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 Type
OBSERVATIONAL
Enrollment
80
No cytoreductive treatment vs cytoreductive drugs (hydroxycarbamide, alpha-interferon, ruxolitinib).
Geneva University Hospitals
Geneva, Switzerland
Guy's Hospital
London, United Kingdom
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).
Time frame: 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.
Time frame: 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)
Time frame: At time of inclusion
Clot permeation; permeation coefficient
Clot permeation will be reported as the calculated permeation coefficient (Ks).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At time of inclusion
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