Assessment of Blood Coagulation Disorders in Patients With Pulmonary Hypertension

Assessment of Blood Coagulation Disorders in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

The objective of the present study is to assess blood coagulation disorders in patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension. The investigators aim to evaluate any possible coagulation abnormalities related to the patients' primary disease and any possible effects the pulmonary hypertension- specific therapy may have on hemostasis.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Artery Hypertension; Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Diagnostic test: Platelet function analyzer-100; Diagnostic test: Light transmission aggregometry; Diagnostic test: Rotational thromboelastometry; Diagnostic test: Endogenous thrombin potential

Detailed Description

Pulmonary hypertension (PH) is a chronic, progressive, pulmonary vascular disease with a multifactorial etiology and a not fully elucidated pathophysiological background. There is a complex and not adequately understood association between PH and the coagulation process.

The aim of the present study is to evaluate hemostasis in patients with PH classified as category 1 of the World Health Organization Pulmonary Hypertension Group (Pulmonary Arterial Hypertension, PAH) and 4 (Chronic Thromboembolic Pulmonary Hypertension, CTEPH). Patients with CTEPH are diagnosed as inoperable. The investigators perform diagnostic tests on blood samples collected directly from the pulmonary artery during the right heart catheterization performed as part of the patients' routine medical care for the diagnosis of the disease or for follow-up 6 months after the initiation of PH-specific treatment. All blood samples are processed by platelet function analyzer-100 (PFA-100), light transmission aggregometry (LTA), rotational thromboelastometry (ROTEM) and endogenous thrombin potential (ETP).The primary objective of the study is to assess platelet function, coagulation and anti-coagulation pathways and fibrinolysis in PAH and inoperable CTEPH patients and to investigate the possible effects of PH- specific therapy on hemostasis.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Eleni Vrigkou, MD, MSc; Phone Number: 00302105832179; Email: elenivrigkou@gmail.com
• Study Contact Backup: Name: Argyrios Tsantes, MD, PhD; Phone Number: 00302105830000; Email: atsantes@med.uoa.gr

Study Locations

• Greece
  • Athens, Greece, 12462
    • Recruiting
    • Attikon University Hospital
    • Contact: Eleni Vrigkou, MD, MSc; Phone Number: 0030-2105832179; Email: elenivrigkou@gmail.com
    • Contact: Iraklis Tsagkaris, MD, PhD; Phone Number: 0030-2105832179; Email: itsagkaris@med.uoa.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study participants are recruited among the pulmonary hypertension patients of the Pulmonary Hypertension Unit, In the Second Department of Critical Care Medicine, Attiko University Hospital, Athens, Greece

Description

Inclusion Criteria:

• Pulmonary Arterial Hypertension,
• Chronic Thromboembolic Pulmonary Hypertension.

Exclusion Criteria:

• renal insufficiency,
• hepatic insufficiency,
• thyroid dysfunction,
• malignancy,
• active infections,
• receiving anticoagulant or antiplatelet therapy,
• history of hemostatic disorders irrelevant to their primary disease,
• abnormal red blood counts.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with PAH; Diagnostic tests will be performed on patients with Pulmonary Artery Hypertension in order to assess any blood coagulation disorders. Platelet function, coagulation and fibrinolysis will be evaluated by platelet function analyzer-100 (PFA-100), light transmission aggregometry, rotational thromboelastometry (ROTEM) and endogenous thrombin potential.	Diagnostic test: Platelet function analyzer-100; The PFA-100 system evaluates primary hemostasis in whole blood samples.; Other Names: PFA-100; Diagnostic test: Light transmission aggregometry; Light transmission aggregometry is the gold standard method for assessing platelet function.; Diagnostic test: Rotational thromboelastometry; ROTEM is a viscoelastic method for hemostasis testing in whole blood.This assay investigates the interaction of blood cells, coagulation factors and their inhibitors during clotting and subsequent fibrinolysis.; Other Names: ROTEM; Diagnostic test: Endogenous thrombin potential; The endogenous thrombin potential assesses the amount of thrombin which can be generated after the in vitro activation of coagulation and represents the balance between pro- and anti-coagulant forces in plasma.; Other Names: ETP
Patients with CTEPH; Diagnostic tests will be performed on patients with Chronic Thromboembolic Pulmonary Hypertension in order to assess any blood coagulation disorders. Platelet function, coagulation and fibrinolysis will be evaluated by platelet function analyzer-100 (PFA-100), light transmission aggregometry, rotational thromboelastometry (ROTEM) and endogenous thrombin potential.	Diagnostic test: Platelet function analyzer-100; The PFA-100 system evaluates primary hemostasis in whole blood samples.; Other Names: PFA-100; Diagnostic test: Light transmission aggregometry; Light transmission aggregometry is the gold standard method for assessing platelet function.; Diagnostic test: Rotational thromboelastometry; ROTEM is a viscoelastic method for hemostasis testing in whole blood.This assay investigates the interaction of blood cells, coagulation factors and their inhibitors during clotting and subsequent fibrinolysis.; Other Names: ROTEM; Diagnostic test: Endogenous thrombin potential; The endogenous thrombin potential assesses the amount of thrombin which can be generated after the in vitro activation of coagulation and represents the balance between pro- and anti-coagulant forces in plasma.; Other Names: ETP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFA-100 in detection of platelet abnormalities in PAH and CTEPH patients.	Change in the percentage of PAH and CTEPH patients who are detected with platelet abnormalities in PFA-100 testing from the date of the first right heart catheterization performed for the diagnosis of their disease (before treatment implementation) to the date of the second right heart catheterization performed for follow-up (after treatment implementation) at 6 months.	6 months
Light transmission aggreggometry in detection of platelet abnormalities in PAH and CTEPH patients.	Change in the percentage of PAH and CTEPH patients who are detected with platelet abnormalities in LTA testing from the date of the first right heart catheterization performed for the diagnosis of their disease (before treatment implementation) to the date of the second right heart catheterization performed for follow-up (after treatment implementation) at 6 months.	6 months
ROTEM in detection of coagulation abnormalities in PAH and CTEPH patients.	Change in the percentage of PAH and CTEPH patients who are detected with coagulation abnormalities in ROTEM testing from the date of the first right heart catheterization performed for the diagnosis of their disease (before treatment implementation) to the date of the second right heart catheterization performed for follow-up (after treatment implementation) at 6 months.	6 months
Endogenous thrombin potential in detection of thrombin abnormalities in PAH and CTEPH patients.	Change in the percentage of PAH and CTEPH patients who are detected with thrombin deficits in endogenous thrombin potential testing from the date of the first right heart catheterization performed for the diagnosis of their disease (before treatment implementation) to the date of the second right heart catheterization performed for follow-up (after treatment implementation) at 6 months.	6 months

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Investigators: Principal Investigator: Eleni Vrigkou, MD, MSc, National and Kapodistrian University of Athens; Study Director: Argyrios Tsantes, MD, PhD, National and Kapodistrian University of Athens; Study Chair: Iraklis Tsagkaris, MD, PhD, National and Kapodistrian University of Athens; Study Chair: Apostolos Armaganidis, MD, PhD, National and Kapodistrian University of Athens

Publications and helpful links

General Publications

• Berger G, Azzam ZS, Hoffman R, Yigla M. Coagulation and anticoagulation in pulmonary arterial hypertension. Isr Med Assoc J. 2009 Jun;11(6):376-9.
• Herve P, Humbert M, Sitbon O, Parent F, Nunes H, Legal C, Garcia G, Simonneau G. Pathobiology of pulmonary hypertension. The role of platelets and thrombosis. Clin Chest Med. 2001 Sep;22(3):451-8. doi: 10.1016/s0272-5231(05)70283-5.
• Lopes AA, Caramuru LH, Maeda NY. Endothelial dysfunction associated with chronic intravascular coagulation in secondary pulmonary hypertension. Clin Appl Thromb Hemost. 2002 Oct;8(4):353-8. doi: 10.1177/107602960200800407.
• Preston IR, Farber HW. Anti-coagulation in pulmonary arterial hypertension: the real blood and guts. J Thorac Dis. 2016 Sep;8(9):E1106-E1107. doi: 10.21037/jtd.2016.08.48. No abstract available.
• Remkova A, Simkova I, Valkovicova T. Platelet abnormalities in chronic thromboembolic pulmonary hypertension. Int J Clin Exp Med. 2015 Jun 15;8(6):9700-7. eCollection 2015.
• Lang IM, Dorfmuller P, Vonk Noordegraaf A. The Pathobiology of Chronic Thromboembolic Pulmonary Hypertension. Ann Am Thorac Soc. 2016 Jul;13 Suppl 3:S215-21. doi: 10.1513/AnnalsATS.201509-620AS.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2015
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: June 8, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (Actual): June 22, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Treatment; Platelets; Thrombin; Blood coagulation disorders
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hypertension; Hemostatic Disorders; Blood Coagulation Disorders; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hemostatics; Coagulants; Thrombin
• Other Study ID Numbers: ΕΒΔ410/17-9-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No