A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type 1

Dieval, J; Nguyen, Geneviève; Gross, Sylvie; Delobel, J.; Kruithof, Egbert K. O.

doi:10.1182/blood.v77.3.528.528

Cited by 137 publications

(58 citation statements)

References 24 publications

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“…Detailed histories of these subjects were not available, but subjects that reported a bleeding history were not included in this analysis [14]. Because the number of case reports of PAI-1 deficiency causing significant bleeding is limited, the true prevalence of this disorder is not established but likely small [5][6][7][8][9][10][11][12][13][15][16][17]. Unfortunately, the lack of precision of currently available activity assays within the lowest range of PAI-1 activity continues to hinder accurate diagnosis.…”

Section: Incidencementioning

confidence: 99%

“…Like most coagulation protein deficiencies, qualitative or quantitative defects may lead to a deficiency state [5][6][7][9][10][11][12][13]15,17]. The first case described in 1989 reported normal levels of PAI-1 antigen, with a marked reduction in PAI-1 activity and t-PA:PAI-1 complexes, suggesting that the PAI-1 present lacked activity [5].…”

Section: Pathophysiologymentioning

confidence: 99%

“…Conversely, it is possible that much of the PAI-1 may have been present in the latent form, resulting in a normal antigenic assay but decreased activity assay. Most of the subsequent reports documented true qualitative deficiencies resulting in decreased PAI-1 activity [5][6][7][9][10][11][12][13]15,17]. Interestingly, two reports detail low plasma levels of PAI-1 activity and antigen, with normal platelet levels [6,10].…”

Section: Pathophysiologymentioning

confidence: 99%

“…The first reported case of low levels of PAI-1 resulting in a lifelong bleeding disorder was published in 1989, when an elderly man was noted to have decreased PAI-1 activity and normal PAI-1 antigen levels, leading to a presumed qualitative defect of the protein [5]. The first person with a quantitative deficiency (undetectable PAI-1 antigen and activity levels) was described two years later [6]. In 1992, the first identified homozygous PAI-1 genetic defect that led to a bleeding disorder was documented [7].…”

Section: Introductionmentioning

confidence: 99%

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Plasminogen activator inhibitor type 1 deficiency

2008

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Summary. Plasminogen activator inhibitor type 1 (PAI‐1) is an important component of the coagulation system that down‐regulates fibrinolysis in the circulation. Reduced PAI‐1 levels may result in increased fibrinolysis and an associated bleeding diathesis. Clear documentation of PAI‐1 deficiency as a cause of a bleeding disorder has been rare. PAI‐1 was initially identified in the 1980s, and the first reported case of PAI‐1 deficiency appeared in 1989. Several reports followed, although only two identified an underlying genetic defect. These reports of PAI‐1 deficiency suggest that affected individuals exhibit mild to moderate bleeding symptoms, including epistaxis, menorrhagia, and delayed bleeding after trauma or surgical procedures. Affected individuals rarely exhibit spontaneous bleeding events commonly seen in other procoagulant deficiencies. The majority of bleeding events are controlled with antifibrinolytic agents, such as tranexamic acid and ε‐aminocaproic acid. A major issue that contributes to difficulty in establishing an accurate diagnosis of PAI‐1 deficiency is that the activity assay is accurate in detection of elevated levels but not at the lowest range. Reported normal ranges begin at zero, thereby making a deficiency state because of a dysproteinaemia difficult to distinguish from that of a normal unaffected individual. Although the antigen assay may be helpful in some circumstances, it assists only with complete quantitative disorders. Because of lack of standardized commercially available PAI‐1 activity assay sensitive in the lowest range, the true prevalence of this rare condition has not been established.

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Section: Incidencementioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasminogen activator inhibitor type 1 deficiency

2008

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“…A similar zone present in human blood, represents t-PA-PAI-I complexes, normally found in plasma, where PAI-I is present in excess (Sprengers and Kluft 1987;Krishnamurti and Alving 1992). The relative PAL I excess protects against indiscriminate clot lysis by t-PA, with subsequent uncontrolled haemorrhage (Dieval et a / . 1991).…”

Section: Discussionmentioning

confidence: 99%

Regulation of equine fibrinolysis in blood and peritoneal fluid based on a study of colic cases and induced endotoxaemia

Collatos

Barton

Schleef

et al. 1994

Equine Veterinary Journal

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Summary Much of the pathophysiology associated with equine gastrointestinal diseases is attributed to the effects of endotoxin on haemostasis. Because little is known about the responses of the equine fibrinolytic system to endotoxin, regulation of the system was investigated. Tissue‐type plasminogen activator (t‐PA) and plasminogen activator inhibitor type‐1 (PAI‐1) were identified as the primary plasminogen activator and plasminogen activator inhibitor, respectively, in equine blood. Under experimental conditions, the equine fibrinolytic system responded to endotoxin in a manner similar to that reported in man, with an early, transient increase in t‐PA activity followed by an overwhelming and prolonged increase in activity of PAI‐1. To investigate the response of the equine fibrinolytic system to clinical endotoxaemia, endotoxin concentrations were measured in plasma and peritoneal fluid, and activities of t‐PA and PAI‐1 were compared between healthy horses (n=38) and horses with naturally occurring gastrointestinal diseases (n=150). It was observed that plasma PAI‐1 and peritoneal t‐PA were increased concurrently in abnormal horses; and that these increases were associated with the presence of endotoxin. The results of this study suggest that 1) fibrinolysis is regulated in horses in a manner similar to that in man; 2) regulation of fibrinolysis is altered in endotoxaemic horses with gastrointestinal diseases; 3) events occurring in the vascular system may not reflect those in the peritoneal cavity; and 4) t‐PA activity is increased in the peritoneal fluid of endotoxaemic horses with gastrointestinal diseases.

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Matrix Proteases in Health and Disease

Ellis

2012

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A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type 1

Cited by 137 publications

References 24 publications

Plasminogen activator inhibitor type 1 deficiency

Plasminogen activator inhibitor type 1 deficiency

Regulation of equine fibrinolysis in blood and peritoneal fluid based on a study of colic cases and induced endotoxaemia

Matrix Proteases in Health and Disease

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