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Evaluation of ADAMTS13 and inflammatory markers in patients with venous thromboembolism

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Author(s):
Bruna de Moraes Mazetto Fonseca
Total Authors: 1
Document type: Master's Dissertation
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Joyce Maria Annichino Bizzacchi; Sergio Paulo Bydlowski; Licio Augusto Velloso
Advisor: Joyce Maria Annichino Bizzacchi
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 (AU)

FAPESP's process: 09/06970-6 - Evaluation of ADAMTS13 activity in Venous Thromboembolism
Grantee:Bruna de Moraes Mazetto Fonseca
Support type: Scholarships in Brazil - Master