Inflammatory biomarkers and extracellular vesicles as predictors of venous thromboembolism in lymphoma patients

Limfomi predstavljaju vrlo heterogenu grupu neoplazmi, čija se biološka raznolikost ogleda u različitim mehanizmima napredovanja bolesti i razvoja komplikacija. Jedna od komplikacija koja izaziva značajan morbiditet i mortalitet kod pacijenata sa malignitetima je venska tromboembolija (VTE). Pacijenti sa malignitetom imaju do 7 puta veći rizik za razvoj tromboze u odnosu na opštu populaciju. Specifična patofiziološka karakteristika limfoma je imunološka disregulacija, koja je usko povezana sa aktivacijom inflamacije. Klasični indikatori nivoa inflamacije su broj leukocita i standardizovani reaktanti akutne faze: C-reaktivni protein (CRP), brzina sedimentacije eritrocita (ESR) i fibrinogen. Međutim, danas postoji značajan broj novih markera sistemske inflamacije poput odnosa neutrofila i limfocita (neutrophil-to-lymphocyte ratio, NLR) i odnosa trombocita i limfocita (platelet-to-lymphocyte ratio, PLR). Ekstracelularne vezikule (EV) predstavljaju generički termin za formacije koje se prirodno oslobađaju iz ćelije, koje su ograničene lipidnim dvoslojem i koje se ne mogu replicirati (tj. ne sadrže funkcionalno jedro). EV imaju vrlo sofisticiranu ulogu u brojnim fiziološkim i patološkim procesima, gde se EV otpuštaju od strane različitih ćelija. Uloga EV u trombozi povezanoj sa tumorom (cancer-associated thrombosis, CAT) ispitivana je u animalnim modelima i kod ljudi. Pored toga, EV su povezane sa stanjima kako akutne tako i hronične inflamacije, a često su i „nosači“ različitih molekula od kojih pojedini imaju protrombotički potencijal. S obzirom na sve navedeno, ciljevi istraživanja bili su ispitivanje povezanosti biomarkera inflamacije i razvoja VTE kod pacijenata sa limfomom koji su lečeni (imuno)hemioterapijom, ispitivanje povezanosti VTE sa tipom terapijskog lečenja i odgovora na terapiju kod pacijenata sa limfomom. Sledeći cilj je bio karakterizacija profila EV kod pacijenata sa difuznim B- krupnoćelijskim limfomom (DBKL), ispitivanje povezanosti EV sa VTE kod pacijenata sa DBKL, ispitivanje testa ukupnog hemostaznog potencijala (overall hemostasis potential, OHP) i povezanosti sa VTE kod pacijenata sa DBKL. Metodologija: U prvom delu istraživanja sprovedena je retrospektivna kohortna studija, u koju je uključeno 706 novodijagnostikovanih i relapsirajućih pacijenata sa limfomom koji su lečeni u Klinici za hematologiju, Univerzitetskog kliničkog centra Srbije. Prikupljeni su podaci o svim VTE kod pacijenata sa novodijagnostikovanim limfomom ili relapsom bolesti. NLR i PLR su računati korišćenjem parametara kompletne krvne slike sa diferencijalnom leukocitarnom formulom. Analizirani su sledeći biohemijski parametri: ESR, CRP, laktat dehidrogenaza (LDH), fibrinogen, ukupni proteini (TP), albumin. Drugi deo istraživanja predstavlja prospektivnu kohortnu studiju, koja je uključila 62 pacijenta sa dijagnozom DBKL i sprovedeno je u kolaboraciji sa Univerzitetskom bolnicom Karolinska, Služba koagulacije i kliničke hemije, Odeljenje za molekularnu medicinu i hirurgiju, Institut Karolinska i klinička hemija, medicinska dijagnostika Karolinska. Ispitivanje EV je sprovedeno korišćenjem protočne citometrije. Korišćen je sledeći panel markera: Annexin V za fosfatidilserin (PS), CD42b/CD61 za EV porekla trombocita (platelet-derived extracellular vesicles, PEV), CD142 za tkivni faktor (TF), CD19, CD20 i CD45 za DBKL/B-ćelijsku populaciju, CD62P/CD62E za P-selektin odnosno E-selektin. Za identifikaciju EV korišćen je specifičan gejting algoritam. EV su definisane kao vezikule veličine ≤1,0 μm i pozitivne na Annexin V. Za poređenje EV kod pacijenata sa DBKL, formirana je kontrolna grupa od 5 zdravih volontera...Lymphomas represent a very heterogeneous group of neoplasms, whose biological diversity is reflected by different mechanisms of disease progression and development of complications. One of the complications that causes significant morbidity and mortality in patients with malignancies is venous thromboembolism (VTE). Patients with malignancy have up to 7-times higher risk of developing thrombosis compared to the general population. A specific pathophysiological characteristic of lymphoma is immune dysregulation, which is closely related to the activation of inflammation. Inflammation has been classically assessed by white blood cell (WBC) count and standardized acute phase reactants including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fibrinogen level. However, today there are a significant number of new markers of systemic inflammation such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to- lymphocyte ratio (PLR). Extracellular vesicles (EVs) are a generic term for formations that are naturally released from cells. They are composed of a lipid bilayer and cannot replicate (i.e., do not contain a functional nucleus). EVs have a very sophisticated role in numerous physiological and pathological processes, where EVs are released by various cells. The role of EVs in cancer-associated thrombosis (CAT) has been investigated in both animal models and in humans. In addition, EVs are associated with conditions of both acute and chronic inflammation, and are often "carriers" of various molecules which possess prothrombotic potential. In view of all the above, the research aims were to examine the association between the biomarkers of inflammation and the development of VTE in patients with lymphoma treated with (immuno)chemotherapy, to examine the association between VTE development with the type of therapeutic treatment and response to therapy in patients with lymphoma. The next objective was to characterize the profile of EVs in patients with diffuse large B- cell lymphoma (DLBCL), to examine the association of EVs with VTE in patients with DLBCL, to examine the overall hemostasis potential (OHP) test and the association with VTE in patients with DLBCL. Methodology: In the first part of the research, a retrospective cohort study was conducted, which included 706 newly diagnosed and relapsed patients with lymphoma, who were treated at Clinic for Hematology, University Clinical Center of Serbia. Data were collected for all VTE events in patients with newly diagnosed lymphoma or relapsed disease. NLR and PLR were calculated using parameters of complete blood count with differential leukocyte formula. The following biochemical parameters were analyzed: ESR, CRP, lactate dehydrogenase (LDH), fibrinogen, total proteins (TP), albumin. The second part of the research was the prospective cohort study, which included 62 patients diagnosed with DLBCL, and was conducted in collaboration with Karolinska University Hospital, Coagulation and Clinical Chemistry Service, Department of Molecular Medicine and Surgery, Karolinska Institute and Clinical Chemistry, Karolinska Medical Diagnostics. The EVs assay was performed using flow cytometry. The following panel of markers was used: Annexin V for phosphatidylserine (PS), CD42b/CD61 for platelet-derived extracellular vesicles (PEVs), CD142 for tissue factor (TF), CD19, CD20 and CD45 for DLBCL/B-cell population, CD62P/CD62E for P- selectin or E-selectin. A specific gating algorithm was used to identify EVs. EVs were defined as vesicles ≤1.0 μm in size and positive for Annexin V. To compare EVs in DLBCL patients, a control group of 5 healthy volunteers was formed..

Histopathological changes of gastric mucosa in celiac disease

Introduction: Celiac disease (CD) is a chronic autoimmune disease caused by ingestion of gluten in genetically susceptible individuals. Lymphocytic gastritis (LG) can be found in CD patients, with possible lower incidence of chronic Helicobacter pylori (Hp) positive gastritis. Aim: The aim was to assess the frequency and type of histopathological changes of gastric mucosa in patients with proven CD. Material and methods: This study included patients who underwent esophagogastroduodenoscopy (EGDS) and histopathological examination. Patients were distributed into two groups: patients with and without histopathological alterations indicative of CD. Results: The study included 351 patients. CD was detected in 145 (41.3%) patients, while the control group consisted of 206 (58.7%) patients without CD confirmation. The most common symptom in CD patients was diarrhea, while patients in the control group most often complained of dyspepsia, fatigue and bloating (p = 0.001). Chronic superficial gastritis was the most common gastritis in both groups of patients (76% and 63.6%; p > 0.05). Gastritis associated with Hp infection was present in 29.3% of CD patients, which is significantly less than in people without CD where 62% of gastritis is associated with Hp infection (p < 0.001). In this study we haven't discovered other forms of gastritis. Patients with CD had significantly lower incidence of Hp infection compared to the control group (15.7% vs. 37.9%; p < 0.001). Marsh IIIa degree was significantly more prevalent in Hp- patients compared to Hp+ patients (39.8% vs. 9.1%; p=0.005). Marsh IIIc was more prevalent in Hp+ patients (63.6% prema 35%; p = 0.011). The presence of Hp infection affects the degree of damage to duodenal mucosa (p = 0.011). Conclusion: The prevalence of Hp infection was significantly lower in CD patients. The higher degree of damage to duodenal mucosa in Hp+ CD patients may contribute to the possible synergistic effect of infection and autoimmunity in CD

The significance of material traces in proving arsons on cars

У овом раду осврнућемо се на пожаре возила који су изазвани умишљајном људском делатношћу. Учиниоци ових кривичниних дела обично се oдлучују да пожар подметну преко поклопца мотора, задњих врата и крова проливањем бензина преко возила и паљењем ужареном материјом или отвореним пламеном, али у криминалистичкој праки нису ретки ни случајеви убацивања запаљиве направе у унутрашњост возила, подметање пожара испод мотора или задњег дела возила. У криминалистичким истрагама у циљу утврђивања узрока пожара најбитнији су материјални докази, док су искази лица веома ретки и непоуздани. Циљ овог рада је да укаже на специфичне материјалне трагове у случајевима намерно запаљених аутомобула, као што су: два центра пожара, плочасто пуцање ветробранског и других стакала, сливање запаљиве течности и разливање запаљиве течности, и њихов значај у поступку откривања и доказивања кривичних дела. Ови трагови несумњиво упућују на закључак да је пожар намерно изазван, те да је учинилац приликом извршења кривичног дела користио неки од поспешивача горења. Основна њихова особина је да су постојани, уочљиви и када је возило у потпуности изгорело, а на поједине од њих уопште не могу утицати ни лоше атмосверске прилике ни радње ватрогасаца приликом гашења пожара.Na nasl. str. : Srpsko udruženje za krivičnopravnu teoriju i praksu, LXI redovno godišnje savetovanje udruženja, septembar 2022

Still not ready for EOSC? Experiences from one co-creation activity

A delay in open and FAIR data policies and practices created a significant gap in the uptake of EOSC between the EU and non-EU Western Balkans countries (Serbia, Montenegro, Bosnia and Herzegovina, and North Macedonia), which can be observed in the lack of infrastructure, policies, incentives, and professional data stewards or librarians with suitable competencies and skills. This lightning talk will present the results of a small team of professionals from the University of Belgrade (Serbia) on the co-creation activity funded by the EOSC Secretariat under the title “Boosting EOSC readiness: Creating a scalable model for capacity building in RDM”. The objective was to create a model for local capacity building in research data management adjusted to the needs of South-Slavic-speaking countries of non-EU Western Balkans countries. The model is applicable in any similar environment struggling with limited financial and human resources. Activities included designing a web portal with guidelines and tutorials about research data management, setting up and localizing an interoperable and scalable Dataverse data repository, devising data management procedures, designing and testing trainings for local communities, and devising research data policy recommendations at various levels. The main results of this Co-creation activity are the web portal with guidelines and training materials, a demo Dataverse data repository SERDAR (SErbian Research DAta Repository), localized (translated in Serbian) software application Argos for creating machine-actionable Data Management Plans, and a proposal for RDM-related amendments to existing national, institutional, and journal policies on Open Science, providing an input for the activities of the national Team for Open Science (established in 2020). Due to similarities between languages in the Western Balkans, all the results, which are freely available under the Creative Commons Attribution license, can be adapted to local needs and reused. This activity contributed to the overall EOSC awareness and readiness in non-EU Western Balkans countries by founding a firm ground for cultural change related to the scientific practices in the research community. This approach can be of great value to the universities and research institutions in countries that do not have already established infrastructure and policies for research data management and sharing. In Serbia, the project will have both a formal and an informal follow-up. All team members are also members of the official national Team for Open Science and they will advocate for policy changes, infrastructure development and the introduction of formal training for data stewards along the lines defined in the project. On the other hand, the same team has recently established the Open Science Community Serbia, which will provide an informal framework for actions aimed at building an Open Science community and culture in Serbia.Conference presentation: [https://doi.org/10.5281/zenodo.5541147]Video recording: [https://youtu.be/bWkcnXTyl0c?t=2342

Efikasnost superkritične fluidne hromatografije u kreiranju ekološki prihvatljivih rešenja u farmaceutskoj analizi

Initially employed primarily at a preparative scale for enantiomer separation of chiral drug candidates, Supercritical Fluid Chromatography (SFC) is nowadays extensively used in the analytical mode. Recent advances in SFC separation science have emphasized its potential for modern and environmentally friendly pharmaceutical analysis. The aim of this review is to provide a deeper insight into the main fundamental and practical aspects of the SFC technique in order to familiarize readers with its versatile nature and efficiency in creating sustainable chromatographic solutions. All considerations are made primarily in the context of the most widely used mode of operation - achiral SFC. In addition, recent applications of this promising technique are presented at the end of the article to further promote its use in pharmaceutical analytical practice.Na početku pretežno korišćena kao preparativna tehnika u enantioseparaciji hiralnih molekula kandidatâ za lek, superkritična fluidna hromatografija (eng. supercritical fluid chromatography, SFC) danas se široko koristi u analitičke svrhe. Noviji naučni napori ukazali su na značaj SFC tehnike u modernoj i ekološki prihvatljivoj farmaceutskoj analizi. Cilj ovog preglednog rada je pružanje dubljeg uvida u najvažnije fundamentalne i praktične aspekte SFC tehnike, kako bi se čitaocima približio njen svestrani karakter, te efikasnost u kreiranju održivih hromatografskih rešenja. Sva razmatranja prevashodno su data u kontekstu najzastupljenijeg režima rada - ahiralne SFC. Takođe, na kraju rada predstavljene su savremene primene ove obećavajuće tehnike kako bi se dodatno ohrabrilo njeno usvajanje u farmaceutsku analitičku praksu

Influence of inflammatory cytokines on S100A proteins expression in CLL patients

Background: S100A proteins possess a broad range of intra- and extracellular functions. The involvement of these proteins in inflammation-mediated responses is of particular interests, considering that inflammation represents one of the landmarks of malignancy. Processes such as inflammation and cellular stress trigger the release of S100A proteins to extracellular space, interacting with their receptors and activating numerous intracellular signaling pathways, for instance NF-κB and AP1. Through them, S100A proteins take part into regulation of some of the most essential cellular processes: cell differentiation, apoptosis, inflammation, proliferation, etc. Aims: The aim of the study is to assess the role of inflammation in activation of S100A proteins via proliferation and inflammation related signaling pathways. Methods: We observed 60 CLL patients’ samples to isolate mononuclear cells (MNC) and CD19+ cells. MNC of CLL patients were treated with pro-inflammatory IL-6 and anti-inflammatory IL-10 cytokines, and inhibitors of JAK1/2, NF-κB and PI3K signaling pathways, to evaluate S100A4, S100A8, S100A9, S100A12 and NF-κB protein expression by immunoblotting. Also, we used immunocytochemistry to analyse the number of the S100As immunopositive MNC of CLL patients.Results: S100A8 showed higher level of protein expression in MNC and CD19+cells in comparison to healthy control. The number of immunopositive S100A4 (p<0.05) and S100A9 cells (p<0.001) was signifi cantly decreased in CD19+cells and MNC, respectively of CLL patients in comparison to healthy control. In addition, S100A4 and S100A9 proteins expression had statistically significant lower level of expression in MNC. Also, IL-6 stimulated expression of S100A8 and S100A4 in MNC of CLL, while the expression of latter one was prevented by NF-κB and JAK1/2 inhibitors. IL-10 reduced expression of S100A8 and S100A12 in MNC of CLL.Summary/Conclusion: Pro-inflammatory IL-6 and anti-inflammatory IL-10 cytokines have opposite effect on inflammatory S100A8 protein in CLL, with a potential to be a prognostic marker

Increased oxidative stress in diffuse large B-cell lymphoma

Background: Oxidative stress is caused by imbalance between excessive production of reactive oxygen species and decreased capabilities of antioxidant system, and it is recognized as a feature in cancerogenesis, as well in hematologic malignancies. Previous studies have shown increasing expression of oxidative stress markers and antioxidant enzymes in lymph nodes progressing to aggressive lymphomas. Aims: The aim of our study was to assess the clinical and prognostic significance of oxidative stress markers in patients with untreated diffuse large B-cell lymphoma (DLBCL). Methods: We analysed 64 patients diagnosed with DLBLC during 2018 and 2019, while 27 healthy volunteers (51.9% males) served as a control group. The plasma sample and laboratory analyses were obtained prior to initiation of specific hematologic treatment. After completion of the therapy, the patients were followed up for up to 4 years and for each of them progression free survival (PFS) and overall survival (OS) were calculated. Malondialdehyde (MDA) and protein carbonyl (PC) were used as markers of oxidative stress in plasma of patients and volunteers, while catalase is used as an antioxidant marker. Results: The mean patients’ age was 56.2 years (range, 20–87); 51.6% were males. Majority of patients were analysed before 1L therapy (n=61; 95,3%), and had following clinical stages: Ann Arbor stage I 23.4%, stage II 37.5%, stage III 15.6% and stage IV 23.4%. Majority of the patients had satisfactory performance status (73.5% had ECOG PS ≥1), bulky tumorous mass was present in 34.4% of patients, whereas 70.3% had extranodal localisation of lymphoma. MDA (6.66±2.7 nmol/ml) was significantly increased (p<0.001, 2.6-fold), while PC (4.29±2.7 nmol/mg) was also significantly increased (p=0.0027, 5-fold) in patients with DLBCL compared to healthy volunteers. In opposite, antioxidant catalase (0.194±0.06 IU/ml) was significantly reduced (p=0.0034, 1.9-fold) in patients with DLBCL. MDA was in significant (p<0.05) negative correlation with hemoglobin (r2=0.586) and LDH (r2=0.59) levels before chemotherapy. MDA was in significant (p<0.01) positive correlation with the age (r2=0.769) of patients with DLBCL at diagnosis. Moreover, MDA was in significant positive correlation with overall survival (p<0.01, r2=0.736) and progression-free survival (p<0.01, r2=0.736) of patients with DLBCL. PC was in negative correlation with the clinical stage (r2=0.103, p=0.146) and therapy response (r2=0.136, p=0.091) of DLBCL but did not reach significance. Summary/Conclusion: The elevated oxidative markers and reduced antioxidant support oxidative stress in patients with DLBCL, while MDA can be a prognostic marker of overall survival

Inflammation mediated thrombus formation in lymphomas

Background: Patients with lymphomas increased the risk of thrombotic complications, especially in diagnosis and during chemotherapy treatment, in the range of 2.9-4.2%. Aims: Our hypothesis is that inflammation and provoked immunity are responsible for generation of thrombus due to disturbed balance between coagulation and fibrinolysis. Methods: Quantification of neutrophil extracellular traps (NETs) from peripheral blood of 80 patients with Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL) measuring circulating cell-free DNA (cfDNA) and myeloperoxidase (MPO) activity. The inflammatory cytokines, coagulation factors and chemokines are measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry in peripheral blood, while fibrinolytic activity by fluorescent tissue-type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) assays. Using a Boyden chamber, trans-endothelial migration of mononuclear cells (MNC) across a monolayer of human microvascular endothelial cells (HMEC-1) will be observed. Results: The pro-inflammatory cytokines IL-1β and TNF-α were significantly increased in DLBCL and HL, but not the chemokines IL-8 and MCP-1. NETs were increased in the peripheral blood of patients with HL (p<0.05) as measured by cfDNA and MPO activity. In contrast, cfDNA was largely reduced in DLBCL with thrombosis (p<0.001). Trans-endothelial migration of MNC was decreased by IL-6, but increased by TNF-α (p<0.001) in DLBCL with thrombosis. In the absence of thrombosis, MNC of HL demonstrated increased trans-endothelial migration in the presence of pro-inflammatory IL-6 (p<0.01), while MNC of HL and DLBCL in the presence of TNF-α (p<0.05). Regarding coagulation, factor VIII was increased in HL (p<0.05), while tissue factor in non-Hodgkin lymphomas (DLBCL and FL, p<0.05). Adhesion molecule P-selectin was increased in lymphomas, mostly in non-Hodgkin lymphomas (p<0.0001), while TGF-β is only in FL (p<0.001). Fibrinogen was negatively correlated with cfDNA (p=0.021, r=-0.767) in HL, while in positive correlation with TNF-α (p=0.028, r=0.517), IL-8 (p=0.009, r=0.598) and MCP-1 (p=0.004, r=0.643) in FL and with TGF-β (p=0.007, r=0.748) in HL. In opposite to uPA, fibrinolytic activity was decreased in the plasma of patients with HL, DLBCL, and FL (p<0.05) as measured by tPA. The tPA was in negative correlation with MPO in HL (p=0.017, r=-0.783) and FL (p=0.006, r=-0.818), while positively correlated with cfDNA in DLBCL (p=0.034, r=0.402, Table 1). The uPA was in positive correlation with cfDNA (p=0.009, r=0.692) and fibrinogen (p=0.009, r=0.692) in FL. Tissue factor (CD142+) procoagulant microparticles derived from monocytes (CD14+: 7.49±0.2, p<0.001) and activated monocytes (CD14+/CD16+: 3.75±0.8%, p<0.05) were increased in DLBCL compared to healthy controls. Summary/Conclusion: Chronic inflammation is present in the examined lymphomas where TNF-α, as an activator of the immune response, is linked with the initiation of thrombus formation. Moreover, augmented innate immunity is accompanied by procoagulants that mutually support thrombosis. F

Prognostic significance of the long non-coding rna malat1 expression in chronic lymphocytic leukemia

Introduction: The long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) dysregulated expression has been reported in a variety of cancers, but has been poorly investigated in chronic lymphocytic leukemia (CLL). The aim of thisstudy wasto investigate the expression pattern of lncRNA MALAT1 in CLL, and evaluate its prognostic significance. Methods: MALAT1 expression was analyzed in peripheral blood mononuclear cells of 114 newly-diagnosed CLL patients and 20 healthy controls by qRT-PCR, and association with clinical and biological features at diagnosis was assessed. Results: MALAT1 was overexpressed in CLL compared to controlsamples(p<0.001). MALAT1 expression was higher in male patients (p=0.003). It showed no correlation with age, leukocyte, lymphocyte and platelet count, and serum β2-microglobulin, but exerted a positive correlation with hemoglobin level (r=0.315, p=0.003) and a negative correlation with lactate dehydrogenase level (r=-0.303, p=0.004). MALAT1 expression was higher in Binet A and B patients vs. Binet C patients (p=0.037). There was also a trend toward higher MALAT1 expression in patients with favorable (del13q) and intermediate (normal karyotype, trisomy12) cytogeneticsin comparison to patients with unfavorable (del11q and del17p) cytogenetics (p=0.059). In addition, high MALAT1 levels were associated with CD38-negative status (p=0.017), but not with IGHV mutational status. While there was no association with the time to first treatment, longer median overall survival in MALAT1 high- vs. MALAT1 low-expressing cases was observed (142 vs. 82 months, log rank p=0.032). Conclusion: LncRNA MALAT1 is up-regulated in CLL. High MALAT1 expression at diagnosis may be associated with better prognosis

Activation of coagulation factors and prothrombic properties of endothelium in hematological malignancies

Introduction: Patients with hematological malignancies have an increased risk of thrombotic complications, ranging from 3-5% in patients with lymphoma and acute myeloid leukemia (AML). The presented study observed the onset of thrombus formation to predict risk factors for thrombosis in lymphoid and myeloid malignancies. Methods: Coagulation factors, inflammatory signaling pathways and adhesion molecules have been observed in patients with Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and AML. Their mononuclear cells (MNC) trans-endothelial migration through human microvascular endothelial cells (HMEC-1) monolayer is observed by Boyden chamber. Results: Thrombin was in positive correlation with tumor necrosis factor alpha (TNF-α) in HL, while with P-selectin (p<0.001), tumor growth factor-beta (TGF-β) and factor VIII (p<0.05) in DLBCL and AML. Transendothelial migration of MNC was increased by TNF-α (p<0.001) in DLBCL regardless of previous thrombosis. Regarding coagulation, factor VIII was increased in HL and AML (p<0.05), while tissue factor in non-Hodgkin lymphomas (DLBCL and FL, p<0.05). Tissue factor was in positive correlation with adhesion molecule P-selectin and factor VIII (p<0.05). P-selectin was increased in non-Hodgkin lymphomas (p<0.0001), while TGF-β only in FL (p<0.001). Fibrinolytic activity was decreased in plasma of patients with HL, DLBCL, and FL (p<0.05), but largely in AML (p<0.01) as measured by tissue-type plasminogen activator. Inflammatory NF-κB signaling has been activated in HL and DLBCL, while p38 signaling only in HL. Conclusion: Coagulation factors and inflammation are increased in hematological malignancies along with the interaction of the endothelium and circulating cells that predispose to thrombus formatio