Treatment of Polycythaemia Vera and Essential Thrombocythaemia: Influence on the Clot Structure (MPNClot)

Myeloproliferative neoplasms (MPN) such as Polycythemia Vera (PV) and, Essential Thrombocythaemia (ET) are rare clonal myeloid neoplasms associated with an increased risk of both venous and arterial thrombosis. Thrombotic complications are the main determinant of morbidity and in a less extend mortality.

Routine haemostasis analysis (TP, aPTT) are usually normal and are useless to demonstrate a hypercoagulable state. However, previous evidence suggests that global coagulation tests such as thrombin generation or thromboelastometry are able to detect signs of procoagulant imbalance in MPN. Similarly, current data seems to demonstrate that fibrin clot properties (clot permeability, turbidimetry, clot lysis time) properties is altered suggesting an hypercoagulable state.

Goals of PV and ET treatments are to control blood count to reduce the risk of thrombotic events. Moreover, new drugs such as Janus Kinase Inhibitors (JAKi) were recently licensed for PV and are under investigations on clinical trial for ET. It is currently unknown if treatments that were used for ET and PV, and especially JAKi are able to modify the hypercoagulable state that is observed in those diseases, and if there is difference between drugs.

To evaluate impact of MPN treatment on prothrombotic haemostatic profile, we propose to evaluate global coagulation and fibrin clot properties in MPN, depending on the treatment.

Study Overview

• Status: Completed
• Conditions: Polycythemia Vera; Thrombocythemia, Essential
• Intervention / Treatment: Drug: No cytoreductive vs cytoreductive drugs

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • Geneva University Hospitals
• United Kingdom
  • London, United Kingdom, SE19RT
    • Guy's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Screening for participation for MPN patients will occur at the outpatient clinic of the division of Haematology at the Geneva University Hospitals (Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland) and at the outpatient clinic of the division of Haematology at Guy's Hospitals (Great Maze Pond, London SE1 9RT, United Kingdom).

Description

Inclusion Criteria:

• All men and women, older than 18 years, with a diagnosis of PV or ET (primary or secondary) according to the 2008 World Health Organization (WHO) classification.

Exclusion Criteria:

• Lack of participant's consent;
• Concomitant treatment with anticoagulant drugs (anti-vitamin K, heparin or direct oral anticoagulant drugs);
• Active cancer other than non-melanoma skin cancer (defined as cancer diagnosis <5 years or treatment <2 years);
• Recent infection (<30d);
• Recent surgery (<30d);
• Recent hospitalization (<30d);
• Recent thromboembolic or cardiovascular event (<3m).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PV; Patients with a diagnosis of polycythaemia vera.	Drug: No cytoreductive vs cytoreductive drugs; No cytoreductive treatment vs cytoreductive drugs (hydroxycarbamide, alpha-interferon, ruxolitinib).
ET; Patients with a diagnosis of essential thrombocythaemia.	Drug: No cytoreductive vs cytoreductive drugs; No cytoreductive treatment vs cytoreductive drugs (hydroxycarbamide, alpha-interferon, ruxolitinib).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrin polymerization; lag-time (in seconds)	Fibrin polymerization will be assessed by turbidity assay on plasma. Fibrin polymerization will be monitored at 340 nm after incubation with human thrombin and CaCl2. Results will report lag-time (seconds).	At time of inclusion
Fibrin polymerization; maximal absorbance	Fibrin polymerization will be assessed by turbidity assay on plasma. Fibrin polymerization will be monitored at 340 nm after incubation with human thrombin and CaCl2. Results will report maximal absorbance.	At time of inclusion
Clot lysis time (in minutes)	Fibrinolysis will be assessed by turbidity assay on plasma. Fibrinolysis will be monitored by adding tissue plasminogen activator (tPA). Results will report clot lysis time (minutes)	At time of inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clot permeation; permeation coefficient	Clot permeation will be reported as the calculated permeation coefficient (Ks).	At time of inclusion
Quantitative parameters of thrombin generation test (TGT); endogenous thrombin potential (nM*minutes)	The measurement of thrombin generation is performed by the technique of calibrated automated thrombogram (CAT). Endogenous thrombin potential will be reported in nM*minutes.	At time of inclusion
Quantitative parameters of thrombin generation test (TGT); peak (nM)	The measurement of thrombin generation is performed by the technique of calibrated automated thrombogram (CAT). Peak will be reported in nM.	At time of inclusion
Quantitative parameters of thrombin generation test (TGT); time to peak (minutes)	The measurement of thrombin generation is performed by the technique calibrated automated thrombogram (CAT). Time to peak will be reported in minutes.	At time of inclusion
Fibrin density by laser scanner confocal microscopy (number per 100 μm)	The fibrin density was determined by counting the number of fibres crossing an arbitrary line of 100 μm drawn through a single optical section. Each fibrin clot is prepared in duplicate and 20 density measurements were performed on each sample.	At time of inclusion

Collaborators and Investigators

• Sponsor: Dr Yan Beauverd
• Investigators: Principal Investigator: Yan Beauverd, University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2016
• Primary Completion (ACTUAL): October 31, 2020
• Study Completion (ACTUAL): October 31, 2020

Study Registration Dates

• First Submitted: September 10, 2016
• First Submitted That Met QC Criteria: September 20, 2016
• First Posted (ESTIMATE): September 23, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: CCER 2016-00950

Plan for Individual participant data (IPD)

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