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

Completed

• Conditions: Polycythemia Vera; Thrombocythemia, Essential
• Interventions: Drug: No cytoreductive vs cytoreductive drugs

• Registration Number: NCT02912884
• Lead Sponsor: Dr Yan Beauverd

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-09
• Study First Submitted: 2016-09-10
• Study First Submitted QC: 2016-09-20
• Study First Posted: 2016-09-23
• Primary Completion: 2020-10-31
• Study Completion: 2020-10-31
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-09
• Last Update Posted: 2020-11-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PV	No cytoreductive vs cytoreductive drugs	Patients with a diagnosis of polycythaemia vera.
ET	No cytoreductive vs cytoreductive drugs	Patients with a diagnosis of essential thrombocythaemia.

Primary Outcome Measures

Name	Time	Method
Fibrin polymerization; lag-time (in seconds)	At time of inclusion	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).
Fibrin polymerization; maximal absorbance	At time of inclusion	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.
Clot lysis time (in minutes)	At time of inclusion	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)

Secondary Outcome Measures

Name	Time	Method
Quantitative parameters of thrombin generation test (TGT); endogenous thrombin potential (nM*minutes)	At time of inclusion	The measurement of thrombin generation is performed by the technique of calibrated automated thrombogram (CAT). Endogenous thrombin potential will be reported in nM\*minutes.
Clot permeation; permeation coefficient	At time of inclusion	Clot permeation will be reported as the calculated permeation coefficient (Ks).
Fibrin density by laser scanner confocal microscopy (number per 100 μm)	At time of inclusion	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.
Quantitative parameters of thrombin generation test (TGT); peak (nM)	At time of inclusion	The measurement of thrombin generation is performed by the technique of calibrated automated thrombogram (CAT). Peak will be reported in nM.
Quantitative parameters of thrombin generation test (TGT); time to peak (minutes)	At time of inclusion	The measurement of thrombin generation is performed by the technique calibrated automated thrombogram (CAT). Time to peak will be reported in minutes.

Trial Locations

Locations (2)

Geneva University Hospitals; 🇨🇭 Geneva, Switzerland

Guy's Hospital; 🇬🇧 London, United Kingdom