Pb2232 the Natural Anticoagulants in Patients With Philadelphia‐negative Myeloproliferative Neoplasms

Abstract

Background:Myeloproliferative neoplasms (MPNs) are characterized by an increased frequency of thrombotic complications. Patients with MPNs show little or no abnormalities in traditional coagulation tests. Chronic inflammation associated with pathological secretion of several inflammatory cytokines leads to activation of endothelial cells and imbalance between coagulation and anticoagulation systems.Aims:To estimate the natural anticoagulants activity and activated protein C resistance in MPNs patients.Methods:The study included 99 MPNs patients (aged 25 – 86 years, median = 55) and 43 healthy controls (aged 30‐73 years, median = 46). There were 65 female and 34 male in the study group. 75 (76%) patients were JAK2V617F positive, 24 (24%) were JAK2V617F negative. Antithrombin (AT), protein C (PC) activities and free protein S level (PS) estimation was performed by standard techniques. Thrombin generation was assessed by calibrated automated thrombinography (CAT) according to Hemker et al. Measurement was conducted in platelet poor plasma with or without thrombomodulin (TM). Such parameters as endogenous thrombin potential (ETP, nM∗min) and peak thrombin (Peak, nM) were evaluated. ETP and Peak sensitivity for TM were calculated as percent of these parameters decrease after TM adding to assay (S ETP, % and S Peak, % respectively). STATISTICA 6.0 package was used for data analysis. Parameter results were presented as median (Me) with 95% confidence intervals (CI), p<0.05 was considered statistically significant.Results:Protein C and protein S activity, Peak and ETP decrease were lower in patients with MPN than controls. Patients with Jak2V617F‐ had a tendency to lower sensitivity for TM in comparison with Jak2V617F+ patients. This fact could have a significant role in thrombotic complication development.Summary/Conclusion: Our results showed presence of activated protein C resistance probably caused by anticoagulant protein C system dysfunction. Jak2V617F influence on hemostatic parameters demands further investigations.image

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

“…studies did not enumerate the specific number of ET and PV patients. 11,12 In the TGA studies, there was a trend toward higher peak heights and shorter lag times among nonspecified MPN patients versus controls, suggestive of hypercoagulability in MPNs regardless of any treatment received. Only two studies reported the thrombosis status/incidence of their cohorts.…”

“…There were 3 studies that combined PV, ET, and PMF patients in their analysis of TGA parameters but did not provide individual disease data (►Table 1). [11][12][13] The number of participants in each study ranged from 25 to 212 including the controls. There were six (18.8%) studies that did not have healthy controls.…”

“…One hundred PMF patients were included in the analysis. Three studies utilized thrombomodulin, 8,30,31 while one utilized platelet-rich plasma and Technothrombin. 16 There were two studies that demonstrated lower median ETP and Peak sensitivity to thrombomodulin suggestive of protein C dysfunction.…”

“…There were three studies that examined TGA between MPNs with and without thrombosis with inconsistent results 22 Efremova 2019 11 Perrin 2011 23 Papakonstantinou 2010 24 Matvienko 2020 12 Lim 2018 18 Stein 2012 25 ET vs. controls Tripodi 2013 8 Marchetti 2008 19 Marchetti 2014 26 Mignon 2013 21 Van Aalderen 2010 27 Vignoli 2009 28 Lower in MPN Panova-Noeva 2013 29 No difference Trappenburg 2009 17 Higher in MPN PV vs. controls Tripodi 2013 8 Mixed results a Van Aalderen 2010 27 Not reported Vignoli 2009 28 Panova-Noeva 2013 29 Marchetti 2008 19…”

“…Tripodi 2013 8 Matvienko 2019 30 Palova 2018 16 Efremova 2018 31 Abbreviations: ET, essential thrombocythemia; ETP, endogenous thrombin potential; LT, lag time; MPN, myeloproliferative neoplasm; PH, peak height; PV, polycythemia vera; PMF, primary myelofibrosis; SETP, ETP sensitivity for thrombomodulin; SPH, peak sensitivity for thrombomodulin; TGA, thrombin generation assay; TP, time to peak. a Mixed results depend on the plasma sample and/or the trigger reagents used.…”