay to evaluate microvesicle plasmin generation capacity: validation in disease with fibrinolysis imbalance

Analysis of the thrombotic and fibrinolytic activities of tumor cell–derived extracellular vesicles

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