Browsing by Author "Bjertnaes, Lars J."

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    Activation of coagulation and fibrinolysis in acute respiratory distress syndrome : a prospective pilot study
    (Vide Leaf, 2020-09-24) Ozoliņa, Agnese; Šarkele, Marina; Sabeļņikovs, Oļegs; Šķesters, Andrejs; Jaunalksne, Inta; Serova, Jeļena; Bjertnaes, Lars J.; Vanags, Indulis; Adeniji, Shola Elijah; Rīga Stradiņš University; Bioķīmijas zinātniskā laboratorija
    Introduction: Coagulation and fibrinolysis remain sparsely addressed with regards to acute respiratory distress syndrome (ARDS). We hypothesized that ARDS development might be associated with changes in plasma coagulation and fibrinolysis. Our aim was to investigate the relationships between ARDS diagnosis and plasma concentrations of tissue factor (TF), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in mechanically ventilated patients at increased risk of developing ARDS. Materials and Methods: We performed an ethically approved prospective observational pilot study. Inclusion criteria: patients with PaO2/FiO2 < 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 hours, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria: age below 18 years; cardiac disease. We sampled plasma prospectively and compared patients who developed ARDS with those who did not using descriptive statistics and chi-square analysis of baseline demographical and clinical data. We also analyzed plasma concentrations of TF, t-PA and PAI-1 at inclusion (T0) and on third (T3) and seventh day (T7) of the ICU stay with nonparametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic (ROC) curve analysis. Statistical significance: p < 0.05. Results: Of 24 patients at risk, six developed mild ARDS and four of each moderate or severe ARDS, respectively, 3 ± 2 (Mean ± SD) days after inclusion. Median plasma concentrations of TF and PAI-1 were significantly higher at T7 in patients with ARDS, as compared to non-ARDS. Simultaneously, we found moderate correlations between plasma concentrations of TF and PAI-1, TF and PaO2/FiO2 and PEEP and TF. TF plasma concentration was associated with ARDS with 71% sensitivity and 100% specificity, a cut off level of 145 pg/ml and AUC 0.78, p = 0.02. PAI-1 displayed 64% sensitivity and 100% specificity with a cut off concentration of 117.5 pg/ml and AUC 0.77, p = 0.02. t-PA did not change significantly during the observation time. Conclusions: This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after seven days in ICU.
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    Activation of coagulation and fibrinolysis in acute respiratory distress syndrome : A prospective pilot study
    (2016) Ozolina, Agnese; Sarkele, Marina; Sabelnikovs, Olegs; Skesters, Andrejs; Jaunalksne, Inta; Serova, Jelena; Ievins, Talis; Bjertnaes, Lars J.; Vanags, Indulis; Rīga Stradiņš University; Bioķīmijas zinātniskā laboratorija
    Introduction: Coagulation and fibrinolysis remain sparsely addressed with regards to acute respiratory distress syndrome (ARDS). We hypothesized that ARDS development might be associated with changes in plasma coagulation and fibrinolysis. Our aim was to investigate the relationships between ARDS diagnosis and plasma concentrations of tissue factor (TF), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) in mechanically ventilated patients at increased risk of developing ARDS. Materials and methods: We performed an ethically approved prospective observational pilot study. Inclusion criteria were patients with PaO 2 /FiO 2 < 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 h, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria were age below 18 years; cardiac disease. We sampled plasma prospectively and compared patients who developed ARDS with those who did not using descriptive statistics and chi-square analysis of baseline demographical and clinical data. We also analyzed plasma concentrations of TF, t-PA, and PAI-1 at inclusion (tissue) and on third (T 3 ) and seventh day (T 7 ) of the ICU stay with non-parametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic curve analysis. Statistical significance: p < 0.05. Results: Of 24 patients at risk, 6 developed mild ARDS and 4 of each moderate or severe ARDS, respectively, 3 ± 2 (mean ± SD) days after inclusion. Median plasma concentrations of TF and PAI-1 were significantly higher at T7 in patients with ARDS, as compared to non-ARDS. Simultaneously, we found moderate correlations between plasma concentrations of TF and PAI-1, TF and PaO 2 /FiO 2 , and positive end-expiratory pressure and TF. TF plasma concentration was associated with ARDS with 71% sensitivity and 100% specificity, a cut off level of 145 pg/ml and AUC 0.78, p = 0.02. PAI-1 displayed 64% sensitivity and 100% specificity with a cut off concentration of 117.5 pg/ml and AUC 0.77, p = 0.02. t-PA did not change significantly during the observation time. Conclusion: This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after 7 days in ICU.
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    Associations between TNF-α, IL-6 and IL-10 Promoter Polymorphisms and Mortality in Severe Sepsis
    (2012) Sabeļņikovs, Oļegs; Ņikitina-Zaķe, Liene; Krūmiņa, Angelika; Jaunberga, Zane; Klovins, Jānis; Vīksna, Ludmila; Bjertnaes, Lars J.; Kovalchuka, Lilija; Vanags, Indulis; Department of Anaesthesiology, Intensive Care and Clinical simulations; Department of Infectology
    Aims: To determine whether an association exists between TNF-α308 A/G,IL-6174G/C, and IL-10-1082 A/G promoter polymorphisms and the corresponding systemic cytokine concentrations and outcome in patients suffering from sepsis. Place and Duration of Study: The study was performed in the Intensive Care Unit (ICU) of Pauls Stradins Clinical University Hospital, Riga. Between 1 August 2006 and 31 July2008. Methodology: We enrolled 103 consecutive intensive care unit patients with sepsis into a prospective case control study. Blood samples were obtained for extraction of DNA amplifying regions of interest by means of polymerase chain reaction technique (PCR)using specific primers for TNF-α, IL-6andIL-10. Simultaneously, plasma cytokines and standard laboratory variables were determined during the first 24 h after the diagnosis. Presence of septic shock, sequential organ failure assessment score (SOFA),demographic data and clinical outcome was noticed P < 0.05 was considered as statistically significant. Results: Non-survivors had significantly higher concentrations of TNF-α, IL-6 and IL-10.The carriage of the IL-6-174C allele and IL-10-1082G allele were associated with a higher risk of mortality in patients with severe sepsis. Presence of the TNF-α-308 A allele did not influence mortality differently from those lacking this allele. Conclusion: The present study demonstrated an association of the IL-6-174 and the IL-10-1082 with increased mortality in patients suffering from severe sepsis. We found no direct association between the examined polymorphisms and the corresponding cytokine levels.
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    PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass
    (2012-10-30) Ozolina, Agnese; Strīķe, Eva; Jaunalksne, Inta; Krumina, Angelika; Bjertnaes, Lars J.; Vanags, Indulis; Department of Anaesthesiology, Intensive Care and Clinical simulations; Department of Infectology
    Background: Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor - 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding.Methods: Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS.Results: Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = - 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively.Conclusions: Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.
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    Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery
    (2015-09-04) Ozolina, Agnese; Strike, Eva; Nikitina-Zake, Liene; Jaunalksne, Inta; Krumina, Angelika; Lacis, Romans; Bjertnaes, Lars J.; Vanags, Indulis; Rīga Stradiņš University; Department of Infectology
    Background: Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding. Methods: We assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation. Results: The lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G. Conclusions: Increased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.
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    Thromboelastometry for Assessing Risks of Free Flap Thrombosis in Patients Undergoing Microvascular Surgery
    (2020-06-23) Vanags, Indulis; Stepanovs, Jevgenijs; Ozolina, Agnese; Mukans, Maksims; Bjertnaes, Lars J.; Mamaja, Biruta; Department of Anaesthesiology, Intensive Care and Clinical simulations; Statistics Unit
    Introduction: Coagulation assessment is often missing in microvascular surgery. We aimed at evaluating the predictive value of thromboelastometry for free flap thrombosis in microvascular surgery patients. Materials and Methods: We enrolled 103 adult patients with traumatic injuries scheduled for microvascular free flap surgery into a prospective observational study. Thirty-six patients with recent trauma underwent surgery within 30 days (ES group), and were compared with 67 trauma patients who underwent surgery later than 30 days (late surgery, LS group) after the injury. Rotational thromboelastometry (RTE) was performed before surgery. Functional fibrinogen to platelet ratio (FPR) ≥ 42 was selected as the main hypercoagulability index. Free flap thrombosis was set as primary outcome. Thrombotic risk factors and duration of surgery related to free flap thrombosis were secondary outcomes. Statistical significance p < 0.05; not significant NS. Results: Six patients (16.7%) in the ES group and 10 (14.9%) in the LS group had free flap thrombosis (NS). In the entire cohort, free flap thrombosis rate increased in the presence of thrombogenic comorbidities (OR 4.059, CI 1.33–12.37; p = 0.014) and prolonged surgery times (OR 1.007, CI 1 – 1.012; p = 0.05). Although hypercoagulability occurred more frequently in the ES group (44.4%) than in the LS group (11.9%; p < 0.001), it was not associated with higher free flap thrombosis rate. In ES group patients with surgery times > 240 min, the risk of free flap thrombosis increased (OR 3.5, CI 1.16-10.6; p = 0.026) with 93.3% sensitivity and 86.7% specificity (AUC 0.85; p = 0.007). In contrast, in LS patients hypercoagulability increased the odds of free flap thrombosis (OR 8.83, CI 1.74–44.76; p = 0.009). Moreover, a positive correlation was found between FPR ≥ 42 and free flap thrombosis rate (r = 0.362; p = 0.003). In the LS group, the presence of thrombogenic comorbidities correlated with free flap thrombosis rate (OR 7, CI 1.591–30.8; p = 0.01). Conclusions: In LS patients with thrombogenic comorbidities, thromboelastometry supports the detection of hypercoagulability and predicts free flap thrombosis risk. In ES patients, postoperative hypercoagulability did not predict free flap thrombosis. Prolonged surgery time should be considered as a risk factor.