Long-term increased factor VIII levels are associated to interleukin-6 levels but not to post-thrombotic syndrome in patients with deep venous thrombosis

Bittar, Luis Fernando; Mazetto, Bruna de Moraes; Orsi, Fernanda Andrade; Collela, Marina Pereira; Paula, Erich Vinícius De; Annichino‐Bizzacchi, Joyce Maria

doi:10.1016/j.thromres.2014.12.024

Cited by 25 publications

(12 citation statements)

References 42 publications

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“…D-dimer levels were analyzed in the acute or subacute phase of the DVT episode, and a few of them found a significant association between D-dimer levels and PTS [21][22][23], whereas other studies found no association [24][25][26][27][28]. Corroborating our results, four previous studies demonstrated no significant association between D-dimer and PTS [29][30][31] during the chronic phase (more than 12 months post DVT). Our results suggest that a hypercoagulability can be present up to several months after acute DVT episode, however with no association with PTS.…”

Section: Discussionsupporting

confidence: 77%

Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

Bittar¹,

Silva²,

Orsi³

et al. 2020

PLoS ONE

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IntroductionPost-thrombotic syndrome (PTS) is a limiting long-term complication present in 20-50% of patients with deep venous thrombosis (DVT) of the lower limbs. A panel of biomarkers with potential relevance to enhance knowledge on the pathophysiology of PTS was investigated. MethodsThis case-control study included 93 patients with DVT in the lower limbs, 31 with severe PTS (cases) and 62 with mild/no PTS (controls), over 24 months after an acute episode. Thirty-one healthy individuals (HI) with no history of DVT were included as a reference to the population. FVIII activity, D-dimer, inflammatory cytokines, endothelial dysfunction markers, matrix metalloproteinases, and their inhibitors, tissue remodeling and growth factor levels were evaluated. The classification of PTS was, by the Villalta scale. ResultsPatients with severe PTS showed elevated levels of CRP, sICAM-1, sE-selectin, and decreased MMP-9 and MCP-1 levels when compared to patients with mild/no PTS. Moreover, DVT patients presented higher levels of FVIII and D-dimer when compared to HI. ConclusionsDVT patients present an inflammatory status, endothelial dysfunction and altered proteolysis MMPs activity, even a long time after the acute thrombotic episode, which is more significant in severe PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS severity.

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Section: Discussionsupporting

confidence: 77%

Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

Bittar¹,

Silva²,

Orsi³

et al. 2020

PLoS ONE

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“…No statistically significant difference in FVIII activity was found between PTS‐positive and PTS‐negative patients in three of them. The same conclusion was reached in two recent studies . In contrast, Roberts et al .…”

Section: Risk Factorssupporting

confidence: 84%

The postthrombotic syndrome: current evidence and future challenges

Rabinovich

Kahn

2017

Journal of Thrombosis and Haemostasis

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Postthrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) that develops in 20-50% of patients. PTS manifests as a spectrum of symptoms and signs of chronic venous insufficiency that can impose significant morbidity and have a negative impact on quality of life. Chronic venous hypertension caused by a combination of residual venous obstruction and valvular reflux is believed to play a major role in the pathophysiology of PTS. The Villalta scale is the most widely applied clinical scale used to diagnose and define PTS. Proximal DVT and recurrent ipsilateral DVT are the two principal established risk factors for PTS, and efforts in recent years have been focused on identifying a combination of clinical and biomarker predictors that will define high-risk patients and possibly new therapeutic targets. The best way to prevent PTS is to prevent the occurrence of DVT, and to provide optimal anticoagulation for the acute phase of DVT once it occurs. Recent years have brought progress in our understanding of the role of endovascular techniques in the prevention and treatment of PTS and the subgroups of patients that may benefit from these modalities. Pharmacomechanical catheter-directed thrombolysis is the most promising interventional modality for prevention of PTS. This review summarizes the current state of evidence on PTS of the lower limbs, and highlights areas where uncertainty still exists that require further research.

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“…At first, the VTEval Project envisages the measurement and evaluation of routine laboratory markers (ie, D-dimer and C reactive protein, CRP), numerous parameters involved in coagulation and inflammation (eg, factor VIII (FVIII), interleukin 6 or resistin), platelet and leucocyte activation (eg, soluble P-selectin (sP-Sel)) as well as regulatory microRNAs (ie, miR-126, miR-155 and miR-200c) and their associations with DVT. 26–36 …”

Section: Methods and Resultsmentioning

confidence: 99%

Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: theVTEval Project

et al. 2015

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IntroductionVenous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date.Methods and analysisThe VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three ‘all-comer’ studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings.Ethics and disseminationThe VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and international scientific meetings.Trial registration numberNCT02156401.

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Long-term increased factor VIII levels are associated to interleukin-6 levels but not to post-thrombotic syndrome in patients with deep venous thrombosis

Cited by 25 publications

References 42 publications

Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

The postthrombotic syndrome: current evidence and future challenges

Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: theVTEval Project

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