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Lindström, Outi; Kylänpää, Leena; Mentula, Panu; Puolakkainen, Pauli; Kemppainen, Esko; Haapiainen, Reijo; Fernández, José A.; Griffin, John H.; Repo, Heikki; Petäjä, Jari

doi:10.1186/cc3966

Cited by 33 publications

(11 citation statements)

References 34 publications

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“…Thus, generation and function of APC in AP are of evident interest. We have previously shown that in severe AP endogenous APC generation is upregulated but insufficient compared to the thrombin challenge [42]. In this study we extend those findings by demonstrating that in vitro exogenous APC seems to retain functionality regardless of the severity of AP.…”

Section: Discussionsupporting

confidence: 80%

Thrombin Generation in vitro and in vivo, and Disturbed Tissue Factor Regulation in Patients with Acute Pancreatitis

et al. 2011

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Section: Discussionsupporting

confidence: 80%

Thrombin Generation in vitro and in vivo, and Disturbed Tissue Factor Regulation in Patients with Acute Pancreatitis

et al. 2011

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“…In addition, APC has been shown to modulate the systematic inflammatory response by inhibition of tumor necrosis factor and nuclear factor-kappa-B (NF-κB) release [32], among other proposed beneficial mechanisms in severe inflammatory disorders [33]. Given that previous studies have detected lower levels of APC and AT III in non-survivors [34] and low endogenous PC levels and high APC:PC ratios are found in MOD patients in human SAP [6], we previously agreed to a biologically plausible rationale for the use of APC in SAP. In keeping with this, APC has been assessed as a potential treatment option for SAP [15,16].…”

Section: Discussionmentioning

confidence: 99%

APCAP - activated protein C in acute pancreatitis: a double-blind randomized human pilot trial

et al. 2010

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IntroductionPrevious human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP.MethodsA prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (Days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means (DIM, 95% CIs) and regarding categorical variables with Fisher's exact test. For all comparisons P < 0.05 was considered significant.ResultsNo serious bleeding was detected clinically or by CT scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found (difference in means (DIM) +2.3, 95% CI -0.7 to +5.3). Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside the hospital were detected.ConclusionsNo serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.Trial registrationClinicalTrials.gov NCT01017107.

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“…The levels of prothrombin, fibrinogen and factor X gradually decreased [ 146 ], and prolonged clotting times (prothrombin time, activated partial thromboplastin time and thrombin time) were observed [ 139 , 146 , 147 ]. Decreased concentrations of natural anticoagulants, especially protein C and antithrombin, were consistently reported [ 139 , 148 , 149 , 150 ]. Activity of tissue plasminogen activator (tPA) and PAI-1 was increased [ 151 , 152 ].…”

Section: Disturbances Of Hemostasis In Relation To Inflammation Inmentioning

confidence: 99%

“…In patients who eventually died from AP as compared to patients who survived, natural anticoagulants (antithrombin and protein C, but not protein S) were lower, and increased levels of PAI-1 and d -dimer were observed during the preceding period [ 150 , 161 , 163 ]. In patients with SAP as defined by the original 1992 Atlanta classification (organ failure and/or local complications), the development of organ failure was associated with decreased protein C concentrations as well as decreased activated protein C [ 148 ]. Protein C and activated protein C levels correlated with the numbers of activated monocytes [ 148 ].…”

Section: Disturbances Of Hemostasis In Relation To Inflammation Inmentioning

confidence: 99%

“…In patients with SAP as defined by the original 1992 Atlanta classification (organ failure and/or local complications), the development of organ failure was associated with decreased protein C concentrations as well as decreased activated protein C [ 148 ]. Protein C and activated protein C levels correlated with the numbers of activated monocytes [ 148 ].…”

Section: Disturbances Of Hemostasis In Relation To Inflammation Inmentioning

confidence: 99%

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The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Dumnicka

Maduzia

Ceranowicz

et al. 2017

IJMS

154

113

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Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

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Cited by 33 publications

References 34 publications

Thrombin Generation in vitro and in vivo, and Disturbed Tissue Factor Regulation in Patients with Acute Pancreatitis

Thrombin Generation in vitro and in vivo, and Disturbed Tissue Factor Regulation in Patients with Acute Pancreatitis

APCAP - activated protein C in acute pancreatitis: a double-blind randomized human pilot trial

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

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