Association between micro particletissue factor a

Authors: Judith Kooiman Paul L den Exter Inci Kilicsoy Suzanne C Cannegieter Jeroen Eikenboom Menno V Huisman Frederikus A Klok Henri H Versteeg

Publish Date: 2015/02/11

Volume: 40, Issue: 3, Pages: 323-330

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Abstract

Studies on the association between microparticle expressing tissue factor MPTF activity FVIII activity FVIIIC and recurrent VTE yielded inconclusive results We studied these associations in patients diagnosed with acute pulmonary embolism Plasma levels of MPTF and FVIII activity were measured in 277 patients with a first and 72 patients with a recurrent VTE All patients were categorized based on the quintiles of MPTF and FVIII activity in those with a single VTE For both markers odds ratios ORs for recurrent VTE were computed using patients in the lowest quintile as a reference group No association was observed between MPTF activity and recurrent VTE with an OR of 14 95  CI 07–29 in the highest quintile of MPTF activity Compared with the reference group patients in the highest quintile of FVIIIC were at increased risk of recurrent VTE OR 42 95  CI 14–122 MPTF activity was not associated with recurrent VTE whereas high FVIIIC levels were associated with a 4fold increased risk of VTE recurrence Future prospective studies are necessary to explore the potential of FVIIIC as a tool for risk stratification either by itself or in combination with other prothrombotic markersVenous thromboembolism VTE is the third most common cardiovascular disease with an incidence rate of 1–2 per 1000 patient years 1 2 After a first event the 5years cumulative risk of recurrent VTE is estimated to be 25  with a casefatality rate of 11  3 4 Treatment with anticoagulants is highly effective in reducing the risk of recurrent VTE 5 6 but this comes at the cost of an increased risk of major bleeding events 7 Understanding of the mechanism of recurrent VTE and identification of patients at high risk of recurrences are therefore the essential step in determining the optimal duration of treatment They requires understanding of factors contributing to the recurrence of VTE such as clinical variables and laboratory markersMicroparticle expressing tissue factor MPTF has recently been proposed as a potential key player in the development of VTE 8 Tissue factor is the main initiator of the coagulation cascade and MPTFs are shed into the circulation by cells mainly platelets and to a lower extent monocytes during activation or apoptosis The influence of MPTF and MPTF activity on the occurrence of VTE has mainly been studied in animal models 9 10 11 12 So far only two small clinical studies analyzed the association between MPTF or MPTF activity and the risk of a first or recurrent VTE 13 14 Therefore the primary aim of our study was to assess the association between MPTF activity and the risk of recurrent VTEAdditionally several studies have been performed on the association between FVIII activity FVIIIC another potential key player in the development of VTE and recurrent VTE but they yielded contradictory results 15 16 17 18 19 20 As FVIIIC was measured in our study population for other purposes we were also interested in studying the association between FVIIIC and recurrent VTEWe performed a post hoc analysis using data of patients included in a cohort study that aimed to evaluate the incidence of chronic thromboembolic pulmonary hypertension CTEPH after a diagnosis of acute pulmonary embolism PE Details of this cohort study have been described in detail previously 21 22 In brief patients diagnosed with acute PE between 2001 and 2007 in an academic and its affiliated teaching hospital ie Leiden University Medical Center Medical Center Haaglanden both the Netherlands were asked to participate in a CTEPH screening program The CTEPH screening program was executed between July 2007 and January 2009 The diagnosis of acute PE was confirmed by detection of an intraluminal filling defect on pulmonary angiography or computed tomography pulmonary angiography a high probability ventilation perfusion scintigraphy VQscan or an intermediate probability VQscan in combination with deep vein thrombosis diagnosed by ultrasonography Patients were excluded if they had known CTEPH or pulmonary hypertension of other etiology at time of screening if they were geographic inaccessible living outside the Netherlands if they were unavailable for objective testing or recently had undergone echocardiography ruling out pulmonary hypertension For this post hoc analysis we included all study patients from the original study cohort except for those without available lab samplesAll patients were treated for acute PE according to local clinical practice with unfractionated heparin or lowmolecularweightheparin for at least 5 days after PE diagnosis followed by a period of at least 6 months of vitamin Kantagonist treatment

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