Effects of hypoxia and acidosis on vascular plasminogen activator release in the pig ear perfusion system

Tappy, Luc; Hauert, J; Bachmann, Fédor

doi:10.1016/0049-3848(84)90172-5

Cited by 27 publications

(5 citation statements)

References 10 publications

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“…[40][41][42][43][44][45] pH also directly influences fibrinolysis; compared with control human blood (pH 7.37), induction of severe acidosis (pH 6.9) enhances tPA-induced hyperfibrinolysis. 46,47 This pattern is consistent with our data in which hyperfibrinolysis patients had significantly lower pH (7.02 ± 0.16) than patients with shutdown (7.30 ± 0.14). Collectively, these data suggest even small changes in pH within the physiologic range may alter clot formation and stability in a complex biochemical milieu that includes multiple enzymes with different susceptibilities to changes in pH.…”

Section: Discussionsupporting

confidence: 91%

“…Several mechanisms mediating this relationship have been proposed, including pH-dependent changes in the activity of coagulation factors (e.g., factors VIIa, Xa), inhibition rate of procoagulant enzymes (e.g., antithrombin inhibition of thrombin), and conversion of fibrinogen to fibrin and assembly of the fibrin network 40–45 . pH also directly influences fibrinolysis; compared with control human blood (pH 7.37), induction of severe acidosis (pH 6.9) enhances tPA-induced hyperfibrinolysis 46,47 . This pattern is consistent with our data in which hyperfibrinolysis patients had significantly lower pH (7.02 ± 0.16) than patients with shutdown (7.30 ± 0.14).…”

Section: Discussionmentioning

confidence: 99%

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Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy

Lawson

Holle

Dow

et al. 2022

J Trauma Acute Care Surg

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BACKGROUND:Trauma patients with abnormal fibrinolysis have increased morbidity and mortality. Knowledge of mechanisms differentiating fibrinolytic phenotypes is important to optimize treatment. We hypothesized that subjects with abnormal fibrinolysis identified by whole blood viscoelastometry can also be distinguished by plasma thrombin generation, clot structure, fibrin formation, and plasmin generation measurements. METHODS:Platelet-poor plasma (PPP) from an observational cross-sectional trauma cohort with fibrinolysis shutdown (% lysis at 30 minutes [LY30] < 0.9, n = 11) or hyperfibrinolysis (LY30 > 3%, n = 9) defined by whole blood thromboelastography were studied. Noninjured control subjects provided comparative samples. Thrombin generation, fibrin structure and formation, and plasmin generation were measured by fluorescence, confocal microscopy, turbidity, and a fluorescence-calibrated plasmin assay, respectively, in the absence/presence of tissue factor or tissue plasminogen activator (tPA). RESULTS:Whereas spontaneous thrombin generation was not detected in PPP from control subjects, PPP from hyperfibrinolysis or shutdown patients demonstrated spontaneous thrombin generation, and the lag time was shorter in hyperfibrinolysis versus shutdown. Addition of tissue factor masked this difference but revealed increased thrombin generation in hyperfibrinolysis samples. Compared with shutdown, hyperfibrinolysis PPP formed denser fibrin networks. In the absence of tPA, the fibrin formation rate was faster in shutdown than hyperfibrinolysis, but hyperfibrinolysis clots lysed spontaneously; these differences were masked by addition of tPA. Tissue plasminogen activator-stimulated plasmin generation was similar in hyperfibrinolysis and shutdown samples. Differences in LY30, fibrin structure, and lysis correlated with pH. CONCLUSION:This exploratory study using PPP-based assays identified differences in thrombin generation, fibrin formation and structure, and lysis in hyperfibrinolysis and shutdown subgroups. These groups did not differ in their ability to promote tPA-triggered plasmin generation. The ability to characterize these activities in PPP facilitates studies to identify mechanisms that promote adverse outcomes in trauma. (

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy

Lawson

Holle

Dow

et al. 2022

J Trauma Acute Care Surg

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“…The mechanisms of tPA release under these conditions are still unknown. Apart from thrombin [23], a variety of compounds, e.g., vasopressin, histamine, bradykinin, serotonin, and catecholamines [24], and various conditions, such as hypoxia, acidosis, and venous stasis [25], are suggested to stimulate the release of tPA. However, no investigation has demonstrated a causal relationship between any one of these mechanisms and tPA-release during CPB.…”

Section: Discussionmentioning

confidence: 99%

Centrifugal and roller pumps — are there differences in coagulation and fibrinolysis during and after cardiopulmonary bypass?

et al. 1995

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A number of hemostatic parameters reflecting the activation of coagulation and fibrinolysis were investigated in a prospective study of 24 patients undergoing cardiopulmonary bypass (CPB) during heart surgery. The patients were randomized to a group in which either a roller (group 1) or a centrifugal pump (group 2) was used. Blood samples were taken preoperatively, at the onset of and every 20 min during CPB, after the administration of protamine, and 4, 20, 44, and 68 h postoperatively. The groups did not differ significantly in hematocrit, fibrinogen, factor XIII, and antithrombin III. Significant differences in favor of group 2 during and after CPB were found in prothrombin fragment F1 + 2, plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), and D-dimer (F1 + 2 P < 0.01 after 80-min CPB, PAP P < 0.005 after 40-min CPB, TAT and D-dimer P < 0.05 after 100-min CPB, D-dimer and PAP P < 0.05 after protamine administration, TAT and F1 + 2 4 h after CPB). These findings indicate the activation of fibrinolysis preceding thrombin generation during cardiopulmonary bypass. In addition, we conclude that centrifugal blood pumping is beneficial in avoiding excessive activation of both coagulation and fibrinolysis.

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“…The release of t-PA by activated monocytes or endothelium can, for example, be caused by hypoxia and acidosis [29], kinins, vasopressin, histamine and serotonin [30], or activated protein C [31]. t-PA is the strongest known activator of the fibrinolytic system and, as shown earlier, plays an important role during CPB [32].…”

Section: Discussionmentioning

confidence: 99%

Changes in coagulation and fibrinolytic parameters caused by extracorporeal circulation

et al. 1996

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During cardiopulmonary bypass (CPB) mechanical stress and the contact of blood with artificial surfaces lead to the activation of pro- and anticoagulant systems and the complement cascade, and to changes in cellular components. This phenomenon causes the "postperfusion-syndrome", with leukocytosis, increased capillary permeability, accumulation of interstitial fluid, and organ dysfunction. In this study, we focused on the influence of the extracorporeal circulation, sternotomy, and heparin administration on the activation of coagulation and fibrinolysis. In 15 patients we investigated coagulation parameters before, during and post CPB, i.e., fibrinogen, antithrombin (AT) III, thrombin-antithrombin complex (TAT), prothrombin fragments F1 + 2 (F1 + 2), factor (F) XIIa, tissue factor (TF), and parameters of the fibrinolytic system, i.e., plasmin-antiplasmin-complex (PAP), D-dimer, tissue-plasminogen-activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen-activator inhibitor type 1 (PAI 1). The results demonstrate distinct alterations in the above mentioned parameters. Despite administration of a high dose of heparin (activated clotting time [ACT] > 450s) combined with a low dose of aprotinin, activation of the coagulation and fibrinolytic pathways was observed. We found this activation was mainly caused by CPB and not by sternotomy. The activation of coagulation was due to foreign surface contact (F XII => F XIIa) as well as to an effect of tissue factor release in the late phase of CPB. The enhanced fibrinolytic activity during CPB was, at least in part, caused by tPA and was followed by PAI 1 release.

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Effects of hypoxia and acidosis on vascular plasminogen activator release in the pig ear perfusion system

Cited by 27 publications

References 10 publications

Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy

Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy

Centrifugal and roller pumps — are there differences in coagulation and fibrinolysis during and after cardiopulmonary bypass?

Changes in coagulation and fibrinolytic parameters caused by extracorporeal circulation

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