<p>The human glucose transporter GLUT1 facilitates glucose to be accumulated on the other side of the cell membrane. The functional state of GLUT1 is uncertain due to diversity of the reports. In this thesis, the activity of red blood cell GLUT1 was extensively studied to further characterize this protein.</p><p>The human red blood cell membranes were stripped to become vesicles with low-ionic alkaline solution in the presence or absence of dithioerithritol. The supernatant of partially solubilized membrane vesicles provided approximately 65% of the vesicle proteins. GLUT1 purified from this supernatant showed a little high-affinity cytochalasin B binding activity. On the other hand, the vesicles stripped with dithioerythritol provided mostly monomeric GLUT1 and those without dithioerythritol provided monomeric and oligomeric GLUT1. MALDI-ToF-MS detected variant GLUT1 fragments between the two preparations. Residual endogenous phospholipids per GLUT1 also showed difference. However, the equilibrium exchange of glucose was retained for both GLUT1 preparations. Cytochalasin B-binding activity of GLUT1 in streptoavidin-biotin-immobilized red blood cells showed that both dissociation constant and binding sites per GLUT1 fell between those of wheat germ lectin-immobilized red blood cells with or without polylysine coating, which indicated the switching of two cytochalasin B-binding states of GLUT1. It is concluded that GLUT1 in red blood cells contains approximately two equal portions, monomeric with high-affinity cytochalasin B-binding activity and oligomeric without high-affinity cytochalasin B-binding activity. In the partial solubilization of the membrane vesicles, GLUT1 which does not have high-affinity cytochalasin B-binding activity is pooled. This might provide a resolution to select oligomerically and functionally different GLUT1 for crystallization.</p><p>In addition a modified micro-Bradford assay with CaPE precipitation was developed to achieve a routine quantitation method for membrane proteins and the effects of cholesterol and PEG(5000)-DSPE on reconstituted GLUT1 were preliminarily determined.</p>

The human glucose transporter GLUT1 facilitates glucose to be accumulated on the other side of the cell membrane. The functional state of GLUT1 is uncertain due to diversity of the reports. In this thesis, the activity of red blood cell GLUT1 was extensively studied to further characterize this protein. The human red blood cell membranes were stripped to become vesicles with low-ionic alkaline solution in the presence or absence of dithioerithritol. The supernatant of partially solubilized membrane vesicles provided approximately 65% of the vesicle proteins. GLUT1 purified from this supernatant showed a little high-affinity cytochalasin B binding activity. On the other hand, the vesicles stripped with dithioerythritol provided mostly monomeric GLUT1 and those without dithioerythritol provided monomeric and oligomeric GLUT1. MALDI-ToF-MS detected variant GLUT1 fragments between the two preparations. Residual endogenous phospholipids per GLUT1 also showed difference. However, the equilibrium exchange of glucose was retained for both GLUT1 preparations. Cytochalasin B-binding activity of GLUT1 in streptoavidin-biotin-immobilized red blood cells showed that both dissociation constant and binding sites per GLUT1 fell between those of wheat germ lectin-immobilized red blood cells with or without polylysine coating, which indicated the switching of two cytochalasin B-binding states of GLUT1. It is concluded that GLUT1 in red blood cells contains approximately two equal portions, monomeric with high-affinity cytochalasin B-binding activity and oligomeric without high-affinity cytochalasin B-binding activity. In the partial solubilization of the membrane vesicles, GLUT1 which does not have high-affinity cytochalasin B-binding activity is pooled. This might provide a resolution to select oligomerically and functionally different GLUT1 for crystallization. In addition a modified micro-Bradford assay with CaPE precipitation was developed to achieve a routine quantitation method for membrane proteins and the effects of cholesterol and PEG(5000)-DSPE on reconstituted GLUT1 were preliminarily determined.

In this study, we demonstrated that membrane immunofluorescence (MIF) with canine erythrocytes is a much more sensitive diagnostic technique compared with the Coombs test to detect auto-antibodies on RBC. We also demonstrate how the evaluation of the MIF test can be made more precisely which results in a more clear interpretation. Till nowadays the Evans syndrome (combined thrombocytopenia and anemia) is not very well diagnosed in dogs. Only a few studies with low animal numbers tested auto-antibodies on RBC and thrombocytes. Here we describe the frequency of Evans syndrome based on the evaluation of a large data set with 557 dogs. The novelty of the thesis also lies in making a research of the amount of CICs in sera of AIHA/AITP patients is described as well as the cytotoxic potential of patient’s sera for canine leucocytes. These new aspects of diagnosis (AIHA) and pathogenesis (AIHA/AITP) are not only relevant for dogs but also for humans and can be used for better differential diagnosis in medicine. The new findings with respect to circulating immune complexes and cytotoxicity are also offer new therapeutic concepts. Besides, the study has resulted in the characterization of monoclonal antibodies which allow for the detection of so far undetectable canine differentiation antigens (CD molecules) on canine erythrocytes (CD235) and thrombocytes (CD42a). The identified mAbs are useful in the identification of relevant target structures for autoantibodies on these cells.

Lors du phénomène d’hémostase primaire ou de thrombose vasculaire, les plaquettes sanguines doivent adhérer aux parois afin de remplir leur fonction réparatrice ou pathologique. Pour ce faire, certains facteurs rhéologiques et hémodynamiques tels que l’hématocrite, le taux de cisaillement local et les contraintes de cisaillement pariétal, entrent en jeu afin d’exclure les plaquettes sanguines de l’écoulement principal et de les transporter vers le site endommagé ou enflammé. Cette exclusion pourrait aussi être influencée par l’agrégation de globules rouges qui est un phénomène naturel présent dans tout le système cardiovasculaire selon les conditions d’écoulement. La dérive de ces agrégats de globules rouges vers le centre des vaisseaux provoque la formation de réseaux d’agrégats dont la taille et la complexité varient en fonction de l’hématocrite et des conditions de cisaillement présentes. Il en résulte un écoulement bi-phasique avec un écoulement central composé d’agrégats de globules rouges avoisinés par une région moins dense en particules où l’on peut trouver des globules rouges singuliers, des petits rouleaux de globules rouges et une importante concentration en plaquettes et globules blancs. De ce fait, il est raisonnable de penser que plus la taille des agrégats qui occupent le centre du vaisseau augmente, plus il y aura de plaquettes expulsées vers les parois vasculaires. L'objectif du projet est de quantifier, in vitro, la migration des plaquettes sanguines en fonction du niveau d’agrégation érythrocytaire présent, en faisant varier l’hématocrite, le taux de cisaillement et en promouvant l’agrégation par l’ajout d’agents tels que le dextran à poids moléculaire élevé. Cependant, le comportement non Newtonien du sang dans un écoulement tubulaire peut être vu comme un facteur confondant à cause de son impact sur l’organisation spatiale des agrégats de globules rouges. De ce fait, les études ont été réalisées dans un appareil permettant de moduler, de façon homogène, la taille et la structure de ces agrégats et de quantifier ainsi leur effet sur la migration axiale des plaquettes. Du sang de porc anti coagulé a été ajusté à différents taux d’hématocrite et insérer dans un appareil à écoulement de Couette, à température ambiante. Les plaquettes sanguines, difficilement isolables in vitro sans en activer certains ligands membranaires, ont été remplacées par des fantômes en polystyrène ayant un revêtement de biotine. La quantification de la migration de ces fantômes de plaquettes a été réalisée grâce à l’utilisation de membranes biologiques fixées sur les parois internes de l’entrefer du rhéomètre de Couette. Ces membranes ont un revêtement de streptavidine assurant une très forte affinité d’adhésion avec les microparticules biotynilées. À 40% d’hématocrite, à un cisaillement de 2 s-1, 566 ± 53 microparticules ont été comptées pour un protocole préétabli avec du sang non agrégeant, comparativement à 1077 ± 229 pour du sang normal et 1568 ± 131 pour du sang hyper agrégeant. Les résultats obtenus suggèrent une nette participation de l’agrégation érythrocytaire sur le transport des fantômes de plaquettes puisque l’adhésion de ces derniers à la paroi du rhéomètre de Couette augmente de façon quasi exponentielle selon le niveau d’agrégation présent. / During the primary hemostatis or thrombosis phenomenon, the human blood platelets must adhere to the vascular wall in order for them to perform their repairing or pathological function. To do so, certain rheological and hemodynamic factors such as the hematocrit, local shear rate and the wall shear stress, must come into play to exclude blood platelets from the main blood stream and transport them to the vicinity of the damaged or inflamed site. This exclusion could also be influenced by red blood cell aggregation which is a natural process present throughout the entire cardiovascular system under certain flow conditions. The displacement of these rouleaux of red blood cells towards the centre of the vessel induces the formation of 3D networks of aggregates whose size and complexity vary as a function of the hematocrit and the shearing conditions present. It results in a two phase flow with an inner core composed of red blood cell aggregates surrounded by single red blood cells or small aggregates and large numbers of white blood cells and platelets. It is therefore reasonable to believe that the larger the inner core becomes, the more platelets will be expulsed towards the vascular wall. The objective of the study was to quantify, in vitro, the lateral migration of blood platelets as a function of the level of red blood cell aggregation present, by changing the hematocrit, the shear rate and by promoting red blood cell aggregation with the use of agents such as high molecular weight dextran. However, the non Newtonian behavior of blood in tube flow can be seen as a confounding factor to the understanding of the spatial organization of the red blood cell aggregates. In this study, whole blood was circulated in a simple shear flow apparatus, which allowed to homogeneously modulate the red blood cell aggregate sizes and structure, and quantify their effect on the axial migration of blood platelets. Anticoagulated porcine bloods were adjusted to different hematocrits and inserted into a Couette flow apparatus, at room temperature. Blood platelets, difficult to isolate in vitro without activating in a non reproducible manner specific membrane ligands, were replaced with biotin coated fluorescent polystyrene beads. The quantification of the migration of these platelet ghosts was conducted with the use of biological membranes fixed on the interior walls of the Couette apparatus. These streptavidin coated membranes ensure a strong adhesive affinity with the biotynilated beads. At 40% hematocrit and at a shear of 2 s-1, 566 ± 53 micro particles were counted for non aggregated erythrocytes, 1077 ± 229 for aggregating red blood cells and 1568 ± 131 for hyper aggregating blood. The results obtained suggest a strong participation of the red blood cell aggregation on the transport of platelet ghosts since the number of ghost cells fixed on the wall of the Couette rheometer increases almost exponentially with the level of aggregation present.

L’agrégation érythrocytaire est le principal facteur responsable des propriétés non newtoniennes sanguines pour des conditions d’écoulement à faible cisaillement. Lorsque les globules rouges s’agrègent, ils forment des rouleaux et des structures tridimensionnelles enchevêtrées qui font passer la viscosité sanguine de quelques mPa.s à une centaine de mPa.s. Cette organisation microstructurale érythrocytaire est maintenue par des liens inter-globulaires de faible énergie, lesquels sont brisés par une augmentation du cisaillement. Ces propriétés macroscopiques sont bien connues. Toutefois, les liens étiologiques entre ces propriétés rhéologiques générales et leurs effets pathophysiologiques demeurent difficiles à évaluer in vivo puisque les propriétés sanguines sont dynamiques et fortement tributaires des conditions d’écoulement. Ainsi, à partir de propriétés rhéologiques mesurées in vitro dans des conditions contrôlées, il devient difficile d’extrapoler leurs valeurs dans un environnement physiologique. Or, les thrombophlébites se développent systématiquement en des loci particuliers du système cardiovasculaire. D’autre part, plusieurs études cliniques ont établi que des conditions hémorhéologiques perturbées constituent des facteurs de risque de thrombose veineuse mais leurs contributions étiologiques demeurent hypothétiques ou corrélatives. En conséquence, un outil de caractérisation hémorhéologique applicable in vivo et in situ devrait permettre de mieux cerner et comprendre ces implications. Les ultrasons, qui se propagent dans les tissus biologiques, sont sensibles à l’agrégation érythrocytaire. De nature non invasive, l’imagerie ultrasonore permet de caractériser in vivo et in situ la microstructure sanguine dans des conditions d’écoulements physiologiques. Les signaux ultrasonores rétrodiffusés portent une information sur la microstructure sanguine reflétant directement les perturbations hémorhéologiques locales. Une cartographie in vivo de l’agrégation érythrocytaire, unique aux ultrasons, devrait permettre d’investiguer les implications étiologiques de l’hémorhéologie dans la maladie thrombotique vasculaire. Cette thèse complète une série de travaux effectués au Laboratoire de Biorhéologie et d’Ultrasonographie Médicale (LBUM) du centre de recherche du Centre hospitalier de l’Université de Montréal portant sur la rétrodiffusion ultrasonore érythrocytaire et menant à une application in vivo de la méthode. Elle se situe à la suite de travaux de modélisation qui ont mis en évidence la pertinence d’un modèle particulaire tenant compte de la densité des globules rouges, de la section de rétrodiffusion unitaire d’un globule et du facteur de structure. Ce modèle permet d’établir le lien entre la microstructure sanguine et le spectre fréquentiel du coefficient de rétrodiffusion ultrasonore. Une approximation au second ordre en fréquence du facteur de structure est proposée dans ces travaux pour décrire la microstructure sanguine. Cette approche est tout d’abord présentée et validée dans un champ d’écoulement cisaillé homogène. Une extension de la méthode en 2D permet ensuite la cartographie des propriétés structurelles sanguines en écoulement tubulaire par des images paramétriques qui mettent en évidence le caractère temporel de l’agrégation et la sensibilité ultrasonore à ces phénomènes. Une extrapolation menant à une relation entre la taille des agrégats érythrocytaires et la viscosité sanguine permet l’établissement de cartes de viscosité locales. Enfin, il est démontré, à l’aide d’un modèle animal, qu’une augmentation subite de l’agrégation érythrocytaire provoque la formation d’un thrombus veineux. Le niveau d’agrégation, la présence du thrombus et les variations du débit ont été caractérisés, dans cette étude, par imagerie ultrasonore. Nos résultats suggèrent que des paramètres hémorhéologiques, préférablement mesurés in vivo et in situ, devraient faire partie du profil de risque thrombotique. / The aggregation of erythrocytes is the main determinant of blood non Newtonian behaviour under low shearing flow conditions. When red blood cells (RBCs) aggregate, they form « rouleaux » and complex tridimensional structures that increase blood viscosity from a few mPa.s to a hundred mPa.s. The reversible RBC aggregation phenomenon is attributed to weak adhesive links between erythrocytes that are readily broken by increasing flow shearing. Blood bulk rheological properties have been comprehensively studied. However, the in vivo physiological impacts of abnormal clustering of RBCs are more difficult to assess. Clinical studies have identified altered hemorheology as a risk factor for thrombosis, but a clear etiological relationship between abnormal aggregation and thrombosis has not yet been established, in part because clinical conclusions were derived from correlative findings. It is to note that cardiovascular diseases such as deep venous thrombosis generally occur at specific locations within the vascular bed, suggesting a hemodynamic contribution to the development of this disease. Consequently, it is postulated that in vivo hemorheological characterization may help shed some light on the role of RBC hyper-aggregation on cardiovascular disorders. Ultrasound imaging, a non-invasive method relying on the propagation of mechanical waves within biological tissues, is sensitive to RBC aggregation. Indeed, the study of backscattered waves allows characterizing blood microstructure in vivo and in situ under physiological flow conditions. The work described in this thesis is based on prior simulation studies, performed at the Laboratory of Biorheology and Medical Ultrasonics of the University of Montreal Hospital Research Center, in which the backscattering of ultrasound from aggregating RBCs was modeled by considering a particle scattering strategy. In this approach, each RBC is a weak ultrasound scatterer (Born assumption) and the backscattering coefficient is modeled as the product of the RBC number density, the RBC backscattering cross section and a structure factor. This model relates variations in the backscattering coefficient to the RBC spatial organisation through the structure factor, which is the only parameter that changes during the aggregation process. A second order expansion in frequency of the structure factor was used to describe blood microstructure in terms of a packing factor W and an ensemble averaged aggregate diameter D. The model was first presented and validated by considering a homogenous shear flow condition using three broadband mono-element transducers. It was then extended in 2D to allow computation of parametric images in tube flow. An extrapolation based on the assumption that viscosity is related to the level of aggregation was used to compute local viscosity maps. Finally, a last contribution was the demonstration that a sudden increase in aggregation tendency directly promoted the formation of venous thrombosis in an experimental animal model. In that study, RBC aggregation, thrombus formation and flow variations were monitored longitudinally for two weeks using ultrasound. The results reported in this thesis suggest that rheological parameters on RBC clustering, ideally assessed in vivo and in situ, should be included in thrombosis risk profiling.

Les transfusions sanguines sont fréquemment employées pour corriger l’anémie secondaire à une arthroplastie de la hanche ou du genou. Il n’y a cependant pas consensus sur les indications de transfuser. La tendance actuelle est d’utiliser une stratégie transfusionnelle restrictive (soit un seuil de 75-80 g/L d’hémoglobine) mais les conséquences d’une telle pratique sur la récupération fonctionnelle et la qualité de vie des patients sont mal connues. Dans un premier temps, nous avons caractérisé la pratique transfusionnelle au Centre hospitalier de l’Université de Montréal (CHUM). Notre hypothèse était que, devant l’imprécision des recommandations, la pratique transfusionnelle serait variable. Une étude rétrospective de 701 dossiers de patients ayant subi une arthroplastie de la hanche ou du genou a été réalisée. Nous avons observé que les transfusions étaient utilisées de la même façon dans les trois hôpitaux et que les médecins basaient leur décision de transfuser principalement sur un seul chiffre, la concentration d’hémoglobine, adoptant une stratégie restrictive. Soixante-six pourcent des patients avaient une concentration d’hémoglobine inférieure à 100 g/L au départ de l’hôpital. Dans un deuxième temps, nous avons évalué l’impact de cette anémie postopératoire sur la récupération fonctionnelle et la qualité de vie des patients. Notre hypothèse était qu’il existe une concentration d’hémoglobine en dessous de laquelle celles-ci sont atteintes. Une étude de cohorte prospective et observationnelle a été menée chez 305 patients regroupés selon leur concentration d’hémoglobine postopératoire. Les groupes d’hémoglobine (≤ 80, 81-90, 91-100 et > 100 g/L) étaient similaires dans l’évolution de la distance de marche en six minutes, de l’évaluation de l’effort fourni, de la force de préhension et des scores de qualité de vie. L’anémie modérée n’est donc pas associée à une atteinte de la récupération fonctionnelle et de la qualité de vie à court terme. D’autres études devront déterminer les conséquences à long terme d’une stratégie transfusionnelle restrictive sur ces patients. / Red blood cell transfusions are frequently used to treat anemia after total hip or knee arthroplasties. The indications for transfusions remain unclear despite published guidelines. Clinicians have adopted a restrictive transfusion threshold (75-80 g/L) but the consequences of such a strategy on functional outcome and quality of life are not known. First, we characterized the transfusion practice inside the Centre hospitalier de l’Université de Montréal (CHUM). Our hypothesis was that transfusion practice varies inside the CHUM due to uncertainty. A retrospective study of 701 charts of patients operated for a hip or knee arthroplasty was conducted. We observed that there was no difference among hospitals regarding the way transfusions are used and that physicians mainly based their decision to transfuse on a single variable, the hemoglobin concentration, adopting a restrictive transfusion strategy. Sixty-six percent of patients had a hemoglobin concentration under 100 g/L after surgery. Second, we evaluated the impact of this postoperative anemia on functional outcome and quality of life. We hypothesized that a threshold hemoglobin concentration exists below which these become impaired. A prospective, observational cohort study was conducted in 305 patients categorized in groups according to their postoperative hemoglobin concentration. Hemoglobin groups (≤ 80, 81-90, 91-100 and > 100 g/L) were similar in the evolution of the distance walked in six minutes, perception of effort, maximal dominant hand strength and quality of life scores. Thus, moderate anemia is not associated with an impaired functional recovery or quality of life early after hip and knee arthroplasties. Further studies will be required to determine the long-term consequences of a restrictive transfusion strategy in these patients.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

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Made available in DSpace on 2014-12-17T14:13:23Z (GMT). No. of bitstreams: 1 TaniaSG.pdf: 391861 bytes, checksum: 1e1c65c6de1e587070af7bb8a918f265 (MD5) Previous issue date: 2007-08-17 / &#65279;Technetium-99m (99mTc) has been used to obtain several radiobiocomplexes utilized to aid in the diagnosis of diseases. Blood constituents, as red blood cells (RBC) and plasma proteins, have been labeled with 99mTc. Natural and synthetic drugs can alter the labeling of these constituents. The aim of this work was to investigate the possibility of a Buzhong YiQi Wan extract to alter (i) the labeling of blood constituents with 99mTc, (ii) the RBC morphology, and (iii) osmotic fragility of RBC withdrawn from Wistar rats. The data showed that the BYQW extract (i) could affect labeling of blood constituintes with 99mTc, (ii) could affect the membrane integrity decreasing the osmotic resistance and (iii) could not alter the shape of RBC. Probably, these findings would be associated &#65279;with properties of the substances present in the aqueous extract of BYQW. This study has multiple disciplinary aspects in knowledge areas: Radiobiology, Botanic, Phytotherapy and Haematology / &#65279;A pesquisa em Ci?ncias da Sa?de, assim como as avalia??es cl?nicas t?m sido favorecidas pelo uso de is?topos radioativos, sendo que o tecn?cio-99m (99mTc) tem sido o mais utilizado para obten??o de radiobiocomplexos com finalidade de diagn?stico. Diversas drogas naturais ou sint?ticas s?o capazes de interferir na marca??o de estruturas sangu?neas com 99mTc, assim como na biodistribui??o de outros radiobiocomplexos. Os procedimentos relacionados com a medicina tradicional chinesa tamb?m v?m ganhando destaque em todo o mundo. O objetivo deste estudo foi investigar o efeito da possibilidade de altera??es pelo extrato de Buzhong Yi Qi Wan (f?rmula magistral chinesa) nos constituintes do sangue marcados com 99mTc, (i) na marca??o de hem?cias e prote?nas plasm?ticas, (ii) na morfologia, e (iii) na fragilidade osm?tica de hem?cias de ratos Wistar. Foi observado, diminui??o significativa (p<0,05) na marca??o dos constituites sangu?neos com 99mTc, n?o altera??o da morfologia das hem?cias e modifica??o da curva de fragilidade das hem?cias (p<0,05). Esses efeitos poderiam estar associados com determinadas propriedades de compostos qu?micos presentes no extrato Buzhong Yi Qi Wan. O estudo tem car?ter multidisciplinar com a participa??o das seguintes ?reas do conhecimento: Radiobiologia, Bot?nica, Fitoterapia e Hematologia

Abstract Coronary artery disease (CAD) is the leading cause of death in developed countries. In patients with complex CAD, coronary artery bypass grafting (CABG) remains the preferred treatment as it can provide long-lasting results. However, CABG carries a significant risk of excessive perioperative bleeding and other complications, which may deteriorate the prognosis. Transfusion of blood products is generally used to compensate blood loss. However, both bleeding and blood transfusions have been shown to be associated with an adverse outcome. This cohort study aimed to clarify the impact of perioperative bleeding and the use of different blood products in the development of perioperative complications in 2,764 patients undergoing isolated CABG. The universal definition of perioperative bleeding classification (UDPB) was employed to stratify the severity of bleeding. Additionally, the impact of storage time of transfused red blood cells (RBCs) on the outcome was investigated. Increased UDPB classes, particularly classes 3 and 4, were associated with significantly poorer immediate and late outcome. RBC transfusion in patients who underwent elective off-pump CABG was independently associated with increased troponin I release indicating myocardial injury. Prolonged storage duration of transfused RBCs did not affect immediate and late outcome of patients with moderate bleeding. The most remarkable risk factors for stroke after off-pump CABG were any degree of atherosclerosis of the ascending aorta as well as transfusion of platelets and/or solvent/detergent-treated plasma. The UDPB classification appears to be a promising research tool to stratify the severity of perioperative bleeding and to assess its prognostic impact after coronary surgery. Prevention of major bleeding that leads to blood transfusion may protect from myocardial injury and stroke and possibly result in better early and late outcomes. Patients with a diseased ascending aorta could be considered at high risk of stroke because of their risk of generalized atherosclerosis. In case of mildly diseased aorta, the “no-touch” aorta policy should be considered with the intention of preventing postoperative stroke. / Tiivistelmä Sepelvaltimotauti on yleisin kuolinsyy kehittyneissä maissa. Potilailla, joilla on vaikea monen suonen tai vasemman sepelvaltimon päärungon tauti, sepelvaltimoiden ohitusleikkaus on edelleen paras hoitovaihtoehto, koska sillä pystytään saavuttamaan pitkäkestoisia tuloksia. Kuitenkin ohitusleikkaukseen liittyy suuri riski leikkauksen aikaiselle tai jälkeiselle verenvuodolle ja muille haittatapahtumille, jotka osaltaan huonontavat potilaan ennustetta. Vuodon hoitona käytetään yleisesti verensiirtoa. Kuitenkin on osoitettu, että sekä verenvuoto että verituotteiden anto lisäävät riskiä komplikaatioille. Tämän kohorttitutkimuksen tavoitteena oli selvittää tarkemmin leikkauksen yhteydessä ilmenevän vuodon ja siihen liittyvän verensiirron vaikutuksia leikkauksen jälkeisten haittatapahtumien kehittymiseen 2764 ohitusleikatulla potilaalla. Universal Definition of Perioperative Bleeding (UDPB) -luokitusta käytettiin vuodon vaikeusasteen luokittelemiseen. Lisäksi tutkittiin siirrettyjen punasolujen varastointiajan vaikutusta potilaan ennusteeseen. Korkeammat UDPB-luokat, erityisesti luokat 3 ja 4, liittyivät merkittävästi huonompaan lyhyen ja pitkän aikavälin ennusteeseen. Potilailla, joille oli tehty kiireetön ohitusleikkaus ilman sydän-keuhkokoneen käyttöä, punasolujen anto oli itsenäinen riskitekijä suurentuneelle troponiini I -päästölle eli sydänlihasvauriolle. Pidentynyt punasolujen varastointiaika ei ollut yhteydessä lyhyen tai pitkän aikavälin ennusteeseen potilailla, jotka olivat vuotaneet kohtalaisesti. Merkittävimmät riskitekijät ilman sydän-keuhkokonetta tehdyn leikkauksen jälkeiselle aivoinfarktille olivat minkä tahansa asteinen nousevan aortan ateroskleroosi sekä verihiutaleiden ja/tai jääplasman anto. UDPB-luokitus vaikuttaa lupaavalta tutkimustyökalulta verenvuodon vaikeusasteen luokitteluun. Lisäksi sitä voidaan käyttää vuodon ennusteellisen vaikutuksen arvioimiseen ohitusleikkauksen jälkeen. Runsaan verenvuodon ja siihen liittyvän verensiirron ehkäiseminen saattaa suojata potilasta sydänlihasvauriolta ja aivoinfarktilta ja mahdollisesti johtaa parempaan lyhyen ja pitkän aikavälin ennusteeseen. Potilaita, joilla on nousevan aortan ateroskleroosi, voisi pitää suuressa aivoinfarktiriskissä yleisen ateroskleroosiriskin vuoksi. Potilailla, joilla on lieväkin nousevan aortan ateroskleroosi, tulisi harkita aortan jättämistä pihdittämättä aivoinfarktin ehkäisemiseksi.