Evaluation of Coagulation and inflammatory Markers in Patients with venous Thromboembolism

Venous thromboembolism (VTE) is a multifactorial disease, and increased levels of coagulation factor VIII (FVIII) has been demonstrated as a risk factor for first and recurrent episodes. Inflammatory processes may play a key role in venous thrombosis by inducing a procoagulant state through the action of cytokines and chemokines on monocytes and endothelial cells. The role of inflammation process in the initiation and evolution of venous thromboembolism is not well understood yet. The aim of the study was to evaluate some coagulation and inflammatory markers in VTE patients.

Between March 2009 and June 2011, 385 consecutive patients with treated VTE were attended at Hematology and Hemotherapy Center of Campinas. The study comprised 71 patients with deep venous thrombosis (DVT) of the lower limbs or pulmonary embolism. We excluded patients with DVT at unusual sites, younger than 18 years old or older than 70 years old, those with cancer, chronic liver, renal or inflammatory disease, antiphospholipid antibody syndrome, natural anticoagulant deficiency. Healthy adult individuals were chosen as controls. FVIII levels (FVIII:C) were measured by a one-stage clotting assay. D-dimer levels were performed by immunoturbidimetric analysis. VWF:Ag, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor- α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA). C-reactive protein (CRP) levels were determined by a nephelometric method. The presence of post-thrombotic syndrome (PTS) was evaluated and classified by the Villalta scale.

Seventy-one patients with VTE (23M:48F) with a median age of 44 years (range 20–70) were included in the study. The control group consisted of 67 subjects (23M:44F) with a median age of 42 years (range 22–70 years). VTE was spontaneous in 41 (57. 7%) patients and secondary to an acquired risk factor in 42. 3%. Patients with VTE had higher plasma levels of FVIII:C (146. 2 IU/dL vs. 105. 4 IU/dL; p<0. 001), VWF:Ag (150. 3 IU/dL vs. 110. 7 IU/dL; p<0. 001) and D-dimer (0. 46 mg/L vs. 030 mg/L; p<0. 001) compared to controls. Furthermore, the inflammatory markers IL-6 (1. 19 pg/mL vs. 0. 98 pg/mL; p<0. 001) and TNF-α (2. 27 pg/mL vs. 1. 57 pg/mL; p<0. 001) also was higher in patients when compared with controls. No significant difference of CRP and IL-8 levels between patients and controls was observed. Patients with PTS showed higher levels of IL-8 when compared with patients without PTS (23. 03 pg/mL vs. 18. 20 pg/mL; p=0. 04). Patients with moderate or severe PTS (176. 3 IU/dL) showed higher levels of VWF when compared with patients without PTS (137. 8 IU/dL) or mild PTS patients (132. 7 IU/dL); p=0. 04.

In a linear regression univariate model, FVIII levels of VTE patients showed association with VWF, D-dimer, IL-6, TNF-α and CRP levels. So, these parameters associated with FVIII were evaluated in a linear regression multivariate model, and VWF and IL-6 levels were independent factors associated with FVIII levels (p<0. 001).

Our results show that patients with previous VTE have increased levels of coagulation and inflammatory markers even long time after the acute episode. Moreover, there seems to be a relationship between moderate/severe post-thrombotic syndrome and increased levels of VWF. A possibility is that in moderate and severe PTS, the vascular injury stimulates a increased endothelial cell secretion of VWF.

No relevant conflicts of interest to declare.