The rupture of an aneurysm in subarachnoid hemorrhage (SAH) is a dramatic event causing a severe impact on the brain and a transient or permanent ischemic condition. Several types of responses to meet the challenges of SAH have been found in the acute phase, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, elevated levels of brain natriuretic peptide (BNP), and disturbances in cerebral and systemic metabolism. Cerebral metabolism and the endocrine stress response in the ultra-early phase was investigated in a novel porcine model of SAH in which autologous blood was injected to the anterior skull base. Early activation of the HPA axis was found with rapid elevation of adrenocorticotrophic hormone, cortisol and aldosterone. The peak values of these hormones were early and may be impossible to catch in patients. There were indications of a sympathetic nervous response with excretion of catecholamines in urine as well as plasma chromogranin-A elevation. Cerebral microdialysis suggested immediate substrate failure followed by hypermetabolism of glucose. The animal model seems suited for further studies of aneurysmal SAH. NT-proBNP was investigated in 156 patients with SAH, there was a dynamic course with increasing levels during the first 4 days of the disease. Factors predicting high NT-proBNP load included female sex, high age, high Troponin-I at admission, angiographic finding of an aneurysm and worse clinical condition at admission. High levels of NT-proBNP were correlated to factors indicating a more severe disease, suggesting the initial injury in aneurysmal SAH is an important factor in predicting high NT-proBNP during the acute stage of the disease. Measurements with indirect calorimetry were performed daily during the first week after SAH on 32 patients with SAH. There was a dynamic course with increasing energy expenditure (EE) the first week after SAH. Comparisons with three predictive equations indicated that measured EE generally is higher than predicted, but considerable variation exists within and between patients, indicating that prediction of EE in SAH is difficult. Altogether, the studies demonstrate a complicated response in acute SAH that needs to be further studied to increase possibility of good outcome in SAH patients.

Abstract Primary intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes. ICH is the most devastating subtype of stroke with high mortality and morbidity; 35–52% of patients die during the first month after the bleeding. The most important risk factor for onset of ICH is hypertension, especially untreated hypertension, and the well-known predictors for early death after ICH are a low GCS (i.e low level of consciousness) score on admission, the size of the hematoma, and the precence of intraventricular blood. Preceeding use of anticoagulants and advanced age further impair the outcome. Thromboembolic complications after the bleed are common and difficult to prevent. The present cohort study included all patients (n = 453) with verified primary ICH admitted to the stroke unit of Oulu University Hospital within a period of 11 years (from January 1993 to January 2004). The impacts of previous diseases, including ischemic heart disease, atrial fibrillation on admission, hypertension, and diabetes as well as of high admission blood pressure and plasma glucose levels on outcome were evaluated. The safety and efficacy of prevention of venous thromboembolism with enoxaparin, a low molecular weight heparin (LMWH), was investigated. In a population-based study covering a 3-year period, the risk factors and seasonal distribution of ICH were investigated. Independent of the severity of bleeding and patients’ age, ischemic heart disease, diabetes, and atrial fibrillation were found to be significant predictors for early death after ICH. High blood pressure on admission predicted early death, whereas elevated admission plasma glucose level was associated with the severity of bleeding but was not an independent predictor for early death. Treatment with enoxaparin (20 mg per day subcutaneously) for prevention of venous thromboembolism was not associated with increased mortality but did not seem to prevent venous thromboembolic complications. The incidence of ICH was higher during the winter among patients with untreated hypertension but not in normotensive and treated hypertensive patients.

Abstract Although in Finland the incidence of maternal and neonatal mortality in labor is very low, labor carries some risks. This study focused on two major complications in labor: fetal asphyxia and maternal hemorrhage. The roles of fetal electrocardiographic ST-analysis (STAN) and pelvic artery embolization in the prevention and management of these complications were investigated. Intrapartum fetal monitoring aims at a timely detection of fetal hypoxemia. When non-selected parturients were randomly assigned to be monitored during labor either by STAN or conventional cardiotocography, no differences between the groups were detected in terms of neonatal outcome and operative delivery rates. Only the incidence of fetal blood sampling was lower in the STAN group. In the interpretation of the STAN tracings according to the guideline matrix provided by the STAN manufacturer, the interobserver agreement was moderate; in terms of clinical decision -making as to whether to intervene in the labor, this agreement varied from moderate to good among STAN-trained obstetricians. The aim of prophylactic pelvic artery occlusion balloon catheterization, with or without embolization, is to reduce hemorrhage in elective cesarean operations in patients with placenta accreta. Furthermore, pelvic arterial embolization may be performed post partum if bleeding continues after cesarean hysterectomy, or may serve as an alternative to hysterectomy. In the present study, pelvic artery catheterization and embolization did not reduce blood loss during cesarean delivery, nor did it decrease the need to perform hysterectomy in patients with placenta accreta. In the management of massive postpartum hemorrhage, pelvic artery embolization was most successful in patients with uterine atony, with a success rate of 75% in achieving hemostasis. However, the angiographic method included risk of complications, the most hazardous being thromboembolic complications. To conclude, STAN does not provide improvement in intrapartum fetal monitoring when compared to cardiotocography, but the need for fetal blood sampling is reduced. This may relate to the fact that subjective interpretation of STAN data is moderate at best. Prophylactic catheterization and embolization of pelvic arteries does not improve the surgical outcome of patients with placenta accreta. In the management of postpartum hemorrhage, pelvic artery embolization should be considered, especially in cases with uterine atony.

Antecedentes y propósito del estudio: la hemorragia digestiva alta es una causa importante de ingreso hospitalario y constituye la principal emergencia gastroenterológica, con una tasa de mortalidad de hasta el 14%. En el Perú no existen estudios sobre el uso de la escala de Glasgow-Blatchford para predecir mortalidad por hemorragia digestiva alta. El objetivo de este estudio es realizar la validación externa de la escala de Glasgow-Blatchford y establecer su mejor punto de corte para predecir mortalidad por hemorragia digestiva alta en un hospital de Lima, Perú. Métodos: estudio de validación diagnóstica, analítico, longitudinal, de tipo retrospectivo, con datos de pacientes con diagnóstico clínico y endoscópico de hemorragia digestiva alta atendidos en la Unidad de Hemorragia Digestiva del Hospital Nacional Edgardo Rebagliati Martins, entre junio de 2012 y diciembre de 2013. Calculamos el área bajo la curva ROC (receiver operating characteristic) de la escala de Glasgow-Blatchford para predecir mortalidad, con un intervalo de confianza al 95%. Resultados: un total de 339 registros fueron analizados. El 57,5% fueron varones y la edad media (desviación estándar) fue de 67,0 (15,7) años. La mediana de la escala de Glasgow-Blatchford obtenida en la población fue de 12. El análisis ROC para mortalidad dio un área bajo la curva de 0,59 (IC95% 0,5-0,7). Se estratificó por tipo de hemorragia digestiva alta, obteniendo un área bajo la curva de 0,66 (IC95% 0,53-0,78) para el tipo no variceal. Conclusiones: en la población estudiada, la escala de Glasgow-Blatchford no posee una validez diagnóstica adecuada para predecir mortalidad.

Doctor of Philosophy / Department of Anatomy and Physiology / David C. Poole / Exercise-induced pulmonary hemorrhage (EIPH) or epistaxis has been recognized in racehorses since the 16th century. Since this time, great strides have been made in terms of identifying the lungs as the source of the hemorrhage via the endoscope, utilization of bronchoalveolar lavage to quantify the hemorrhage, and the discovery of successful treatments such as furosemide and the nasal strip that ameliorate, but do not abolish EIPH. It has been determined that, in addition to extremely high pulmonary arterial pressures and the negative intrapleural pressures being the major physiologic forces causing pulmonary capillary stress failure, other factors have the potential for influencing the severity of EIPH including locomotory impact trauma, inflammatory airway disease (IAD), upper airway obstruction, coagulation anomalies, and high blood viscosity. It has been hypothesized that EIPH is detrimental to performance and this was recently confirmed by Hinchcliff et al. in 2004. EIPH is a complex multi-factorial condition with much still unknown about the etiology, best method for diagnosis, and most effective form of treatment. Chapter one of this dissertation determined the effectiveness of a novel treatment, concentrated equine serum, in ameliorating EIPH via reduction of IAD. Chapter two refuted the hypothesis that herbal formulations commonly used in the field with anecdotal success would decrease EIPH by correcting coagulation deficits during exercise, as scientific efficacy was not evident, at least at the dose and duration used in our investigation. Chapter three addressed the dogma that EIPH only occurs during maximal intensity exercise, and in demonstrating significant EIPH during sub-maximal exercise, emphasized the role that the airways play in contributing to the initiation and severity of EIPH. Chapter four examined the occurrence and severity of EIPH in the horse’s canine counterpart, the racing Greyhound. The demonstrated presence of mild EIPH in the Greyhound, a physiologically similar yet different athlete in comparison to the horse sheds new light on the etiology of this condition in both species. The results of these investigations have advanced the frontiers of our knowledge concerning EIPH. Specifically, they have generated novel information on the mechanistic bases of EIPH and have provided evidence supporting additional treatment options for reducing the severity of EIPH in horses.

L’augmentation de la prévalence des hémorragies cérébrales (HC) sous traitement antithrombotique constitue un problème de Santé Publique à cause du mauvais pronostic vital et fonctionnel et du risque compétitif de récidive hémorragique ou ischémique chez les survivants, qui pose le problème d’une prévention secondaire adaptée._x000D_L’objectif de la thèse était d’étudier l’impact des traitements antithrombotiques sur le pronostic des HC. Le terme d’HC, entendu au sens large, regroupe les HC spontanées et les microhémorragies cérébrales.La première partie avait comme objectif de comparer les caractéristiques des HC survenant avec ou sans traitement par antagonistes de la vitamine K (AVK), stratifiant l’analyse selon la localisation de l’HC. L’analyse a porté sur 545 patients de la cohorte Lilloise (PITCH), parmi lesquels 83 (15%) étaient sous AVK. La prise d’un traitement par AVK n’influençait pas la localisation de l’HC, mais était prédictive d’HC plus volumineuses (25 ml vs 12 ; p=0.002) chez les victimes d’HC non lobaire, alors que aucune différence existait en cas d’HC lobaire (26 ml vs 30; p=0.507). Ces résultats suggèrent que l’impact des AVK diffère en fonction de la localisation de l’HC et de la vasculopathie sous-jacente.La deuxième partie avait comme objectif d’analyser l’impact du traitement antithrombotique sur l’apparition de nouvelles microhémorragies cérébrales stratifiant l’analyse selon la localisation de l’HC. L’étude a porté sur 168 survivants à 6 mois d’une HC (cohorte PITCH) ayant bénéficié d’une IRM cérébrale 1.5T lors de l’HC et durant le suivi. Lors de l’HC, 89 (53%) patients présentaient des microhémorragies, et 80 (48%) ont développé des microhémorragies durant le suivi. La présence sur la première IRM de microhémorragies (aOR 2,3; IC 95%1,2-4,3), leur position mixte, lobaire et profonde (aOR 3.7; IC95% 1,7-8,3), et la présence de séquelles de macrohémorragies (aOR 6,8; IC95% 2,8-16,7), étaient associées à l’apparition de microhémorragies. Chez les patients avec HC non lobaire, l’apparition de microhémorragies était associée à l’utilisation d’un traitement antithrombotique durant le suivi (aOR 2,9 ; IC95% 1,1-7,3) et avec l’apparition de lacunes (aOR: 2,9; 95%CI 1,0-7,8). Chez les patients avec HC lobaire, l’apparition de microhémorragies était associée à l’apparition de macrohémorragie (aOR 9.8 ; IC95% 1,1-88,8). Ces résultats suggèrent que l’impact des traitements antithrombotiques diffère en fonction de la vasculopathie sous-jacente.La troisième partie avait comme objectif de : (i) comparer les proportions de survivants d’une HC ayant une indication formelle au traitement antithrombotique chez lesquels ce traitement était repris à la sorite ; (ii) identifier les caractéristiques associées à la reprise du traitement antithrombotique, au sein de 5 cohortes européennes (Lille, n=542; Utrecht, n=389 ; Amsterdam, n= 403 ; Londres, n=667 ; Lothian, n=137). Un traitement antithrombotique était recommencé chez 96 (20%) des 469 survivants ayant une indication formelle, mais en proportions différentes dans les 5 cohortes (Lille 18%, Utrecht 45%, Amsterdam 30% ; Londres 11% ; Lothian 15%; p<0.001). Nous n’avons retrouvé aucun autre facteur prédictif de reprise du traitement antithrombotique en dehors de la cohorte d’origine. Ces résultats montrent que la décision de reprise du traitement antithrombotique ne repose pas sur des critères reproductibles, et soulignent la nécessité de réaliser des essais randomisés.La quatrième partie, actuellement en cours, prévoit d’évaluer chez ces mêmes patients (survivants d’une HC ayant une indication formelle au traitement antithrombotique) le risque de récidive hémorragique ou ischémique en fonction de la reprise ou de l’arrêt du traitement antithrombotique. Il s’agit d’une étude observationnelle portant sur 274 patients de 4 cohortes Européennes, avec un suivi d’environ 2.5 ans. L’analyse statistique est en cours. / The proportion of patients who are taking antithrombotic drugs at the time they suffer a spontaneous intracerebral hemorrhage (ICH) is increasing over time, and this is a major issue in public health because of the poor prognosis of patients. Also, the decision to restart or not antithrombotic drugs in survivors is still a clinical dilemma. _x000D_The aim of this work was to evaluate the impact of antithrombotic drugs on ICH prognosis. The term ICH regroups (i) spontaneous ICH and (ii) cerebral microbleeds (CMBs).As a first step, we compared baseline characteristics of 545 consecutive patients with ICH included in the PITCH cohort (Lille, France), receiving or not Vitamin K Antagonists (VKAs) at the time of ICH, stratifying the analysis according to the ICH location (lobar vs non lobar). VKAs-ICH accounted for 83 patients (15%). The use of VKAs did not influence ICH location, but influenced ICH volume: in non lobar ICH, VKAs use was associated with larger ICH volumes (25 ml versus 12 ml, p=0.002). In lobar ICH, no difference was observed (26ml versus 30ml; p=0.507). The different impact of VKAs on ICH volumes according to location suggests a different susceptibility of the underlying vasculopathies to VKAs.As a second step, we aimed to evaluate the impact of antithrombotic drugs on the incidence of CMBs in 168 ICH survivors from the PITCH cohort who underwent 1.5T Magnetic resonance imaging (MRI) at ICH onset and during follow-up, stratifying the analysis according to the index ICH location. At the time of ICH, 89 (53%) patients had CMBs at ICH onset, and 80 (48%) showed new CMBs during follow-up. Predictors of incident CMBs were the presence on the first MRI of: at least 1 CMB (aOR 2.3; 95% CI: 1.2-4.3), old macro-hemorrhage (aOR 6.8; 95%CI 2.8-16.7), and CMBs in mixed location (aOR 3.7; 95%CI 1.7-8.3). In non lobar ICH, incident CMBs were associated with incident lacunes (aOR: 2.9; 95%CI 1.0-7.8) and with the use of antiplatelet agents (aOR 2.9; 95%CI 1.1-7.3). In lobar ICH, incident CMBs were associated with incident macro-hemorrhage (aOR 9.8; 95%CI 1.1-88.8). These results suggest that the impact of antithrombotic drugs differs according to the index ICH location, and therefore according to the underlying vasculpathy.The third step consisted in comparing the characteristics and proportions of patients taking antithrombotic drugs at ICH discharge in five European cohorts (Lille, France, n=542; Utrecht, The Netherlands, n=389; Amsterdam, The Netherlands, n=403; multicenter UK cohort, n=667; Lothian, Scotland, n=137). We then identified characteristics associated with restarting. Antithrombotic drugs were restarted in 96 (20%) of the 469 survivors who had an indication for antithrombotic drugs (secondary prevention or atrial fibrillation), but in different proportions according to the cohort of origin (Lille 18%, Utrecht 45%, Amsterdam 30%, CROMIS-2 ICH 11%, Lothian 15%; p<0.001). We did not find other consistent associations with restarting antithrombotic drugs. The variation in clinical practice in restarting antithrombotic drugs after ICH supports the need for randomized controlled trials.In the fourth step, we aim to analyse the risk of ICH recurrences or ischemic events in the same population of patients (ICH survivors who suffered from ICH while on antithrombotic drugs because of secondary prevention or atrial fibrillation) according to the antithrombotic drug status during follow-up. We included 274 patients from 4 European cohorts, with a median follow-up of 2.5 years. Statistical analysis is ongoing.

Introducción: El sangrado digestivo bajo (SDB) es una entidad cuyas tasas de complicaciones y mortalidad se han incrementado en las últimas décadas. Si bien se han identificado algunos factores relacionados a mal pronóstico, aún quedan variables por evaluar. Objetivo: Identificar factores de mal pronóstico en pacientes que presentaron SDB en el Hospital Nacional Edgardo Rebagliati Martins de Lima, Perú. Materiales y métodos: Se realizó un estudio observacional analítico de tipo cohorte retrospectivo. Se realizó un censo de todos los pacientes que presentaron SDB agudo entre Enero 2010 y Diciembre 2013. Las variables principales a evaluar fueron frecuencia cardiaca ≥ 100/min, presión arterial sistólica < 100 mmHg y hematocrito bajo (≤ 35%) al ingreso. Se definió mal pronóstico como cualquiera de los siguientes criterios: muerte durante la hospitalización, sangrado que requiera transfusión de ≥ 4 unidades de sangre, reingreso dentro del primer mes, o necesidad de cirugía de hemostasia. Resultados: Se incluyó un total de 341 pacientes con SDB, de los cuales el 27% tuvo mal pronóstico y 2% fallecieron. Se encontró como variables asociadas a mal pronóstico: frecuencia cardiaca ≥ 100/min al ingreso (RR: 1,75 IC 95% 1,23-2,50), presión arterial sistólica < 100 mmHg al ingreso (RR: 2,18 IC 95% 1,49-3,19), hematocrito ≤ 35% al ingreso (RR: 1,98 IC 95% 1,23-3,18) y sangrado de origen no determinado (RR: 2,74 IC 95% 1,73-4,36). Conclusiones: Frecuencia cardiaca elevada al ingreso, hipotensión sistólica al ingreso, hematocrito bajo al ingreso y presentar un sangrado en el cual no se encuentra el punto de origen son factores que incrementan el riesgo de presentar mal pronóstico, por lo que se recomienda un monitoreo más estricto en estos pacientes. / Background: Lower gastrointestinal bleeding (LGIB) is an event that has shown an increase in complications and mortality rates in the last decades. Although some factors associated with poor outcome have been identified, there are several yet to be evaluated. Objective: To identify risk factors for poor outcome in patients with LGIB in the Hospital Nacional Edgardo Rebagliati Martins of Lima, Peru. Material and methods: A prospective analytic observational cohort study was made, and a census was conducted with all patients with acute LGIB between January 2010 and December 2013. The main variables were heart rate ≥ 100/min, systolic blood pressure < 100 mmHg and low hematocrit (≤ 35%) at admission. Poor outcome was defined as any of the following: death during hospital stay, bleeding requiring transfusion of ≥ 4 blood packs, readmission within one month of hospital discharge, or the need for hemostatic surgery. Results: A total of 341 patients with LGIB were included, of which 27% developed poor outcome and 2% died. Variables found to be statistically related to poor outcome were: heart rate ≥ 100/min at admission (RR: 1,75 IC 95% 1,23-2,50), systolic blood pressure < 100 mmHg at admission (RR: 2,18 IC 95% 1,49-3,19), hematocrit ≤ 35% at admission (RR: 1,98 IC 95% 1,23-3,18) and LGIB of unknown origin (RR: 2,74 IC 95% 1,73-4,36). Conclusions: Elevated heart rate at admission, systolic hypotension at admission, low hematocrit at admission and having a LGIB of unknown origin are factors that increase the risk of developing poor outcome, and these patients should be monitored closely due to their higher risk of complications.

Objective: This study aims to derive a clinically-applicable decision rule to predict the risk of symptomatic vasospasm, a neurological deficit primarily due to abnormal narrowing of cerebral arteries supplying an attributable territory, in aneurysmal subarachnoid hemorrhage (SAH). Methods: SAH patients presenting from 2002 to 2011 were analyzed using logistic regression and recursive partitioning to identify clinical, radiological, and laboratory features that predict the occurrence of symptomatic vasospasm. Results: The incidence of symptomatic vasospasm was 21.0%. On multivariate logistic regression analysis, significant predictors of symptomatic vasospasm included age 40-59 years, high Modified Fisher Grade (Grades 3 and 4), and anterior circulation aneurysms. Conclusion: Development of symptomatic vasospasm can be reliably predicted using a clinical decision rule created by logistic regression. It exhibits increased accuracy over the Modified Fisher Grade alone and may serve as a useful clinical tool to individualize vasospasm risk once prospectively validated in other neurosurgical centres.

Orientadores: Maria Aparecida Mesquita, Ciro Garia Montes / Dissertação (mestrado profissional) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T06:48:46Z (GMT). No. of bitstreams: 1 CustodioLima_Juliana_M.pdf: 1668374 bytes, checksum: ee0f2db5e25a3f2b8735d67b17331357 (MD5) Previous issue date: 2013 / Resumo: A hemorragia digestiva alta (HDA) é a emergência gastrointestinal mais frequente em todo o mundo. De acordo com a etiologia, a HDA se divide em varicosa e não varicosa. Existem poucos dados recentes da literatura nacional com relação à evolução dos pacientes com HDA, especialmente no que se refere à população idosa. Além disso, o uso de escalas prognósticas para avaliar o risco dos pacientes, como o escore de Rockall, embora recomendado por várias diretrizes, ainda não foi incorporado na prática clínica da maior parte dos hospitais brasileiros. Os objetivos do presente estudo foram avaliar as características clínicas, os achados endoscópicos e a evolução em 30 dias de pacientes com HDA não varicosa, e identificar os principais aspectos associados com a idade avançada...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: Upper gastrointestinal bleeding (UGIB) is the most frequent gastrointestinal emergency worldwide. According to the etiology, UGIB is classified into variceal and non variceal bleeding. There is a lack of recent data regarding the outcomes of non variceal UGIB in Brazil, specially in the elderly. Furthermore, although recommended by several guidelines, the use of prognostic scales for risk assessment, such as the Rockall score, has not yet been included in the daily practice of most Brazilian hospitals. The aims of this study were to evaluate the clinical features, endoscopic findings and outcomes within 30 days in patients with non variceal UGIB, and to identify the main characteristics related to advanced age...Note: The complete abstract is available with the full electronic document / Mestrado / Clinica Medica / Mestra em Clínica Médica

A proteólise de componentes do plasma e da matriz extracelular é um fator importante no quadro hemorrágico desencadeado pela ação de venenos de serpentes. Neste estudo, avaliamos o papel dos domínios estruturais de metaloproteinases na interação com seus alvos. Ensaios de hidrólise in vitro mostraram que as metaloproteinases HF3 e bothropasina (classe P-III), e BJ-PI (classe P-I) do veneno da Bothrops jararaca, degradaram proteínas plasmáticas (fibrinogênio, fibronectina e vitronectina), além de colágeno VI e Matrigel, mostrando diferentes perfis de hidrólise. Experimentos de N-deglicosilação das proteinases mostraram que suas porções glicosídicas são importantes para a manutenção da integridade de suas estruturas e da atividade proteolítica. E ensaios para avaliar a interação das proteinases e da proteína DC (domínios tipo disintegrina/rico em cisteínas) com alguns substratos protéicos mostraram que além de seus domínios estruturais (catalítico/tipo disintegrina/rico em cisteínas) suas cadeias de carboidratos também são importantes no reconhecimento dos mesmos. / Proteolysis of plasma and extracellular matrix proteins is a key factor in the local hemorrhage induced by snake venom metalloproteinases (SVMPs). In this work we evaluated the role of the structural domains of SVMPs in the interaction with their targets. In vitro hydrolysis assays showed that the SVMPs HF3 and bothropasin (P-III class) and BJ-PI (P-I class) from Bothrops jararaca venom degraded plasma proteins (fibrinogen, fibronectin and vitronectin), collagen VI and Matrigel resulting in different hydrolysis profiles. N-deglycosylation of these proteinases showed that their carbohydrate moieties are important for keeping their structural integrity and proteolytic activity. The assays to analyze the interaction of the proteinases and of the DC protein (composed of the disintegrin-like and cysteine-rich domains) with some proteins confirmed that not only the structural domains (catalytic, disintegrin-like and cysteine-rich) but also the sugar moieties are important in the recognition of plasma and extracellular matrix proteins.