Activation Of Fibrinolytic System Research Articles

Activation of intravascular blood coagulation in the early postoperative period in reconstructive abdominoplasty

Purpose of the study: to determine the activity of intravascular blood coagulation during the abdominoplasty and justify pharmacological thromboprophylaxis.Material and Methods. An open prospective study was conducted on a group of 100 patients undergoing abdominoplasty. The risk of venous thromboembolism (VTE) before the surgery was assessed using the Caprini risk assessment model in 2010. Prothrombin (PT) and fibrinogen (FG) levels, soluble fibrin-monomer complexes (SFMC), euglobulin clot lysis time (ECLT), antithrombin III (AT-III) level, and protein C (PC) level were determined before and after the surgery.Results. Using the Caprini risk assessment model, patients were categorized by VTE risk as follows: moderate risk – 64% and high risk – 36%. After the surgery, an increase in PT by 12.3% and 15.5% on days 3 and 5 was observed (p < 0.01); an increase in FG by 0.49; 2.34 and 2.04 g/L on days 1, 3, and 5 was observed (p < 0.01); an increase in SFMC at all postoperative stages by 4.7; 8.2; 10.8 and 10.0 times (p < 0.01); an increase in ECLT by 2.8; 9.7, and 6.3 minutes on days 1, 3, and 5 (p < 0.001); and a decrease in AT-III and PC levels immediately after the operation by 18.8% and 8.9%, on day 1 by 14.2% and 11.2%, and on day 3 by 8.8% and 6.3% (p < 0.01).Conclusion. All patients undergoing abdominoplasty require pharmacological thromboprophylaxis due to moderate and high risk of venous thromboembolic complications. Abdominoplasty in the early postoperative period is accompanied by activation of plasma coagulation, inhibition of fibrinolytic system activity, and reduced activity of natural anticoagulants, which justifies the need for pharmacological thromboprophylaxis for at least 5 days.

Assessment of plasma hemostasis system in the early postoperative period in patients after abdominoplasty

Introduction Venous thromboembolic complications after abdominoplasty are associated with increased intraabdominal pressure and altered venous return without taking into account possible changes in the activity of the blood coagulation system.Purpose of work was to evaluate the state of the plasma hemostasis system in the early postoperative period in patients after abdominoplasty.Materials and methods The study included 100 patients who underwent aesthetic abdominoplasty. Prothrombin (PT), fibrinogen (FG), activated partial thromboplastin time (APTT), soluble fibrin-monomer complexes (SFMC), euglobulin clot lysis (ECL), antithrombin-III (AT-III), and protein C (PrC) levels were evaluated before surgery, immediately after surgery, on the first, third and fifth days after surgery. Statistical data analysis was performed using SPSS 16, Excel 2010 for Windows, using the Kruskal – Wallis criterion.Results Coagulation hemostasis was characterized by a decrease in PT immediately after the surgery and on the first day by 13.9 and 5.3, and an increase in PT on the third and fifth days by 12.3 and 15.5 (p < 0.001), decrease in FG on the first, third and fifth days by 0.49 g/L, 2.34 g/L, and 2.04 g/L, respectively (p < 0.001). SFMC increased at all postoperative stages by 4.7, 8.2, 10.8, and 10.0 times (p < 0.001). Inhibition of XII-dependent fibrinolysis was characterized by an increase in ECL time on the first, third and fifth days by 2.8, 9.7, and 6.3 minutes, respectively (p < 0.001). AT-III and PrC levels decreased immediately after the surgery by 18.8 and 8.9, on the first day by 14.2 and 11.2, and on the third day by 8.8 and 6.3 respectively (p < 0.001).Discussion Activation of blood coagulation processes with imbalance of coagulation, anticoagulation, and fibrinolytic systems create conditions for venous thrombosis formation after abdominoplasty, which substantiates the necessity of VTE pharmacoloprophylaxis for at least five days.Conclusion In the early postoperative period abdominoplasty is accompanied by activation of plasma coagulation, inhibition of fibrinolytic system activity and reduction of natural anticoagulant activity.

The use of d-dimer in the diagnosis and risk assessment of intracardiac thrombus among patients with dilated cardiomyopathy

d-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the body's hypercoagulable state. The study aims to investigate the usefulness of d-dimer in diagnosing and assessing the risk of intracardiac thrombus in patients with dilated cardiomyopathy (DCM). Consecutively enrolled in this study were patients with DCM who were admitted to our center for the first time. The diagnostic value was evaluated using the receiver operating characteristic (ROC) curve. Additionally, we used univariate and multivariate logistic regression to investigate the association between d-dimer and intracardiac thrombus. We also performed smooth curve fitting, threshold saturation effect analysis, and subgroup analysis. In total, 534 patients were enrolled in the study, and among them, 65 patients had intracardiac thrombus. Mural thrombus was the predominant type of thrombus, which was mainly located in the left ventricular apex. The optimal cut-off value of d-dimer for the diagnosis of intracardiac thrombus was 484 ng/mL, with a sensitivity and specificity of 0.769 and 0.646, respectively. In both unadjusted and adjusted logistic regression models, a positive association was found between d-dimer and intracardiac thrombus. Curve fitting and threshold effect analysis revealed two inflection points in the relationship between d-dimer and intracardiac thrombus (non-linear test: P = 0.032). When d-dimer was equal to 362 ng/mL, the odds ratio (OR) was 1, and the risk of thrombus gradually increased until it reached 4096 ng/mL, after which the trend no longer increased. Within this range, a twofold increase in d-dimer was associated with a 103.2% increased risk (OR = 2.032; 95% CI 1.293–3.193; P < 0.01). In the subgroup analysis, there was a significant interaction between d-dimer and BMI on intracardiac thrombus (P value for interaction was 0.013), and the risk was higher in patients with a BMI ≥ 25 kg/m2 (OR = 3.44; 95% CI 1.86–6.36; P < 0.01).

The Recruitment and Activation of Plasminogen by Bacteria—The Involvement in Chronic Infection Development

The development of infections caused by pathogenic bacteria is largely related to the specific properties of the bacterial cell surface and extracellular hydrolytic activity. Furthermore, a significant role of hijacking of host proteolytic cascades by pathogens during invasion should not be disregarded during consideration of the mechanisms of bacterial virulence. This is the key factor for the pathogen evasion of the host immune response, tissue damage, and pathogen invasiveness at secondary infection sites after initial penetration through tissue barriers. In this review, the mechanisms of bacterial impact on host plasminogen—the precursor of the important plasma serine proteinase, plasmin—are characterized, principally focusing on cell surface exposition of various proteins, responsible for binding of this host (pro)enzyme and its activators or inhibitors, as well as the fibrinolytic system activation tactics exploited by different bacterial species, not only pathogenic, but also selected harmless residents of the human microbiome. Additionally, the involvement of bacterial factors that modulate the process of plasminogen activation and fibrinolysis during periodontitis is also described, providing a remarkable example of a dual use of this host system in the development of chronic diseases.

Functional properties of individual sub-domains of the fibrin(ogen) αC-domains

BackgroundFibrinogen is a large polyfunctional plasma protein consisting of a number of structural and functional domains. Among them, two αC-domains, each formed by the amino acid residues Аα392–610, are involved in fibrin polymerization, activation of fibrinolysis, platelet aggregation, and interaction with different cell types. Previous study revealed that each fibrinogen αC-domain consists of the N-terminal and C-terminal sub-domains. The major objections of the present study were to test functional role of these sub-domains in the above mentioned processes. MethodsTo achieve these objections, we used specific proteases to prepare two truncated forms of fibrinogen, fibrinogen desAα505–610 and fibrinogen desAα414–610, missing their N-terminal and both N- and C-terminal sub-domains, respectively. ResultsOur study with these truncated forms using turbidity measurements and electron microscopy revealed that the N- and C-terminal subdomains both contribute to protofibril formation and their lateral aggregation into fibers during fibrin polymerization process. These two sub-domains also contributed to platelet aggregation with the N-terminal sub-domains playing a more significant role in this process. At the same time, the C-terminal sub-domains make the major contribution to the plasminogen activation process. Further, our experiments revealed that the C-terminal sub-domains are involved in endothelial cell viability and migration of cancer cells. ConclusionsThus, the results obtained establish the functional role of individual sub-domains of the αC-domains in fibrin polymerization, activation of fibrinolytic system, platelet aggregation, and cellular interactions. General significanceThe present study expands our understanding of the functional role of individual fibrinogen domains and their specific portions in various fibrin(ogen)-dependent processes.

The role of D-dimer in stroke risk stratification in patients with atrial fibrillation

Introduction. D-dimer is an important indicator, which reflects the activation of intravascular blood coagulation and fibrinolytic system. There are some data confirming that D-dimer is associated with stroke development in patients with atrial fibrillation. However, D-dimer is not included in modern stoke risk stratification scales in patients with atrial fibrillation.Aim — to analyze the data devoted to the role of D-dimer in stroke risk stratification in patients with atrial fibrillation.General findings. D-dimer, despite several limitations, could be used in clinical practice as an indicator that is associated with stroke development in patients with atrial fibrillation. D-dimer level estimation could help to decide whether to use anticoagulant treatment in patients with low risk of stroke development or in those patients with a single non-sex CHA2DS2-VASc score risk factor.

Gelatinized PLCL Electrospun Membrane for the Prevention of Postoperative Abdominal Adhesion Through Fibrinolysis Activation

AbstractAbdominal adhesion is a common complication after surgery, which causes pain to patient and increases the risks of reoperation. Electrospinning polyester membrane serving as a physical barrier is used for preventing abdominal adhesion; however, the efficacy is limited due to the lacking of bioactivity necessary for antiadhesion. Here, hydrophobic poly(l‐lactide‐co‐caprolactone) (PLCL) electrospinning membranes are hydrophilized with photo‐crosslinked methacrylic anhydride gelatin (GelMA) hydrogel for postoperative abdominal adhesion prevention. The composite membranes show fibrous network architecture, good cytocompatibility, and hydrophilicity than commercial poly(d,l‐lactide acid) (PDLLA) film. Importantly, the composite membrane provides superior antiadhesion effect over PLCL membrane alone or commercial PDLLA film, against abdominal wall–cecum adhesion models in Sprague Dawley (SD) rats. The underlying mechanism is that PLCL/GelMA membrane successfully promotes the secretion of matrix metalloproteinases 9 (MMP‐9) that can reduce the collagen deposition in extracellular matrix (ECM). Furthermore, the composite membrane significantly upregulates the expression of tissue‐type plasminogen activator (t‐PA) and downregulates the production of plasminogen activator inhibitor‐1 (PAI‐1), leading to the activation of fibrinolytic system, which inhibits the formation of adhesive tissues. Collectively, gelatinized PLCL electrospun membrane is a promising bioactive barrier for preventing postsurgery abdominal adhesions.

Fibrinolytic system activation immediately following trauma was quickly and intensely suppressed in a rat model of severe blunt trauma

In severe trauma, excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. However, in the first several hours after a blunt trauma, changes in fibrinolytic activation, suppression, and activation–suppression balance have not yet been elucidated, which the present study aimed to clarify. Anesthetized 9-week-old male Wistar S/T rats experienced severe blunt trauma while being placed inside the Noble–Collip drum. Rats were randomly divided into four groups of seven. The no-trauma group was not exposed to any trauma; the remaining groups were analysed 0, 60, and 180 min after trauma. Immediately following trauma, total tissue-plasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 min after trauma returned quickly to levels comparable to those in the no-trauma group. In conclusion, fibrinolytic activation was observed only immediately following trauma. Therefore, immediately after trauma, the fibrinolytic system was activated; however, its activation was quickly and intensely suppressed.

An association of low-density lipoproteins and fibrinolysis in patients with severe aortic stenosis- valvular expression of fibrinolytic proteins

Abstract Background Aortic stenosis (AS) is associated with hyperlipidemia and hypofibrinolysis. The contribution of serum lipids to the valvular expression of fibrinolytic proteins is not known. Aims To evaluate whether fibrinolytic factors are present within stenotic aortic valves and to determine their potential associations with LDL cholesterol concentrations, their oxidized forms (oxPL-LDL), and AS severity. Methods We enrolled 75 patients with isolated severe AS aged 66±8 years (mean gradient 52 mmHg, max gradient 84 mmHg) undergoing valve replacement surgery. Aortic valve leaflets obtained from AS patients (n=30) and from age-matched healthy autopsy donors (n=3) were used to evaluate in loco the presence of plasminogen (PLG), tissue plasminogen activator (tPA), and fibrinolysis inhibitors (α2-antiplasmin and plasminogen activator inhibitor, PAI-1). PLG activity, plasma tPA and PAI-1 levels, along with cholesterol and oxPL-LDL were assayed. Clot lysis time (CLT) was performed to assess the overall fibrinolytic system activity. Results AS patients with LDL cholesterol ≥3.0 mM (n=25, 56% taking statin) compared to those with LDL cholesterol &amp;lt;3.0 mM (n=50, 86% taking statin) had higher oxPL-LDL levels (+80%, p=0.0014). Moreover, AS subjects with LDL cholesterol ≥3.0 mM, compared to those with LDL cholesterol &amp;lt;3.0 mM had longer CLT (+22.4%, p=0.0022) along with higher plasma tPA (+31.5%, p=0.004) and PAI-1 (+47.4%, p=0.01), while PLG activity tended to be higher (+10.8%, p=0.056). For the first time the valvular expression of fibrinolytic proteins was detected in AS patients, but not in healthy donors. The expression of studied proteins was observed mainly on the aortic side of the leaflets and only trace amounts were detectable in deeper layers of valves. The valve area positive for PLG was 4.4±1.8%, for tPA 1.6±0.8%, while the expression of α2-antiplasmin was 4.2±1.7% and 6.9±2.3% for PAI-1. In the whole AS group, oxPL-LDL, but not LDL cholesterol showed associations with mean (r=0.34, p=0.041) and max (r=0.3, p=0.016) gradients. Serum concentrations of LDL cholesterol correlated with CLT (r=0.42, p=0.0002), blood PLG activity (r=0.56, p=0.0012) and with tPA (r=0.43, p=0.0001) and PAI-1 (r=0.32, p=0.006) levels. Similarly, oxPL-LDL were associated with CLT, PLG activity, and tPA (r=0.34; r=0.59; r=0.47, all p&amp;lt;0.01). Valvular expression of fibrinolytic proteins did not correlate with LDL cholesterol, ox-PL-LDL or transvalvular gradients. Conclusions This study is the first to demonstrate that in AS patients hypercholesterolemia and enhanced lipid oxidation are associated with impaired systemic fibrinolysis, which supports the concept of beneficial effects of cholesterol-lowering therapy in mild-to-moderate AS. Moreover, valvular expression of fibrinolytic factors suggests that these factors are delivered with circulating blood but not synthesized de novo. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Centre (NCN)

Аспекты применения транексамовой кислоты у пациентов с политравмой

Актуальность. В статье проанализированы особенности применения транексамовой кислоты у пациентов с политравмой. Цель исследования: изучить данные литературы об эффективности применения транексамовой кислоты у пациентов с политравмой и проанализировать частоту переливания компонентов крови у пациентов с политравмой в зависимости от времени назначения транексамовой кислоты после получения травмы. Материалы и методы. Проведено ретроспективное когортное исследование, в которое были включены 40 пациентов в возрасте от 22 до 56 лет с политравмой. Всех пациентов разделили на 2 группы: I группа — пациенты, у которых применяли транексамовую кислоту до 3 часов после возникновения политравмы, и II группа — больные, которые принимали транексамовую кислоту во временном промежутке 3–8 часов после возникновения политравмы. Результаты. Основным многофакторным условием для возникновения ранней коагулопатии у пациентов с политравмой является сочетание шока, вызванного кровотечением, и повреждения тканей, что приводит к генерации тромбин-тромбомодулинового комплекса, активации антикоагулянтной и фибринолитической систем. У пациентов, включенных в анализ данных в нашем исследовании, основными причинами политравмы были: дорожно-транспортное происшествие — у 34 пациентов (85 %), падение с высоты — у 6 пациентов (15 %). Средний возраст пациентов I группы составил 39,2 ± 17,3 года, во II группе — 41,9 ± 12,8 года. В исследование вошли 29 мужчин и 11 женщин. Не выявлено достоверных различий в тяжести состояния, структуре компонентов полиорганной недостаточности, антропометрических характеристиках пациентов обеих групп. Мы установили, что в I группе пациентов переливание эритроцитарной массы и свежезамороженной плазмы проводили в 14 случаях из 26, что составило 53 % от всех случаев политравмы в данной группе. Во II группе пациентов переливание компонентов крови проводили в 9 случаях из 14, то есть в 64 % от всех случаев из данной группы. Соответственно, частота переливания компонентов крови у пациентов II группы на 11 % выше по сравнению с пациентами I группы (p ≥ 0,05). Выводы. Полученные нами предварительные результаты свидетельствуют, что введение транексамовой кислоты до 3 часов после возникновения политравмы может снижать частоту гемотрансфузий.

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Аналіз протеолітичної та фібринолітичної активності плазми крові у хворих на бронхіальну астму, поєднану з ожирінням

Мета дослідження — провести аналіз стану протеолітичної та фібринолітичної активностей плазми крові у хворих на бронхіальну астму (БА), поєднану з ожирінням. Матеріали та методи. Обстежено 40 хворих, які були розподілені на групи. Основну групу становили 20 хворих на БА в поєднанні з ожирінням (ІІ група), дві групи порівняння — 10 хворих на БА з нормальною масою тіла (І група) та 10 хворих з ожирінням і без патології бронхолегеневої системи (ІІІ група). Контрольну групу становили 10 практично здорових осіб. У хворих на БА досліджували показники протеолітичної та фібринолітичної активностІ плазми крові. Результати. Аналіз отриманих даних у хворих на БА показав зростання активності плазмових факторів згортання крові: cумарна фібринолітична активність зростала порівняно із контрольною групою та становила 1,46 ± 0,13 Е440/мл/год при показниках у практично здорових осіб 1,23 ± 0,16 Е440/мл/год (р &lt; 0,05). Крім того, зростання відзначалося і в групі пацієнтів з ізольованим ожирінням (на 38,5 % порівняно з групою практично здорових осіб), що можна пояснити підвищенням активності запального процесу за рахунок імунних зрушень, пов’язаних із біологічною активністю жирової тканини, як додаткового джерела прозапальних цитокінів. Висновки. При поєднанні бронхіальної астми та ожиріння спостерігається активація фібринолітичної та протеолітичної систем крові, що сприяє виникненню мікроциркуляторних і гемостатичних розладів, посиленню запального процесу. При ожирінні як стані системної запальної відповіді відзначається активація фібринолітичної та протеолітичної систем крові більш виражено, ніж при бронхіальній астмі.

Endothelial Activation Markers in Polytransfused Children with Beta Thalassemia: Study from a Tertiary Care Centre in India.

Beta thalassemia major is associated with a subclinical hypercoagulable state. Endothelial activation markers like soluble Intercellular adhesion molecule (sICAM-1) and E-selectin have been implicated in the pathogenesis of endothelial dysfunction and hemostatic alterations. In this study we aimed to study serum levels of sICAM-1 and E-selectin in polytransfused children with β thalassemia major and their association with serum ferritin and D-dimer levels. Sixty-two polytransfused β-thalassemia major children aged between 5 and 17years and 26 age and gender matched healthy controls were enrolled in the study. Complete blood count with peripheral smear, liver function tests, serum ferritin, coagulation tests [PT, APTT, D-dimer] and endothelial activation marker tests [ICAM-1 and E-selectin] were performed. PT, APTT and D-dimer levels were significantly higher in beta-thalassemia major patients than in control group (p = 0.003, p < 0.001, p < 0.001 respectively). Mean ICAM-1 and E-selectin levels were 731.34 ± 343.97ng/ml and 111.75 ± 40.13ng/ml respectively which were significantly higher than control group (p < 0.001, p < 0.001 respectively). No significant correlation of ICAM-1 and E-selectin was observed with serum ferritin, PT, APTT and D-dimer levels. The findings of the present study suggest that there is ongoing subclinical activation of coagulation cascade and fibrinolytic system in these patients. Endothelial activation markers may be used as early indicators of endothelial dysfunction to assess the thrombotic complications in beta thalassemia.

The effects of streptokinase in a Chacma baboon (Papio ursinus) model of acquired thrombotic thrombocytopenic purpura

TTP is a life-threatening disorder with limited pharmaceutical treatment options. Recently, the potential of streptokinase in the treatment of acquired TTP was demonstrated in humans in vitro, and in vivo in a mouse model. We aimed to determine the in vitro and in vivo effects of streptokinase in an established Papio ursinus model of acquired TTP. In vitro: VWF activities & multimer patterns and thromboelastograms were assessed with increasing concentrations of streptokinase. In vivo: After induction of TTP, escalating streptokinase doses (ranging from 50,000 to 900,000IU) were administered, and the effects of streptokinase assessed on peripheral blood counts, fibrinolysis, VWF activities & multimer patterns and thromboelastograms. In an extension of the study, high-dose streptokinase (1,500,000-3,000,000IU) was administered to another baboon. After spiking, fibrinolysis with loss of large VWF multimers was observed at [2200IU/mL]-roughly equivalent to 1,500,000IU. However, administration of escalating intravenous streptokinase doses had no in vivo effect on the TTP phenotype, and in vivo increases in plasmin activity were mild when compared with baseline, even at high doses. Minimal effect on VWF multimer patterns was observed but only at doses ≥ 1500,000IU. Streptokinase is not effective in resolving TTP in a Papio ursinus model of TTP, possibly due to limited activation of the baboon fibrinolytic system. Modifications to this model, the use of alternative higher animal models, or alternative thrombolytics, should be considered to establish proof-of-concept.

Edoxaban Dosing Time Affects Blood Coagulation Inhibition in Rats.

Coagulation–fibrinolytic system activity shows daily rhythmicity, with hypercoagulability in the morning and hypocoagulability in the evening. Consequently, the efficacy of anticoagulants may be influenced by their dosing time. Edoxaban, a selective inhibitor of the active form of coagulation factor X (FXa), is taken orally once daily, but the optimal dosing time is unknown. This study evaluated the dosing time-dependent effects of edoxaban on coagulation activity and thrombus formation in rats. Edoxaban (10 mg/kg) or vehicle was administered to Wistar rats at zeitgeber time (ZT)-2 (beginning of the light phase) or ZT14 (beginning of the dark phase), followed by blood collection at ZT4, ZT10, ZT16, or ZT22, to measure the activity of coagulation factors and edoxaban concentrations, or followed by inferior vena cava ligations at ZT4 or ZT16, to assess the efficacy of edoxaban against thrombus formation. Coagulation FX activity was high during the light phase, and a single dose of edoxaban administered at ZT2 inhibited FX activity and thrombus formation more potently compared with the same dose administered at ZT14. The inhibitory effects during the light phase could be attributed, at least in part, to the high blood concentration of edoxaban achieved by dosing at ZT2. Morning dosing of edoxaban leads to a high blood concentration of the drug during the morning hours and thus may better counteract the hypercoagulability and hypofibrinolytic activity characteristic of the morning hours. Optimizing the dosing time may contribute to improving the efficacy of edoxaban.

Interrelation between markers of system of hemostasis and hemocoagulation disorders in patients with tuberculosis of respiratory organs and comorbid diabetes mellitus after surgical intervention on respiratory organs

The relevance of the work is determined by the necessity to study markers of coagulation system of blood and hemocoagulation disorders in patients with pulmonary tuberculosis and comorbid diabetes mellitus in different stages of postoperative period.&#x0D; Aim. To determine the interrelation between markers of system of hemostasis and signs of development of intravascular blood coagulation in patients with pulmonary tuberculosis and comorbid diabetes mellitus (TB-DM) depending on the volume of surgical intervention on the respiratory organs.&#x0D; Materials and Methods. The extent of changes of markers of the system of hemostasis was determined in 89 patients with TB-DM before and after surgical treatment. Parameters of coagulation system of blood: concentration of fibrinogen, the level of soluble fibrin-monomer complexes, compensatory potentials by the level of fibrinolysis, activity of fibrinolytic system and of anticoagulation system (antithrombin III) were determined; parameters of prothrombin activity were studied. Besides, operation material of lungs was prepared for morphological examination.&#x0D; Results. A general tendency to increase in the parameters of hypercoagulation syndrome was identified in all the study groups starting from the 3rd-5th day and reaching maximum on the 7th-10th and 14th-17th days of the postoperative period, with compensatory activation of fibrin-stabilizing factor and of fibrinolytic system. Changes in the markers of hemostasis were most prominent in the group of patients after lobectomy. Microthrombotic lesions of the vessels of pulmonary microcirculation with partial or complete obturation of the lumen were morphologically visualized.&#x0D; Conclusion. On the basis of the data obtained a conclusion can be made about the existence of pronounced hypercoagulation syndrome with phenomena of intravascular coagulation of blood in this category of patients, which evidently requires timely prevention and treatment of thromboembolic complications. The results obtained may be used for development of measures aimed at prevention of hemocoagulation complications in patients with TB-DM after the conducted surgical treatment.

In-Silico Transcriptome Analyses of Hemostasis Triggers in Inflamed Vs Normal Mucosa of IBD Patients

Background:inflammatory bowel disease (IBD) is characterized by chronic inflammation associated with an increased tendency to thrombosis and thromboembolic complications. The underlying mechanisms of VTE are not yet fully understood. Several studies reported different expressions of circulating procoagulant factors or fibrinolysis inhibitors in IBD. Others linked podoplanin overexpression with thrombosis, hypercoagulability, and increased risk of VTE. Here, we aimed to identify, among genes able to trigger thrombosis, those aberrantly expressed in IBD samples as compared with matched normal mucosa. Methods:we analyzed the transcriptome of matched normal and inflamed lesions in 168 patients with Adult Crohn Disease (CD) and 245 pediatric IBD using publicly available datasets. We intentionally assessed the expression levels of triggers and inhibitors of the coagulation system (Tissue Factor, TFI), the fibrinolytic system (PLAU, PLAT, PAI-1/2/3, TAFI, PN-1, SERPINF2, A2M, SNX1, SERPINC1) and platelets activation (podoplanin). Analyses were finally performed using additional datasets with 219 ulcerative colitis (UC) adult patients, 198 IBD patients and compared to normal colon transciptome. Results:in all datasets, when compared to matched normal mucosal transcriptome, CD and UC inflamed tissues over-expressed Podoplanin mRNA (p=2.46e-25). TF mRNA was also consistently up-regulated in inflamed mucosal of IBD patients, even if paralleled with up-regulation of TFPI as well, questioning on the functional role of TF in IBD. Among the regulators of the fibrinolytic system the urokinase-activator of the plasminogen is consistently deregulated in inflamed areas. Conclusion: our in-silico analyses on gene expression profiles, using matched normal and pathological mucosa of the same patients, suggested that IBD inflamed mucosa favors platelets activation due to podoplanin over-expression. These observations require further studies to assess the biological role of podoplanin in IBD patients and opens new insights on how to perform antithrombotic prophylaxis in IBD patients. Disclosures No relevant conflicts of interest to declare.

Bleeding and Bleeding Risk in COVID-19.

Coronavirus disease 2019 (COVID-19) is a new, emerging medical challenge worldwide, with those affected showing a variety of clinical presentations, ranging from asymptomatic or mild conditions to critical illness. Patients affected by the causative virus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—usually experience cough, fever, dyspnea, myalgia, less frequently gastrointestinal (GI) manifestations and, rarely, neurological complications. Coagulopathy is common among those afflicted and appears to be one of the most significant adverse prognostic signs.[1] [2] Coagulopathy results from concomitant activation of coagulation and fibrinolytic systems, most likely due to a severe proinflammatory state (i.e., the so-called cytokine storm) and/or by viral sepsis that sometimes leads to consumption of coagulation factors and decreased platelet count, resulting in thrombohemorrhagic events.[3] In this process, plasmin breaks down fibrin present in plasma and the bronchoalveolar lavage fluid, as well as potentially other organs, and leading to excess D-dimer/fibrin(ogen) degradation product (FDP) formation. This may also lead to reduction in platelet count and increased risk for hemorrhage.[4] In a systematic review of 6,892 patients and meta-analysis of 3,496 patients, platelets were low in 22.9% and D-dimer was high in 34.8%; D-dimer was associated with a severe clinical course with an odds ratio (OR) of 4.03, and low platelets with an OR of 1.78.[5] Disseminated intravascular coagulation (DIC) in COVID-19 is accompanied by a significant decrease of fibrinogen, and a marked increase of FDP and D-dimer, which are characteristics of DIC with hyperfibrinolysis, whereas the DIC caused by infection is accompanied by plasminogen activator inhibitor-1 release and suppression of fibrinolysis. Administration of antiproteases may prove beneficial.[6] Elevated D-dimer, and FDP, often mildly prolonged prothrombin time and mildly decreased platelet counts were also reported as common findings by Tang et al, more common and more profound in severely affected patients.[2] Fibrinogen levels are sometimes lowered, but may instead be elevated, while activated partial thromboplastin time is sometimes prolonged, but may instead be shortened, with these potentially suggestive of acute phase events.[2] [6] Although hypercoagulability and thrombotic events are common in COVID-19, bleeding may occur at any time during the course of disease. Several factors make patients with COVID-19 prone to bleeding, including thrombocytopenia, hyperfibrinolytic state, consumption of coagulation factors, and thromboprophylaxis administration of anticoagulants. A proposed cytokine storm, prolonged tissue hypoxia, and direct invasion of affected tissues are other possible causes.[2] [7] [8] Although thrombosis is relatively well studied in COVID-19, bleeding and bleeding risk appear to be the forgotten side of this story, most probably due to the less-fatal consequences; however, hemorrhagic diatheses represents a significant morbidity and potential cause of death in COVID-19 in at least in a subset of patients.[7] [8]

Role of Tissue-Type Plasminogen Activator in Remodeling of the Ductus Arteriosus

Vascular remodeling (e.g., intimal thickening) is necessary for complete closure of the ductus arteriosus (DA). Smooth muscle cells are reported to contribute to DA remodeling. In contrast, the contribution of endothelial cells remains largely unknown. Recent data showed that tissue-type plasminogen activator (t-PA) was highly expressed in the endothelial cells of rat and human DA. It is well known that t-PA is an activator of the blood fibrinolytic system, but t-PA-induced localized proteolysis has been reported to play an important role in vascular development. We found that t-PA-induced plasminogen-plasmin conversion promoted matrix metalloproteinase-2 activation in endothelial cells of rat DA. Gelatinase activity was noted at the internal elastic laminae (IEL) of rat and human DA on in situ gelatin zymography. The in vivo injection of plasminogen to pre-term rats increased gelatinase activation, IEL disruption, and the subsequent intimal thickening formation in the pre-term rat DA. Human DA results partly supported the rat DA findings, suggesting that t-PA-mediated DA remodeling may also be present in the human DA. Current pharmacotherapy for patent DA (PDA) mainly focuses on increasing vascular constriction. Elucidating the molecular mechanisms of DA remodeling may help to expand the range of therapeutic strategies for PDA.

Successful conservative treatment for massive uterine bleeding with non-septic disseminated intravascular coagulation after termination of early pregnancy in a woman with huge adenomyosis: case report

BackgroundAdenomyosis is a benign gynecological condition in which endometrial tissue or endometrial-like tissue develops within the uterine myometrium. Few cases of disseminated intravascular coagulation has been reported in the patients with adenomyosis. Although hysterectomy is indicated for refractory massive uterine bleeding in the patients with advanced uterine adenomyosis, conservative treatment is often desired in women in the late reproductive age. Recently such cases are increasing due to the social trend of late marriage.Case presentationA 37-year-old woman with huge adenomyosis, gravida 2 para 0, was referred to our hospital to terminate her pregnancy. Acute, non-septic, disseminated intravascular coagulation (DIC) developed after early pregnancy was terminated in a woman with huge adenomyosis. Massive bleeding and DIC occurred 3 days after the dilatation and curettage. There was no evidence of infection as the cause of the DIC, because neither bacteria nor endotoxin could be detected in her blood, and antithrombin 3 (AT3), which would be expected to decrease in septic patients, was not decreased. Hemorrhage in the adenomyotic tissue after the termination presumably developed inflammation, with numerous microthrombi and necrosis in the adenomyotic tissue, which subsequently promoted coagulation and fibrinolysis, leading to the onset of massive uterine bleeding and DIC. Although severe hyperfibrinolysis is observed in peripheral blood, the fibrinolysis state in the uterine myometrium is considered to be even more severe. The newly formed clots for hemostasis under the uterine mucosa could be removed due to the excessive activation of fibrinolytic system happened in the adjacent myometrium, leading to the onset of massive uterine bleeding. Massive bleeding and DIC resolved quickly after the patient was treated with nafamostat mesilate, which is effective for both excessive coagulation and fibrinolysis.ConclusionsAdenomyosis could cause massive bleeding and DIC when pregnancy is terminated. Massive bleeding was considered to occur because the excessive fibrinolysis system inside adenomyosis affected the adjacent endometrium. Before considering hysterectomy to control refractory uterine bleeding, nafamostat mesilate should be considered as one option, thinking the pathophysiology of the massive bleeding due to uterine adenomyosis.