The evaluation of the relevance of thrombin generation and procoagulant activity in thrombotic risk assessment in BCR‐ABL‐negative myeloproliferative neoplasm patients

Abstract

The MP procoagulant activity did not predict thrombosis in MPN patients. The contribution of TG assay in the assessment of the thrombotic risk is still in debate.

Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm

“…Importantly, we observed this effect with JAK2 V617F erythrocyte microvesicles from mice as well as microvesicles isolated from patients carrying JAK2 V617F . We thus highlight here a crucial vascular role for microvesicles in MPNs, beyond their already described involvement in coagulation in this setting (27)(28)(29)(30)(31). Although patients with MPNs have higher circulating levels of microvesicles than healthy individuals, we assessed vascular reactivity using the same concentrations of from JAK2 V617F erythrocytes in the increase in endothelial oxidative stress.…”

The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms and Future Challenges

“…The five published studies that compared nonspecified MPNs with JAK2 versus without JAK2 mutations yielded inconsistent results ( Table 3 ), 8 14 21 26 32 despite all utilizing the same (CAT) platform. One study utilized filtration to remove microparticles from the plasma before assay.…”

“…37 Another study noted higher median peak height (p < 0.05) and band velocity index (p < 0.05) from patients on hydroxyurea or pegylated interferon-alpha compared to untreated MPN patients. 34 When thrombomodulin was added to the plasma samples, it decreased the values of the 11 Marchetti 2008 19 Lower in MPN Marchetti 2014 26 No difference Nonspecified MPNs w/ JAK2 vs. controls Efremova 2019 11 Higher in MPN Lim 2018 18 Mixed results a Marchetti 2008 19 Not reported Marchetti 2014 26 Nonspecified MPNs w/ JAK2 vs. w/o JAK2 Tripodi 2013 8 Baccouche 2017 32 Duchemin 2010 14 Mignon 2013 21 Marchetti 2014 26 Nonspecified MPNs w/ thrombosis vs. w/o thrombosis Korsakova 2020 13 Baccouche 2017 32 Mignon 2013 21 Abbreviations: ET, essential thrombocythemia; ETP, endogenous thrombin potential; ETP ratio, ETP ratio (with-to-without thrombomodulin); LT, lag time; MPN, myeloproliferative neoplasm; PH, peak height; PL, phospholipids; PV, polycythemia vera; PMF, primary myelofibrosis; SETP, ETP sensitivity for thrombomodulin; SPH, peak sensitivity for thrombomodulin; TGA, thrombin generation assay; TP, time to peak; VI, velocity index; w/, with; w/o, without. a Mixed results depend on the plasma sample and/or the trigger reagents used.…”

“…30,31 Thrombin Generation Assay and Thrombosis Status in the MPN Population Out of the 27 TGA studies, 12 (44.4%) reported history of arterial and/or venous thrombotic events in their MPN patients which ranged from 19 to 45%. 13,14,16,17,21,23,25,26,29,[32][33][34] Six studies (22.2%) did not specify whether the thrombotic events were arterial or venous but had a combined 88 thrombosis events. 13,14,16,17,25,29 Out of 751 MPN patients (697 ET and PV; 54 PMF) included in these 12 studies, there were 206 (27.4%) combined arterial and venous thrombotic events.…”

“…(►Table 3). 13,21,32 All three studies utilized the CAT platform with platelet-poor plasma and tissue factor and phospholipid as triggering reagents. These collectively included 170 ET and PV patients and 1 PMF patient.…”