189 results on '"Lassila R"'
Search Results
2. Química comprensible. Enlaces químicos
- Author
-
M. E. Kenney, Gordon M. Barrow, J. D. Lassila, R. L. Litle, W. E. Thompson and M. E. Kenney, Gordon M. Barrow, J. D. Lassila, R. L. Litle, W. E. Thompson
- Published
- 2022
3. PB1082 Comprehensive Coagulation Activity Assessments of Escalating Doses of Intravenous APAC, a Heparin Proteoglycan Mimic, in Pigs
- Author
-
Jouppila, A., primary, Bagoly, Z., additional, Orbán-Kálmándi, R., additional, Lóczi, L., additional, Bomberák, D., additional, Deák, Á., additional, Mátrai, Á., additional, Németh, N., additional, and Lassila, R., additional
- Published
- 2023
- Full Text
- View/download PDF
4. OC 62.2 Antiplatelet and Anticoagulant Compound (APAC) Restricts Thromboinflammation to Ameliorates Myocardial Ischemia Reperfusion Injury
- Author
-
Fatima, S., primary, Ambreen, S., additional, Kohli, S., additional, Lassila, R., additional, Isermann, B., additional, and Shahzad, K., additional
- Published
- 2023
- Full Text
- View/download PDF
5. PB1245 Efficacy, Safety and Dosing of Pasteurized Plasma-Derived von Willebrand Factor/Factor VIII Concentrate for the Treatment of von Willebrand Disease: A Systematic Review
- Author
-
Escuriola-Ettingshausen, C., primary, Lassila, R., additional, Escolar, G., additional, Male, C., additional, Schirner, K., additional, Heyder, L., additional, and Berntorp, E., additional
- Published
- 2023
- Full Text
- View/download PDF
6. APAC treatment limits collar-induced carotid atherosclerotic plaque development in apoE-/- mice
- Author
-
Bot, I., primary, Delfos, L., additional, Hemme, E., additional, Kovanen, P.T., additional, Jouppila, A., additional, and Lassila, R., additional
- Published
- 2022
- Full Text
- View/download PDF
7. APAC treatment limits collar-induced carotid atherosclerotic plaque development in apoE-/- mice
- Author
-
Bot, I., Delfos, L., Hemme, E., Kovanen, P.T., Jouppila, A., and Lassila, R.
- Subjects
Physiology ,Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Introduction and aim: Mimics of mast cell-derived heparin proteoglycans (HEP-PG) can be tailored to molecules carrying both antiplatelet and anticoagulant properties. These dual antiplatelet and anticoagulant (APAC) constructs can also shield adhesion molecules such as P-selectin and VCAM-1 expressed by endothelial cells upon atherosclerosis development. We hypothesize that via this way, APAC prevents macrophage accumulation and lesion development. In this study, we therefore determined the efficacy of APAC in inhibiting atherosclerosis. Methods Male western-type diet fed apoE-/- mice were equipped with perivascular carotid artery collars to induce atherosclerosis. In this collar model, mRNA expression of adhesion molecules such as ICAM-1, VCAM-1, P-Selectin but also of Platelet Factor 4 (PF4) are significantly upregulated upon lesion development (all P Results APAC treatment did not affect body weight or plasma total cholesterol levels of the mice during the experiment. Interestingly, carotid artery plaque size was reduced by over 50% upon APAC treatment (APAC: 50±10*10E3 versus controls: 102±13*10E3 square µm; P Conclusion We here show that APAC effectively inhibits atherosclerotic lesion development when administered during lesion initiation and may have potential as therapeutic agent to prevent atherosclerosis.
- Published
- 2022
8. Combined oral contraceptives containing estradiol valerate vs ethinylestradiol on coagulation:a randomized clinical trial
- Author
-
Haverinen, A. H. (Annina H.), Luiro, K. M. (Kaisu M.), Szanto, T. (Timea), Kangasniemi, M. H. (Marika H.), Hiltunen, L. (Leena), Sainio, S. (Susanna), Piltonen, T. T. (Terhi T.), Lassila, R. (Riitta), Tapanainen, J. S. (Juha S.), and Heikinheimo, O. (Oskari)
- Subjects
estradiol valerate ,thrombin generation ,dienogest ,combined oral contraception ,coagulation - Abstract
Introduction: Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E₂] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. Material and methods: We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2–3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). Clinical trial registration: NCT02352090. Results: Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change −24%, 95% confidence interval [CI] −32% to −15%; p
- Published
- 2022
9. Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series
- Author
-
Iorio, A., Barbara, A. M., Makris, M., Fischer, K., Castaman, G., Catarino, C., Gilman, E., Kavakli, K., Lambert, T., Lassila, R., Lissitchkov, T., Mauser‐Bunschoten, E., Mingot‐Castellano, M. E., Ozdemir, N., Pabinger, I., Parra, R., Pasi, J., Peerlinck, K., Rauch, A., Roussel‐Robert, V., Serban, M., Tagliaferri, A., Windyga, J., and Zanon, E.
- Published
- 2017
- Full Text
- View/download PDF
10. Neoadjuvant Treatment and the Prolonged Risk of Venous Thromboembolism in Resectable Pancreatic Cancer
- Author
-
Eurola, A., primary, Mustonen, H., additional, Mattila, N., additional, Lassila, R., additional, Haglund, C., additional, and Seppänen, H., additional
- Published
- 2022
- Full Text
- View/download PDF
11. 3. Heparin-induced thrombocytopenia
- Author
-
Lassila, R., primary
- Published
- 2016
- Full Text
- View/download PDF
12. Productization of building information models
- Author
-
Lassila, R. (Reetta)
- Abstract
Building information models contain a great amount of data in various lifecycle phases throughout building projects. Data is generally not seen as an asset yet building information models’ (BIM) value is recognized. Seeing BIM models value as an asset and maintaining a structured product lifecycle management (PLM) in organization leads to need of productization of BIM Models, just like tangible products. Building information modeling is a known term within the building industry, but product lifecycle management is unconventional. Productization practices that include PLM have few examples in the academia or of use in the building industry. This thesis aims to study the possibilities of productizing building information models to commercial and technical items and presents background to it. Building information models are currently not seen as commercial products, but it is acknowledged they are valuable and have great potential in changing the practices and productivity in the whole building industry. BIM models are not handled as products, and they are not included to order-delivery-invoicing practices and systems as commercial products. BIM models can contain a broad and multidimensional amount of information and some structuring practices of BIM models remind closely of bill of material (BOM) in technical product structures. Information content of BIM models increases and becomes more precise continuously, but to benefit financially of the additional value of BIM models is insufficient in terms of understanding their possibilities in content and commercial value. This thesis presents the definition and current state of the productization practices of BIM models and offers a recommendation to productize BIM models as a part of construction object configuration commercially and technically. The work is done reviewing current literature and via a current state analysis of a case company. Within the thesis, it is recommended to be establish a new product category into construction product offering alongside to hardware, software, and services: BIM products. From the commercial aspect, it is recommended to divide BIM models into three categories based on their status in a commercial product portfolio: open BIM models, BIM model products and BIM model systems. The recommendations of building a BIM model product structure are based on a BIM framework theory, which allows to separate the broad and multidimensional information structures of BIM models in structured and understandable form. The results of this study can be generalized and used in the building industry internationally. The results of this thesis are significant for any organization wanting to change their building information models’ status from technical tools into commercial products in a structured way.Tiivistelmä. Rakennusalan tietomallit sisältävät merkittävän määrän dataa rakennushankkeen eri elinkaaren vaiheissa. Datan ei ole tyypillisesti ajateltu olevan yrityksen pääomaa, mutta kuitenkin on tunnistettu, että tietomalleilla on arvo. Mikäli tietomallien arvo tunnistetaan, ja niitä halutaan alkaa kohtelemaan yrityksen pääomana, johtaa se tuotteen elinkaarenhallinnan (PLM) käytäntöjä noudattavalta organisaatiolta tarpeeseen tuotteistaa tietomallit, kuten fyysiset tuotteetkin. Termeinä tietomalli on tunnettu rakennusalalla, kun taas PLM on harvinaisempi; PLM ja tuotteistuskäytännöt ovat rakennusalalla vähän tutkittuja ja vähän käytössä. Tämän opinnäytetyön tarkoituksena on tutkia mahdollisuuksia siihen, miten tietomallit tuotteistettaisiin kaupallisiksi ja teknisiksi tuotteen osiksi, sekä esittää taustatietoja tietomallien tuotteistukselle. Tällä hetkellä tietomalleja ei ajatella kaupallisina tuotteina, vaikka niiden arvo ja mahdollisuudet jopa koko rakennusalan muuttamiseen ja tuottavuuden parantamiseen tunnistetaan. Tietomalleja ei myöskään käsitellä kuten tuotteita, eivätkä ne ole osa tilaus-toimitus-laskutus-käytäntöjä tai -ohjelmistoja kaupallisina tuotteina. Tietomallit voivat kuitenkin sisältää huomattavan määrän monimuotoista informaatiota, ja jotkut tietomallien rakenteen kuvaukset muistuttavat jopa tuotteistamisesta tuttuja teknisten tuoterakenteiden BOM:a (Bill-of-Material). Tietomallien datasisältö lisääntyy ja tarkentuu jatkuvasti, mutta kuitenkin ymmärrys tietomallien sisältöön liittyvistä kaupallisista mahdollisuuksista on liian vähäistä, jotta niistä voitaisiin hyötyä kaupallisesti. Tämä tutkimus esittelee ja määrittelee tämänhetkiset tietomallien tuotteistuskäytännöt ja tarjoaa ratkaisuehdotuksen tietomallien tekniseen ja kaupalliseen tuotteistukseen osaksi rakennusalan tuotevalikoimaa. Työ on tehty perehtymällä kirjallisuuskatsaukseen ja tekemällä nykytila-analyysi valitusta case-yrityksestä. Tämän työn tuloksena suositellaan uuden tietomalli-tuotekategorian perustamista nykyisten rakennusalan tuotevalikoiman fyysisten tuotteiden (HW), ohjelmistotuotteiden (SW) ja palvelutuotteiden (service) rinnalle. Tutkimuksen perusteella tietomallituotteet olisi myös syytä jakaa kaupallisen käytön perusteella kolmeen pääkategoriaan; ilmaiset tietomallituotteet, kaupalliset tietomallituotteet ja tietomallijärjestelmätuotteet. Tietomallien tuoterakenteen muodostamiseen ehdotetaan käytettävän BIM framework-teoriaa, jonka avulla monimuotoisia tietorakenteita on helpompi strukturoida. Tämän tutkimuksen tuloksia voidaan käyttää yleisesti rakennusalalla niin kansallisesti kuin kansainvälisesti. Tutkimuksen tulokset ovat merkittäviä sellaisille organisaatioille, jotka tunnistavat tietomalliensa datasisällön arvon pääomana ja siten haluavat johdonmukaisesti muuttaa heidän tietomalliensa statuksen teknisestä apuvälineestä kaupalliseksi tuotteeksi ja siten osaksi tuoteportfoliotaan.
- Published
- 2021
13. Thromboelastometry detects enhancement of coagulation in blood by emicizumab via intrinsic pathway
- Author
-
Szanto, T, Vaide, I, Jouppila, A, Lemponen, M, Lassila, R, Clinicum, Research Programs Unit, HUS Internal Medicine and Rehabilitation, Department of Medicine, Hematologian yksikkö, and HUS Comprehensive Cancer Center
- Subjects
3121 General medicine, internal medicine and other clinical medicine ,education ,3122 Cancers - Abstract
Non
- Published
- 2021
14. Safety surveillance in haemophilia and allied disorders
- Author
-
Lassila, R. and Makris, M.
- Published
- 2016
- Full Text
- View/download PDF
15. Impact of Platelet Function on Clinical Phenotypes in Von Willebrand Disease: Re-Evaluation of 83 Patients with Historical Diagnosis: OR08
- Author
-
JOKELA, V. H., LASSILA, R., JOUTSIKORHONEN, L., ARMSTRONG, E., and SZANTO, T.
- Published
- 2016
16. Complications associated with central venous access device in children with haemophilia: a nationwide multicentre study in Finland
- Author
-
VEPSÄLÄINEN, K., LASSILA, R., AROLA, M., LÄHTEENMÄKI, P., MÖTTÖNEN, M., MÄKIPERNAA, A., and RIIKONEN, P.
- Published
- 2015
- Full Text
- View/download PDF
17. Systemic matrix metalloproteinase-8 and tissue inhibitor of metalloproteinases-1 levels in severe sepsis-associated coagulopathy
- Author
-
Sivula, M., Hästbacka, J., Kuitunen, A., Lassila, R., Tervahartiala, T., Sorsa, T., and Pettilä, V.
- Published
- 2015
- Full Text
- View/download PDF
18. Levels of the cancer biomarker CA 19-9 are associated with thrombin generation in plasma from treatment-naïve pancreatic cancer patients
- Author
-
Mattila, N., primary, Hisada, Y., additional, Przybyla, B., additional, Posma, J., additional, Jouppila, A., additional, Haglund, C., additional, Seppänen, H., additional, Mackman, N., additional, and Lassila, R., additional
- Published
- 2021
- Full Text
- View/download PDF
19. Neoadjuvant Therapy and Venous Thromboembolism after Surgery in Pancreatic Cancer
- Author
-
Eurola, A., primary, Mattila, N., additional, Lassila, R., additional, Mustonen, H., additional, Haglund, C., additional, and Seppänen, H., additional
- Published
- 2021
- Full Text
- View/download PDF
20. Bleeding symptoms in patients diagnosed as type 3 von willebrand disease: results from 3WINTERS‐IPS, an international and collaborative cross‐sectional study
- Author
-
Tosetto, A., Badiee, Z., Baghaipour, M., Baronciani, L., Battle, J., Berntorp, E., Bodó, I., Budde, U., Castaman, G., Eikenboom, J.C.J., Eshghi, P., Ettorre, C., Goodeve, A., Goudemand, J., Charles Richard Morris, H., Hoorfar, H., Karimi, M., Keikhaei, B., Lassila, R., Leebeek, F.W.G., Lopez Fernandez, M.F., Mannucci, P.M., Mazzucconi, M.G., Morfini, M., Oldenburg, J., Peake, I., Parra Lòpez, R., Peyvandi, F., Schneppenheim, R., Tiede, A., Toogeh, G., Trossaert, M., Zekavat, O., Zetterberg, E.M.K., and Federici, A.B.
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,hemic and lymphatic diseases - Abstract
Background\ud Type 3 von Willebrand’s disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD.\ud \ud Aims\ud To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients; to investigate any possible clustering of bleeding symptoms within type 3 patients.\ud \ud Methods\ud We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM‐1VWD bleeding questionnaire in patients enrolled in the 3WINTERS‐IPS and MCMDM‐1VWD studies.\ud \ud Results\ud In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15. vs. 6.0 and 5 vs. 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five‐fold over‐represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having VWF:Ag levels
- Published
- 2020
21. Fundamentals for a systematic approach to mild and moderate inherited bleeding disorders
- Author
-
Rodeghiero, F., Pabinger, I., Ragni, M., Abdul-Kadir, R., Berntorp, E., Blanchette, V., Bodó, I., Casini, A., Gresele, P., Lassila, R., Leebeek, F., Lillicrap, D., Mezzano, D., Noris, P., Srivastava, A., Tosetto, A., Windyga, J., Zieger, B., Makris, M., and Key, N.
- Abstract
Healthy subjects frequently report minor bleedings that are frequently ‘background noise’ of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Understanding the underlying pathologic mechanism in patients with an excessive bleeding is essential for their counseling and treatment. Most of these patients with significant bleeding will result affected by non-severe inherited bleeding disorders (BD), collectively denominated mild or moderate BD for their relatively benign course. Unfortunately, practical recommendations for the management of these disorders are still lacking due to the current state of fragmented knowledge of pathophysiology and lack of a systematic diagnostic approach. To address this gap, an International Working Group (IWG) was established by the European Hematology Association (EHA) to develop consensus-based guidelines on these disorders. The IWG agreed that grouping these disorders by their clinical phenotype under the single category of mild-to-moderate bleeding disorders (MBD) reflects current clinical practice and will facilitate a systematic diagnostic approach. Based on standardized and harmonized definitions a conceptual unified framework is proposed to distinguish normal subjects from affected patients. The IWG proposes a provisional comprehensive patient-centered initial diagnostic approach that will result in classification of MBD into distinct clinical-pathological entities under the overarching principle of clinical utility for the individual patient. While we will present here a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence-based, disease-specific guidelines under development by the IWG.
- Published
- 2019
22. Hemostatic profile under fluid resuscitation during rivaroxaban anticoagulation: an in vitro survey
- Author
-
Helin, T. A., Zuurveld, M., Manninen, M., Meijers, J. C. M., Lassila, R., Brinkman, H. J. M., HUSLAB, Department of Clinical Chemistry and Hematology, Medicum, Clinicum, Department of Medicine, and HUS Comprehensive Cancer Center
- Subjects
PLASMA ,IMPACT ,REVERSAL ,3121 General medicine, internal medicine and other clinical medicine ,TRANEXAMIC ACID ,FACTOR-XA INHIBITOR ,THROMBIN GENERATION ,PROTHROMBIN COMPLEX CONCENTRATE ,THROMBOPROPHYLAXIS ,SUPPLEMENTATION ,TRAUMA - Abstract
BACKGROUND: Uncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown. STUDY DESIGN AND METHODS: In this study, we investigated the effect of the resuscitation fluid s saline, albumin, fresh frozen plasma (FFP) and solvent/ detergent (S/D)-treated plasma, fibrinogen concentrate, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban-anticoagulated whole blood and plasma. We used rivaroxaban-spiked whole blood and plasma from healthy donors, as well as plasma from patients on rivaroxaban, and mimicked a resuscitation approach in a 50% plasma dilution setting. Thromboelastography, thrombin generation, and fibrin generation clot lysis test were assessed using tissue factor to initiate coagulation and tissue plasminogen activator to induce clot lysis. RESULTS: Rivaroxaban resulted in a hypocoagulant state that remained largely unaltered upon subsequent 50% dilution with S/D-treated plasma or FFP. Using SID treated plasma as a diluent, clot stability decreased due to its low (12-antiplasmin. Dilution with saline and albumin induced a profibrinolytic state and further deteriorated the impaired hemostatic potential of rivaroxabananticoagulated blood, even after PCC and fibrinogen support. Combined use of plasma (either FFP or S/D treated) and PCC, however, considerably improved both coagulation and clot stability. CONCLUSION: In the setting of rivaroxaban anticoagulation and major blood loss, transfusing plasma together with PCC may provide the most effective resuscitation approach with the notion that additional antifibrinolytic drug support (e.g., tranexamic acid) is likely required.
- Published
- 2018
23. PF797 APAC, A DUAL ANTIPLATELET AND ANTICOAGULANT - TOWARDS A LOCAL, VASCULAR TARGETING ANTITHROMBOTIC
- Author
-
Jouppila, A., primary, Barreiro, K., additional, Tulamo, R., additional, Parry, M., additional, Albäck, A., additional, and Lassila, R., additional
- Published
- 2019
- Full Text
- View/download PDF
24. Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely III Medical Patients: An APEX Trial Substudy
- Author
-
Gibson, C. M., Korjian, S., Chi, G., Daaboul, Y., Jain, P., Arbetter, D., Goldhaber, S. Z., Hull, R., Hernandez, A. F., Lopes, R. D., Gold, A., Cohen, A. T., Harrington, R. A., Bello, F., Ferrari, A. E., Jure, H., Macin, S., Oliva, M., Parody, M., Poy, C., Baker, R., Colquhoun, D., Coughlin, P., Finfer, S., Hammerschlag, G., Rubinfeld, A., Huber, K., Konig, J., Mathies, R., Pilger, E., Schoenerr, H., Adzerikho, I., Koryk, V., Mikhailova, E., Mitkovskaya, N., Pimanov, S., Polonetsy, L., Soroka, N., Blockmans, D., Delforge, M., Dive, A., Lienart, F., Motte, S., Annichino Bizzacchi, J., Fiss, E., Freire, A., Manenti, E., Ramacciotti, E., Raymuno, S., Rocha, A., Saraiva, J. F., Dimov, B., Grigorov, M., Kalpachki, R., Kamenova, Z., Kostadinova, M., Milanova, M., Mincheva, V., Pencheva, G., Raev, D., Runev, N., Stoeva, N., Stoyanov, M., Syulemzova, S., Todorov, G., Tokmakova, M., Dhar, A., Douketis, J., Kahn, S., Le Gal, G., Pearce, M., Provencher, S., Verreault, S., Arias Alarcon, M., Olivares Canon, C., Opazo Lazcano, M., Potthoff Cardenas, S., Butkovic-Soldo, S., Car, S., Ciglenecki, N., Francetic, I., Jakopovic, M., Kalinic-Grgorinic, H., Knezevic, A., Malojcic, B., Marusic, S., Sikic Vagic, J., Skerk, V., Cermak, O., Cervinka, P., Chlumsky, J., Chochola, J., Cizek, V., Dunaj, M., Dusek, J., Francek, L., Havelka, J., Herold, M., Holaj, R., Horny, I., Hubac, J., Jajtner, P., Kolman, P., Lang, P., Mayer, O., Mikulova, J., Podpera, I., Reiterer, P., Spacek, R., Vejvoda, J., Vyhnanek, M., Christensen, H., Lassen, M., Storgaard, M., Tuxen, C., Urhammer, S., Lember, M., Marandi, T., Uuetoa, T., Airaksinen, J., Honkaniemi, J., Kaaja, R., Lassila, R., Saarinen, J., Tatlisumak, T., Vikman, S., Agraou, B., Aquilanti, S., Belhassane, A., Brisot, D., De Geeter, G., Debourdeau, P., Decoulx, E., El Kouri, D., Falvo, N., Grange, C., Lacroix, P., Messas, E., Mismetti, P., Montaclair, K., Mottier, D., Paleiron, N., Payot, L., Pernod, G., Pottier, P., Proust, A., Quere, I., Roy, P. -M., Schmidt, J., Simoneau, G., Datikashvili-David, I., Khabeishvili, G., Khintibidze, I., Kobulia, B., Megreladze, I., Pagava, Z., Paposhvili, K., Shaburishvili, T., Amann, B., Berrouschot, J., Beyer-Westendorf, J., Blessing, E., Bott, M., Dengler, T., Diehm, C., Dziewas, R., Genth-Zotz, S., Hamann, F., Horacek, T., Klimpe, S., Kroning, R., Lapp, H., Lawall, H., Licka, M., Rizos, T., Schellong, S., Schmidt-Lucke, J., Singer, C., Tiefenbacher, C., Veltkamp, R., Weimar, C., Zeymer, U., Alkonyi, B., Falukozy, J., Futo, L., Katona, A., Kirschner, R., Kristof, P., Lakatos, F., Laszlo, Z., Lupkovics, G., Merkely, B., Nagy Andras, C., Nemeth, L., Papp, A., Soltesz, P., Sudar, Z., Szabo, G., Szegedi, N., Timar, G., Valco, J., Vertes, A., Efrati, S., Elias, M., Gafter, A., Hayek, T., Hussein, O., Lishner, M., Lugassy, G., Zeltser, D., Ageno, W., Cerveri, I., D'Angelo, A., De Pellegrin, A., Imberti, D., Landolfi, R., Lembo, G., Lodigiani, C., Luisetti, M., Moia, M., Molteni, M., Mumoli, N., Novo, S., Orlandini, F., Parisi, R., Pizzini, A., Pomero, F., Salvi, A., Schenone, A., Visona, A., Krievins, D., Martinova, V., Pontaga, N., Rozitis, V., Stukena, I., Alekniene, B., Bagdonas, A., Basijokiene, V., Butkiene, Z., Griskeviciene, V., Naudziunas, A., Norvaisiene, R., Norviliene, R., Petrauskiene, R., Poskiene, R., Susinskiene, D., Valavicius, A., Castillo Leon, R., Cotrina Pereyra, R., Farjardo Karlo, L., Horna, M., Lema Osores, J., Salas, M., Toche Yanez, L., Fryze, W., Gaciong, Z., Gniot, J., Gorecka, D., Gruenpeter, P., Grzelakowski, P., Jastrzebski, D., Kucharski, L., Mirek-Bryniarska, E., Pulkowski, G., Sobkowicz, B., Sulik, P., Tomkowski, W., Walasek, L., Waldemar, K., Wrzesinski, K., Balogh, Z. E., Bojinca, M., Marin, I., Mot, S., Musetescu, R., Podoleanu, C., Popescu, M., Stamate, S., Stanciulescu, G., Vida-Simiti, L., Abashev, A., Andreev, D., Apartsin, K., Arkhipov, M., Averkov, O., Barbarash, O., Belskaya, G., Bogdanov, E., Boldueva, S., Chefranova, Z., Dovgalevskiy, Y., Ershova, O., Goloshchekin, B., Khachatryan, N., Khurs, E., Klein, G., Kobalava, Z., Kosmacheva, E., Kostenko, V., Malygin, A., Martynenko, T., Martynenko, V., Maslova, N., Mordovin, V., Nikolaev, K., Nilk, R., Panchenko, E., Popov, D., Privalova, E., Reshetko, O., Sergeeva, E., Shapovalova, Y., Shpagina, L., Shvarts, Y., Simanenkov, V., Solovyov, O., Vishneva, E., Vishnevskiy, A., Apostolovic, S., Celic, V., Ilic, S., Kovacevic-Kuzmanovic, A., Miloradovic, V., Tan, R. S., Bodikova, S., Cervenakova, A., Dvorak, M., Gaspar, L., Herman, O., Hrubon, A., Kokles, M., Krastev, G., Payer, J., Prokop, D., Spisakova, M., Adler, D., Basson, M., Breedt, J., Engelbrecht, J., Jacobson, B., Mitha, I., Van Dyk, C., Alvarez Sala, L. A., Barbagelata Lopez, C., Bisbe, J., Castro Guardiola, A., Cepeda, J. M., Cereto, F., Diaz Santos, E., Ferrer, R., Gomez Cerezo, J., Gonzales-Porras, J. R., Grandes, J., Jimenez, D., Martin Loeches, I., Mellibovsky, L., Richart, C., Riera, A., Trujillo, J., Vargas Nunez, J. A., Villalta, J., Akgul, O., Guneri, S., Kilichesmez, K., Kirma, C., Kutluk, H., Nazliel, B., Okumus, G., Ongen, G., Tigen, K., Topcuoglu, M., Tuncay, E., Abrahamovych, O., Batushkin, V., Brozhyk, J., Burmak, I., Godlevska, O., Goloborodko, A., Goloborodko, B., Goncharova, Y., Gryb, V., Karpenko, O., Kopytsya, M., Koshlia, V., Krakhmalova, O., Kyrychenko, I., Legkonogov, O., Malynovsky, Y., Maslovaskyi, V., Nikonov, V., Parkhomenko, O., Perepeliuk, M., Reshotko, D., Rudenko, L., Ryabichenko, T., Svyridova, I., Svyshchenko, Y., Tseluyko, V., Ursol, G., Vakaliuk, I., Vishnivestsky, I., Voronkov, L., Yagensky, A., Body, R., Chandra, D., Davis, M., Kesteven, P., Maccallum, P., Mccollum, C., Natarajan, I., Almasri, E., Amin, M., Anderson, C., Baker, S., Barney, J., Bastani, B. B. A., Bercz, P., Bidair, M., Carman, T., Chang, H., Clark, C., Concha, M., Cornell, J., Dhingra, R., Doshi, A., Ebrahimi, R., Farley, B., Fermann, G., Foster, G., Fraiz, J., Fulmer, J., Gaggin, H., Goytia-Leos, D., Hahn, B., Haidar, A., Hamad, A., Hazelrigg, M., Ioachimescu, O., Johnson, B., Kabler, H., Kao, C. -K., Kazimir, M., Kouras, F., Kung, M., Lerner, R., Lopez, J., Macchiavelli, A., Mahal, S., Margolis, B., Mclaren, G., Milling, T., Mittal, M., Nadar, V., Ohaju, V., Ortel, T., Overcash, J., Parthiban, K., Pearl, R., Pineda, L., Pratt, R., Pullman, J., Quintana, O., Rajan, R., Rastogi, P., Rees, C., Rodriguez, W., Saba, F., Shammas, N., Sharma, S., Sokol, S., Stoltz, S., Subich, D., Tuck, M., Updegrove, J., Warner, A., Welch, M., Welker, J., Whitman, B., Wichman, T., Yousef, K., Yusen, R., and Zakai, N.
- Subjects
Male ,pulmonary embolism ,Time Factors ,Pyridines ,Intracranial hemorrhage ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Risk Factors ,Clinical Studies ,Medicine ,030212 general & internal medicine ,Myocardial infarction ,Original Research ,Ischemic stroke ,Hazard ratio ,Absolute risk reduction ,Venous Thromboembolism ,Middle Aged ,Interventional Cardiology ,Pulmonary embolism ,Death ,myocardial infarction ,Treatment Outcome ,Cardiovascular Diseases ,Anesthesia ,Acute Disease ,Benzamides ,Number needed to treat ,Female ,Cardiology and Cardiovascular Medicine ,Intracranial Hemorrhages ,Adult ,venous thromboembolism ,Hemorrhage ,03 medical and health sciences ,Double-Blind Method ,death ,ischemic stroke ,Humans ,Enoxaparin ,Aged ,Proportional Hazards Models ,Inpatients ,Venous thromboembolism ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Anticoagulants ,Thrombosis ,medicine.disease ,Clinical trial ,chemistry ,Betrixaban ,business ,Acute Coronary Syndromes ,intracranial hemorrhage ,Factor Xa Inhibitors - Abstract
Background Extended‐duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. Methods and Results This was a post hoc analysis of the APEX trial—a multicenter, double‐blind, randomized controlled trial comparing extended‐duration betrixaban versus standard‐of‐care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time‐to‐first event analysis. In patients with positive D‐dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [ P =0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [ P =0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [ P =0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [ P =0.002]). Conclusions Among hospitalized medically ill patients, extended‐duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard‐duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. Clinical Trial Registration URL : http://www.ClinicalTrials.gov . Unique identifier: NCT 01583218.
- Published
- 2017
25. Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment
- Author
-
Pitkänen, H. H., primary, Kärki, M., additional, Niinikoski, H., additional, Tanner, L., additional, Näntö-Salonen, K., additional, Pikta, M., additional, Kopatz, W. F., additional, Zuurveld, M., additional, Meijers, J. C. M., additional, Brinkman, H. J. M., additional, and Lassila, R., additional
- Published
- 2018
- Full Text
- View/download PDF
26. P6559APAC, a dual antiplatelet and anticoagulant, attenuates platelet procoagulant activity and localizes to extravascular matrix during vascular injury
- Author
-
Jouppila, A, primary, Barreiro, K, additional, Tulamo, R, additional, Alback, A, additional, Lemponen, M, additional, and Lassila, R, additional
- Published
- 2018
- Full Text
- View/download PDF
27. Long-term clinical and economic outcomes in previously untreated paediatric patients with severe haemophilia A: A nationwide real-world study with 700 person-years
- Author
-
Vepsäläinen, K., primary, Riikonen, P., additional, Lassila, R., additional, Arola, M., additional, Huttunen, P., additional, Lähteenmäki, P., additional, Möttönen, M., additional, Selander, T., additional, and Martikainen, J., additional
- Published
- 2018
- Full Text
- View/download PDF
28. Comprehensive re-evaluation of historical von Willebrand disease diagnosis in association with whole blood platelet aggregation and function
- Author
-
Nummi, V., primary, Lassila, R., additional, Joutsi-Korhonen, L., additional, Armstrong, E., additional, and Szanto, T., additional
- Published
- 2018
- Full Text
- View/download PDF
29. Characterization Of Health Care Utilization And Cost Of Hemophilia A And B In Real-Life: A 4-Year Follow-UP Study In Finland
- Author
-
Ventola, H, primary, Jokelainen, J, additional, Linna, M, additional, Lepäntalo, A, additional, Ylisaukko-oja, T, additional, and Lassila, R, additional
- Published
- 2017
- Full Text
- View/download PDF
30. Inhibitor development in non-severe haemophilia across Europe
- Author
-
Fischer, K., Iorio, A., Lassila, R., Peyvandi, F., Calizzani, G., Gatt, A., Lambert, T., Windyga, J., Gilman, E.A., Makris, M., and Participants, E.U.H.A.S.S.
- Subjects
Multicenter Study ,congenital, hereditary, and neonatal diseases and abnormalities ,Research Support, Non-U.S. Gov't ,hemic and lymphatic diseases ,Journal Article - Abstract
Evidence about inhibitor formation in non-severe haemophilia and the potential role for clotting factor concentrate type is scant. It was the aim of this study to report inhibitor development in non-severe haemophilia patients enrolled in the European Haemophilia Safety Surveillance (EUHASS) study. Inhibitors are reported quarterly and total treated patients annually. Incidence rates and 95 % confidence intervals (95 % CI) were calculated according to diagnosis and concentrate used. Between 1–10–2008 and 31–12–2012, 68 centres reported on 7,969 patients with non-severe haemophilia A and 1,863 patients with non-severe haemophilia B. For haemophilia A, 37 inhibitors occurred in 8,622 treatment years, resulting in an inhibitor rate of 0.43/100 treatment years (95 % CI 0.30–0.59). Inhibitors occurred at a median age of 35 years, after a median of 38 exposure days (EDs; P25-P75: 20–80); with 72 % occurring within the first 50 EDs. In haemophilia B, one inhibitor was detected in 2,149 treatment years, resulting in an inhibitor rate of 0.05/100 years (95% CI 0.001–0.26). This inhibitor developed at the age of six years, after six EDs. The rate of inhibitors appeared similar across recombinant and plasma derived factor VIII (FVIII) concentrates. Rates for individual concentrates could not be calculated at this stage due to low number of events. In conclusion, inhibitors in non-severe haemophilia occur three times more frequently than in previously treated patients with severe haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100 years (haemophilia B). Although the majority of inhibitors developed in the first 50 EDs, inhibitor development continued with increasing exposure to FVIII.
- Published
- 2015
31. Weekly recombinant FIX prophylaxis for severe haemophilia B in normal clinical practice: data from UKHCDO and Finland
- Author
-
Scott, M., primary, Nummi, V., additional, Lassila, R., additional, Xiang, H., additional, and Hay, C. R. M., additional
- Published
- 2017
- Full Text
- View/download PDF
32. Monitoring once-weekly recombinant factor IX prophylaxis in hemophilia B with thrombin generation assay and factor IX activity
- Author
-
Nummi, V., primary, Jouppila, A., additional, and Lassila, R., additional
- Published
- 2017
- Full Text
- View/download PDF
33. Can Vascular Calcification be Associated with Warfarin Treatment?
- Author
-
Siltari, A., primary, Helin, T., additional, Wickholm, N., additional, Lassila, R., additional, Korpela, R., additional, Kautiainen, H., additional, and Vapaatalo, H., additional
- Published
- 2016
- Full Text
- View/download PDF
34. Inhibitor development in previously untreated patients with severe haemophilia A: a nationwide multicentre study in Finland
- Author
-
Vepsäläinen, K., primary, Lassila, R., additional, Arola, M., additional, Huttunen, P., additional, Koskinen, S., additional, Ljung, R., additional, Lähteenmäki, P., additional, Möttönen, M., additional, and Riikonen, P., additional
- Published
- 2016
- Full Text
- View/download PDF
35. PHS45 - Characterization Of Health Care Utilization And Cost Of Hemophilia A And B In Real-Life: A 4-Year Follow-UP Study In Finland
- Author
-
Ventola, H, Jokelainen, J, Linna, M, Lepäntalo, A, Ylisaukko-oja, T, and Lassila, R
- Published
- 2017
- Full Text
- View/download PDF
36. Systemic matrix metalloproteinase-8 and tissue inhibitor of metalloproteinases-1 levels in severe sepsis-associated coagulopathy
- Author
-
SIVULA, M., primary, HÄSTBACKA, J., additional, KUITUNEN, A., additional, LASSILA, R., additional, TERVAHARTIALA, T., additional, SORSA, T., additional, and PETTILÄ, V., additional
- Published
- 2014
- Full Text
- View/download PDF
37. P1.13 - Can Vascular Calcification be Associated with Warfarin Treatment?
- Author
-
Siltari, A., Helin, T., Wickholm, N., Lassila, R., Korpela, R., Kautiainen, H., and Vapaatalo, H.
- Published
- 2016
- Full Text
- View/download PDF
38. From laboratory to clinical practice: Dabigatran effects on thrombin generation and coagulation in patient samples.
- Author
-
Helin, T. A., Lemponen, M., Hjemdahl, P., Rönquist-Nii, Y., Lassila, R., and Joutsi-Korhonen, L.
- Subjects
- *
THROMBIN , *LIQUID chromatography , *MASS spectrometry , *FIBRINOGEN , *PROTHROMBIN time , *HYPERCOAGULATION disorders - Abstract
INTRODUCTION: Dabigatran (Dabi) is not routinely monitored. However, in emergency cases quantitative assessment is required and laboratories must provide suitable tests at all hours. Little is known about Dabi effects on thrombin generation. MATERIALS AND METHODS: Patient samples (n=241) were analyzed for functional Dabi concentrations (Dabi-TT) using a combination of the Hemoclot Thrombin Inhibitors assay (HTI®) and, for samples with low levels, undiluted thrombin time (TT). Results were compared to prothrombin time (PT) and activated partial thromboplastin time (APTT). In 49 samples Dabi effects were further investigated with Calibrated Automated Thrombogram (CAT®) for thrombin generation and with Russell's viper venom time (RVVT), prothrombinase-induced clotting time (PiCT®), chromogenic Anti-IIa® and ecarin clotting assay (ECA®). Fibrinogen and D dimer were assessed to reflect the coagulation status of the patient. A subset of these samples (n=21) were also analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Dabi-TT correlated with RVVT (R(2)=0.49), PiCT® (R(2)=0.73), ECA® (R(2)=0.89), Anti-IIa® (R(2)=0.90) and LC-MS/MS (R(2)=0.81). APTT correlated curvi-linearly with Dabi-TT (R(2)=0.71), but was normal in many cases (18/70) despite Dabi-TT>40ng/mL. There was no association between Dabi-TT and fibrinogen or D dimer levels. Increasing Dabi concentrations prolonged lag time (R(2)=0.54) and, surprisingly, elevated the ETP and Peak of CAT® (p<0.001). CONCLUSIONS: Thrombin-specific tests measure Dabi accurately, whereas coagulation time based assays depend more on other factors. The enhanced thrombin generation in Dabi-treated patients may predict clinically relevant hypercoagulability and warrants further investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
39. Heparin-like effect of a dual antiplatelet and anticoagulant (APAC) agent on red blood cell deformability and aggregation in an experimental model.
- Author
-
Matrai AA, Varga A, Bedocs-Barath B, Vanyolos E, Orban-Kalmandi R, Loczi L, Bagoly Z, Jouppila A, Lassila R, Nemeth N, and Deak A
- Abstract
Treatments with different antithrombotic agents can affect micro-rheological variables, such as red blood cell (RBC) deformability and aggregation. Since the effect of dual antiplatelet and anticoagulant (APAC) treatment on micro-rheology is unknown, we aimed to investigate the effect of different intravenous doses of APAC on hematological and micro-rheological variables in a porcine model. Two groups were formed (APAC group, Control group), and blood was collected from the animals at preset intervals. Hematological variables, RBC deformability, and aggregation were measured. We observed an improvement in the RBC deformability measured at a low shear stress range (< 3 Pa). However, after both doses, a decrease in the maximal elongation index of RBC values occurred in the APAC group. RBC aggregation increased after APAC bolus dose, while it gradually and dose-dependently decreased. Supposedly, the improvement in RBC deformability that was observed at a lower shear rate could facilitate aggregation. Administration of APAC and unfractionated heparin (UFH) caused comparable changes in hematological and hemorheological variables. Signs of thrombosis or bleeding did not occur. APAC and UFH had comparable micro-rheological effects., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
40. Treatment with APAC, a dual antiplatelet anticoagulant heparin proteoglycan mimetic, limits early collar-induced carotid atherosclerotic plaque development in Apoe -/- mice.
- Author
-
Bot I, Delfos L, Hemme E, Bernabé Kleijn MNA, van Santbrink PJ, Foks AC, Kovanen PT, Jouppila A, and Lassila R
- Abstract
Background and Aims: Mast cell-derived heparin proteoglycans (HEP-PG) can be mimicked by bioconjugates carrying antithrombotic and anti-inflammatory properties. The dual antiplatelet and anticoagulant (APAC) construct administered, either locally or intravenously (i.v.), targets activated endothelium, its adhesion molecules, and subendothelial matrix proteins, all relevant to atherogenesis. We hypothesized that APAC influences cellular interactions in atherosclerotic lesion development and studied APAC treatment during the initiation and progression of experimental atherosclerosis., Methods: Male western-type diet-fed Apoe
-/- mice were equipped with perivascular carotid artery collars to induce local atherosclerosis. In this model, mRNA expression of adhesion molecules including ICAM-1, VCAM-1, P-Selectin, and Platelet Factor 4 (PF4) are upregulated upon lesion development. From day 1 (prevention) or from 2.5 weeks after lesion initiation (treatment), mice were administered 0.2 mg/kg APAC i.v. or control vehicle three times weekly for 2.5 weeks. At week 5 after collar placement, mice were sacrificed, and lesion morphology was microscopically assessed., Results: APAC treatment did not affect body weight or plasma total cholesterol levels during the experiments. In the prevention setting, APAC reduced carotid artery plaque size and volume by over 50 %, aligning with decreased plaque macrophage area and collagen content. During the treatment setting, APAC reduced macrophage accumulation and necrotic core content, and improved markers of plaque stability., Conclusions: APAC effectively reduced early atherosclerotic lesion development and improved markers of plaque inflammation in advanced atherosclerosis. Thus, APAC may have potential to alleviate the progression of atherosclerosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RL is the CSO and CMO of Aplagon Ltd. The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
41. Prognostic role of the neutrophil/lymphocyte ratio in high-risk BCG-naïve non-muscle-invasive bladder cancer treated with intravesical gemcitabine/docetaxel.
- Author
-
Chakra MA, Lassila R, El Beayni N, Mott SL, and O'Donnell MA
- Abstract
Objectives: To investigate the role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in the prediction of response to sequential intravesical therapy, gemcitabine and docetaxel (Gem/Doce), given to patients with bacille Calmette-Guérin (BCG)- naïve high-risk non-muscle-invasive bladder cancer (NMIBC)., Patients and Methods: A retrospective analysis was conducted on 115 patients who received intravesical Gem/Doce for high-risk NMIBC between January 2011 and December 2021. Data were computed as the median (interquartile range [IQR]) or mean (standard deviation [sd]). Cox regression analysis was performed to determine if neutrophilia, NLR, platelet counts, and PLR before instillation therapy were predictive of recurrence-free survival (RFS) and overall survival (OS). Predictive performance was estimated using Uno's C-statistic., Results: The median (IQR) follow-up for the overall cohort was 23 (13-36) months. The mean (sd) values for NLR, PLR and platelet counts were 3.4 (2.3), 142.2 (85.5), and 225.2 (75.1) × 10
9 /L, respectively. NLR was associated with RFS, with a hazard ratio of 1.32 (95% confidence interval CI 1.19-1.46). Concordance analysis showed that NLR had a good ability to predict RFS (C-index: 0.7, P < 0.01). The PLR and platelet count were not associated with RFS and did not predict recurrence. In terms of OS, none of these cellular inflammatory markers showed any prediction value., Conclusion: Pre-treatment NLR provides some predictive accuracy for RFS in high-risk BCG-naïve patients receiving Gem/Doce. Further prospective trials are needed to validate this finding., (© 2024 BJU International.)- Published
- 2024
- Full Text
- View/download PDF
42. Moving towards Normalization of haemostasis and health equity: Evolving treatment goals for haemophilia A.
- Author
-
Holme PA, Blatný J, Chowdary P, Lassila R, O'Connell N, Hermans C, Álvarez Román MT, Négrier C, Coppola A, and Oldenburg J
- Abstract
Background: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile., Treatment Goals: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care. These outcomes also do not address the complexity of health-related quality of life impacted by haemophilia and its treatment., Conclusion: Capitalizing on the major potential of therapeutic innovations, 'Normalization' of haemostasis, as a concept, should include the aspiration of enabling individuals to live as normal a life as possible, free from haemophilia-imposed limitations. To achieve this-being supported by the data reviewed in this manuscript-the concept of haemostatic and life Normalization needs to be explored and debated within the wider multidisciplinary teams and haemophilia community., (© 2024 The Author(s). Haemophilia published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
43. Venous thromboembolism incidence and association with overall survival in pancreatic cancer: A Finnish nationwide cohort study.
- Author
-
Aaltonen P, Mustonen H, Puolakkainen P, Haglund C, Peltola K, Carpén O, Lassila R, and Seppänen H
- Subjects
- Humans, Male, Finland epidemiology, Female, Aged, Incidence, Middle Aged, Aged, 80 and over, Palliative Care, Risk Factors, Cohort Studies, Venous Thromboembolism epidemiology, Venous Thromboembolism mortality, Venous Thromboembolism etiology, Pancreatic Neoplasms mortality, Pancreatic Neoplasms epidemiology, Pancreatic Neoplasms complications, Registries
- Abstract
Introduction: Pancreatic cancer (PC) is associated with a high risk of venous thromboembolic events (VTEs). We investigated the incidence of VTE before and after the diagnosis of PC and its association with overall survival., Methods: We identified PC patients diagnosed in 2013-2016 from the Finnish Cancer Registry. Data on healthcare visits and death were collected, along with follow-up data through the end of 2020. We compared patients who underwent radical-intent surgery (RIS) to those who underwent palliative treatment (PT) alone., Results: We identified 4086 PC patients, of whom 343 (8.4%) underwent RIS and 3743 (91.6%) received PT. VTE incidence within 1 year before a PC diagnosis was higher in the PT (4.2%, n = 156) than in the RIS group (0.6%, n = 2; p < 0.001). The cumulative incidence of VTE at 12 and 24 months after a PC diagnosis was 6% (n = 21) and 9% (n = 31), respectively, within the RIS group, and 8% (n = 286) and 8% (n = 304) within the PT group. In the PT group, a VTE within 1 year before a PC diagnosis was independently associated with a worse survival {hazard ratio, HR 1.9 [95% confidence interval (CI) 1.6-2.2]}. In both groups, VTE after a PC diagnosis was associated with a worse survival [RIS group: HR 2.6 (95%CI 1.8-3.7) vs. PT group: HR 2.2 (95%CI 1.9-2.4)]., Conclusions: A VTE within 1 year before a PC diagnosis more often occurred among PT PC patients than among patients who underwent RIS. VTE might serve as a diagnostic clue to detect PC at an earlier stage., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
44. Development of a Coagulation Disorders Unit.
- Author
-
Szanto T, Helin T, Joutsi-Korhonen L, Lehtinen AE, El Beayni N, Lepäntalo A, and Lassila R
- Subjects
- Humans, Finland, SARS-CoV-2, Thrombosis, Blood Coagulation Disorders diagnosis, Blood Coagulation Disorders therapy, COVID-19
- Abstract
Our Coagulation Disorders Unit in Helsinki, Finland, provides 24/7 services for local and national hospitals and colleagues upon requests regarding bleeding and thrombosis diagnostics and management, including follow-up. The unit has a tight connection between the clinic and laboratory, and its maintenance and sharing knowledge and observations have been priorities, already for over 20 years and will continue to be of major importance. The consultation service is provided by phone during daytime and on-call hours, and in written form sent electronically to the consulting stakeholders. Thrombosis and hemostasis-targeted outpatient clinics are also available for the patients referred to the center. Writing local guidance and official guidelines, Nordic, European and international collaboration, and educational activities including social communication are critical elements for the Coagulation Disorders Unit. Alertness to acute coagulation abnormalities, such as occurred during COVID-19 and vaccine-induced thrombosis and thrombocytopenia, and development of strategies to manage cross-disciplinary problems are topics which call upon broad networking. The Nordic community has an ongoing historical meeting, which has been circulating among coagulation centers for the past 56 years. At the European level, the European Association of Haemophilia and Allied Disorders focuses on bleeding disorders and their management, including safety surveillance. The International Society of Thrombosis and Haemostasis offers excellent basic and clinical benchmarks for any Coagulation Disorders Unit. We hope that the description of the development and implementation of our Coagulation Disorders Unit in Helsinki achieves international interest and broadens international collaboration. Finally, we congratulate STH on its great contributions around the globe and for providing a vivid forum to foster the discipline of thrombosis and hemostasis., Competing Interests: None declared., (Thieme. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
45. Highly thrombogenic phenotype and impaired wound healing in a patient with congenital dysfibrinogenemia: case report.
- Author
-
El Beayni N, Szanto T, Neerman-Arbez M, Casini A, and Lassila R
- Abstract
Background: Congenital fibrinogen disorders are classified based on both fibrinogen levels and the clinical phenotype. For dysfibrinogenemia, normal fibrinogen levels are typical., Key Clinical Question: We highlight the importance of comprehensive thrombotic risk assessment, including lipoprotein a (Lp[a]) and hypertriglyceridemia in association with severe thrombosis and poor wound healing in dysfibrinogenemia., Clinical Approach: We report the case of a 42-year-old male patient with a rare congenital thrombotic-related dysfibrinogenemia (fibrinogen Naples) and multiple thrombotic episodes throughout his life and an unhealing ankle wound. Despite all thrombotic episodes and surgery, the patient had undetectable D-dimer, suggestive of fibrinolytic defect, further supported by over 4-fold elevated Lp(a) levels. The last arterial thrombosis was preoperatively managed by plasma exchange, antithrombotics, and thereafter continued fibrinogen replacement therapy, under which the chronic wound has healed., Conclusion: The combination of thrombogenesis, abnormal fibrinogen, and high Lp(a) levels is a clinical and research topic deserving more attention., (© 2024 The Authors.)
- Published
- 2024
- Full Text
- View/download PDF
46. Impact of therapeutic plasma exchange on intact protein S, apolipoproteins, and thrombin generation.
- Author
-
Pitkänen HH, Haapio M, Saarela M, Taskinen MR, Brinkman HJ, and Lassila R
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Aged, Plasma Exchange methods, Thrombin metabolism, Apolipoproteins blood, Protein S metabolism
- Abstract
Introduction: Therapeutic plasma exchange (TPE), with solvent/detergent (S/D)-treated plasma as replacement fluid, is an extracorporeal blood purification technique with major impact on both coagulation and lipids. Our previous in vitro study showed that S/D-plasma enhances thrombin generation by lowering intact protein S (PS) levels., Aims: To evaluate the impact of altered lipid balance on coagulation phenotype during heparin-anticoagulated TPE with S/D-plasma, and to investigate whether the lowered intact PS levels with concomitant procoagulant phenotype, are recapitulated in vivo., Methods: Coagulation biomarkers, thrombin generation with Calibrated Automated Thrombogram (CAT), and lipid levels were measured before and after the consecutive 1st, 3rd and 5th episodes of TPE performed to six patients with Guillain-Barré syndrome or myasthenia gravis. The effects of in vitro dilution of S/D-plasma on thrombin generation were explored with CAT to mimic TPE., Results: Patients did not have coagulation disorders, except elevated FVIII. Intact PS, lipoproteins, especially LDL, Apolipoprotein CIII (ApoC3) and ApoB/ApoA1 ratio declined (p < 0.05). In contrast, VLDL and triglyceride levels stayed intact. CAT lag time shortened (p < 0.05). In vitro dilution of S/D plasma with co-transfused Ringer's lactate and 4% albumin partially reduced its procoagulant phenotype in CAT, which is mainly seen as peak thrombin, and modestly shortened lag time., Conclusions: After the five settings of TPE using S/D-plasma in vivo, which associated with heparinization and reduced coagulation factor activities, our observations of declining natural anticoagulant intact PS and apolipoproteins refer to rebalance of the hemostatic and lipid profiles., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
47. Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS).
- Author
-
Fischer K, Lassila R, Peyvandi F, Gatt A, Gouw SC, Hollingsworth R, Lambert T, Kaczmarek R, Carbonero D, and Makris M
- Abstract
Background: Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited., Objectives: To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B., Methods: Inhibitor development in PTPs was collected since 2008 from 97 centers participating in European HAemophilia Safety Surveillance. Per concentrate, inhibitors were reported quarterly and the number of PTPs treated annually. Incidence rates (IRs)/1000 treatment years with 95% CIs were compared between concentrate types (plasma derived FVIII/FIX, standard half-life recombinant FVIII/FIX, and extended half-life recombinant (EHL-rFVIII/IX) concentrates using IR ratios with CI. Medians and IQRs were calculated for inhibitor characteristics., Results: For severe haemophilia A, inhibitor rate was 66/65,200 treatment years, IR 1.00/1000 years (CI 0.80-1.30), occurring at median 13.5 years (2.7-31.5) and 150 EDs (80-773). IR on plasma-derived pdFVIII (IR, 1.13) and standard half-life recombinant FVIII (IR, 1.12) were similar, whereas IR on EHL-rFVIII was lower at 0.13 (incidence rate ratio, 0.12; 95% CI, <0.01-0.70; P < .01).For severe hemophilia B, inhibitor rate was 5/11,160 treatment years and IR was 0.45/1000 years (95% CI, 0.15-1.04), at median 3.7 years (95% CI, 2.1-42.4) and 260 EDs (95% CI, 130 to >1000). Data were insufficient to compare by type of FIX concentrates., Conclusion: Low inhibitor rates were observed for PTPs with severe hemophilia A and B. Data suggested reduced inhibitor development on EHL-rFVIII, but no significant difference between plasma-derived FVIII and standard half-life recombinant FVIII. FIX inhibitor rates were too low for robust statistical analysis., (© 2024 The Authors.)
- Published
- 2024
- Full Text
- View/download PDF
48. A pharmacoepidemiological nested case-control study of risk factors for venous thromboembolism with the focus on diabetes, cancer, socioeconomic group, medications, and comorbidities.
- Author
-
Myllylahti L, Niskanen L, Lassila R, and Haukka J
- Subjects
- Humans, Female, Risk Factors, Male, Case-Control Studies, Middle Aged, Aged, Risk Assessment, Adult, Socioeconomic Factors, Social Determinants of Health, Neoplasms epidemiology, Comorbidity, Venous Thromboembolism epidemiology, Venous Thromboembolism diagnosis, Pharmacoepidemiology, Diabetes Mellitus epidemiology, Diabetes Mellitus drug therapy, Diabetes Mellitus diagnosis
- Abstract
Objectives: A pharmacoepidemiological study to assess VTE risk factors in a diabetes-rich population., Methods: The study comprised 299,590 individuals. We observed 3450 VTEs and matched them with 15,875 controls using a nested case-control approach and collected data on comorbidities and prescriptions. By multivariable conditional logistic regression, we calculated ORs with 95%CIs for comorbidities and medications to evaluate their associations with VTE., Results: Diabetes (aOR 2.16; 95%CI 1.99-2.34), inflammatory bowel disease (1.84; 1.27-2.66), and severe psychiatric disorders (1.72; 1.43-2.05) had the strongest associations among the non-cancer comorbidities. Pancreatic (12.32; 7.11-21.36), stomach (8.57; 4.07-18.03), lung and bronchus (6.26; 4.16-9.43), and ovarian (6.72; 2.95-15.10) cancers were ranked as high-risk for VTE. Corticosteroids, gabapentinoids, psychotropic drugs, risedronic acid, and pramipexole were most strongly associated (aOR exceeding 1.5) with VTE. Insulin (3.86; 3.33-4.47) and sulphonylureas (2.62; 2.18-3.16) had stronger associations than metformin (1.65; 1.49-1.83). Statins and lercanidipine (0.78; 0.62-0.98) were associated with a lowered risk of VTE., Conclusions: In this cohort, with 50% diabetes prevalence, pancreatic, stomach, lung and bronchus, and ovarian cancers were strongly associated with VTE. Corticosteroids, gabapentinoids, and psychotropic medications had the strongest associations with VTE among medications. This may be valuable for generating hypotheses for the further research. Lercanidipine may be a novel protective medication against VTE., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
- View/download PDF
49. Challenges in ageing persons with haemophilia.
- Author
-
Makris M, Lassila R, and Kennedy M
- Subjects
- Humans, Aged, Quality of Life, Blood Coagulation Factors, Aging, Comorbidity, Hemophilia A complications, Hemophilia A therapy, Hemophilia A epidemiology
- Abstract
As treatments for individuals with inherited bleeding disorders improve, life expectancy increases and is approaching that of the normal population. Concomitant with this we are now seeing the problems of ageing in the bleeding disorder population. Although the clear-cut association between low clotting factor levels and risk of bleeding is well recognised, a relationship between high levels, some non-factor therapies and thrombotic risk also exists. The management of thrombosis in persons with inherited bleeding disorders is complex but manageable with modern treatments and collaboration in decision making between health care professionals and patients. Despite the improvements in treatment and reduction in bleeding, mostly musculoskeletal pain continues to be a major issue with advancing age. The management of pain amongst older people with haemophilia who may have multiple comorbidities should involve a person-centred, holistic, multi-disciplinary approach to support and optimise long-term physical functioning and overall quality of life., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
50. Pretreatment with a dual antiplatelet and anticoagulant (APAC) reduces ischemia-reperfusion injury in a mouse model of temporary middle cerebral artery occlusion-implications for neurovascular procedures.
- Author
-
Denorme F, Frösen J, Jouppila A, Lindgren A, Resendiz-Nieves JC, Manninen H, De Meyer SF, and Lassila R
- Subjects
- Mice, Animals, Anticoagulants pharmacology, Anticoagulants therapeutic use, Infarction, Middle Cerebral Artery drug therapy, Brain metabolism, Heparin pharmacology, Heparin therapeutic use, Brain Ischemia drug therapy, Brain Ischemia metabolism, Reperfusion Injury drug therapy, Brain Injuries
- Abstract
Background: Several neurovascular procedures require temporary occlusion of cerebral arteries, leading to ischemia of unpredictable length, occasionally causing brain infarction. Experimental models of cerebral ischemia-reperfusion injury have established that platelet adhesion and coagulation play detrimental roles in reperfusion injury following transient cerebral ischemia. Therefore, in a model of cerebral ischemia-reperfusion injury (IRI), we investigated the therapeutic potential of a dual antiplatelet and anticoagulant (APAC) heparin proteoglycan mimetic which is able to bind to vascular injury sites., Methods: Brain ischemia was induced in mice by transient occlusion of the right middle cerebral artery for 60 min. APAC, unfractionated heparin (UFH) (both at heparin equivalent doses of 0.5 mg/kg), or vehicle was intravenously administered 10 min before or 60 min after the start of ischemia. At 24 h later, mice were scored for their neurological and motor behavior, and brain damage was quantified., Results: Both APAC and UFH administered before the onset of ischemia reduced brain injury. APAC and UFH pretreated mice had better neurological and motor functions (p < 0.05 and p < 0.01, respectively) and had significantly reduced cerebral infarct sizes (p < 0.01 and p < 0.001, respectively) at 24 h after transient occlusion compared with vehicle-treated mice. Importantly, no macroscopic bleeding complications were observed in either APAC- or UFH-treated animals. However, when APAC or UFH was administered 60 min after the start of ischemia, the therapeutic effect was lost, but without hemorrhaging either., Conclusions: Pretreatment with APAC or UFH was safe and effective in reducing brain injury in a model of cerebral ischemia induced by transient middle cerebral artery occlusion. Further studies on the use of APAC to limit ischemic injury during temporary occlusion in neurovascular procedures are indicated., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.