Circulating Endothelial Cell Levels Correlate with Treatment Outcomes of Splanchnic Vein Thrombosis in Patients with Chronic Myeloproliferative Neoplasms

Abstract

Circulating endothelial cells (CECs) are viable, apoptotic or necrotic cells, identified by CD 146 surface antigen expression, considered a biomarker of thrombotic risk, given their active role in inflammatory, procoagulant and immune processes of the vascular compartment. Growing evidence establishes that CECs are also involved in the pathogenesis of several hematological and solid malignancies. The primary aim of this study was to verify if CEC levels could predict both the course and treatment responses of splanchnic vein thrombosis (SVT), either in patients affected by myeloproliferative neoplasms (MPNs) or liver disease. Thus, a retrospective multicenter study was performed; fifteen patients receiving anticoagulant oral treatment with vitamin k antagonists (VKA) for SVT were evaluated. Nine patients were affected by MPN, and all of them received cytoreduction in addition to anticoagulant therapy; four of these patients had primary myelofibrosis (PMF) and were treated with ruxolitinib (RUX), and one patient with primary myelofibrosis, two patients with essential thrombocythemia (ET), and two patients with polycythemia vera (PV) were treated with hydroxyurea (HU). Six patients affected by liver diseases (three with liver cirrhosis and three with hepatocellular carcinoma) were included as the control group. CECs were assayed by flow cytometry on peripheral blood at specific time points, for up to six months after enrollment. The CEC levels were related to C-reactive protein (CRP) levels, splenic volume reduction, and thrombus recanalization, mainly in MPN patients. In patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC), for which the mechanism of SVT development is quite different, the relationship between CEC and SV reduction was absent. In conclusion, the CEC levels showed a significant correlation with the extent of venous thrombosis and endothelial cell damage in myeloproliferative neoplasm patients with splanchnic vein thrombosis. Although preliminary, these results show how monitoring CEC levels during cytoreductive and anticoagulant treatments may be useful to improve SVT outcome in MPN patients.

Keywords: circulating endothelial cells; myeloproliferative neoplasms; portal vein thrombosis; recanalization.

Figure 1

Ruxolitinib (A) group. CEC: circulating endothelial cells, CRP: C-reactive protein, D-DIM: d-dimers, RECAN: % of recanalization, SV: % of splenic volume reduction. Values on y-axis are in arbitrary measures.

Figure 2

Hydroxyurea (B) group. CEC: circulating endothelial cells, CRP: C-reactive protein, D-DIM: d-dimers, RECAN: % of recanalization, SV: % of splenic volume reduction. Values on y-axis are in arbitrary measures.

Figure 3

VKA (C) group. CEC: circulating endothelial cells, CRP: C-reactive protein, D-DIM: d-dimers, RECAN: % of recanalization, SV: % of splenic volume reduction. Values on y-axis are in arbitrary measures.