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EN
Thrombangiitis obliterans (TAO marked by coexistence of thrombotic and inflammatory changes of neurovascular tract has evoked a considerable dispute concerning pathogenesis of this disease. The aim of the study was to define the level of activation of fibirinolitic system in course of TAO disease by means of determination its basic constituents as well as to examine the essence of level of fibrinolysis disorders in pathogenesis and development of this disease. Material and methods. Fifty patients with thrombangiitis obliterans (TAO), 30 patients with peripheral occlusive disease - PAOD (ASO) and 20 healthy volunteers (K) have been subjected to the examination. We determined the activity some factors of fibrinolysis: t-PA, PAI-1, PAP, plasminogen, α2-antiplasminogen, D-dimmer as well as euglobulin lysis time. The analysis comprised 7 features and 8 factors of variability: a membership to a group of patients, sex, age, smoking, aggravation of the disease within last 3 months, occurrence of Raynaud’s symptom, a degree of ischemia according to Fontaine, time the disease lasted. Results. The significant differences between the average were checked by means of t-Student test or variance analysis (ANOVA) and co-relation rate r (Pearson). We concluded that the average value of PAI-1 in the group TAO was significantly higher than in comparison with ASO group. The increased values were revealed in case of 76 % of patients. The euglobulin lysis time was vitally extended in case of 60% of patients in ASO group. In all three groups higher levels of α2-antiplasmin were detected in case of elderly patients compared to the younger ones. Conclusions. The obtained results allow us to ascertain the state of potentially weakened fibrinolysis in case of patients with Buerger’s disease as well as with PAOD.
EN
Deep venous thrombosis is widespread disease, which complications, like: pulmonary embolism and postphlebitis syndrome areimportant social problem. There are many well-known and accurately described risk factors, though in many cases etiology remains unexplained. Further research into causes of deep venous thrombosis seem to be fully justified. The aim of the study was the evaluation of the influence of apolipoprotein (a) serum level in patients with deep venous thrombosis and the changes of its concentration during the treatment. Materials and methods. 26 patients with newly diagnosed deep venous thrombosis (DVT) were enrolled to the study. Diagnosis of DVT was established by use of physical examination and duplex Doppler. Measurements of apolipoprotein (a) and D-dimers serum level were recorded on the following days, starting from the day of the initial diagnosis: 1, 7, 14 and 84. Results. Statistically significant increase of the level of serum apolipoprotein (a) has been found during properly conducted treatment. Conclusions. Alterations of the concentration of serum apoliprotein (a) during the deep venous thrombosis treatment, indicates the involvement of apolipoprotein (a) in pathogenesis of deep venous thrombosis.
EN
Pathogenic microbes can recruit to their cell surface human proteins that are components of important proteolytic cascades involved in coagulation, fibrinolysis and innate immune response. Once located at the bacterial or fungal surface, such deployed proteins might be utilized by pathogens to facilitate invasion and dissemination within the host organism by interfering with functionality of these systems or by exploiting specific activity of the bound enzymes. Aim of the study presented here was to characterize this phenomenon in Candida parapsilosis (Ashford) Langeron et Talice - an important causative agent of systemic fungal infections (candidiases and candidemias) in humans. We have investigated the interactions of fungal surface-exposed proteins with plasminogen (HPG) and high-molecular-mass kininogen (HK) - the crucial components of human fibrinolytic system and proinflammatory/procoagulant contact-activated kinin-forming system, respectively. After confirming ability of the fungal surface-exposed proteins to bind HPG and HK, four of them - two agglutinin-like sequence (Als) proteins CPAR2_404780 and CPAR2_404800, a heat shock protein Ssa2 and a moonlighting protein 6-phosphogluconate dehydrogenase 1 - were purified using ion-exchange chromatography, gel filtration and chromatofocusing. Then, their affinities to HPG and HK were characterized with surface plasmon resonance measurements. The determined dissociation constants for the investigated protein-protein complexes were within a 10-7 M order for the HPG binding and in a range of 10-8-10-9 M for the HK binding. Detailed characterization of adsorption of these two important plasma proteins on the fungal cell surface may help to increase our understanding of molecular mechanisms of C. parapsilosis-dependent candidiasis.
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Factor XII – A Limitation for Divers?

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EN
The lack of evidence for the tissue-factor dependent activation of the coagulation system and the release of thrombin on one hand, and a decreased concentration of factor XII after short term air, saturated air and heliox exposures, as well as an increased concentration of the plasmin-antiplasmin complex (PAP) after short dives indicate that diving and decompression possibly affect fibrinolysis. The aim of our research was to verify the assumption that diving and decompression activate the system of fibrinolysis and the clarification of the pathomechanism of this activation. The study involved 50 healthy volunteers who were subjected to short-term, air hyperbaric exposures at 400 kPa and 700 kPa, which correspond to 30m and 60m dives. Decompression was applied in accordance with Naval tables of decompression. Before hyperbaric exposition and after decompression the following factors were determined: activity of factor XII, concentration and activity of t-PA, concentration and activity of PAI-1, concentration of alpha2- antiplasmin, concentration of PAP, concentration of neutrophil elastase. The following observations have been made: a statistically significant increase in the factor XII activity, increase in the PAP complex concentration and a simultaneous significant decline in the α2-AP activity. No measurable t-PA activity or significant changes in t-PA concentration have been observed. In addition, a statistically significant decline in both the activity and concentration of PAI-1 has been observed, which was more pronounced after the expositions that corresponded to 60 m dives. The concentrations of granulocyte elastase did not differ significantly before and after decompression. Conclusions: People qualified for diving should have the following risk factors examined: risk factors of increased fibrynolytic activity - haemostasis abnormalities that increase the risk of haemorrhage, possibility of parietal blood clots/thrombi.
EN
The aim of the study. Assessment of dynamic changes in the expression of activators and inhibitors of coagulation and fibrinolysis in the neointima of polyester vascular grafts during their healing process.Material and methods. The study was carried out on 18 dogs that underwent replacement of infrarenal abdominal aorta with a polyester DALLON - double velour prosthesis. Grafts were removed after 1, 4 and 12 months and fixed according to the AMeX method. Immunohistochemical labeling for tissue factor (TF), tissue factor pathway inhibitor (TFPI), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), prothrombin activation fragment F1+2 (F1+2) and D-dimer (DD) was performed on the neointima of the grafts.Results. TF expression did not demonstrate any significant differences in all study periods. TFPI expression appeared at 4 months and was increased at 12 months. Intensive F1+2 expression was shown at 1 month; its mild expression was still present in the following periods of the study. Plasminogen activators were demonstrated at 1 month and their expression was increased at 4 and 12 months, whereas weak expression of PAI-1 and DD was shown in all study periods.Conclusions. High thrombotic potential of polyester vascular graft neointima is present in all periods of the graft healing process. Increasing TFPI and plasminogen activators expression in the late postoperative follow-up favors graft patency maintenance.
EN
Assessing hemocompatibility of anticancer drug candidate is very important task due to the fact that coagulation disorders are often correlated with malignancy or induced by chemotherapy. The aim of this study was to examine the influence of some polyamine conjugates with bicyclic systems on the process of coagulation and fibrinolysis. In addition their effect on the healthy human erythrocytes (RBCs) was assessed. Prothrombin Time (PT), Activated Partial Tromboplastin Time (APTT), clot formation and lysis test (CL-test) were performed to evaluate the influence of some polyamine conjugates on plasma hemostasis. The effects of tested compounds on RBCs were assessed using hemolysis assays and microscopy studies. APTT and PT examination revealed that all tested compounds apart from the highest concentrations of compounds 3 and 5 did not exert significant effects on intrinsic and extrinsic coagulation pathways. Despite their substantial influence on the kinetic parameters of the process of clot formation and fibrinolysis, the examined compounds, over the entire concentration range, did not alter the overall potential of clot formation and lysis (CLAUC) suggesting that they might be regarded as biocompatible concerning plasma hemostasis. At potential therapeutic concentrations (constituting IC50 value for MCF-7 cells) tested polyamine conjugates showed no adverse effects on the membranes of RBCs. Promising antiproliferative activity of representative polyamine conjugates together with their hemocompatibility make them good anticancer drug candidates for further preclinical evaluation.
EN
Disturbances of hemostatic system are commonly observed in chronic kidney disease (CKD) patients. Along with CKD progression, the levels of tryptophan-derived uremic toxins increase, including quinolinic acid (QA). Objective of the study was to evaluate the effect of QA, a representative of tryptophan metabolites, on coagulation and fibrinolytic activity in male Wistar rats in vivo and platelet activity in vitro. Rats received QA dissolved in drinking water in doses of 3, 10, and 30 mg/kg (or water, VEH) for 14 days. Next, the following parameters were measured in the rat‘s whole blood or plasma ex vivo: thromboelastometric (ROTEM) parameters, standard coagulation parameters and fibrinolytic parameters. To evaluate the direct effect of QA on coagulation and platelet activity, blood from control rats was drawn and analyzed in vitro in the following scheme: samples of whole blood were incubated with QA (100µM) before thromboelastometric (ROTEM) analysis and collagen-induced platelet aggregation, or samples of platelet rich plasma (PRP) were incubated with QA (100µM, 1 and 2mM) 10 minutes before collagen (1µg/ml) or ADP (10µM)-induced platelet aggregation. QA administrated for 14 days in drinking water had no effect per se on activation of coagulation and fibrinolytic parameters in rats ex vivo. Similarly, no changes were observed in a whole blood incubated directly with QA regarding coagulation parameters or collagen-induced platelet aggregation. QA inhibited ADP-induced platelets aggregation in PRP only at higher concentrations of 1 and 2 mM and when aggregation was initiated by the addition of 10µM ADP in vitro.
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EN
Haemostasis is a set of processes with the aim to maintain blood in the liquid state in the vascular bed, and in the case of damage to the vessel – to prevent extravasation by clot formation (initially a platelet clot and then a fibrin clot). The main components of haemostasis include: platelets, vessel wall, plasma coagulation system, endogenous inhibitors of coagulation and fibrinolytic system. The stream of blood is also an important factor. Haemostasis is divided into two main phases: coagulation and fibrinolysis. These two phases take place simultaneously and remain in equilibrium. The prevalence of any of these processes is the result of the advantage of enzyme complex activity over the complex of the other process. In everyday practice, every physician encounters drugs that affect haemostasis. At the end of the article, the most commonly used anticoagulants and antiplatelet agents available in Poland are described with the mechanisms of their action. The effect of oral anticoagulants results from the inhibition of the transformation of vitamin K1 which is essential for the production of coagulation factors II, VII, IX and X. Acenocoumarol and warfarin are currently available in Poland. The group of new oral anticoagulants includes direct inhibitors of activated factor X: rivaroxaban, apixaban and dabigatran – a potent, competitive and reversible direct thrombin inhibitor. Anticoagulants which are used parenterally include unfractionated heparin, low molecular weight heparins and fondaparinux. Antiplatelet drugs can be divided into two groups based on the mechanism of action – drugs acting through the metabolism of arachidonic acid (aspirin) and acting on the platelet membrane receptors (ticlopidine, clopidogrel and prasugrel).
PL
Hemostaza to zespół procesów mających na celu utrzymanie krwi w stanie płynnym w łożysku naczyniowym, a w przypadku uszkodzenia naczynia – zapobieganie wynaczynieniu poprzez utworzenie skrzepu (początkowo płytkowego, następnie fibrynowego). Spośród głównych elementów hemostazy należy wymienić płytki krwi, ścianę naczyń krwionośnych, osoczowy układ krzepnięcia, endogenne inhibitory krzepnięcia i układ fibrynolizy. Istotnym czynnikiem jest także strumień przepływającej krwi. Najczęściej hemostazę dzieli się na dwa główne etapy: krzepnięcie i fibrynolizę. Oba te procesy zachodzą jednocześnie i pozostają w równowadze. Dominacja któregoś z nich to rezultat przewagi aktywności kompleksu enzymatycznego nad aktywnością kompleksu drugiego procesu. W codziennej praktyce każdy lekarz spotyka się z lekami wpływającymi na hemostazę – na końcu artykułu omówiono więc najpowszechniej stosowane leki przeciwkrzepliwe i przeciwpłytkowe dostępne w Polsce oraz mechanizmy ich działania. Działanie doustnych leków przeciwkrzepliwych wynika z hamowania przemiany witaminy K1, niezbędnej do wytwarzania w organizmie człowieka czynników krzepnięcia: II, VII, IX i X. Obecnie dostępne są acenokumarol i warfaryna. W grupie nowych doustnych antykoagulantów znalazły się bezpośrednie inhibitory aktywnego czynnika X: rywaroksaban, apiksaban i dabigatran, który jest silnym, kompetycyjnym, odwracalnym, bezpośrednim inhibitorem trombiny. Antykoagulanty stosowane parenteralnie to heparyna niefrakcjonowana, heparyny drobnocząsteczkowe i fondaparynuks. Ze względu na mechanizm działania leki przeciwpłytkowe można podzielić na dwie grupy: leki działające przez metabolizm kwasu arachidonowego (kwas acetylosalicylowy) i działające na receptory błonowe płytek krwi (tiklopidyna, klopidogrel, prasugrel).
EN
Background: Radiotherapy and chemotherapy increase the likelihood of development of thromboembolic complications. Activation of coagulation and inhibition of fibrinolysis may lead to formation of thrombi in microcirculation of several organs, compromising their function. Appearance of serum coagulation proteins in urine indicates a compromised renal function. Aims of the paper: 1) To assess changes of serum level of coagulation inhibitors and serum fibrinolytic activity in patients with renal failure undergoing treatment for advanced cervical cancer. 2) To develop methods of improving renal function in this clinical setting. Material and method: This was a prospective randomized study, including patients with a diagnosis of FIGO stage IIB-IIIB cervical cancer, with subclinical renal insufficiency. Treatment protocol consisted in radiotherapy (46-65 Gy; box technique), cisplatin (40 mg/m2 QW) in patients with normal serum creatinin level. Renal function was assessed using dynamic scintigraphy to determine glomerular filtration rate (GFR). Serum hemostatic system was assessed by determining levels of D-dimers, PAP, PAI-I, tPA, FDP and C protein. The same parameters were concomitantly assessed in urine. Only patients with GFR below normal range limit were included in the study. Lower limit of age-adjusted normal range was considered 100%. Half of the patients were irradiated without concomitant anticoagulant prophylaxis (group 1). The other half received a standard dose of nadroparin – 2850 IU aXa/0.3 ml. Results: The study revealed a decrease of GFR in the control and in the treatment group not receiving nadroparin. The treatment group receiving nadroparin experienced an increase of GFR. Significant differences were noticed in endpoints between the control group and the treatment group receiving nadroparin, as well as between treatment groups with and without nadroparin (p=0.0001). Lab tests of coagulation system revealed activation of fibrinolysis in patients receiving nadroparin and its further inhibition in the group without nadroparin. Similar alterations were noticed in urine. Conclusions: One of the causes of subclinical renal failure in patients with late-stage cervical cancer may be inhibition of fibrinolysis. Renal insufficiency deteriorates after termination of radiochemotherapy. Unfavorable alterations in the hemostatic system become more pronounced. Administration of low-molecular-weight heparins results in activation of fibrinolysis, unblocking of renal glomeruli and improvement of glomerular filtration.
PL
Wstęp: Radioterapia i chemioterapia zwiększają prawdopodobieństwo wystąpienia zmian zakrzepowo-zatoro-wych. Aktywacja krzepnięcia i zahamowanie fibrynolizy może prowadzić do powstania zakrzepów w mikro-krążeniu wielu narządów, upośledzając ich czynność. Pojawienie się osoczowych białek układu krzepnięcia w moczu świadczy o nieprawidłowej czynności nerek. Cele pracy: 1) Ocena zmian stężeń inhibitorów krzepnięcia i zmian w aktywności fibrynolitycznej osocza u chorych z niewydolnością nerek leczonych z powodu zaawansowanego raka szyjki macicy. 2) Wypracowanie metod poprawiających funkcję nerek w tej grupie chorych. Materiał i metoda: Badanie miało charakter prospektywny, randomizowany. Obejmowało chore z rozpoznanym rakiem szyjki macicy w stopniu IIB-IIIB wg FIGO, u których stwierdzono subkliniczną niewydolność nerek. Leczenia zakładało podanie dawki 46-65 Gy techniką box i cisplatyny w dawce 40 mg/m2 co 7 dni u chorych z prawidłowymi wartościami kreatyniny we krwi. Czynność nerek oceniano za pomocą scyntygrafii dynamicznej, oznaczając filtrację kłębkową (GFR). W osoczowym układzie hemostazy oznaczano stężenia D-dimerów, PAP, PAI-1, tPA. FDP, białka C. Jednocześnie wymienione parametry zostały oznaczone w moczu. Do badania zakwalifikowano chore z GFR poniżej dolnej granicy normy dla wieku uznanej za 100%. Połowa pacjentek napromieniana była bez profilaktyki przeciwzakrzepowej (grupa 1.). Pozostała część otrzymywała standardową, profilaktyczną dawkę nadroparyny - 2850 j.m. aXa/0,3 ml. Wyniki: Stwierdzono spadki GRF w grupie kontrolnej i grupie badanej nieotrzymującej nadroparyny. W grupie badanej otrzymującej nad-roparynę zaobserwowano wzrost GRF. Stwierdzono znamienne różnice między zmianami w grupie kontrolnej i badanej otrzymującej nadroparynę oraz między grupą badaną bez nadroparyny i grupą badaną otrzymującą nadroparynę (p=0,0001). Badania układu hemostazy wykazały aktywację fibrynolizy u chorych otrzymujących nadroparynę oraz dalsze jej blokowanie w grupie bez nadroparyny. Analogiczne zmiany wykazano w moczu. Wnioski: Jedną z przyczyn subklinicznej niewydolności nerek u chorych na zaawansowanego raka szyjki macicy może być zahamowanie fibrynolizy. Niewydolność pogłębia się po zakończeniu radiochemioterapii. Nasilają się niekorzystne zmiany w układzie hemostazy. Zastosowanie heparyn drobnocząsteczkowych powoduje aktywację fibrynolizy, „odblokowanie kłębków nerkowych” i poprawę filtracji.
EN
The review presents the development of causative treatment in the acute phase of ischaemic stroke over the past 20 years. The earliest methods of brain reperfusion, still in use today, are based on intravenous administration of a thrombolytic agent, but as the protocols improved, it was possible to extend the therapeutic time window for this method from initial 3 hours up to 4.5 hours (as standard), and even up to 6 hours in selected patients. The next step of brain reperfusion evolution was local, intra-arterial administration of a thrombolytic drug, and finally mechanical intravascular procedures were developed, which allowed the therapeutic window to be extended to 8 hours. The most advanced approaches, which combine 2 or 3 methods, enable safe and efficacious treatment of the acute phase of ischaemic stroke even up to 12 hours from its onset. This creates new perspectives for a development of vascular neurology and neurointerventional radiology, which in the future will give patients suffering from acute ischaemic stroke much more chances for survival and functional recovery than it has been very recently.
PL
W artykule przedstawiono, jak w ostatnich 20 latach rozwijały się metody przyczynowego – a więc rekanalizującego – leczenia w ostrej fazie niedokrwiennego udaru mózgu. Najwcześniejsze sposoby reperfuzji mózgu, wciąż stosowane, opierają się na dożylnym podaniu środka trombolitycznego; dzięki dopracowaniu protokołów leczenia udało się poszerzyć okno terapeutyczne dla tej metody z 3 godzin do 4,5 godziny (standardowo), a w niektórych przypadkach – nawet do 6 godzin. Kolejnym etapem rozwoju metod reperfuzji mózgu było lokalne, dotętnicze podawanie leku trombolitycznego. Wreszcie pojawiły się mechaniczne procedury wewnątrznaczyniowe, pozwalające poszerzyć okno terapeutyczne do 8 godzin. Najbardziej zaawansowane podejścia, łączące dwie lub trzy metody, umożliwiają bezpieczne i skuteczne leczenie chorych nawet w ciągu 12 godzin od wystąpienia objawów udaru mózgu. Stwarza to nowe perspektywy rozwoju neurologii naczyniowej i radiologii neurointerwencyjnej. W przyszłości pacjenci doznający niedokrwiennego udaru mózgu będą zatem mieć znacznie większe szanse na przeżycie i sprawne funkcjonowanie niż jeszcze bardzo niedawno.
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