Elsevier

Thrombosis Research

Volume 126, Issue 6, December 2010, Pages e418-e422
Thrombosis Research

Regular Article
Calibrated automated thrombography demonstrates hypercoagulability in patients with idiopathic pulmonary arterial hypertension

https://doi.org/10.1016/j.thromres.2010.08.020Get rights and content

Abstract

Introduction

Pathogenesis of idiopathic pulmonary arterial hypertension (iPAH) includes endothelial dysfunction and in situ thrombosis. A hypercoagulable state has also been postulated but never demonstrated. Our objective was to determine whether patients with iPAH had a hypercoagulable state using calibrated automated thrombography (CAT), a new tool to phenotype coagulation in vitro.

Patients and methods

16 patients with iPAH and 29 controls were studied. In vitro platelet dependent coagulation phenotyping by CAT monitored the activity of thrombin generation over time. Plasma levels of soluble thrombomodulin, tissue factor pathway inhibitor (TFPI) and von Willebrand factor (VWF) were measured as endothelial biomarkers.

Results

Endogenous thrombin potential (ETP) in the absence of activated protein C (APC) tended to be increased in patients compared to controls (1769 versus 1656 nM.min; p = 0.053). ETP was higher in the presence of APC 25 nM (ETP-APC) in patients (781 versus 494 nM.min; p = 0.005). Five patients had ETP-APC higher than the 95th centile of controls. Other CAT parameters (lag time, peak thrombin and time to peak) were all consistent with some degree of hypercoagulability in patients. Regarding endothelial plasma biomarkers sTM was lower (28.4 versus 40.6 μg/l, p = 0.0108) in patients; TFPI antigen and activity (respectively: 14.3 versus 10.5 μg/l, p = 0.0167; 1.155 versus 1.070, p = 0.0021) and VWF (1300 versus 976%, p = 0.0108) were higher in patients.

Conclusion

We have demonstrated that at least some patients with iPAH have a hypercoagulable phenotype.

Section snippets

Patients

This prospective study included consecutive patients with iPAH without any comorbidity. All clinical data and plasma samples were collected at diagnosis when patients were not yet on oral anticoagulant treatment. Patients were referred for diagnosis at the Department of Respiratory Diseases at the Nancy University Hospital. All patients were investigated to identify an underlying cause of pulmonary hypertension, following the guidelines [3]. The procedure of haemodynamic measurements was part

Patients and controls

Patients’ characteristics are displayed in Table 1. Sixteen patients (6 females), aged 57 ± 4, were studied. Three patients were in the New York Heart Association (NYHA) functional class II, 9 in class III and 4 in class IV. Twenty-nine healthy subjects (12 females) aged 58 ± 3 (range 17 to 82) were also studied as controls.

Standard laboratory data

The mean PT was 1.1 (range 0.99 to 1.3). The mean of plasma fibrinogen level was 3.8 g/l (range 2.2 to 6). The mean of plasma CRP was 6.2 mg/l (< 5 mg/l).

CAT and biomarkers of the in vivo activation of coagulation

All CAT parameters are

Discussion

To our knowledge, the present study is the first to demonstrate a hypercoagulable phenotype using CAT in iPAH patients. This method assesses thrombin generation taken into account all coagulation proteins in the plasma. Thereby, we have shown that iPAH patients have some degree of hypercoagulability in a population, which was similar in terms of age and pulmonary haemodynamics to the one of the French registry [31].

Our team has been involved in the development and the standardization of the CAT

Conflict of interest statement

No authors have any conflict of interest to declare.

Acknowledgments

Supported grants from the Conseil Régional de Lorraine, Association Régionale d'Aide aux Insuffisants Respiratoires de Lorraine, Glaxo Smith Kline, Bayer and Association des Chefs de Service du CHU de Nancy. Study sponsors had no involvement in the study design, in the collection, analysis and interpretation of data nor in the writing of the manuscript.

The authors thank Pr Athanase Benetos for his help for the recruitment of controls and acknowledge controls, and patients for their agreement to

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