Serine peptidases are involved in many physiological processes including digestion, haemostasis and complement cascade. Parasites regulate activities of host serine peptidases to their own benefit, employing various inhibitors, many of which belong to the Kunitz-type protein family. In this study, we confirmed the presence of potential anticoagulants in protein extracts of the haematophagous monogenean Eudiplozoon nipponicum which parasitizes the common carp. We then focused on a Kunitz protein (EnKT1) discovered in the E. nipponicum transcriptome, which structurally resembles textilinin-1, an antihemorrhagic snake venom factor from Pseudonaja textilis. The protein was recombinantly expressed, purified and biochemically characterised. The recombinant EnKT1 did inhibit in vitro activity of Factor Xa of the coagulation cascade, but exhibited a higher activity against plasmin and plasma kallikrein, which participate in fibrinolysis, production of kinins, and complement activation. Anti-coagulation properties of EnKT1 based on the inhibition of Factor Xa were confirmed by thromboelastography, but no effect on fibrinolysis was observed. Moreover, we discovered that EnKT1 significantly impairs the function of fish complement, possibly by inhibiting plasmin or Factor Xa which can act as a C3 and C5 convertase. We localised Enkt1 transcripts and protein within haematin digestive cells of the parasite by RNA in situ hybridisation and immunohistochemistry, respectively. Based on these results, we suggest that the secretory Kunitz protein of E. nipponicum has a dual function. In particular, it impairs both haemostasis and complement activation in vitro, and thus might facilitate digestion of a host's blood and protect a parasite's gastrodermis from damage by the complement. This study presents, to our knowledge, the first characterisation of a Kunitz protein from monogeneans and the first example of a parasite Kunitz inhibitor that impairs the function of the complement.

• Klíčová slova
• Anticoagulant, Diplozoidae, Factor X, Haematophagy, Helminth, Kunitz, Peptidase inhibitor, Plasmin,
• MeSH
• antifibrinolytika chemie   imunologie   MeSH
• antikoagulancia chemie   imunologie   MeSH
• faktor Xa imunologie   MeSH
• hemostáza * MeSH
• infekce červy třídy Trematoda krev   imunologie   parazitologie   veterinární   MeSH
• inhibitory enzymů chemie   imunologie   MeSH
• inhibitory faktoru Xa chemie   imunologie   MeSH
• interakce hostitele a parazita MeSH
• kapři krev   imunologie   parazitologie   MeSH
• komplement imunologie   MeSH
• nemoci ryb krev   imunologie   parazitologie   MeSH
• plasmin imunologie   MeSH
• plazmatický kalikrein antagonisté a inhibitory   imunologie   MeSH
• proteiny červů chemie   genetika   imunologie   MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• Trematoda chemie   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antifibrinolytika MeSH
• antikoagulancia MeSH
• faktor Xa MeSH
• inhibitory enzymů MeSH
• inhibitory faktoru Xa MeSH
• komplement MeSH
• plasmin MeSH
• plazmatický kalikrein MeSH
• proteiny červů MeSH

BACKGROUND: Unfractionated heparin is used worldwide as a standard anticoagulation therapy for extracorporeal membrane oxygenation (ECMO) machines. However, its use brings about significant bleeding and thrombotic complications for critically ill patients. This case report shows that low molecular weight heparin together with ECMO-produced primary haemostasis pathology can be used as an alternative way of ECMO anticoagulation. CASE PRESENTATION: This paper presents the case of a patient with respiratory failure who subsequently suffered from cardiac failure and spent 94 days on combined V-V and V-A ECMO devices (two ECMO devices running simultaneously on one patient) with intravenous enoxaparin used instead of unfractionated heparin anticoagulation. No life-threatening bleeding/thrombotic events happened during this period, nor did any technical problems with ECMO occur. CONCLUSIONS: In this case report, continuous intravenous low molecular weight heparin anticoagulation was used as a safe alternative to ECMO anticoagulation.

• Klíčová slova
• ECMO, Enoxaparin, Extracorporeal membrane oxygenation, LMWH, PFA 200, Primary haemostasis,
• MeSH
• antikoagulancia škodlivé účinky   MeSH
• enoxaparin MeSH
• heparin nízkomolekulární MeSH
• heparin škodlivé účinky   MeSH
• krvácení etiologie   MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   MeSH
• trombóza * etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antikoagulancia MeSH
• enoxaparin MeSH
• heparin nízkomolekulární MeSH
• heparin MeSH

PURPOSE: Various forms of local haemostats are increasingly used routinely in surgical procedures. Our work is the first comparison of the efficacy and safety of non-regenerated and regenerated oxidized cellulose based fibrous haemostats. METHODS: The haemostatic efficacy and safety of fibrous haemostats based on ONRC and ORC were compared in a randomized multicenter study. The primary endpoint was successful haemostasis within 3 minutes of application and no need for surgical revision within 12 hours after the procedure for recurrent bleeding. RESULTS: There was a significant difference in the rate of successful haemostasis in 3 minutes that was achieved in 82% and 55% in the ONRC and ORC groups, respectively (confidence interval 99%; p = 0.009). Mean time to haemostasis was 133.9 ± 53.95 seconds and 178.0 ± 82.33 seconds, in the ONRC, and ORC group, respectively (p = 0.002). Revision surgery for re-bleeding was necessary in 0 (0%), and 1 (2%) of patients in the ONRC, and ORC group, respectively. No adverse events were reported. CONCLUSION: Fibrous haemostat based on ONRC was non-inferior compared to fibrous haemostat based on ORC when used in accordance with its intended purpose, and was safe and efficient.

• Klíčová slova
• haemostasis, oxidized cellulose, perioperative bleeding, traumacel,
• MeSH
• celulosa oxidovaná * terapeutické užití   MeSH
• hemostatika * terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• celulosa oxidovaná * MeSH
• hemostatika * MeSH

The authors examined the thrombocyte aggregation in 10 controls and 17 patients with the diagnosis of primary hypothyroidism before and after 2 months substitution treatment with levothyroxine. They recorded a significantly reduced intensity of the aggregation response in untreated patients as compared with controls after adrenaline (p < 0.01), ADP (p < 0.01) but not after ristocetin. Impaired thrombocyte aggregation was observed in 11 of 17 patients, i.e. in 65%. After treatment the thrombocytopathy improved in 7 of 11 patients (63%), in four it persisted. Except one female patient the thrombocytopathy improved in all patients with manifest hypothyroidism. In patients with the latent form of hypothyroidism probably an independent coincidence of elevated TSH levels and impaired thrombocyte function was involved. The authors did not detect any cases of acquired von Willebrand's disease. In the conclusion the authors mention that impaired thrombocyte aggregation is a frequent phenomenon after thyroxine treatment. It may be of clinical significance when combined with other changes of haemostasis or in conjunction with the use of some drugs.

• MeSH
• agregace trombocytů * MeSH
• dospělí MeSH
• hypotyreóza krev   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

BACKGROUNDS: Neuroendoscopic biopsy is one of the techniques that can be used for histological verification of a suspected brain tumor. The use of neuroendoscopy is particularly useful for cystic tumors and para- and intraventricular brain tumors that are risky for stereotactic biopsy. The technique of navigated neuroendoscopy enables biopsy sampling under visual control, haemostasis of biopsy site and treatment of cerebrospinal fluid pathways obstruction. PATIENTS AND METHODS: Neuroendoscopic technique was used for biopsy in one patient with a solid brain tumor. 23 patients (12 males, mean age 49.7 years, range 21-75 years and 11 females, mean age 59.1 years, range 22-76 years) with a suspected cystic brain tumor underwent neuroendoscopic biopsy. Suspected intra- or paraventricular brain tumor presented indication for neuroendoscopic biopsy in 36 patients (20 males, mean age 43.9 years, range 6-80 years and 16 females, mean age 46.2 years, range 11-78 years). RESULTS: High grade glioma was most frequently diagnosed in patients with cystic brain tumors, followed by low grade gliomas and metastatic tumors. Diagnostic sample was obtained from all patients. Tumor resection was performed in 7 patients with a cystic tumor after neuroendoscopic biopsy and histological findings were identical in 70.1% of them. Similarly, high grade glioma was most frequently diagnosed in patients with intra or paraventricular tumors, followed by tumors originating from pineal region tissues. Diagnostic sample was obtained from 94.3% of patients. Tumor resection was performed in 5 patients after neuroendoscopic biopsy and histological findings of the resected tissue was identical with neuroendoscopic biopsy in 4 of them (80%). CONCLUSIONS: Neuroendoscopy is a safe biopsy technique for a subset of patients who are high risk for the use of stereotactic biopsy, with comparable results. Neuroendoscopy also provides for cerebrospinal fluid circulation obstruction treatment. The use of neuronavigation or stereotactic planning is particularly useful for the planning of an optimal surgical approach, helps to maintain anatomical orientation in distorted anatomy and facilitates haemostasis in case of intraoperative bleeding.

• MeSH
• biopsie * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory mozku diagnóza   patologie   chirurgie   MeSH
• neuroendoskopie * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. DESIGN: We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. METHODS: Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. RESULTS: During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 μg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. CONCLUSIONS: An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.

• MeSH
• dospělí MeSH
• fibrinolýza účinky léků   MeSH
• hormonální substituční terapie MeSH
• hormony štítné žlázy krev   MeSH
• hypertyreóza krev   komplikace   etiologie   MeSH
• koagulační faktory metabolismus   MeSH
• lidé MeSH
• nádory štítné žlázy metabolismus   radioterapie   chirurgie   MeSH
• pooperační komplikace krev   MeSH
• radioizotopy jodu terapeutické užití   MeSH
• thyroxin terapeutické užití   MeSH
• trombóza etiologie   MeSH
• tyreoidektomie MeSH
• vyšetření funkce trombocytů MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hormony štítné žlázy MeSH
• koagulační faktory MeSH
• radioizotopy jodu MeSH
• thyroxin MeSH

During 1988-1994 at the Second Surgical Clinic in Brno and in the surgical department of the Hospital of Merciful Brethren in Valtice a total of 5200 fibroscopic examinations were made incl. 560 on account of haemorrhage into the upper gastrointestinal tract. The purpose of fibroscopy was to detect sites of haemorrhage and treat them, or to establish at least the level of the haemorrhage. Visualization of the source was achieved in 90%, the level was assessed in 7.5% and failure was recorded in 2.5%. By treatment of the source of haemorrhage primary haemostasis was achieved in 83.32%, definitive haemostasis in 77.01%. Endoscopy of acute haemorrhage into the GIT is at present the method of choice when resolving these conditions. Classical procedures involving supplementation of the blood volume and waiting for spontaneous haemostasis should be considered as "non lege artis" procedures.

• MeSH
• dospělí MeSH
• gastrointestinální endoskopie * škodlivé účinky   MeSH
• gastrointestinální krvácení diagnóza   terapie   MeSH
• hemostáza endoskopická MeSH
• lidé středního věku MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

• MeSH
• bodová mutace * MeSH
• faktor V genetika   MeSH
• frekvence genu MeSH
• hemochromatóza genetika   MeSH
• heterozygot MeSH
• lidé MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• factor V Leiden MeSH Prohlížeč
• faktor V MeSH

BACKGROUND: Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. METHODS: In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. FINDINGS: Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14-1·68) for asundexian 20 mg (three events), 0·16 (0·01-0·99) for asundexian 50 mg (one event), and 0·33 (0·09-0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. INTERPRETATION: The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. FUNDING: Bayer.

• MeSH
• antikoagulancia * škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• fibrilace síní * farmakoterapie   MeSH
• inhibitory faktoru Xa * škodlivé účinky   MeSH
• krvácení chemicky indukované   MeSH
• lidé MeSH
• pyrazoly škodlivé účinky   MeSH
• pyridony škodlivé účinky   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antikoagulancia * MeSH
• apixaban MeSH Prohlížeč
• inhibitory faktoru Xa * MeSH
• pyrazoly MeSH
• pyridony MeSH

The authors investigated haemostatic parameters of 43 patients with monoclonal gammapathy with principal diagnosis of multiple myeloma (MM-35), non-Hodgkin's lymphoma (NHL-3), M. Waldenström (3) and monoclonal gammapathy of undetermined significance (MGUS-2). Primary haemostasis defect was found in 24 patients. With the exception of 2 thrombocytopenic patients, the defect of aggregation, procoagulant activity and retraction is supposed to be caused by paraprotein. The examination of the 14C 5-HT release and TX B2 synthesis in thrombocytes showed, that platelet activation is unaffected and the paraprotein interferes with interactions of thrombocytes or with coagulation system. In plasma coagulation system explicit abnormalities were found only in thrombin time in 12 patients. The more detailed examination disclosed, that the defect resulted from paraprotein interference with fibrin monomer polymerisation. The thrombin proteolytic activity remained unaffected. In 3 patients shortened euglobulin lysis time was observed. Laboratory haemostasis defect was found in 26 patients (60%), however, the bleeding symptoms manifested in 5 cases (11%) only. The analysis of study results showed, that the most important abnormalities leading to overt bleeding are thrombocytopenia or combined haemostasis defect. Isolated laboratory defects remained silent in most cases.

• MeSH
• hemostáza * MeSH
• lidé MeSH
• paraproteinemie krev   etiologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH