Contrasting Post-Traumatic Serial Changes for D-Dimer and PAI-1 in Critically Injured Patients

Chen, James P.; Rowe, Dennis W.; Enderson, Blaine L.

doi:10.1016/s0049-3848(98)00211-4

Cited by 26 publications

(15 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because excess fibrin can damage endothelia, 21 we assayed circulating plasma levels of D-dimer (a specific fibrin degradation product [FDP]) to determine whether loss of PAI-1 provides protection by allowing increased breakdown of fibrin. 22 As shown in Fig. 6A, after HS-R, circulating D-dimer levels rose significantly in both KO and WT mice.…”

Section: Pai-1 Protein Causes Acute Damage To Endothelia and Hepatocymentioning

confidence: 72%

The role of hepatic type 1 plasminogen activator inhibitor (PAI‐1) during murine hemorrhagic shock†

et al. 2005

View full text Add to dashboard Cite

Hemorrhagic shock (HS) followed by resuscitation (HS-R) is characterized by profound physiological changes. Even if the patient survives the initial blood loss, these poorly understood changes can lead to morbidity. One of the tissues most often affected is liver. We sought to recognize specific hepatic changes induced by this stressor to identify targets for therapeutic intervention. Gene array analyses using mouse liver mRNAs were used to identify candidate genes that contribute to hepatic damage. To verify the role of one of the genes identified using the arrays, mice were subjected to HS-R, and multiple parameters were analyzed. A profound increase in plasminogen activator inhibitor type 1 (PAI-1) mRNA was observed using hepatic mRNAs from C57Bl/6 mice after HS, both with and without resuscitation. Constitutive loss of PAI-1 resulted in notable tissue preservation and lower (P < .05) alanine aminotransferase (ALT) levels. Fibrin degradation products (FDPs) and interleukins 6 and 10 (IL-6 and IL-10) were unaffected by loss of PAI-1; however, enhanced urokinase activity, an elevation of active hepatocyte growth factor (HGF), an increase in unprocessed transforming growth factor-␤1 (TGF-␤1), and retention of ERK phosphorylation after HS-R were associated with improved hepatic function. In conclusion, PAI-1 protein is a negative effector of hepatic damage after HS-R through its influence on classic regulators of hepatic growth, as opposed to its role in fibrinolysis. (HEPATOLOGY 2005;42: 390-399.)H emorrhagic shock (HS) is characterized by a diverse range of physiological changes. 1,2 The body's exact response to shock depends on the type and severity of the original insult, combined with the host's genetic factors. These act in concert to determine the sequence of inflammatory events, degree of end-organ damage, and patient fate. Unfortunately, despite successful resuscitation and surgical intervention, HS often results in complications, leading to increased mortality. 3 We have previously demonstrated the upregulation of inducible nitric oxide synthase during shock. This increase precedes significant pro-inflammatory events such as nuclear factor-kappaB activation, cytokine expression, and neutrophil infiltration. 4 We also have demonstrated the importance of interleukin-6 (IL-6) in posthemorrhage inflammation and organ damage/dysfunction. 5,6 Nevertheless, knowledge regarding the pathogenesis of HS is limited.DNA microarray analysis provides a rapid, efficient method for identifying global changes in mRNA transcription. 7 We carried out DNA microarray analyses on mouse livers using an array capable of interrogating ϳ12,000 genes. In accordance with previous findings in rat, 8 examination of hepatic mRNAs from mice subjected to HS or HS followed by resuscitation (HS-R) indicated a potential role for plasminogen activator type 1 (PAI-1), an appealing candidate for therapeutic intervention after shock. Hence, we designed studies to verify the role of PAI-1 after HS-R.PAI-1 inhibits plasmin generation, playing a ...

show abstract

Section: Pai-1 Protein Causes Acute Damage To Endothelia and Hepatocymentioning

confidence: 72%

The role of hepatic type 1 plasminogen activator inhibitor (PAI‐1) during murine hemorrhagic shock†

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Endothelial cell activation, stimulated by thrombin and various cytokines, as well as hypoxia and hypoperfusion [48], generates a prothrombotic environment. Hypoperfusion plays a critical role in the pathogenesis of ATC as demonstrated in numerous clinical studies [3,6,[42][43][44][45][46][47][48][49][50][51], animal models [6,50] and in vitro experiments [22,51]. These data indicate that as shock severity increases, the PT and INR rise [4,5,7,52] and coagulation factor levels fall [6,48].…”

Section: Pathophysiologymentioning

confidence: 97%

“…The plasmin-antiplasmin complex (PAP) is perhaps the most sensitive indicator of fibrinolytic activation, and its levels are increased in approximately 60% of trauma patients [43]. Plasmin activation and generation of fibrin degradation products such as Ddimers [3,4,39,[44][45][46] are characteristic of bleeding trauma patients. Furthermore, free plasmin can break down coagulation factors, and the extent of this effect has not been fully evaluated in traumatic coagulopathy [47].…”

Section: Pathophysiologymentioning

confidence: 99%

See 1 more Smart Citation

The pathogenesis of traumatic coagulopathy

2014

View full text Add to dashboard Cite

SummaryOver the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are bleeding when they come in to the emergency department have an established coagulopathy before the haemodilution effects of fluid resuscitation. This has led to the use of new terminology: acute traumatic coagulopathy, acute coagulopathy of trauma shock or trauma‐induced coagulopathy. The recognition of acute traumatic coagulopathy is important, because we now understand that its presence is a prognostic indicator, as it is associated with poor clinical outcome. This has driven a change in clinical management, so that the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with coagulopathy, has changed to haemostatic resuscitation as early as possible. While there is as yet no universally accepted assay or definition, many experts use prolongation of the prothrombin time to indicate that there is, indeed, a coagulopathy. Hypoxia, acidosis and hypothermia and hormonal, immunological and cytokine production, alongside consumption and blood loss, and the dilutional effects of resuscitation may occur to varying extents depending on the type of tissue damaged, the type and extent of injury, predisposing to, or amplifying, activation of coagulation, platelets, fibrinolysis. These are discussed in detail within the article.

show abstract

“…upregulation of tissue factor (TF) and markers of thrombin generation [19,[24][25][26] and simultaneous reduction of natural anticoagulants/fibrinolytic factors such as antithrombin (AT), protein C (PC), and protein S (PS) [25,26]. However, to which extent the posttraumatic hypofibrinolytic state contributes to this hypercoagulability with all its deleterious clinical consequences remains unclear [18,27].…”

Section: Discussionmentioning

confidence: 99%

Markers of blood coagulation and fibrinolysis in patients with early and delayed microsurgical reconstructions in the lower extremities

Kloeters

Vasilic

Hupkens

et al. 2017

Journal of Plastic Surgery and Hand Surgery

View full text Add to dashboard Cite

Background: In this study, markers of coagulation and fibrinolysis were assessed during early and delayed microsurgical reconstruction in patients with traumatic defects of their lower legs to analyse whether an imbalance of the hemostasis after trauma might predispose the development of vascular complications. Methods: The prospective study included 70 patients. In 35 patients, surgery was performed within 72 hours after injury. In 35 other patients, delayed free flap transfer was performed between 14-21 days after trauma. In each group, reconstruction was performed with a fasciocutaneous anterior-lateral thigh flap (ALT, n ¼ 18) or a myocutaneous flap (latissimus dorsi flap; n ¼ 17). Blood samples were collected preoperatively, intraoperatively, and 3,6,12,24,36, 48, 72, 96 and 120 hours after the operation. Analysed parameters included markers of coagulation such as prothrombin fragment 1 þ 2 (F1 þ 2), thrombin-antithrombin III-complex (TAT), and antithrombin, as well as fibrinolysis markers such as plasminogenactivator inhibitor-I (PAI-1), tissue-plasminogenactivator (t-PA), and plasminogen. Results: Preoperatively, levels of F1 þ 2, TAT, and PAI-1 were significantly higher in patients with delayed reconstruction (p < .05). Patients with later vascular complications in this group (n ¼ 5) presented a significant higher concentration of TAT, F1 þ 2, and PAI-1 (p < .05). Twelve and 24 hours after free flap surgery, patients with vascular complications presented significant elevated levels of these markers (p < .05). Conclusions: Patients with delayed free flap surgery after lower leg trauma present a hypercoagulable state in their blood due to activation of the coagulation system and hypofibrinolysis. Early reconstruction might minimise the risk of flap failure caused by hypercoagulability.

show abstract

Contrasting Post-Traumatic Serial Changes for D-Dimer and PAI-1 in Critically Injured Patients

Cited by 26 publications

References 21 publications

The role of hepatic type 1 plasminogen activator inhibitor (PAI‐1) during murine hemorrhagic shock†

The role of hepatic type 1 plasminogen activator inhibitor (PAI‐1) during murine hemorrhagic shock†

The pathogenesis of traumatic coagulopathy

Markers of blood coagulation and fibrinolysis in patients with early and delayed microsurgical reconstructions in the lower extremities

Contact Info

Product

Resources

About