Orientador: Joyce Maria Annichino-Bizzacchi / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T16:00:11Z (GMT). No. of bitstreams: 1 Fonseca_BrunadeMoraesMazetto_M.pdf: 657024 bytes, checksum: 715789e040378f27c5de278879f4535b (MD5) Previous issue date: 2011 / Resumo: Níveis elevados de marcadores inflamatórios e fatores de coagulação têm sido relacionados com a patogênese do TEV. Particularmente, a relação inversa entre o FVW e a atividade da ADAMTS13 já foi previamente descrita em pacientes com trombose arterial. Níveis de FVW também mostraram-se elevados durante processos inflamatórios e portanto, poderiam desempenhar um papel de ligação entre inflamação e coagulação nos pacientes com TEV. Objetivo: Avaliar a atividade da ADAMTS13 e do FVW e sua associação com marcadores inflamatórios e evolução clínica pós-trombótica em pacientes com TEV. Pacientes e Métodos: Setenta e sete pacientes com TEV, entre sete meses e seis anos após o episódio agudo, atendidos no Hemocentro de Campinas - UNICAMP foram incluídos neste estudo e 77 indivíduos normais foram selecionados como controles, pareados por idade, gênero, etnia e grupo sanguíneo. A atividade da ADAMTS13 e do FVW foram avaliados pela ligação do FVW ao colágeno, o dímero-D por turbidimetria, a PCR por nefelometria, TNF-'alfa', IL-6, IL-8, antígeno do FVW e da ADAMTS13 foram determinados por ELISA. A presença de trombo residual foi avaliada por ultrassom com Doppler e a SPT através da escala Villalta. Resultados: Trinta pacientes (39%) tiveram TEV causado por fatores de risco transitórios, especialmente pelo uso de anticoncepcional e 47 pacientes tiveram TVE espontâneo. A atividade inflamatória estava aumentada nos pacientes em comparação aos controles, demonstrada pelo aumento significativo dos níveis séricos de TNF-'alfa' and IL-6 nos primeiros (mediana= 2,25 vs 1,59pg/mL, P?0,001; 1,16 vs 0,98pg/ml, P=0,013, respectivamente). Os níveis de IL-8 e PCR foram similares entre os 2 grupos (mediana= 18,3 vs 18,27pg/mL, P=0,47; 0.21 vs 0,17mg/dL, P=0,29, respectivamente). Trinta e dois pacientes (42,8%) foram definidos como tendo um aumento da atividade coagulante, expressa pelo dímero-D > 0,55mg/dL. Nesse grupo de pacientes todos os marcadores inflamatórios como TNF-'alfa', IL-6, IL-8 and PCR, estavam significativamente aumentados quando comparados aos pacientes com dímero-D ? 0,55 mg/L (P=0,0057; 0,001; 0,0093 e 0,0075; respectivamente). A presença de SPT e trombo residual não foram associados ao aumento da atividade coagulante. A atividade da ADAMTS13 e os níveis séricos de IL-8 estavam aumentados em pacientes com SPT quando comparados aos pacientes sem SPT. Todos os marcadores inflamatórios e parâmetros da coagulação estudados foram similares em pacientes independentemente da presença do trombo residual. Conclusão: Este estudo sugere que exista atividade inflamatória e procoagulante nos pacientes mesmo após o episódio agudo do TEV, que, entretanto, não se mostrou estar relacionada com a persistência das seqüelas clínicas e radiológicas da TVP. Além disso, o aumento do FVW nos pacientes corrobora a hipótese de ativação crônica da inflamação. Neste contexto, o aumento observado da ADAMTS 13 poderia ser compensatório frente ao aumento crônico do FVW e poderia inclusive atuar com um mecanismo protetor contra a atividade pró-trombótica observada nestes pacientes / Abstract: Introduction: Increased levels of inflammatory markers and clotting factors have been related to the pathogenesis of VTE. Particularly, the inverse relation between VWF and ADAMTS13 activity has been previously described in patients with arterial thrombosis. VWF levels are also known to be increased during inflammatory processes and therefore could play a role linking the inflammatory and coagulation systems activities in patients with VTE. Objective: To evaluate the activity of ADAMTS13 and VWF in patients with VTE and its association with inflammatory markers and clinical outcome of post-thrombotic syndrome. Patients and methods: Seventy-seven patients with VTE, 7 months to six years after the acute episode, attended at the Hemocentro of Campinas - UNICAMP, were included in this study and 77 normal subjects were selected as controls, matched by gender, age, ethnicity and ABO blood group. The activity of ADAMTS 13 was performed by VWF collagen binding, D-dímer by turbidimetry, CRP by nephelometry , and TNF-'alpha', IL-6 and IL-8, VWF and ADAMTS13 antigen by ELISA. The presence of RVO was investigated by duplex examination and PTS by Villalta scale. Results: Thirty patients (39%) had VTE caused by transient risk factors, mainly the use of oral contraceptives, and 47 patients had spontaneous VTE. Serum levels of TNF-'alpha' and IL-6 were significantly increased in patients when compared to controls (median= 2.25 vs 1.59pg/mL, P?0.001; 1.16 vs 0.98pg/ml, P=0.013, respectively) whereas levels of IL-8 and CRP were similar among the groups (median= 18.3 vs 18.27pg/mL, p=0.47; 0.21 vs 0.17mg/dL, P=0.29, respectively). Thirty-two patients (42,8%) had D-dimer > 0.55 mg/L and were defined as having increased coagulation activity. Inflammatory markers, such as TNF-'alpha', IL-6, IL-8 and CRP, were significantly higher in those patients, comparing to patients with D-dimer ? 0.55 mg/L (P=0.0057, 0.001, 0.0093 and 0.0075, respectively). The presence of PTS or RVO were not associated with increased inflammatory or coagulation activity. Only ADAMTS13-CBA and plasma levels of IL-8 were higher in patients with PTS comparing to patients without PTS. All inflammatory markers and coagulation parameters studied were similar in patients regardless the presence of RVO. Conclusion: Our findings suggest that there is an inflammatory and pro-coagulant activity in patients even after the acute episode of VTE, however, these activities were not related to the persistence of clinical and radiological sequels of DVT. Moreover, the increasing levels of VWF, observed in patients, support the hypothesis that the inflammation is chronically activated. In this context, the increasing levels of ADAMTS13, also observed in patients, could be explained as a compensatory mechanism and maybe act as a protection against pro-thrombotic activity seen in these patients / Mestrado / Biologia Estrutural, Celular, Molecular e do Desenvolvimento / Mestre em Fisiopatologia Médica

Bakgrund: Djup ventrombos (DVT) är en allvarlig komplikation postoperativt och kan leda till ett livshotande tillstånd för patienten. Graderade kompressionsstrumpor (GCS) används på många postoperativa avdelningar tillsammans med andra profylaktiska åtgärder för att förebygga utvecklingen av DVT. Kompressionsstrumpor används även till att förebygga posttrombotiskt syndrom (PTS) efter en DVT. PTS kan utvecklas på grund av att de venösa klaffarna skadas vid en DVT, till följd stockar sig blodet och ödem bildas vilket leder till försämrad näring- och syretillförsel till vävnaderna. Syfte: Syftet var att genom en litteraturstudie undersöka om kompressionsstrumpor hade någon effekt för att förebygga DVT postoperativt samt om kompressionsstrumpor hade någon effekt att förebygga PTS efter en DVT. Metod: Litteraturstudie som baserads på 11 RCT studier. Resultat: GCS utan andra profylaktiska åtgärder visade sig ha en god effekt för att undvika utvecklingen av DVT på patienter som genomgått en operation. Däremot visade sig användandet av GCS i kombination med andra beprövade profylax inte ha någon större effekt för att reducera uppkomsten av DVT ytterligare. Resultatet angående GCS effekt för att undvika utvecklingen av PTS visade ingen entydighet. Slutsats: GCS har en förebyggande effekt för att undvika uppkomsten av DVT. Användningen av GCS i kombination med andra profylax potentierar däremot inte effekten av preventionen för DVT. GCS verkan för att förebygga uppkomsten av PTS är inte entydigt och flera studier behövs för att se evidens kring detta. / ABSTRACT  Background: Deep vein thrombosis (DVT) is a serious complication postoperatively and can lead to a life threatening condition for the patient. Graded compression stockings (GCS) are used in many post-operative departments along with other prophylactic measures to prevent the development of DVT. Compression stockings are also used to prevent postthrombotic syndrome (PTS) after a DVT. PTS can develop because the venous valves are damaged by a DVT, as a result, the blood is stored and edema is formed, which leads to poor nutritional and oxygen supply to the tissues. Aim: The aim of the literature study was to investigate whether compression stockings had any effect in preventing DVT postoperatively, and also whether the compression stockings had any effect in preventing PTS after a DVT. Method: Literature study based on 11 RCT studies. Results: GCS without other prophylactic measures was found to have a good effect in avoiding the development of DVT in patients who underwent surgery. However, the use of GCS in combination with other proven prophylaxis was found to have no significant effect in further reducing the onset of DVT. The results regarding the GCS effect to avoid the development of PTS showed no unambiguity. Conclusion: GCS has a preventive effect to avoid the onset of DVT. However, the use of GCS in combination with other prophylaxis does not potentiate the effect of prevention for DVT. The effect of GCS in preventing the onset of PTS is not unambiguous and several studies are needed to see evidence of this.

Postthrombotic syndrome (PTS) is a frequent complication of venous thromboembolism (VTE). Using MarketScan claims data from January 2012 to June 2015, we identified adults with a primary diagnosis code for VTE during a hospitalization/emergency department visit, ≥6 months of insurance coverage prior to the index event and newly started on rivaroxaban or warfarin within 30 days of the index VTE. Patients with <4-month follow-up postindex event or a claim for any anticoagulant during 6-month baseline period were excluded. Differences in baseline characteristics between rivaroxaban and warfarin users were adjusted for using inverse probability of treatment weights based on propensity scores. Patients were followed for the development of PTS starting 3 months after the index VTE. Cox regression was performed and reported as hazard ratios with 95% confidence intervals (CIs). In total, 10 463 rivaroxaban and 26 494 warfarin users were followed for a mean of 16 ± 9 (range, 4-39) months. Duration of anticoagulation was similar between cohorts (median = 6 months). Rivaroxaban was associated with a 23% (95% CI: 16-30) reduced hazard of PTS versus warfarin. Rivaroxaban was associated with a significant risk reduction in symptoms of PTS compared to warfarin in patients with VTE treated in routine practice.