Inherited thrombophilias in thrombosis advancement in microvascular flap surgery

Publisher Copyright: © 2021 Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences. All right reserved.Microvascular flap surgery is a reliable method for reconstructive surgery. To avoid and foresee free flap thrombosis advancement after microvascular flap surgery, patient assessment, flawless surgical technique, and eligible perioperative care are pivotal. In this prospective observational study, we aimed to elucidate the most common inherited single nucleotide polymorphisms (SNPs) attributable to free flap thrombosis. A total of 152 patients undergoing microvascular flap surgery during the study period of 2016–2019 were analysed for five SNPs: rs6025 in Factor V Leiden (FVL) gene, rs1799963 in Factor II (FII) gene, rs2066865 in Fibrinogen Gamma Chain gene (FGG), rs2227589 in SERPINC 1 gene and rs1801133 in Methylene Tetrahydrofolate Reductase (MTHFR) gene. Activated protein C resistance (aPCR), prothrombin, antithrombin (AT), fibrinogen and homocysteine plasma levels were measured to determine association with the analysed SNPs and with free flap thrombosis advancement. Our preliminary results show that carriers of FVL mutation were associated with aPCR, as we observed significantly lower aPCR plasma levels in carriers of genotype C/T, as compared to C/C; p = 0.006 (CI 95%, 0.44 to 1.19). Additionally, mean fibrinogen plasma levels were higher in carriers of FGC gene rs2066865 genotype A/A (5.6 ± 1.81 g/l), as compared to G/A and G/G; p = 0.04 (CI 95%, 0.007 to 1.09); p = 0.004 (CI 95%, 0.48 to 2.49), respectively. The study group included 12 patients (7.9%) with free flap thrombosis. For one patient free flap thrombosis advancement might have been related to the rs6025T – FVL mutation with a PCR plasma level 1.21. Lower aPCR levels was associated with carriers of FVL rs6025 C/T and higher fibrinogen plasma levels with carriers of FGG rs2066865 A/A, suggesting that these genotypes might predict higher free flap thrombosis risk, but we found no significant association between analysed SNPs and free flap thrombosis advancement.publishersversionPeer reviewe

Polymorphism rs2066865 in the Fibrinogen Gamma chain (FGG) gene increases plasma fibrinogen concentration and is associated with an increased microvascular thrombosis rate

Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Background and Objective: Thrombosis due to inherited hypercoagulability is an issue that has been raised in microvascular flap surgery previously. We analyzed the association of a single nucleotide polymorphism (SNP) in rs2066865 in the fibrinogen gamma chain (FGG) gene, alteration in plasma fibrinogen concentration, and presence of microvascular flap thrombosis. Materials and Methods: A total of 104 adult patients with microvascular flap surgery were subjected to an analysis of the presence of SNP rs2066865 in the FGG gene. Alterations in plasma fibrinogen concentration according to genotype were determined as a primary outcome, and flap thrombosis was defined as a secondary outcome. Results: Flap thrombosis was detected in 11.5% of patients (n = 12). Successful revision of anastomosis was performed in four patients, resulting in a microvascular flap survival rate of 92.3%. We observed an increase in plasma fibrinogen concentration in genotype G/A and A/A carriers (G/G, 3.9 (IQR 4.76-3.04); G/A, 4.28 (IQR 5.38-3.18); A/A, 6.87 (IQR 8.25-5.49) (A/A vs. G/A, p = 0.003 and A/A vs. G/G, p = 0.001). Within group differences in microvascular flap thrombosis incidence rates were observed—G/G 6/79 (7.59%); G/A 5/22 (22.7%); A/A 1/3 (33.3%) (OR 0.30 95%; CI 0.044 to 0.57), p = 0.016; RR 3.2—when G/G versus G/A and A/A were analyzed respectively. Conclusions: A/A and G/A genotype carriers of a single nucleotide polymorphism in rs2066865 in the fibrinogen gamma chain gene had a higher plasma fibrinogen concentration, and this might be associated with an increased microvascular flap thrombosis incidence rate. Determined polymorphism could be considered as a genetic marker associated with microvascular flap thrombosis development. To confirm the results of this study, the data should be replicated in a greater sample size.Peer reviewe

The activity of oxidative stress markers in acute respiratory distress syndrome

Publisher Copyright: © by Marina Šarkele 2015.Acute respiratory distress syndrome is a common complication characterised by severe hypoxemia, which leads to high mortality rates in ICU patients. Imbalance between oxidative stress markers like oxidants and antioxidants may play an important role in pathophysiology of the syndrome. We observed 17 ARDS patients during seven days after inclusion, with the main goal to describe dynamic changes in the level of oxidative stress markers in patients with acute respiratory distress syndrome. We found that there are dynamic differences in the level of malondialdechyde (MDA) and nitric oxide (NO) in patients with acute respiratory distress syndrome. There were also different levels of oxidative stress markers in non-survivor compared with survivor groups. Increased level of an oxidant like a thiobarbituric acid substance with malondialdechyde (TBS-MDA) and antioxidant glutathionperoxidase (GPx) at the first day after inclusion was related with poor outcome in patients with acute respiratory distress syndrome.publishersversionPeer reviewe

Prediction of the Difficult Laryngoscopy with Ultrasound Measurements of Hyomental Distance

Ultrasound measurement of hyomental distance is promising as a predictor for difficult laryngo-scopy in cases of difficult airway management. The aim of the study was to evaluate the prognos-tic value of ultrasound measurement of hyomental distance (HMD) for prediction of difficultlaryngoscopy. Hyomental distance was sonographically measured in neutral (HMDn) and extremehead extension (HMDe) positions for fifty-six patients scheduled for elective surgery requiring tra-cheal intubation. Then the hyomental distance ratio (HMDR) was calculated. According to pres-ence of difficult laryngoscopy assessed by the Cormack–Lehane (CL) score, patients weredivided into a difficult laryngoscopy group (DL, n = 15) and easy laryngoscopy group (EL, n = 41).We calculated the sensitivity and specificity of HMDn, HMDe, and HMDR for difficult laryngo-scopy. DL was present in 15 (27%) patients. We found a significant intergroup difference inHMDR between the DL and EL groups (1.12 ± 0.04 vs. 1.24 ± 0.06, respectively;p< 0.001). Incontrast, we were not able to find a significant difference for HMDn and HMDr. HMDR had thehighest sensitivity 86.7% and specificity 85.4% (p< 0.01) to predict difficult laryngoscopy, wherethe area under the curve was 0.939;p< 0.01 for HDMR < 1.2 cm. Moreover, we found that diffi-cult laryngoscopy was associated with higher body mass index (BMI), with higher values in theDL group compared to EL patients (34.3 ± 9.1 vs. 28.5 ± 5.7 kg/m2, respectively;p= 0.035).HMDR < 1.2 cm measured by ultrasound might have a good predictive value for prediction of diffi-cult laryngoscopy.publishersversionPeer reviewe

Anaesthesia management with deep hypothermia and circulatory arrest during surgery for chronic thromboembolic pulmonary hypertension

Publisher Copyright: © by Roberts Leibuss 2015.Chronic thromboembolic pulmonary hypertension (CTEPH) occurs in 1 to 4% after acute pulmonary embolism. CTEPH can be cured by pulmonary endarterectomy (PEA), which is approved golden standard in chronic condition. There were performed three cases of PEA in Latvian Cardiology Centre during 2013-2014. General anaesthesia under cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrests was provided. The core issue is correct patient selection (in terms of central PA obstruction by thrombus) as well as pulmonary circulation recovery capacity. Neuroprotection was provided by deep hypothermia, topical cooling of the head, Trendelenburg position, mild hypocapnia, Hb 9-10 g/L and pharmacological agents. For screening postoperative cognitive function the mini mental state examination (MMSE) was used before and after the surgery. Postoperative pulmonary vascular resistance index decreased by 56.3% (right ventricular systolic pressure decreased from 93.3 ± 25.7 to 44.5 ± 11.2 mmHg). Before the surgery three patients had NYHA functional class III or IV, at the time of discharge - I or II. In one case moderate (MMSE 18) cognitive disorders was observed at discharge from the ICU. No one died neither in the hospital nor within 30 days of discharge. The surgery improved RV function and pulmonary perfusion with no considerable organ failure, except mild cognitive disorders.Peer reviewe

Activation of coagulation and fibrinolysis in acute respiratory distress syndrome : a prospective pilot study

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.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. Thefollowing fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimerlevel 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 inthe levels of the t-PA/PAI-1 complex comparing different genotype groups. Conclusions. Thecarriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chesttube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis.publishersversionPeer reviewe

The role of oxidative stress markers in developing of acute respiratory distress syndrome

Publisher Copyright: © by Marina arkele 2015.Acute respiratory distress syndrome (ARDS) is common and multi factorial, clinically described as an inflammatory lung disorder that is associated with major morbidity and high mortality in intensive care patients. Recently, investigators have revised the AECC criteria from 1994. To diagnose ARDS and discover its severity we presently use Berlin definition criteria. An important role in developing of ARDS may be through a disbalance between reactive oxygen species (ROS), which have both oxidant and antioxidant compartments. The pathogenesis of ARDS is very complex, and unfortunately, the dynamic development of ARDS in an individual patient is difficult to recognise. ROS can initiate cellular tissue damage by modifying lipids, proteins and DNA, which can seriously compromise cell life ability or induce a large number of cellular responses through generation of secondary reactive species, leading, at last, to cell death by necrosis or apoptosis. Studies have shown that many patients with organ malfunction at admission to the intensive care units (ICU) show decreased antioxidative properties, worsening the harmful effects of lipid peroxidation. That is the reason why predicting development of ARDS has great value for intensive care specialists.publishersversionPeer reviewe

The Impact of Different Ventilatory Strategies on Clinical Outcomes in Patients with COVID-19 Pneumonia

Funding Information: The authors declare that the article publication fee has been covered with the support of Educational Centre of Riga East University Hospital. No funders were involved in the study design, collection, analysis, interpretation of data or writing of this article. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Introduction: The aim was to investigate the impact of different ventilator strategies (non-invasive ventilation (NIV); invasive MV with tracheal tube (TT) and with tracheostomy (TS) on outcomes (mortality and intensive care unit (ICU) length of stay) in patients with COVID-19. We also assessed the impact of timing of percutaneous tracheostomy and other risk factors on mortality. Methods: The retrospective cohort included 868 patients with severe COVID-19. Demographics, MV parameters and duration, and ICU mortality were collected. Results: MV was provided in 530 (61.1%) patients, divided into three groups: NIV (n = 139), TT (n = 313), and TS (n = 78). Prevalence of tracheostomy was 14.7%, and ICU mortality was 90.4%, 60.2%, and 30.2% in TT, TS, and NIV groups, respectively (p < 0.001). Tracheostomy increased the chances of survival and being discharged from ICU (OR 6.3, p < 0.001) despite prolonging ICU stay compared to the TT group (22.2 days vs. 10.7 days, p < 0.001) without differences in survival rates between early and late tracheostomy. Patients who only received invasive MV had higher odds of survival compared to those receiving NIV in ICU prior to invasive MV (OR 2.7, p = 0.001). The odds of death increased with age (OR 1.032, p < 0.001), obesity (1.58, p = 0.041), chronic renal disease (1.57, p = 0.019), sepsis (2.8, p < 0.001), acute kidney injury (1.7, p = 0.049), multiple organ dysfunction (3.2, p < 0.001), and ARDS (3.3, p < 0.001). Conclusions: Percutaneous tracheostomy compared to MV via TT significantly increased survival and the rate of discharge from ICU, without differences between early or late tracheostomy.publishersversionPeer reviewe

Factors Affecting the Risk of Free Flap Failure in Microvascular Surgery

Publisher Copyright: © 2016 Jevgeņijs Stepanovs et al.Microvascular free flap surgery, has become an important part of reconstructive surgery during the last decades, as it allows closure of various tissue defects and recovery of organs function. Despite surgical progress resulting in high rates of transferred tissue survival, the risk of pedicle vessels thrombosis still remains a significant problem. A total of 108 articles from Pubmed and Science Direct databases published in 2005-2015 were analysed. This review of the literature assessed the influence of patient-dependent risk factors and different perioperative management strategies on development of microvascular free flap thrombosis. Sufficient evidence for risk associated with hypercoagulation, advanced age and certain comorbidities was identified. Presently, rotational thromboelastometry allows early hypercoagulability detection, significantly changing further patient management. Identification of flap thrombosis promoting surgery-related aspects is also essential in preoperative settings. Choice of anaesthesia and postoperative analgesia, administration of different types and amounts of fluids, blood products and vasoactive agents, temperature control are no less important in perioperative anaesthesiological management. More attention should be focused on timely preoperative evaluation of patient-dependent risk factors, which can influence anaesthesiological and surgical tactics during and after microvascular free flap surgery. Perioperative anaesthesiological management strategy continues to be controversial and therefore it should be performed based on thrombotic risk assessment and patient individual needs, thus improving flap survival rates and surgical outcome.publishersversionPeer reviewe