Characteristics of fibrinolytic disorders in acute promyelocytic leukemia

Wang, Ping; Zhang, Yingmei; Yang, Huohai; Hou, Wenyi; Jin, Bo; Hou, Jian; Li, Haitao; Zhao, Hongli; Zhou, Jin

doi:10.1080/10245332.2018.1470069

Cited by 22 publications

(17 citation statements)

References 30 publications

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“…In an earlier study, PAI-1 was found to be elevated in the plasma of some patients, 37 but more recent findings indicated otherwise. 71 PAI-1 forms a complex with tPA and with uPA. In another study, the specific and unbound PAI-1 activity is decreased.…”

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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“…Recent studies have called into question the role of annexin II in hyperfibrinolysis seen in APL and reported low circulating levels of this protein. In these studies, it was the increased urokinase-type plasminogen activator receptor (uPAR) that claimed a role in fibrin and fibrinogen degradation (27). Since cellular annexin II levels were not assessed in these studies, the contribution of this mechanism cannot be refuted.…”

Section: Mechanisms Of Hemorrhage In Aplmentioning

confidence: 99%

Coagulopathy in Acute Promyelocytic Leukemia: Can We Go Beyond Supportive Care?

2021

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Acute promyelocytic leukemia (APL) is characterized by frequent complications due to a distinct coagulopathy. While advances in treatments have improved long-term survival, hemorrhagic and thrombotic complications remain the most common causes of death and morbidity. Improved understanding of the mechanisms of the coagulopathy associated with APL may lead to therapeutic interventions to mitigate the risk of hemorrhage and thrombosis.

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“…Other PG parameters (time-to-peak, velocity, and peak) showed better correlation with TXA concentration and less variability compared to either ROTEM LI30 or maximum lysis [ 88 ]. Since TXA is used as an antifibrinolytic in a number of clinical situations (e.g., shock [ 113 ], trauma [ 114 ], cardiopulmonary bypass [ 115 ], postpartum hemorrhage [ 116 ], and malignancy [ 59 , 117 , 118 , 119 ]), the PGA may have broad utility for identifying fibrinolytic dysfunction and optimizing antifibrinolytic therapy.…”

Section: Plasmin Generation In Health and Diseasementioning

confidence: 99%

Assessing Plasmin Generation in Health and Disease

Miszta

Huskens

Donkervoort

et al. 2021

IJMS

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Fibrinolysis is an important process in hemostasis responsible for dissolving the clot during wound healing. Plasmin is a central enzyme in this process via its capacity to cleave fibrin. The kinetics of plasmin generation (PG) and inhibition during fibrinolysis have been poorly understood until the recent development of assays to quantify these metrics. The assessment of plasmin kinetics allows for the identification of fibrinolytic dysfunction and better understanding of the relationships between abnormal fibrin dissolution and disease pathogenesis. Additionally, direct measurement of the inhibition of PG by antifibrinolytic medications, such as tranexamic acid, can be a useful tool to assess the risks and effectiveness of antifibrinolytic therapy in hemorrhagic diseases. This review provides an overview of available PG assays to directly measure the kinetics of plasmin formation and inhibition in human and mouse plasmas and focuses on their applications in defining the role of plasmin in diseases, including angioedema, hemophilia, rare bleeding disorders, COVID-19, or diet-induced obesity. Moreover, this review introduces the PG assay as a promising clinical and research method to monitor antifibrinolytic medications and screen for genetic or acquired fibrinolytic disorders.

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Characteristics of fibrinolytic disorders in acute promyelocytic leukemia

Abstract: In APL, activated coagulation system activated fibrinolytic system, and increased uPAR levels could contribute to the hyperfibrinolysis. Annexin II might not be involved in the coagulopathy.

Cited by 22 publications

References 30 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

Coagulopathy in Acute Promyelocytic Leukemia: Can We Go Beyond Supportive Care?

Assessing Plasmin Generation in Health and Disease

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