Fibrinolytic system changes in liver surgery : A pilot observational study

Publisher Copyright: © 2018 Ozolina, Nemme, Ozolins, Bjertnæs, Vanags, Gardovskis, Viksna and Krumina.Introduction: Bleeding occurs frequently in liver surgery. Unbalance between tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) concentrations might increase bleeding. Our aim was to analyze perioperative fibrinolytic changes during liver surgery. Materials and Methods: We evaluated 15 patients for inclusion into a prospective pilot study of liver surgery. We assessed fibrinolysis by plasma PAI-1 and t-PA: before surgery (T1), before Pringle maneuver (PM;T2), at the end of surgery (T3) and 24 h postoperatively (T4), and registered demographic and laboratory data, extent and duration of surgery, hemodynamic parameters, blood loss, and transfused volumes of blood products. Data presented as mean ± SD. Significance at P < 0.05. Results: After exclusion of six patients only undergoing biopsies, we included six women and three men aged 49.1 ± 19.6 years; two patients with liver metastases of colorectal cancer and hepatocellular carcinoma, respectively, two with focal nodular hyperplasia, two with hepatic hemangioma, and one with angiomyolipoma. Six patients underwent PM. PAI-1 plasma concentration (n = 9) rose from 6.25 ± 2.25 at T1 through 17.30 ± 14.59 ng/ml at T2 and 28.74 ± 20.4 (p = 0.007) and 22.5 ± 16.0 ng/ml (p = 0.04), respectively, at T3 and T4. Correspondingly, t-PA plasma concentration (n = 9) increased from 4.76 ± 3.08 ng/ml at T1 through 8.00 ± 5.10 ng/ml (p = 0.012) at T2 and decreased to 4.25 ± 2.29 ng/ml and 3.04 ± 3.09 at T3 and T4, respectively. Plasma t-PA level at T2 was significantly different from those at T1, T3, and T4 (p < 0.004). In PM patients, t-PA levels increased from T1, peaked at T2 (p = 0.001), and subsequently decreased at T3 and T4 (p = 0.011 and p = 0.037), respectively. Mean blood loss was 1,377.7 ± 1,062.8 ml; seven patients received blood products. Patients with higher PAI-1 levels at T3 received more fresh frozen plasma (r = 0.79; p = 0.01) and red blood cells (r = 0.88; p = 0.002). Conclusions: During liver surgery, fibrinolysis increased, as evidenced by rises in plasma PAI-1and t-PA, especially after start of surgery and following PM. Transfused volumes of blood products correlated with higher plasma concentrations of PAI-1. Confirming this tendency requires a larger cohort of patients.publishersversionPeer reviewe

Leukocytosis and C-Reactive Protein May Predict Development of Secondary Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Background and Objectives: Secondary cerebral vasospasm (CV) with subsequent delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains an unpredictable pathology. The aim of this retrospective study was to investigate the association between inflammatory parameters, white blood cell (WBC) count, and C-reactive protein plasma levels (CRP) and the occurrence of secondary CV in patients with aSAH. Materials and Methods: The medical records of 201 Intensive Care Unit patients in Riga East University Hospital with aSAH were retrospectively reviewed in a 24-month period. WBC count and CRP values were observed at admission to the hospital and on the third day. According to the inclusion criteria, 117 (48 males) participants were enrolled for further analysis, with average age of 56 ± 15 years (mean ± SD). In total, secondary CV was diagnosed in 21.4% of cases, and DCI in 22.4% of cases. The patients were classified into three groups: SAH-CV group (n = 25), SAH-DCI group (n = 12), and SAH or control group (n = 80), for comparative analysis. Results: We found that SAH-CV patients demonstrated notably higher inflammatory parameters compared to controls: WBC 13.2 ± 3.3 × 109 /L vs. 11.2 ± 3.7 × 109 /L; p = 0.01 and CRP median 9.3 mg/L vs. 1.9 mg/L; p <0.001, respectively. We found that the odds of developing CV increased by 5% for each CRP increase of 1 mg/L at admission (OR, 1.05; CI, 1.014–1.087; p = 0.006). Concomitantly, the odds increased by 16% for every rise in WBC count of 1 × 109 /L (OR, 1.16; CI, 1.02–1.32; p = 0.02). WBC count was associated with the occurrence of CV with 96% sensitivity and 40% specificity, with a cut off level of 10.015 × 109 /L and AUC 0.683; p = 0.006. CRP displayed 54% sensitivity and 90% specificity with a cut off value of 8.9 mg/L and AUC 0.751; p < 0.001. Moreover, higher values of inflammatory parameters at admission correlated with a longer stay in ICU (r = 0.3, p = 0.002 for WBC count and r = 0.305, p = 0.002 for CRP values), and poor outcome (death) was significantly associated with higher CRP values at admission and on the third day (16.1. vs. 2.2. and 57.4. vs. 11.1, p < 0.001, respectively). Higher mortality was detected in SAH-CV patients (32%) compared to controls (6.3%; p < 0.001). Conclusions: Inflammatory parameters such as WBC count and CRP values at admission might be helpful to predict the development of secondary CV.publishersversionPeer reviewe

Perineural Administration of Dexmedetomidine in Axillary Brachial Plexus Block Provides Safe and Comfortable Sedation : A Randomized Clinical Trial

Publisher Copyright: Copyright © 2022 Rocans, Ozolina, Andruskevics, Narchi, Ramane and Mamaja.Dexmedetomidine prolongs the duration of regional block while its systemic sedative effect when administered perineurally is unknown. We aimed to evaluate the systemic sedative effect of perineural dexmedetomidine in patients after axillary brachial plexus block (ABPB). This single-blinded prospective randomized control trial included 80 patients undergoing wrist surgery receiving ABPB. Patients were randomized into two groups – Control group (CG, N = 40) and dexmedetomidine group (DG, N = 40). Both groups received ABPB with 20 ml of 0.5% Bupivacaine and 10 ml of 2% Lidocaine. Additionally, patients in DG received 100 mcg of dexmedetomidine perineurally. Depth of sedation was evaluated using Narcontrend Index (NI) and Ramsay Sedation Scale (RSS) immediately after ABPB and in several time points up to 120 min. Duration of block as well as patient satisfaction with sedation was evaluated using a postoperative survey. Our results showed that NI and RSS statistically differed between groups, presenting a deeper level of sedation during the first 90 min in DG compared to controls, P < 0.001. In the first 10 to 60 min after ABPB the median RSS was 4 (IQR within median) and median NI was 60 (IQR 44–80) in DG group, in contrast to CG patients where median RSS was 2 (IQR within median) and median NI was 97 (IQR 96–98) throughout surgery. The level of sedation became equal in both groups 90 and 120 min after ABPB when the median NI value was 98 (97–99) in DG and 97.5 (97–98) in CG, P = 0.276, and the median RSS was 2 (IQR within median) in both groups, P = 0.128. No significant intergroup differences in hemodynamic or respiratory parameters were found. Patients in DG expressed satisfaction with sedation and 86.5% noted that the sensation was similar to ordinary sleep. In DG mean duration of motor block was 13.5 ± 2.1 h and sensory block was 12.7 ± 2.8 h which was significantly longer compared to CG 6.3 ± 1.5 h, P < 0.001 and 6.4 ± 1.8 h, P < 0.001. We found that beside prolongation of analgesia, perineural administration of dexmedetomidine might provide rather safe and comfortable sedation with no significant effect on hemodynamic or respiratory stability and yields a high level of patient satisfaction.publishersversionPeer reviewe

Purine Auxotrophic Starvation Evokes Phenotype Similar to Stationary Phase Cells in Budding Yeast

Funding Information: Funding: A.K. and K.P. were supported by the Latvian Council of Science, Project LZP-2018/2-0213, J.L. was supported by the State Education Development Agency of the Republic of Latvia PostDoc Project 1.1.2/1/16/067, Z.O. was supported by Latvian basic science grant no. ZD2016AZ03. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Purine auxotrophy is an abundant trait among eukaryotic parasites and a typical marker for many budding yeast strains. Supplementation with an additional purine source (such as adenine) is necessary to cultivate these strains. If not supplied in adequate amounts, purine starvation sets in. We explored purine starvation effects in a model organism, a budding yeast Saccharomyces cerevisiae ade8 knockout, at the level of cellular morphology, central carbon metabolism, and global transcriptome. We observed that purine-starved cells stopped their cycle in G1/G0 state and accumulated trehalose, and the intracellular concentration of AXP decreased, but adenylate charge remained stable. Cells became tolerant to severe environmental stresses. Intracellular RNA concentration decreased, and massive downregulation of ribosomal biosynthesis genes occurred. We proved that the expression of new proteins during purine starvation is critical for cells to attain stress tolerance phenotype Msn2/4p targets are upregulated in purine-starved cells when compared to cells cultivated in purine-rich media. The overall transcriptomic response to purine starvation resembles that of stationary phase cells. Our results demonstrate that the induction of a strong stress resistance phenotype in budding yeast can be caused not only by natural starvation, but also starvation for metabolic intermediates, such as purines.publishersversionPeer reviewe

Thromboelastometry for Assessing Risks of Free Flap Thrombosis in Patients Undergoing Microvascular Surgery

Publisher Copyright: © Copyright © 2020 Vanags, Stepanovs, Ozolina, Mukans, Bjertnaes and Mamaja. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.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 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.Peer reviewe

Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery

Publisher Copyright: © 2015 Ozolina et al.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.publishersversionPeer reviewe

PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass

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.publishersversionPeer reviewe

Influence of PAI-1 Gene Promoter-675 (4G/5G) Polymorphism on Fibrinolytic Activity After Cardiac Surgery Employing Cardiopulmonary Bypass

Background and Objective. The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery.Material and Methods. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/ PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery.Results. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups.Conclusions. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis