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Pylephlebitis is a rare but serious complication, associated with risks such as liver abscesses, sepsis, and acute liver failure that results in post-appendectomy portal vein thrombosis. Therefore, the objective of the study was to evaluate the effectiveness of care and management protocols for post-appendectomy pylephlebitis, in order to identify the best clinical practices and improve patient care. A systematic review of scientific literature was carried out, applying non-probabilistic convenience sampling 40 scientific works published between 2018 and 2023 were selected, using databases such as PubMed/Medline, Elsevier Scopus, Science Direct, and Taylor & Francis. The results revealed that post-appendectomy pylephlebitis has a low incidence, predominantly affecting men, with symptoms such as fever and abdominal pain. The most common causes are diverticulitis and acute appendicitis. The preferred treatment includes broad-spectrum antibiotics and, in some cases, anticoagulants. Research suggests the need for standardized care protocols to optimize the management of this complication., A pileflebite é uma complicação rara, mas grave, associada a riscos como abscessos hepáticos, sepse e insuficiência hepática aguda com repercussões na forma de trombose da veia porta pós-apendicectomia. Portanto, o objetivo do estudo foi avaliar a eficácia dos protocolos de atendimento e gerenciamento para a pileflebite pós-apendicectomia a fim de identificar as melhores práticas clínicas e melhorar o atendimento ao paciente. Foi realizada uma revisão sistemática da literatura científica, aplicando amostragem não probabilística por conveniência. Foram selecionados 40 artigos científicos publicados entre 2018 e 2023, usando bancos de dados como PubMed/Medline, Elsevier Scopus, Science Direct e Taylor & Francis. Os resultados revelaram que a pileflebite pós-apendicectomia tem uma baixa incidência, afetando predominantemente homens, com sintomas como febre e dor abdominal. As causas mais comuns são diverticulite e apendicite aguda. O tratamento preferencial inclui antibióticos de amplo espectro e, em alguns casos, anticoagulantes. Pesquisas sugerem a necessidade de protocolos de atendimento padronizados para otimizar o gerenciamento dessa complicação., La pileflebitis es una complicación rara pero grave, asociada a riesgos como abscesos hepáticos, sepsis, e insuficiencia hepática aguda que repercute como trombosis de la vena porta post-apendicectomía. Por ello el objetivo del estudio fue evaluar la efectividad de los protocolos de atención y manejo para la pileflebitis post-apendicectomía, con el fin de identificar las mejores prácticas clínicas y mejorar el cuidado de los pacientes. Se realizó una revisión sistemática de literatura científica, aplicando un muestreo no probabilístico por conveniencia. Se seleccionaron 40 trabajos científicos publicados entre 2018 y 2023, utilizando bases de datos como PubMed/Medline, Elsevier Scopus, Science Direct, y Taylor & Francis. Los resultados revelaron que la pileflebitis post-apendicectomía presenta una incidencia baja, que afecta predominantemente a hombres, con síntomas como fiebre y dolor abdominal. Las causas más frecuentes son la diverticulitis y la apendicitis aguda. El tratamiento preferido incluye antibióticos de amplio espectro y, en algunos casos, anticoagulantes. La investigación sugiere la necesidad de protocolos de atención estandarizados para optimizar el manejo de esta complicación.

In chapter 2 the pathophysiology of acute pulmonary embolism (PE) is summarised. Central in the pathophysiology of acute PE is acute right ventricular (RV) pressure overload, leading to adaptive and ultimately maladaptive responses of the RV, with RV failure as the final common pathway. CTEPH has many similarities with acute PE. The response to an increased RV afterload, with pulmonary vascular resistance (PVR) and compliance as the main determinants of afterload, differs between CTEPH patients. In chapter 3 we analysed RV afterload and function in 21 patients with proximal CTEPH and 25 patients with distal CTEPH. While mean pulmonary artery pressure, PVR and compliance were similar, RV ejection fraction was more severely compromised and RV dilatation more pronounced in patients with proximal CTEPH. It was concluded that the site of vascular obstruction did affect RV function while lumped parameters of load were similar. Chapters 4 and 5 focused on the determinants of residual pulmonary hypertension (PH). Residual PH after pulmonary endarterectomy (PEA) is relatively frequent, but its pathophysiology is less well understood. Distal vasculopathy is assumed to be the major determinant of residual PH. In chapter 4 we analysed the role of residual (sub)segmental macrovascular lesions. In 31 patients CTPA and magnetic resonance perfusion were performed 6 months post-PEA, and compared to CTPA and MR perfusion before PEA. Although 20% of the pulmonary arteries remained abnormal after PEA, no association was found with residual PH. Residual PH was also present in patients without residual macrovascular lesions on CTPA, leading to the conclusion that remaining (sub)segmental macrovascular lesions are a contributor at most but not a major determinant of residual PH. Parenchymal perfusion as determined by MR perfusion improved after PEA, but was similar between patients with and without residual PH. In chapter 5 the role of recurrent thrombosis was analysed in 33 patients: new

In chapter 2 the pathophysiology of acute pulmonary embolism (PE) is summarised. Central in the pathophysiology of acute PE is acute right ventricular (RV) pressure overload, leading to adaptive and ultimately maladaptive responses of the RV, with RV failure as the final common pathway. CTEPH has many similarities with acute PE. The response to an increased RV afterload, with pulmonary vascular resistance (PVR) and compliance as the main determinants of afterload, differs between CTEPH patients. In chapter 3 we analysed RV afterload and function in 21 patients with proximal CTEPH and 25 patients with distal CTEPH. While mean pulmonary artery pressure, PVR and compliance were similar, RV ejection fraction was more severely compromised and RV dilatation more pronounced in patients with proximal CTEPH. It was concluded that the site of vascular obstruction did affect RV function while lumped parameters of load were similar. Chapters 4 and 5 focused on the determinants of residual pulmonary hypertension (PH). Residual PH after pulmonary endarterectomy (PEA) is relatively frequent, but its pathophysiology is less well understood. Distal vasculopathy is assumed to be the major determinant of residual PH. In chapter 4 we analysed the role of residual (sub)segmental macrovascular lesions. In 31 patients CTPA and magnetic resonance perfusion were performed 6 months post-PEA, and compared to CTPA and MR perfusion before PEA. Although 20% of the pulmonary arteries remained abnormal after PEA, no association was found with residual PH. Residual PH was also present in patients without residual macrovascular lesions on CTPA, leading to the conclusion that remaining (sub)segmental macrovascular lesions are a contributor at most but not a major determinant of residual PH. Parenchymal perfusion as determined by MR perfusion improved after PEA, but was similar between patients with and without residual PH. In chapter 5 the role of recurrent thrombosis was analysed in 33 patients: new

AIMS: To review the historical reports on antiphospholipid antibodies (aPL) from the early years of the 20th century; to outline the cardinal features of the antiphospholipid syndrome (APS) from 1983 on, including clinical criteria, etiopathogenesis and current therapy.METHODS: Literature review using PubMed. Articles on the history of aPL and APS were selected.RESULTS: The original aPL were described in patients with syphilis yet in 1906 by Wassermann. A first definition of lupus anticoagulant was proposed in 1963,while the anticardiolipin antibody (aCL) test was depicted twenty years later. The APS, initially reported by Hughes in 1985as the “aCL syndrome”, is one of the most prevalent acquired thrombophilia. Venous and arterial thrombosis, associated or not to pregnancy morbidity, comprise the main features. It is a novel disorder firstly associated to systemic lupus erythematosus. A primary form of APS was put forward in 1989, and many APS variants are currently known. Lifelong, full-dose anticoagulation is the mainstream for treatment of thrombotic APS. In obstetric APS, the combination of acetil-salicilic acid and enoxoparin has been a mostly effective therapy.CONCLUSIONS: The sequential characterization of aPL since Wassermann in 1906, and later of the APS in the 1980-thies, is a rather interesting example of how a new entity is sketched step by step. APS is an intriguing novel cause of autoimmune thrombophilia, with a complex pathogenesis and a plethora of clinical and laboratory abnormalities. Treatment is based on life-long anticoagulation., ***Uma breve história dos anticorpos antifosfolípides e da síndrome antifosfolípide***OBJETIVOS: Revisar os relatos históricos sobre anticorpos antifosfolípides (aAF) dos primeiros anos do século XX; delinear as características cardinais da síndrome antifosfolípide (SAF) a partir de 1983, incluindo critérios clínicos, etiopatogênese e terapia atual.MÉTODOS: Revisão de literatura utilizando o PubMed. Foram selecionados artigos com foco na história dos aAF e da SAF.RESULTADOS: Os aAF foram originalmente descritos em pacientes com sífilis ainda em 1906 por Wassermann. Uma primeira definição do anticoagulante lúpico foi proposta em 1963, enquanto o anticorpo anticardiolipina (aCL) foi descrito 20 anos mais tarde. A SAF, inicialmente reportada por Hughes em 1985 como "síndrome do aCL" é uma das mais prevalentes trombofilias adquiridas. Tromboses arteriais e venosas, associadas ou não à morbidade gestacional, compreendem os achados principais. É uma nova entidade, tendo sido primeiramente associada ao lupus eritematoso sistêmico. Uma forma primária de SAF foi reconhecida em1989, e muitas variantes de SAF são modernamente conhecidas. A terapia-padrão para a SAF trombótica é a anticoagulação plena e ininterrupta. Na SAF obstétrica, a combinação de ácido acetil-salicílico com enoxaparina tem-se mostrado altamente efetiva.CONCLUSÕES: A caracterização sequencial dos aAF desde Wasserman em 1906, e mais tarde da SAF nos anos 1980, é um interessante exemplo de como uma nova entidade é concebida passo a passo. A SAF é uma nova e intrigante causa de trombofilia autoimune, com uma complexa patogênese e uma pletora de manifestações clínicas e laboratoriais. O tratamento é baseado em anticoagulação contínua.

Trombose of tromboflebitis van de melkader komt vaak voor. Een aderontsteking is een niet te verwaarlozen complicatie na het toedienen van calciuminfusen of andere medicijnen bij melkkoeien, vooral als de ader flink beschadigd wordt door de infuusnaald en als het materiaal of de koe niet schoon is

Oral anticoagulation has been shown to be effective in the prevention and treatment of thromboembolic events. Vitamin K antagonists (VKA) are the drugs of choice for over 50 years in treatment for prevention of thromboembolic events and the most commonly used are warfarin and phenprocoumon. Currently there are new oral anticoagulants, the direct factor Xa inhibitors, and direct thrombin inhibitors which demonstrate similar efficacy to VKA and low bleeding risk and do not require monitoring because they have low interaction with other drugs and foods. Despite these advantages, the AVK still widely used due to the long experience of its use, the possibility of monitoring through the control of international normalized ratio (INR), the existence of an antidote to reverse its effect (vitamin K) and at low cost. The main difference between the AVK is pharmacological half-life, which is shorter for warfarin, approximately 30 hours versus 216 hours for phenprocoumon. There are few data in the literature that compare the efficacy, stability and drug interactions of these two drugs. Changes in therapeutic levels of AVK and the difficulty of keeping it stable due to interactions with drugs and food is a limiting factor for the efficacy and safety of these drugs. Due to the lack of evidence comparing the stability of the therapeutic level of warfarin and phenprocoumon, it is necessary that studies comparing these two drugs in relation to maintaining therapeutic level of anticoagulation., A anticoagulação oral tem se mostrado efetiva na prevenção e no tratamento de eventos tromboembólicos. Os antagonistas da vitamina K (AVK) são as drogas de escolha a mais de 50 anos no tratamento para prevenção de eventos tromboembólicos e os mais comumente utilizados são a varfarina e a femprocumona. Atualmente existem novos anticoagulantes orais, os inibidores diretos do fator Xa, e os inibidores diretos da trombina os quais demonstram eficácia semelhante aos AVK e baixo risco de sangramento e não necessitam de monitoramento por apresentarem baixa interação com outras drogas e alimentos. Apesar dessas vantagens, os AVK continuam sendo amplamente utilizado devido à longa experiência de seu uso, possibilidade de monitorização através do controle da razão normatizada internacional (RNI), pela existência de um antídoto para reversão de seu efeito (vitamina K) e pelo baixo custo. A principal diferença farmacológica entre os AVK é sua meia-vida, a qual é mais curta para a varfarina, aproximadamente 30 horas, versus 216 horas para a femprocumona. Existem poucos dados na literatura que comparem a eficácia, estabilidade e interações medicamentosas dessas duas drogas. As variações dos níveis terapêuticos dos AVK e a dificuldade de mantê-lo estável devido a interações com os medicamentos e com a alimentação é um fator limitante da eficácia e segurança dessas drogas. Devido à ausência de evidências comparando a estabilidade do nível terapêutico entre a varfarina e femprocumona, é necessário que existam estudos que comparem essas duas drogas em relação à manutenção de anticoagulação em nível terapêutico.

Oral anticoagulation has been shown to be effective in the prevention and treatment of thromboembolic events. Vitamin K antagonists (VKA) are the drugs of choice for over 50 years in treatment for prevention of thromboembolic events and the most commonly used are warfarin and phenprocoumon. Currently there are new oral anticoagulants, the direct factor Xa inhibitors, and direct thrombin inhibitors which demonstrate similar efficacy to VKA and low bleeding risk and do not require monitoring because they have low interaction with other drugs and foods. Despite these advantages, the AVK still widely used due to the long experience of its use, the possibility of monitoring through the control of international normalized ratio (INR), the existence of an antidote to reverse its effect (vitamin K) and at low cost. The main difference between the AVK is pharmacological half-life, which is shorter for warfarin, approximately 30 hours versus 216 hours for phenprocoumon. There are few data in the literature that compare the efficacy, stability and drug interactions of these two drugs. Changes in therapeutic levels of AVK and the difficulty of keeping it stable due to interactions with drugs and food is a limiting factor for the efficacy and safety of these drugs. Due to the lack of evidence comparing the stability of the therapeutic level of warfarin and phenprocoumon, it is necessary that studies comparing these two drugs in relation to maintaining therapeutic level of anticoagulation., A anticoagulação oral tem se mostrado efetiva na prevenção e no tratamento de eventos tromboembólicos. Os antagonistas da vitamina K (AVK) são as drogas de escolha a mais de 50 anos no tratamento para prevenção de eventos tromboembólicos e os mais comumente utilizados são a varfarina e a femprocumona. Atualmente existem novos anticoagulantes orais, os inibidores diretos do fator Xa, e os inibidores diretos da trombina os quais demonstram eficácia semelhante aos AVK e baixo risco de sangramento e não necessitam de monitoramento por apresentarem baixa interação com outras drogas e alimentos. Apesar dessas vantagens, os AVK continuam sendo amplamente utilizado devido à longa experiência de seu uso, possibilidade de monitorização através do controle da razão normatizada internacional (RNI), pela existência de um antídoto para reversão de seu efeito (vitamina K) e pelo baixo custo. A principal diferença farmacológica entre os AVK é sua meia-vida, a qual é mais curta para a varfarina, aproximadamente 30 horas, versus 216 horas para a femprocumona. Existem poucos dados na literatura que comparem a eficácia, estabilidade e interações medicamentosas dessas duas drogas. As variações dos níveis terapêuticos dos AVK e a dificuldade de mantê-lo estável devido a interações com os medicamentos e com a alimentação é um fator limitante da eficácia e segurança dessas drogas. Devido à ausência de evidências comparando a estabilidade do nível terapêutico entre a varfarina e femprocumona, é necessário que existam estudos que comparem essas duas drogas em relação à manutenção de anticoagulação em nível terapêutico.

Tromboelastografie (TEG) is een visco-elastische, globale stollingstest op volbloed, die aan het bed van de patiënt kan worden uitgevoerd en snel resultaten genereert. TEG visualiseert hierbij de effecten van zowel plasmafactoren als cellulaire bloedelementen. Aanvankelijk werd TEG voornamelijk in de lever-, cardio- en traumachirurgie gebruikt bij de analyse en correctie van complexe stollingsstoornissen. Tegenwoordig vindt de techniek zijn toepassing in zeer diverse, zowel klinische als experimentele, gebieden betreffende hemostase en trombose. Het primaire doel van het proefschrift is om de kennis van TEG bij clinici en onderzoekers werkzaam op het terrein van de hemostase en trombose te verbeteren, waarbij zowel de mogelijkheden als de beperkingen van de techniek worden belicht. De rol die “point-of-care” testen van hemostase (o.a. TEG) spelen bij het voorspellen en behandelen van massaal bloedverlies wordt geëvalueerd. Daarnaast zijn TEG referentiewaarden bepaald, waarbij duidelijke effecten van leeftijd, geslacht en orale anticonceptiva op de stolling zijn aangetoond. Ook is de TEG techniek gevalideerd wat betreft de analyse en detectie van een tekort aan bloedplaatjes. TEG bleek goed in staat om de effecten van (getransfundeerde) bloedplaatjes en rode bloedcellen op de stolling aan te tonen. De techniek kan wellicht nuttig zijn als in vivo kwaliteitstest van bloedproducten. Tenslotte lijkt TEG bruikbaar bij patiënten met sikkelcelziekte ter detectie van zowel verhoogde stollingsstatus alsook de gunstige effecten van behandeling met hydroxyureum hierop.

Het onderzoek in dit proefschrift is ontworpen om de werking van sommige systemische geneesmiddelen te ontcijferen en een aantal andere risicofactoren van open-kamerhoek glaucoom (OKG) te onderzoeken. De studies gepresenteerd in de eerste drie hoofdstukken zijn gebaseerd op het Erasmus Rotterdam Gezondheids Onderzoek (ERGO/ Rotterdamstudie), een prospectief populatie-gebaseerde cohort studie van ouderdomgerelateerde aandoeningen. Onze studie populatie bestaat uit 3939 van de oorspronkelijke 7983 deelnemers van 55 jaar en ouder uit het Rotterdamse onderzoek. In hoofdstuk een hebben we onderzocht of het gebruik van cholesterol- verlagende geneesmiddelen geassocieerd is met een verlaagd risico op (OKG). We hebben de relatie tussen het gebruik van corticosteroïden en incident OKG onderzocht in hoofdstuk twee. In hoofdstuk 3 is onderzocht of antitrombotica het risico van OKG kan verminderen. Het centrale thema van de hoofdstukken 4, 5 en 6 is het gebruik van statistische methodologie, systematische review en meta-analyse om andere risicofactoren van OKG te verhelderen. Hoofdstuk 4 beschrijft de risico's die samenhangen met visuele veldprogressie in OKG door het vergelijken van verschillende statistische benaderingen in de Groningen Longitudinal Glaucoma Study (GLGS), een prospectieve cohort studie in een klinische setting. Hoofdstuk 5 presenteert in een systematische review en meta-analyse de relatie tussen bijziendheid en OKG. Hoofdstuk 6 biedt een overzicht van de huidige stand van kennis van het effect van systemische geneesmiddelen op OKG.

Alledaagse, relatief onschuldige ontstekingsklachten zoals luchtweginfecties, diarree of een grieperig gevoel, brengen een verhoogde kans op trombose met zich mee. Hierdoor vergroot het risico op een longembolie of een trombosebeen. Dat blijkt uit onderzoek van promovendus Vladimir Tichelaar. Ook andere ziekten, zoals chronische infecties en auto-immuunziekten, zorgen voor een verhoogd risico op trombose, zo stelt Tichelaar vast in analyse van studies die de afgelopen vijftien jaar werden verricht. De ziekte van Crohn en colitis ulcerosa zijn hier voorbeelden van. Tijdens een opvlamming van een chronische darmziekte is het risico op veneuze trombose tot acht maal verhoogd. Verder laat Tichelaar zien dat patiënten met een HIV-infectie een hoog risico hebben op veneuze en arteriële trombose, zoals een hartinfarct of een beroerte, en dat een infectie met cytomegalovirus bij deze patiënten een extra verstoring van de stollingsfactoren in het bloed veroorzaakt. Bij patiënten met een acute veneuze trombose bestaat er een relatie tussen het bloedglucose en de trombose, zo ontdekte Tichelaar. Hoe hoger de glucosewaarden, hoe groter de waarschijnlijkheid dat er een veneuze trombose gevonden wordt. Dokters moeten alert zijn op het gebruik van nieuwe antistollingsmedicijnen, waaronder Rivaroxaban, stelt Tichelaar ten slotte vast. Gebruik van dit medicijn blijkt de meting van onder andere factor VIII te beïnvloeden.

Decennialang werd verondersteld dat arteriële (slagaderlijke) en veneuze (aderlijke) trombose twee verschillende ziekten waren. In de afgelopen tien jaar is deze tweedeling echter in twijfel getrokken. In het huidige proefschrift onderzochten we of veneuze en arteriële trombose gerelateerd zijn en hoe we deze relatie kunnen verklaren. In een groot populatiecohort van ruim 40 000 mensen vonden we dat mensen die een veneuze trombose ontwikkelden, zonder aanwijsbare uitlokkende factor, het jaar daarop een drievoudig verhoogd risico hadden op het ontwikkelen van een arteriële trombose (o.a. hartinfarct, herseninfarct). Deze relatie kan mogelijk verklaard worden door een overlap in risicofactoren. In een subgroep van ruim 7000 mensen onderzochten we enkele van deze risicofactoren. Hieruit bleek dat insulineresistentie en een afwijkend lipidenprofiel, bekende risicofactoren voor arteriële trombose, het risico op veneuze trombose niet beïnvloeden. Overgewicht en afwijkende spiegels van de stollingsfactoren factor VIII en vrij proteine S daarentegen, verhogen het risico op beide ziekten. Ook vonden we dat mensen met een onuitgelokte veneuze trombose en een verhoogde albuminespiegel in de urine (marker voor vaatwandschade) een ruim drievoudig verhoogde kans hadden op het ontwikkelen van een tweede veneuze trombose. De resultaten van dit onderzoek bieden handvaten om het aantal nieuwe gevallen van zowel arteriële als veneuze trombose te reduceren.

Oral anticoagulation has been shown to be effective in the prevention and treatment of thromboembolic events. Vitamin K antagonists (VKA) are the drugs of choice for over 50 years in treatment for prevention of thromboembolic events and the most commonly used are warfarin and phenprocoumon. Currently there are new oral anticoagulants, the direct factor Xa inhibitors, and direct thrombin inhibitors which demonstrate similar efficacy to VKA and low bleeding risk and do not require monitoring because they have low interaction with other drugs and foods. Despite these advantages, the AVK still widely used due to the long experience of its use, the possibility of monitoring through the control of international normalized ratio (INR), the existence of an antidote to reverse its effect (vitamin K) and at low cost. The main difference between the AVK is pharmacological half-life, which is shorter for warfarin, approximately 30 hours versus 216 hours for phenprocoumon. There are few data in the literature that compare the efficacy, stability and drug interactions of these two drugs. Changes in therapeutic levels of AVK and the difficulty of keeping it stable due to interactions with drugs and food is a limiting factor for the efficacy and safety of these drugs. Due to the lack of evidence comparing the stability of the therapeutic level of warfarin and phenprocoumon, it is necessary that studies comparing these two drugs in relation to maintaining therapeutic level of anticoagulation., A anticoagulação oral tem se mostrado efetiva na prevenção e no tratamento de eventos tromboembólicos. Os antagonistas da vitamina K (AVK) são as drogas de escolha a mais de 50 anos no tratamento para prevenção de eventos tromboembólicos e os mais comumente utilizados são a varfarina e a femprocumona. Atualmente existem novos anticoagulantes orais, os inibidores diretos do fator Xa, e os inibidores diretos da trombina os quais demonstram eficácia semelhante aos AVK e baixo risco de sangramento e não necessitam de monitoramento por apresentarem baixa interação com outras drogas e alimentos. Apesar dessas vantagens, os AVK continuam sendo amplamente utilizado devido à longa experiência de seu uso, possibilidade de monitorização através do controle da razão normatizada internacional (RNI), pela existência de um antídoto para reversão de seu efeito (vitamina K) e pelo baixo custo. A principal diferença farmacológica entre os AVK é sua meia-vida, a qual é mais curta para a varfarina, aproximadamente 30 horas, versus 216 horas para a femprocumona. Existem poucos dados na literatura que comparem a eficácia, estabilidade e interações medicamentosas dessas duas drogas. As variações dos níveis terapêuticos dos AVK e a dificuldade de mantê-lo estável devido a interações com os medicamentos e com a alimentação é um fator limitante da eficácia e segurança dessas drogas. Devido à ausência de evidências comparando a estabilidade do nível terapêutico entre a varfarina e femprocumona, é necessário que existam estudos que comparem essas duas drogas em relação à manutenção de anticoagulação em nível terapêutico.

Oral anticoagulation has been shown to be effective in the prevention and treatment of thromboembolic events. Vitamin K antagonists (VKA) are the drugs of choice for over 50 years in treatment for prevention of thromboembolic events and the most commonly used are warfarin and phenprocoumon. Currently there are new oral anticoagulants, the direct factor Xa inhibitors, and direct thrombin inhibitors which demonstrate similar efficacy to VKA and low bleeding risk and do not require monitoring because they have low interaction with other drugs and foods. Despite these advantages, the AVK still widely used due to the long experience of its use, the possibility of monitoring through the control of international normalized ratio (INR), the existence of an antidote to reverse its effect (vitamin K) and at low cost. The main difference between the AVK is pharmacological half-life, which is shorter for warfarin, approximately 30 hours versus 216 hours for phenprocoumon. There are few data in the literature that compare the efficacy, stability and drug interactions of these two drugs. Changes in therapeutic levels of AVK and the difficulty of keeping it stable due to interactions with drugs and food is a limiting factor for the efficacy and safety of these drugs. Due to the lack of evidence comparing the stability of the therapeutic level of warfarin and phenprocoumon, it is necessary that studies comparing these two drugs in relation to maintaining therapeutic level of anticoagulation., A anticoagulação oral tem se mostrado efetiva na prevenção e no tratamento de eventos tromboembólicos. Os antagonistas da vitamina K (AVK) são as drogas de escolha a mais de 50 anos no tratamento para prevenção de eventos tromboembólicos e os mais comumente utilizados são a varfarina e a femprocumona. Atualmente existem novos anticoagulantes orais, os inibidores diretos do fator Xa, e os inibidores diretos da trombina os quais demonstram eficácia semelhante aos AVK e baixo risco de sangramento e não necessitam de monitoramento por apresentarem baixa interação com outras drogas e alimentos. Apesar dessas vantagens, os AVK continuam sendo amplamente utilizado devido à longa experiência de seu uso, possibilidade de monitorização através do controle da razão normatizada internacional (RNI), pela existência de um antídoto para reversão de seu efeito (vitamina K) e pelo baixo custo. A principal diferença farmacológica entre os AVK é sua meia-vida, a qual é mais curta para a varfarina, aproximadamente 30 horas, versus 216 horas para a femprocumona. Existem poucos dados na literatura que comparem a eficácia, estabilidade e interações medicamentosas dessas duas drogas. As variações dos níveis terapêuticos dos AVK e a dificuldade de mantê-lo estável devido a interações com os medicamentos e com a alimentação é um fator limitante da eficácia e segurança dessas drogas. Devido à ausência de evidências comparando a estabilidade do nível terapêutico entre a varfarina e femprocumona, é necessário que existam estudos que comparem essas duas drogas em relação à manutenção de anticoagulação em nível terapêutico.

Tromboelastografie (TEG) is een visco-elastische, globale stollingstest op volbloed, die aan het bed van de patiënt kan worden uitgevoerd en snel resultaten genereert. TEG visualiseert hierbij de effecten van zowel plasmafactoren als cellulaire bloedelementen. Aanvankelijk werd TEG voornamelijk in de lever-, cardio- en traumachirurgie gebruikt bij de analyse en correctie van complexe stollingsstoornissen. Tegenwoordig vindt de techniek zijn toepassing in zeer diverse, zowel klinische als experimentele, gebieden betreffende hemostase en trombose. Het primaire doel van het proefschrift is om de kennis van TEG bij clinici en onderzoekers werkzaam op het terrein van de hemostase en trombose te verbeteren, waarbij zowel de mogelijkheden als de beperkingen van de techniek worden belicht. De rol die “point-of-care” testen van hemostase (o.a. TEG) spelen bij het voorspellen en behandelen van massaal bloedverlies wordt geëvalueerd. Daarnaast zijn TEG referentiewaarden bepaald, waarbij duidelijke effecten van leeftijd, geslacht en orale anticonceptiva op de stolling zijn aangetoond. Ook is de TEG techniek gevalideerd wat betreft de analyse en detectie van een tekort aan bloedplaatjes. TEG bleek goed in staat om de effecten van (getransfundeerde) bloedplaatjes en rode bloedcellen op de stolling aan te tonen. De techniek kan wellicht nuttig zijn als in vivo kwaliteitstest van bloedproducten. Tenslotte lijkt TEG bruikbaar bij patiënten met sikkelcelziekte ter detectie van zowel verhoogde stollingsstatus alsook de gunstige effecten van behandeling met hydroxyureum hierop.

Het onderzoek in dit proefschrift is ontworpen om de werking van sommige systemische geneesmiddelen te ontcijferen en een aantal andere risicofactoren van open-kamerhoek glaucoom (OKG) te onderzoeken. De studies gepresenteerd in de eerste drie hoofdstukken zijn gebaseerd op het Erasmus Rotterdam Gezondheids Onderzoek (ERGO/ Rotterdamstudie), een prospectief populatie-gebaseerde cohort studie van ouderdomgerelateerde aandoeningen. Onze studie populatie bestaat uit 3939 van de oorspronkelijke 7983 deelnemers van 55 jaar en ouder uit het Rotterdamse onderzoek. In hoofdstuk een hebben we onderzocht of het gebruik van cholesterol- verlagende geneesmiddelen geassocieerd is met een verlaagd risico op (OKG). We hebben de relatie tussen het gebruik van corticosteroïden en incident OKG onderzocht in hoofdstuk twee. In hoofdstuk 3 is onderzocht of antitrombotica het risico van OKG kan verminderen. Het centrale thema van de hoofdstukken 4, 5 en 6 is het gebruik van statistische methodologie, systematische review en meta-analyse om andere risicofactoren van OKG te verhelderen. Hoofdstuk 4 beschrijft de risico's die samenhangen met visuele veldprogressie in OKG door het vergelijken van verschillende statistische benaderingen in de Groningen Longitudinal Glaucoma Study (GLGS), een prospectieve cohort studie in een klinische setting. Hoofdstuk 5 presenteert in een systematische review en meta-analyse de relatie tussen bijziendheid en OKG. Hoofdstuk 6 biedt een overzicht van de huidige stand van kennis van het effect van systemische geneesmiddelen op OKG.

Alledaagse, relatief onschuldige ontstekingsklachten zoals luchtweginfecties, diarree of een grieperig gevoel, brengen een verhoogde kans op trombose met zich mee. Hierdoor vergroot het risico op een longembolie of een trombosebeen. Dat blijkt uit onderzoek van promovendus Vladimir Tichelaar. Ook andere ziekten, zoals chronische infecties en auto-immuunziekten, zorgen voor een verhoogd risico op trombose, zo stelt Tichelaar vast in analyse van studies die de afgelopen vijftien jaar werden verricht. De ziekte van Crohn en colitis ulcerosa zijn hier voorbeelden van. Tijdens een opvlamming van een chronische darmziekte is het risico op veneuze trombose tot acht maal verhoogd. Verder laat Tichelaar zien dat patiënten met een HIV-infectie een hoog risico hebben op veneuze en arteriële trombose, zoals een hartinfarct of een beroerte, en dat een infectie met cytomegalovirus bij deze patiënten een extra verstoring van de stollingsfactoren in het bloed veroorzaakt. Bij patiënten met een acute veneuze trombose bestaat er een relatie tussen het bloedglucose en de trombose, zo ontdekte Tichelaar. Hoe hoger de glucosewaarden, hoe groter de waarschijnlijkheid dat er een veneuze trombose gevonden wordt. Dokters moeten alert zijn op het gebruik van nieuwe antistollingsmedicijnen, waaronder Rivaroxaban, stelt Tichelaar ten slotte vast. Gebruik van dit medicijn blijkt de meting van onder andere factor VIII te beïnvloeden.

Decennialang werd verondersteld dat arteriële (slagaderlijke) en veneuze (aderlijke) trombose twee verschillende ziekten waren. In de afgelopen tien jaar is deze tweedeling echter in twijfel getrokken. In het huidige proefschrift onderzochten we of veneuze en arteriële trombose gerelateerd zijn en hoe we deze relatie kunnen verklaren. In een groot populatiecohort van ruim 40 000 mensen vonden we dat mensen die een veneuze trombose ontwikkelden, zonder aanwijsbare uitlokkende factor, het jaar daarop een drievoudig verhoogd risico hadden op het ontwikkelen van een arteriële trombose (o.a. hartinfarct, herseninfarct). Deze relatie kan mogelijk verklaard worden door een overlap in risicofactoren. In een subgroep van ruim 7000 mensen onderzochten we enkele van deze risicofactoren. Hieruit bleek dat insulineresistentie en een afwijkend lipidenprofiel, bekende risicofactoren voor arteriële trombose, het risico op veneuze trombose niet beïnvloeden. Overgewicht en afwijkende spiegels van de stollingsfactoren factor VIII en vrij proteine S daarentegen, verhogen het risico op beide ziekten. Ook vonden we dat mensen met een onuitgelokte veneuze trombose en een verhoogde albuminespiegel in de urine (marker voor vaatwandschade) een ruim drievoudig verhoogde kans hadden op het ontwikkelen van een tweede veneuze trombose. De resultaten van dit onderzoek bieden handvaten om het aantal nieuwe gevallen van zowel arteriële als veneuze trombose te reduceren.

Oral anticoagulation has been shown to be effective in the prevention and treatment of thromboembolic events. Vitamin K antagonists (VKA) are the drugs of choice for over 50 years in treatment for prevention of thromboembolic events and the most commonly used are warfarin and phenprocoumon. Currently there are new oral anticoagulants, the direct factor Xa inhibitors, and direct thrombin inhibitors which demonstrate similar efficacy to VKA and low bleeding risk and do not require monitoring because they have low interaction with other drugs and foods. Despite these advantages, the AVK still widely used due to the long experience of its use, the possibility of monitoring through the control of international normalized ratio (INR), the existence of an antidote to reverse its effect (vitamin K) and at low cost. The main difference between the AVK is pharmacological half-life, which is shorter for warfarin, approximately 30 hours versus 216 hours for phenprocoumon. There are few data in the literature that compare the efficacy, stability and drug interactions of these two drugs. Changes in therapeutic levels of AVK and the difficulty of keeping it stable due to interactions with drugs and food is a limiting factor for the efficacy and safety of these drugs. Due to the lack of evidence comparing the stability of the therapeutic level of warfarin and phenprocoumon, it is necessary that studies comparing these two drugs in relation to maintaining therapeutic level of anticoagulation., A anticoagulação oral tem se mostrado efetiva na prevenção e no tratamento de eventos tromboembólicos. Os antagonistas da vitamina K (AVK) são as drogas de escolha a mais de 50 anos no tratamento para prevenção de eventos tromboembólicos e os mais comumente utilizados são a varfarina e a femprocumona. Atualmente existem novos anticoagulantes orais, os inibidores diretos do fator Xa, e os inibidores diretos da trombina os quais demonstram eficácia semelhante aos AVK e baixo risco de sangramento e não necessitam de monitoramento por apresentarem baixa interação com outras drogas e alimentos. Apesar dessas vantagens, os AVK continuam sendo amplamente utilizado devido à longa experiência de seu uso, possibilidade de monitorização através do controle da razão normatizada internacional (RNI), pela existência de um antídoto para reversão de seu efeito (vitamina K) e pelo baixo custo. A principal diferença farmacológica entre os AVK é sua meia-vida, a qual é mais curta para a varfarina, aproximadamente 30 horas, versus 216 horas para a femprocumona. Existem poucos dados na literatura que comparem a eficácia, estabilidade e interações medicamentosas dessas duas drogas. As variações dos níveis terapêuticos dos AVK e a dificuldade de mantê-lo estável devido a interações com os medicamentos e com a alimentação é um fator limitante da eficácia e segurança dessas drogas. Devido à ausência de evidências comparando a estabilidade do nível terapêutico entre a varfarina e femprocumona, é necessário que existam estudos que comparem essas duas drogas em relação à manutenção de anticoagulação em nível terapêutico.

Introdução: síndrome metabólica (SM) é definida como um conjunto de anormalidades aterotrombóticas e inflamatórias. Seus portadores apresentam predisposição aumentada a morbi-mortalidade por doenças cardiovasculares (DCV) e diabetes mellitus tipo 2 (DM2). Diversos biomarcadores inflamatórios, do metabolismo lipídico, oxidativo e isquêmico, ligados a fisiopatologia da SM têm sido investigados. Recentes estudos sugerem que a albumina modificada pela isquemia (IMA) é um biomarcador de isquêmia e que seus níveis elevados representam uma possível indicação de disfunção microvascular em pacientes com SM. Objetivo: investigar a associação de marcadores lipidicos, oxidativos e inflamatórios potencialmente associados a processos isquêmicos em pacientes com síndrome metabólica. Material e métodos: estudo prospectivo, do tipo caso-controle, onde foram incluídos 32 (30,2%) indivíduos saudáveis (grupo controle – C) e 74 (69,8%) indivíduos com SM (grupo caso – SM). Os indivíduos com SM foram recrutados no ambulatório de risco cardiometabólico do Serviço de Cardiologia do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul e os saudáveis foram recrutados na Universidade Federal de Santa Maria (UFSM - alunos, funcionários e professores). O critério diagnóstico de SM utilizado foi o NCEP-ATPIII. Glicose, colesterol total (CT), HDL e triglicerídeos (TG) foram determinados por método enzimático colorimétrico (Ortho-clinical Diagnostics); LDL foi determinada pela equação de Friedwald; Proteína C ultra Sensível (PCR-us) foi determinada por nefelometria, autoanticorpo anti-LDL-oxidada (anti-OxLDL) e LDL oxidada (OxLDL) foram determinadas por ensaio imunoenzimatico (ELISA); IMA foi mensurada por ensaio colorimétrico com cobalto.Resultados: a amostra incluiu 34 homens e 72 mulheres. A média de idade do grupo C foi 55,2±8,8 anos e do grupo SM 57,6±8,3 anos (p=0,142). O grupo SM apresentou maior IMC (32,6±6,1 kg/m2, p=0,0001), pressão arterial sistólica (147±26,8 mmHg, Introduction: metabolic syndrome (MS) is defined as a set of atherothrombotic and inflammatory abnormalities. These patients are predisposed to increased morbidity and mortality from cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). Several inflammatory biomarkers of lipid metabolism-related oxidative and ischemic pathophysiology of MS have been investigated. Recent studies suggest that ischemia modified albumin (IMA) is a biomarker of ischemia and that its levels are a possible indication of microvascular dysfunction in patients with MS. Objective: to investigate the association between these lipids, oxidatives and inflammatory processes potentially associated with ischemic in patients with MS. Material and methods: prospective, case-control study that included 32 (30. 2%) healthy subjects (control - C) and 74 (69. 8%) subjects with MS (case group - MS). Individuals with MS were recruited at cardiometabolic risk center of Cardiology Service, Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sul and the healthy were recruited from the Universidade Federal de Santa Maria (UFSM - students, staff and teachers). The diagnostic criteria of MS was used NCEP-ATPIII. Glucose, total cholesterol (TC), HDL and triglycerides (TG) were determined by enzymatic colorimetric method (Ortho-Clinical Diagnostics), LDL was determined by the Friedewald equation; ultra C-sensitive protein (CRP) was measured by nephelometry, autoantibody anti-oxidized LDL (anti -oxLDL) and oxidized LDL (oxLDL) were determined by ELISA; IMA was measured by colorimetric assay with cobalt.Results: The sample included 34 men and 72 women. The average age of group C was 55. 2 ± 8. 8 years and the MS group 57. 6 ± 8. 3 years (p = 0. 142). The MS group had a higher BMI (32. 6 ± 6. 1 kg/m2, p = 0. 0001), systolic blood pressure (147 ± 26. 8 mmHg, p = 0. 001), diastolic blood pressure (85. 9 ± 15. 9 mmHg, p = 0. 01), glucose (133. 7 ± 68. 7 mg/dL, p=0. 001), TC (204 ± 58. 1 mg

Introdução: síndrome metabólica (SM) é definida como um conjunto de anormalidades aterotrombóticas e inflamatórias. Seus portadores apresentam predisposição aumentada a morbi-mortalidade por doenças cardiovasculares (DCV) e diabetes mellitus tipo 2 (DM2). Diversos biomarcadores inflamatórios, do metabolismo lipídico, oxidativo e isquêmico, ligados a fisiopatologia da SM têm sido investigados. Recentes estudos sugerem que a albumina modificada pela isquemia (IMA) é um biomarcador de isquêmia e que seus níveis elevados representam uma possível indicação de disfunção microvascular em pacientes com SM. Objetivo: investigar a associação de marcadores lipidicos, oxidativos e inflamatórios potencialmente associados a processos isquêmicos em pacientes com síndrome metabólica. Material e métodos: estudo prospectivo, do tipo caso-controle, onde foram incluídos 32 (30,2%) indivíduos saudáveis (grupo controle – C) e 74 (69,8%) indivíduos com SM (grupo caso – SM). Os indivíduos com SM foram recrutados no ambulatório de risco cardiometabólico do Serviço de Cardiologia do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul e os saudáveis foram recrutados na Universidade Federal de Santa Maria (UFSM - alunos, funcionários e professores). O critério diagnóstico de SM utilizado foi o NCEP-ATPIII. Glicose, colesterol total (CT), HDL e triglicerídeos (TG) foram determinados por método enzimático colorimétrico (Ortho-clinical Diagnostics); LDL foi determinada pela equação de Friedwald; Proteína C ultra Sensível (PCR-us) foi determinada por nefelometria, autoanticorpo anti-LDL-oxidada (anti-OxLDL) e LDL oxidada (OxLDL) foram determinadas por ensaio imunoenzimatico (ELISA); IMA foi mensurada por ensaio colorimétrico com cobalto.Resultados: a amostra incluiu 34 homens e 72 mulheres. A média de idade do grupo C foi 55,2±8,8 anos e do grupo SM 57,6±8,3 anos (p=0,142). O grupo SM apresentou maior IMC (32,6±6,1 kg/m2, p=0,0001), pressão arterial sistólica (147±26,8 mmHg, Introduction: metabolic syndrome (MS) is defined as a set of atherothrombotic and inflammatory abnormalities. These patients are predisposed to increased morbidity and mortality from cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). Several inflammatory biomarkers of lipid metabolism-related oxidative and ischemic pathophysiology of MS have been investigated. Recent studies suggest that ischemia modified albumin (IMA) is a biomarker of ischemia and that its levels are a possible indication of microvascular dysfunction in patients with MS. Objective: to investigate the association between these lipids, oxidatives and inflammatory processes potentially associated with ischemic in patients with MS. Material and methods: prospective, case-control study that included 32 (30. 2%) healthy subjects (control - C) and 74 (69. 8%) subjects with MS (case group - MS). Individuals with MS were recruited at cardiometabolic risk center of Cardiology Service, Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sul and the healthy were recruited from the Universidade Federal de Santa Maria (UFSM - students, staff and teachers). The diagnostic criteria of MS was used NCEP-ATPIII. Glucose, total cholesterol (TC), HDL and triglycerides (TG) were determined by enzymatic colorimetric method (Ortho-Clinical Diagnostics), LDL was determined by the Friedewald equation; ultra C-sensitive protein (CRP) was measured by nephelometry, autoantibody anti-oxidized LDL (anti -oxLDL) and oxidized LDL (oxLDL) were determined by ELISA; IMA was measured by colorimetric assay with cobalt.Results: The sample included 34 men and 72 women. The average age of group C was 55. 2 ± 8. 8 years and the MS group 57. 6 ± 8. 3 years (p = 0. 142). The MS group had a higher BMI (32. 6 ± 6. 1 kg/m2, p = 0. 0001), systolic blood pressure (147 ± 26. 8 mmHg, p = 0. 001), diastolic blood pressure (85. 9 ± 15. 9 mmHg, p = 0. 01), glucose (133. 7 ± 68. 7 mg/dL, p=0. 001), TC (204 ± 58. 1 mg

Introdução: síndrome metabólica (SM) é definida como um conjunto de anormalidades aterotrombóticas e inflamatórias. Seus portadores apresentam predisposição aumentada a morbi-mortalidade por doenças cardiovasculares (DCV) e diabetes mellitus tipo 2 (DM2). Diversos biomarcadores inflamatórios, do metabolismo lipídico, oxidativo e isquêmico, ligados a fisiopatologia da SM têm sido investigados. Recentes estudos sugerem que a albumina modificada pela isquemia (IMA) é um biomarcador de isquêmia e que seus níveis elevados representam uma possível indicação de disfunção microvascular em pacientes com SM. Objetivo: investigar a associação de marcadores lipidicos, oxidativos e inflamatórios potencialmente associados a processos isquêmicos em pacientes com síndrome metabólica. Material e métodos: estudo prospectivo, do tipo caso-controle, onde foram incluídos 32 (30,2%) indivíduos saudáveis (grupo controle – C) e 74 (69,8%) indivíduos com SM (grupo caso – SM). Os indivíduos com SM foram recrutados no ambulatório de risco cardiometabólico do Serviço de Cardiologia do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul e os saudáveis foram recrutados na Universidade Federal de Santa Maria (UFSM - alunos, funcionários e professores). O critério diagnóstico de SM utilizado foi o NCEP-ATPIII. Glicose, colesterol total (CT), HDL e triglicerídeos (TG) foram determinados por método enzimático colorimétrico (Ortho-clinical Diagnostics); LDL foi determinada pela equação de Friedwald; Proteína C ultra Sensível (PCR-us) foi determinada por nefelometria, autoanticorpo anti-LDL-oxidada (anti-OxLDL) e LDL oxidada (OxLDL) foram determinadas por ensaio imunoenzimatico (ELISA); IMA foi mensurada por ensaio colorimétrico com cobalto.Resultados: a amostra incluiu 34 homens e 72 mulheres. A média de idade do grupo C foi 55,2±8,8 anos e do grupo SM 57,6±8,3 anos (p=0,142). O grupo SM apresentou maior IMC (32,6±6,1 kg/m2, p=0,0001), pressão arterial sistólica (147±26,8 mmHg, Introduction: metabolic syndrome (MS) is defined as a set of atherothrombotic and inflammatory abnormalities. These patients are predisposed to increased morbidity and mortality from cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). Several inflammatory biomarkers of lipid metabolism-related oxidative and ischemic pathophysiology of MS have been investigated. Recent studies suggest that ischemia modified albumin (IMA) is a biomarker of ischemia and that its levels are a possible indication of microvascular dysfunction in patients with MS. Objective: to investigate the association between these lipids, oxidatives and inflammatory processes potentially associated with ischemic in patients with MS. Material and methods: prospective, case-control study that included 32 (30. 2%) healthy subjects (control - C) and 74 (69. 8%) subjects with MS (case group - MS). Individuals with MS were recruited at cardiometabolic risk center of Cardiology Service, Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sul and the healthy were recruited from the Universidade Federal de Santa Maria (UFSM - students, staff and teachers). The diagnostic criteria of MS was used NCEP-ATPIII. Glucose, total cholesterol (TC), HDL and triglycerides (TG) were determined by enzymatic colorimetric method (Ortho-Clinical Diagnostics), LDL was determined by the Friedewald equation; ultra C-sensitive protein (CRP) was measured by nephelometry, autoantibody anti-oxidized LDL (anti -oxLDL) and oxidized LDL (oxLDL) were determined by ELISA; IMA was measured by colorimetric assay with cobalt.Results: The sample included 34 men and 72 women. The average age of group C was 55. 2 ± 8. 8 years and the MS group 57. 6 ± 8. 3 years (p = 0. 142). The MS group had a higher BMI (32. 6 ± 6. 1 kg/m2, p = 0. 0001), systolic blood pressure (147 ± 26. 8 mmHg, p = 0. 001), diastolic blood pressure (85. 9 ± 15. 9 mmHg, p = 0. 01), glucose (133. 7 ± 68. 7 mg/dL, p=0. 001), TC (204 ± 58. 1 mg

Introdução: síndrome metabólica (SM) é definida como um conjunto de anormalidades aterotrombóticas e inflamatórias. Seus portadores apresentam predisposição aumentada a morbi-mortalidade por doenças cardiovasculares (DCV) e diabetes mellitus tipo 2 (DM2). Diversos biomarcadores inflamatórios, do metabolismo lipídico, oxidativo e isquêmico, ligados a fisiopatologia da SM têm sido investigados. Recentes estudos sugerem que a albumina modificada pela isquemia (IMA) é um biomarcador de isquêmia e que seus níveis elevados representam uma possível indicação de disfunção microvascular em pacientes com SM. Objetivo: investigar a associação de marcadores lipidicos, oxidativos e inflamatórios potencialmente associados a processos isquêmicos em pacientes com síndrome metabólica. Material e métodos: estudo prospectivo, do tipo caso-controle, onde foram incluídos 32 (30,2%) indivíduos saudáveis (grupo controle – C) e 74 (69,8%) indivíduos com SM (grupo caso – SM). Os indivíduos com SM foram recrutados no ambulatório de risco cardiometabólico do Serviço de Cardiologia do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul e os saudáveis foram recrutados na Universidade Federal de Santa Maria (UFSM - alunos, funcionários e professores). O critério diagnóstico de SM utilizado foi o NCEP-ATPIII. Glicose, colesterol total (CT), HDL e triglicerídeos (TG) foram determinados por método enzimático colorimétrico (Ortho-clinical Diagnostics); LDL foi determinada pela equação de Friedwald; Proteína C ultra Sensível (PCR-us) foi determinada por nefelometria, autoanticorpo anti-LDL-oxidada (anti-OxLDL) e LDL oxidada (OxLDL) foram determinadas por ensaio imunoenzimatico (ELISA); IMA foi mensurada por ensaio colorimétrico com cobalto.Resultados: a amostra incluiu 34 homens e 72 mulheres. A média de idade do grupo C foi 55,2±8,8 anos e do grupo SM 57,6±8,3 anos (p=0,142). O grupo SM apresentou maior IMC (32,6±6,1 kg/m2, p=0,0001), pressão arterial sistólica (147±26,8 mmHg, Introduction: metabolic syndrome (MS) is defined as a set of atherothrombotic and inflammatory abnormalities. These patients are predisposed to increased morbidity and mortality from cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). Several inflammatory biomarkers of lipid metabolism-related oxidative and ischemic pathophysiology of MS have been investigated. Recent studies suggest that ischemia modified albumin (IMA) is a biomarker of ischemia and that its levels are a possible indication of microvascular dysfunction in patients with MS. Objective: to investigate the association between these lipids, oxidatives and inflammatory processes potentially associated with ischemic in patients with MS. Material and methods: prospective, case-control study that included 32 (30. 2%) healthy subjects (control - C) and 74 (69. 8%) subjects with MS (case group - MS). Individuals with MS were recruited at cardiometabolic risk center of Cardiology Service, Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sul and the healthy were recruited from the Universidade Federal de Santa Maria (UFSM - students, staff and teachers). The diagnostic criteria of MS was used NCEP-ATPIII. Glucose, total cholesterol (TC), HDL and triglycerides (TG) were determined by enzymatic colorimetric method (Ortho-Clinical Diagnostics), LDL was determined by the Friedewald equation; ultra C-sensitive protein (CRP) was measured by nephelometry, autoantibody anti-oxidized LDL (anti -oxLDL) and oxidized LDL (oxLDL) were determined by ELISA; IMA was measured by colorimetric assay with cobalt.Results: The sample included 34 men and 72 women. The average age of group C was 55. 2 ± 8. 8 years and the MS group 57. 6 ± 8. 3 years (p = 0. 142). The MS group had a higher BMI (32. 6 ± 6. 1 kg/m2, p = 0. 0001), systolic blood pressure (147 ± 26. 8 mmHg, p = 0. 001), diastolic blood pressure (85. 9 ± 15. 9 mmHg, p = 0. 01), glucose (133. 7 ± 68. 7 mg/dL, p=0. 001), TC (204 ± 58. 1 mg

Venous thromboembolism is considered a multicausal disease. The risk of a first thrombotic event and recurrence depends on the number of exogenous and thrombophilic risk factors, their weight, interactions, exposure time and age. As a consequence, the risk may vary widely, both within and between individuals. The results of anticoagulant treatment and prohylaxis of venous thromboemb0olism can probably be improved when these are adjusted to the individual risk. However, it is not possible to assess the individual risk because the absolute risk for most currently know risk factors, either single or combined is still unknown. In the here presented studies, we assessed the absolute risk for a number of thrombophilic defects.

The overall incidence of venous thrombosis is 1-3 per 1000 persons each year and rises exponentially from < 0.005% in children to 1% per year in the elderly. Most venous thromboses start in the calf veins, from where they may extend and cause proximal deep vein thrombosis (DVT), and subsequently pulmonary embolism (PE). Patients with DVT or PE remain at risk for recurrent venous thrombosis. This risk is most pronounced in the first months after the acute episode and declines slowly over subsequent years. Risk factors for venous thrombosis are presented in Table 1 [Chapter 1]. Despite anticoagulant treatment for 3-6 months, the recurrence rate of venous thrombosis is 25% within 5 years, while the immediate death rate due to pulmonary embolism is 2.6% and the post-thrombotic syndrome occurs in up to 50% of patients. Recurrent venous thrombosis usually leads to life-long anticoagulant treatment, which increases long term health care costs substantially and has serious potential side effects as major bleeding. Therefore, it is pivotal to try to decrease the risk of first venous thrombosis as well as recurrence, rather than to start with indefinite anticoagulant treatment after a first episode of venous thrombosis. Prevention will probably be more profitable if it becomes possible both to identify more precisely those persons who are at risk of venous thrombosis and to quantify the risk to which they are exposed.

Venous thromboembolism is considered a multicausal disease. The risk of a first thrombotic event and recurrence depends on the number of exogenous and thrombophilic risk factors, their weight, interactions, exposure time and age. As a consequence, the risk may vary widely, both within and between individuals. The results of anticoagulant treatment and prohylaxis of venous thromboemb0olism can probably be improved when these are adjusted to the individual risk. However, it is not possible to assess the individual risk because the absolute risk for most currently know risk factors, either single or combined is still unknown. In the here presented studies, we assessed the absolute risk for a number of thrombophilic defects.

The overall incidence of venous thrombosis is 1-3 per 1000 persons each year and rises exponentially from < 0.005% in children to 1% per year in the elderly. Most venous thromboses start in the calf veins, from where they may extend and cause proximal deep vein thrombosis (DVT), and subsequently pulmonary embolism (PE). Patients with DVT or PE remain at risk for recurrent venous thrombosis. This risk is most pronounced in the first months after the acute episode and declines slowly over subsequent years. Risk factors for venous thrombosis are presented in Table 1 [Chapter 1]. Despite anticoagulant treatment for 3-6 months, the recurrence rate of venous thrombosis is 25% within 5 years, while the immediate death rate due to pulmonary embolism is 2.6% and the post-thrombotic syndrome occurs in up to 50% of patients. Recurrent venous thrombosis usually leads to life-long anticoagulant treatment, which increases long term health care costs substantially and has serious potential side effects as major bleeding. Therefore, it is pivotal to try to decrease the risk of first venous thrombosis as well as recurrence, rather than to start with indefinite anticoagulant treatment after a first episode of venous thrombosis. Prevention will probably be more profitable if it becomes possible both to identify more precisely those persons who are at risk of venous thrombosis and to quantify the risk to which they are exposed.

RIVM rapport:Beschreven wordt de medisch-technologische ontwikkelingen, toekomstige mogelijkheden en kosten van coronaire stents voor de behandeling van hart- en vaatziekten, die doodsoorzaak nummer een zijn in Nederland. De toepassing van deze medische hulpmiddelen heeft een grote impact op de interventiecardiologie. De recente ontwikkelingen hebben met name betrekking op technologische verbeteringen en verfijningen van coronaire stents en het plaatsingssysteem. Hernieuwde vernauwing van de arterie en de vorming van bloedstolsels vormen de belangrijkste complicaties na stentimplantatie in een coronaire arterie. De medische ontwikkelingen hebben betrekking op diverse aanvullende therapieen c.q. innovatieve technologieen die ontwikkeld worden om de hiervoor genoemde complicaties te behandelen en de diagnostiek te verbeteren. Op korte termijn zullen stents die geneesmiddelen afgeven, de zogenaamde drug eluting stent, de conventionele stents vervangen waardoor een hernieuwde vernauwing van het bloedvat aanzienlijk vermindert. Stentcoatings en orale geneesmiddelen vervullen inmiddels een prominente rol om de vorming van bloedstolsels te reduceren. Het aantal mensen met hart- en vaatziekten in Nederland zal toenemen van 168.100 in 2000 tot 239.900 in 2020. Schattingen van de toekomstige kosten van stentimplantatie geven aan dat de kosten tot 2020 met circa 40% zullen stijgen. Deze schatting dient met de nodige voorzichtigheid te worden betracht, omdat voor de berekening expliciete aannamen zijn gemaakt. Deze literatuurstudie werd uitgevoerd door het RIVM en aangevuld met interviews voor de Volksgezondheid Toekomst Verkenning 2002 om een bijdrage te leveren aan de informatiebehoefte van de beleidsontwikkeling van het Ministerie van VWS., This study describes the state-of-the-art of coronary stents and future expectations for these medical devices in the treatment of patients with coronary heart diseases. The National Institute of Public Health and the Environment in the Netherlands has carried out a literature study and additional interviews for the study as part of the Public Health Status and Forecast, 2002. The clinical introduction of coronary stents in the late eighties has significantly changed intervention cardiology, with stent technology continuously evolving over the past 10 to 15 years to meet the demands of clinical practice. The implantation of coronary stents in stenosed blood vessels is nowadays one of the most frequently performed medical interventions in cardiology. However, in-stent restenosis and thrombosis remain major complications of stent implantation. Adjunctive therapies and new stent designs have been developed to treat these serious problems. Extension of the positive results of drug eluting stents in clinical pilot studies to practice may mean a revolution in interventional cardiology, reducing the rate of in-stent restenosis. The number of people with coronary heart diseases will increase from 168,100 in 2000 up to about 239,900 in 2020 in the Netherlands. In this report the cost estimates of implanting coronary stents indicate an increase of approximately 40% in 2020. Nevertheless, the progressive developments of stents have been translated into tangible benefits to patients with coronary heart diseases, namely, in the reduced incidence of restenosis and thrombosis, and a lower risk of procedural complications.

Beschreven wordt de medisch-technologische ontwikkelingen, toekomstige mogelijkheden en kosten van coronaire stents voor de behandeling van hart- en vaatziekten, die doodsoorzaak nummer een zijn in Nederland. De toepassing van deze medische hulpmiddelen heeft een grote impact op de interventiecardiologie. De recente ontwikkelingen hebben met name betrekking op technologische verbeteringen en verfijningen van coronaire stents en het plaatsingssysteem. Hernieuwde vernauwing van de arterie en de vorming van bloedstolsels vormen de belangrijkste complicaties na stentimplantatie in een coronaire arterie. De medische ontwikkelingen hebben betrekking op diverse aanvullende therapieen c.q. innovatieve technologieen die ontwikkeld worden om de hiervoor genoemde complicaties te behandelen en de diagnostiek te verbeteren. Op korte termijn zullen stents die geneesmiddelen afgeven, de zogenaamde drug eluting stent, de conventionele stents vervangen waardoor een hernieuwde vernauwing van het bloedvat aanzienlijk vermindert. Stentcoatings en orale geneesmiddelen vervullen inmiddels een prominente rol om de vorming van bloedstolsels te reduceren. Het aantal mensen met hart- en vaatziekten in Nederland zal toenemen van 168.100 in 2000 tot 239.900 in 2020. Schattingen van de toekomstige kosten van stentimplantatie geven aan dat de kosten tot 2020 met circa 40% zullen stijgen. Deze schatting dient met de nodige voorzichtigheid te worden betracht, omdat voor de berekening expliciete aannamen zijn gemaakt. Deze literatuurstudie werd uitgevoerd door het RIVM en aangevuld met interviews voor de Volksgezondheid Toekomst Verkenning 2002 om een bijdrage te leveren aan de informatiebehoefte van de beleidsontwikkeling van het Ministerie van VWS., This study describes the state-of-the-art of coronary stents and future expectations for these medical devices in the treatment of patients with coronary heart diseases. The National Institute of Public Health and the Environment in the Netherlands has carried out a literature study and additional interviews for the study as part of the Public Health Status and Forecast, 2002. The clinical introduction of coronary stents in the late eighties has significantly changed intervention cardiology, with stent technology continuously evolving over the past 10 to 15 years to meet the demands of clinical practice. The implantation of coronary stents in stenosed blood vessels is nowadays one of the most frequently performed medical interventions in cardiology. However, in-stent restenosis and thrombosis remain major complications of stent implantation. Adjunctive therapies and new stent designs have been developed to treat these serious problems. Extension of the positive results of drug eluting stents in clinical pilot studies to practice may mean a revolution in interventional cardiology, reducing the rate of in-stent restenosis. The number of people with coronary heart diseases will increase from 168,100 in 2000 up to about 239,900 in 2020 in the Netherlands. In this report the cost estimates of implanting coronary stents indicate an increase of approximately 40% in 2020. Nevertheless, the progressive developments of stents have been translated into tangible benefits to patients with coronary heart diseases, namely, in the reduced incidence of restenosis and thrombosis, and a lower risk of procedural complications.

RIVM rapport:Beschreven wordt de medisch-technologische ontwikkelingen, toekomstige mogelijkheden en kosten van coronaire stents voor de behandeling van hart- en vaatziekten, die doodsoorzaak nummer een zijn in Nederland. De toepassing van deze medische hulpmiddelen heeft een grote impact op de interventiecardiologie. De recente ontwikkelingen hebben met name betrekking op technologische verbeteringen en verfijningen van coronaire stents en het plaatsingssysteem. Hernieuwde vernauwing van de arterie en de vorming van bloedstolsels vormen de belangrijkste complicaties na stentimplantatie in een coronaire arterie. De medische ontwikkelingen hebben betrekking op diverse aanvullende therapieen c.q. innovatieve technologieen die ontwikkeld worden om de hiervoor genoemde complicaties te behandelen en de diagnostiek te verbeteren. Op korte termijn zullen stents die geneesmiddelen afgeven, de zogenaamde drug eluting stent, de conventionele stents vervangen waardoor een hernieuwde vernauwing van het bloedvat aanzienlijk vermindert. Stentcoatings en orale geneesmiddelen vervullen inmiddels een prominente rol om de vorming van bloedstolsels te reduceren. Het aantal mensen met hart- en vaatziekten in Nederland zal toenemen van 168.100 in 2000 tot 239.900 in 2020. Schattingen van de toekomstige kosten van stentimplantatie geven aan dat de kosten tot 2020 met circa 40% zullen stijgen. Deze schatting dient met de nodige voorzichtigheid te worden betracht, omdat voor de berekening expliciete aannamen zijn gemaakt. Deze literatuurstudie werd uitgevoerd door het RIVM en aangevuld met interviews voor de Volksgezondheid Toekomst Verkenning 2002 om een bijdrage te leveren aan de informatiebehoefte van de beleidsontwikkeling van het Ministerie van VWS., This study describes the state-of-the-art of coronary stents and future expectations for these medical devices in the treatment of patients with coronary heart diseases. The National Institute of Public Health and the Environment in the Netherlands has carried out a literature study and additional interviews for the study as part of the Public Health Status and Forecast, 2002. The clinical introduction of coronary stents in the late eighties has significantly changed intervention cardiology, with stent technology continuously evolving over the past 10 to 15 years to meet the demands of clinical practice. The implantation of coronary stents in stenosed blood vessels is nowadays one of the most frequently performed medical interventions in cardiology. However, in-stent restenosis and thrombosis remain major complications of stent implantation. Adjunctive therapies and new stent designs have been developed to treat these serious problems. Extension of the positive results of drug eluting stents in clinical pilot studies to practice may mean a revolution in interventional cardiology, reducing the rate of in-stent restenosis. The number of people with coronary heart diseases will increase from 168,100 in 2000 up to about 239,900 in 2020 in the Netherlands. In this report the cost estimates of implanting coronary stents indicate an increase of approximately 40% in 2020. Nevertheless, the progressive developments of stents have been translated into tangible benefits to patients with coronary heart diseases, namely, in the reduced incidence of restenosis and thrombosis, and a lower risk of procedural complications.

RIVM rapport:Beschreven wordt de medisch-technologische ontwikkelingen, toekomstige mogelijkheden en kosten van coronaire stents voor de behandeling van hart- en vaatziekten, die doodsoorzaak nummer een zijn in Nederland. De toepassing van deze medische hulpmiddelen heeft een grote impact op de interventiecardiologie. De recente ontwikkelingen hebben met name betrekking op technologische verbeteringen en verfijningen van coronaire stents en het plaatsingssysteem. Hernieuwde vernauwing van de arterie en de vorming van bloedstolsels vormen de belangrijkste complicaties na stentimplantatie in een coronaire arterie. De medische ontwikkelingen hebben betrekking op diverse aanvullende therapieen c.q. innovatieve technologieen die ontwikkeld worden om de hiervoor genoemde complicaties te behandelen en de diagnostiek te verbeteren. Op korte termijn zullen stents die geneesmiddelen afgeven, de zogenaamde drug eluting stent, de conventionele stents vervangen waardoor een hernieuwde vernauwing van het bloedvat aanzienlijk vermindert. Stentcoatings en orale geneesmiddelen vervullen inmiddels een prominente rol om de vorming van bloedstolsels te reduceren. Het aantal mensen met hart- en vaatziekten in Nederland zal toenemen van 168.100 in 2000 tot 239.900 in 2020. Schattingen van de toekomstige kosten van stentimplantatie geven aan dat de kosten tot 2020 met circa 40% zullen stijgen. Deze schatting dient met de nodige voorzichtigheid te worden betracht, omdat voor de berekening expliciete aannamen zijn gemaakt. Deze literatuurstudie werd uitgevoerd door het RIVM en aangevuld met interviews voor de Volksgezondheid Toekomst Verkenning 2002 om een bijdrage te leveren aan de informatiebehoefte van de beleidsontwikkeling van het Ministerie van VWS., This study describes the state-of-the-art of coronary stents and future expectations for these medical devices in the treatment of patients with coronary heart diseases. The National Institute of Public Health and the Environment in the Netherlands has carried out a literature study and additional interviews for the study as part of the Public Health Status and Forecast, 2002. The clinical introduction of coronary stents in the late eighties has significantly changed intervention cardiology, with stent technology continuously evolving over the past 10 to 15 years to meet the demands of clinical practice. The implantation of coronary stents in stenosed blood vessels is nowadays one of the most frequently performed medical interventions in cardiology. However, in-stent restenosis and thrombosis remain major complications of stent implantation. Adjunctive therapies and new stent designs have been developed to treat these serious problems. Extension of the positive results of drug eluting stents in clinical pilot studies to practice may mean a revolution in interventional cardiology, reducing the rate of in-stent restenosis. The number of people with coronary heart diseases will increase from 168,100 in 2000 up to about 239,900 in 2020 in the Netherlands. In this report the cost estimates of implanting coronary stents indicate an increase of approximately 40% in 2020. Nevertheless, the progressive developments of stents have been translated into tangible benefits to patients with coronary heart diseases, namely, in the reduced incidence of restenosis and thrombosis, and a lower risk of procedural complications.