Increased adhesive properties of neutrophils and inflammatory markers in venous thromboembolism patients with residual vein occlusion and high D-dimer levels

Zapponi, Kiara Cristina Senger; Mazetto, Bruna de Moraes; Bittar, Luis Fernando; Barnabé, Aline; Santiago-Bassora, Fernanda Dutra; Paula, Erich Vinícius De; Orsi, Fernanda Andrade; Franco‐Penteado, Carla F.; Conran, Nicola; Annichino‐Bizzacchi, Joyce Maria

doi:10.1016/j.thromres.2014.01.035

Cited by 23 publications

(19 citation statements)

References 44 publications

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“…Hence, we speculate that RVT is the result of a systemic state, which could involve hypercoagulability and/or inflammatory conditions. [21][22][23][24] Exploratory studies are needed to elucidate the underlying pathophysiologic mechanism behind the association.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of PTS was assessed at predefined times (6,12,18,24, and 36 months) after the acute episode, using the Villalta scale, 5 The presence of five leg symptoms (i.e., pain, cramps, heaviness, pruritus, and paresthesia) and six objective signs (i.e., pretibial edema, induration of the skin, hyperpigmentation, new venous ectasia, redness, and pain during calf compression) was scored. For each item, a score of 0 (not present) up to 3 (most severe) was assigned, using the contralateral unaffected leg as reference.…”

Section: Assessment Of Study Outcomesmentioning

confidence: 99%

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The Impact of Residual Thrombosis on the Long-Term Outcome of Patients with Deep Venous Thrombosis Treated with Conventional Anticoagulation

Prandoni

Lensing

Prins

et al. 2015

Semin Thromb Hemost

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The impact of residual vein thrombosis (RVT) on the long-term outcome of patients with deep vein thrombosis (DVT) is unknown. We assessed the incidence of recurrent venous thromboembolism (VTE), postthrombotic syndrome (PTS), arterial thrombotic events, and cancer in patients with DVT with and without RVT. For this purpose, we evaluated up to 3 years 869 consecutive patients with acute proximal DVT who had conventional anticoagulation. RVT, defined as ultrasound incompressibility of at least 4 mm in the common femoral and/or the popliteal vein after 3 months, was detected in 429 (49.4%) patients, and was more likely in males (adjusted odds ratio [OR], 1.82; 95% confidence interval [CI], 1.37-2.04), in patients with previous VTE (OR, 1.64; 95% CI, 1.06-2.54), and in those with extensive thrombosis (OR, 3.58; 95% CI, 2.19-5.86). During the 3-year follow-up, recurrent VTE developed in 84 (19.6%) patients with RVT and 43 (9.8%) patients without RVT (adjusted hazard ratio [HR], 2.03; 95% CI, 1.40-2.94); PTS in 225 (52.4%) and 118 (26.8%), respectively (HR, 2.34; 95% CI, 1.87-2.93); arterial thrombosis in 29 (6.7%) and 14 (3.2%), respectively (HR, 2.05; 95% CI, 1.08-3.88); and cancer in 21 (4.9%) and 8 (1.8%), respectively (HR, 3.09; 95% CI, 1.31-7.28). In conclusion, in patients treated with vitamin K antagonists for prevention of recurrent VTE, RVT doubles the risk of recurrent VTE, PTS, arterial thrombosis, and cancer. Males, patients with previous VTE, and those with extensive thrombosis are independent risk factors of RVT development. Studies addressing the impact of the novel direct anticoagulants on the development of RVT as well as the long-term complications of DVT are needed.

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Section: Discussionmentioning

confidence: 99%

Section: Assessment Of Study Outcomesmentioning

confidence: 99%

The Impact of Residual Thrombosis on the Long-Term Outcome of Patients with Deep Venous Thrombosis Treated with Conventional Anticoagulation

Prandoni

Lensing

Prins

et al. 2015

Semin Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…Additionally, adhesive properties of neutrophils remained high in patients with RVO and high levels of D-dimer one to six years after VTE compared to patients without RVO and normal levels of D-dimer or controls without VTE. Interestingly, there was no difference in the number of neutrophils between PTE patients and controls at this time (i.e., one to six years after PTE) and 10 days after PTE [20,46]. Moreover, a post-mortem study on the RV samples from people who died due to PTE shows presence of neutrophils in most of the samples [47].…”

Section: Neutrophilsmentioning

confidence: 78%

“…Proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-8, are considerably elevated in patients with residual vein occlusion (RVO) with high levels of D-dimer (months to years after occurrence of VTE) compared to patients without RVO with normal levels of D-dimer and controls without VTE [20,21]. Regardless of the levels of D-dimer, VTE patients have higher levels of TNF-α and IL-6 than controls without VTE, even after discontinuation of anti-coagulant therapy [21,22].…”

Section: Proinflammatory Cytokinesmentioning

confidence: 99%

Inflammation in venous thromboembolism: Cause or consequence?

Saghazadeh

Hafizi

Rezaei

2015

International Immunopharmacology

111

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“…In patients with acute ischemic stroke, there was significant up-regulation of neutrophil Mac-1 immediately after the event, and persisting into the subacute phase of the stroke (41). In patients with venous thromboembolism, increased adhesive potential of neutrophils was associated with a higher rate of recurrence (42). As indicated in Supplementary Table 1 (http://onlin elibr ary.wiley.com/doi/10.1002/art.41057/ abstract), the average time from last thrombotic event to blood collection for patients with APS included in this study was approximately 4.5 years.…”

Section: Discussionmentioning

confidence: 99%

Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac‐1

Sule

Kelley

Gockman

et al. 2019

Arthritis & Rheumatology

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Objective While the role of antiphospholipid antibodies in activating endothelial cells has been extensively studied, the impact of these antibodies on the adhesive potential of leukocytes has received less attention. This study was undertaken to investigate the extent to which antiphospholipid syndrome (APS) neutrophils adhere to resting endothelial cells under physiologic flow conditions and the surface molecules required for that adhesion. Methods Patients with primary APS (n = 43), patients with a history of venous thrombosis but negative test results for antiphospholipid antibodies (n = 11), and healthy controls (n = 38) were studied. Cells were introduced into a flow chamber and perfused across resting human umbilical vein endothelial cells (HUVECs). Surface adhesion molecules were quantified by flow cytometry. Neutrophil extracellular trap release (NETosis) was assessed in neutrophil‐HUVEC cocultures. Results Upon perfusion of anticoagulated blood through the flow chamber, APS neutrophils demonstrated increased adhesion as compared to control neutrophils under conditions representative of either venous (n = 8; P < 0.05) or arterial (n = 15; P < 0.0001) flow. At the same time, APS neutrophils were characterized by up‐regulation of CD64, CEACAM1, β2‐glycoprotein I, and activated Mac‐1 on their surface (n = 12–18; P < 0.05 for all markers). Exposing control neutrophils to APS plasma or APS IgG resulted in increased neutrophil adhesion (n = 10–11; P < 0.0001) and surface marker up‐regulation as compared to controls. A monoclonal antibody specific for activated Mac‐1 reduced the adhesion of APS neutrophils in the flow‐chamber assay (P < 0.01). The same monoclonal antibody reduced NETosis in neutrophil–HUVEC cocultures (P < 0.01). Conclusion APS neutrophils demonstrate increased adhesive potential, which is dependent upon the activated form of Mac‐1. In patients, this could lower the threshold for neutrophil–endothelium interactions, NETosis, and possibly thrombotic events.

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Increased adhesive properties of neutrophils and inflammatory markers in venous thromboembolism patients with residual vein occlusion and high D-dimer levels

Cited by 23 publications

References 44 publications

The Impact of Residual Thrombosis on the Long-Term Outcome of Patients with Deep Venous Thrombosis Treated with Conventional Anticoagulation

The Impact of Residual Thrombosis on the Long-Term Outcome of Patients with Deep Venous Thrombosis Treated with Conventional Anticoagulation

Inflammation in venous thromboembolism: Cause or consequence?

Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac‐1

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