The sFLT-1 to PlGF Ratio is Impaired in Patients with Thalassemia and Sickle Cell Disease.
Authors: Papassotiriou Ioannis , Kouraklis-Symeonidis Alexandra , Apostolakou Filia , Akalestos Athanassios , Vlazakis Vlassis , Ladis Vassilios , Kattamis Antonios 
Published: October 2019

Abstract 2010

Poster Board I-1032

Background:

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is associated with inflammation and with pathologic angiogenesis. PlGF is released from marrow erythroid cells. Serum PlGF concentrations have been reported to be elevated in patients with sickle cell disease. The fms-like tyrosine kinase-1 or sFlt-1 is a soluble form of vascular endothelial growth factor receptor-1 (VEGF-R1), which binds to and sequesters circulating free vascular endothelial growth factor (VEGF) and free PlGF, thereby neutralizing their pro-angiogenic effects. PlGF and VEGFR-1 are key molecules in regulating the angiogenic switch during pathological conditions maintaining the proangio-and anti-angiogenic balance. Perturbations of this balance leads to various degree of endothelial dysfunction, a common pathology in patients with hemoglobinopathies and specifically induce pulmonary hypertension (PHT). In this study we assessed the PlGF and sFLT-1 levels in patients with hemoglobinopathies at steady state.

Patients and Methods:

One hundred twenty three patients with hemoglobinopathies and 20 apparently healthy individuals were included in the study divided in groups as follows: Group A: 38 patients with thalassemia intermedia; Group B: 41 patients with transfusion-dependent beta-thalassemia; Group C: 33 patients with beta-thallassemia/sickle cell disease (SCD) Group D: 11 patients with beta-thallassemia and clinical evidence of PHT, and; Group E: 20 individuals served as control group In patients and controls we performed measurements of PlGF and sFLT-1 with fully automated electrochemiluminescence assays using the immunochemistry autoanalyzer Roche cobas e411. This method provides rapid and reliable assessments and follow-up of patients any time in the day compared to immunoenzymatic assays.

Results:

We found that: a) serum PlGF levels were increased in all groups of patients compared to controls (42.7±19.9 pg/mL, 49.9±23.4 pg/mL, 27.5±9.4 pg/mL, 58.1±27.6 pg/mL for group A, B, C and D, respectively vs 17.1±3.9 pg/mL for control group, p<0.001), b) serum sFLT-1 levels were also increased in all groups of patients compared to controls (89.3±18.3 pg/mL, 90.2±24.0 pg/mL, 89.4±15.3 pg/mL, 117.2±43.5 pg/mL, respectively vs 76.7±11.1 pg/mL, p<0.001 for control group and c) sFLT-1 to PlGF ratio was decreased in all groups of patients compared to controls (2.4±0.9, 2.2±1.2, 3.5±1.0, 2.2±0.8, respectively vs 4.7±1.1 for control group, p<0.001. The most significant changes were found in patients with PHT.

Conclusions:

These findings indicate that patients with thalassemia syndromes and SCD appear to have increased degree of angiogenesis, which is more pronounced in patients with thalassemia compared to patients with SCD and markedly increased in patients with PHT. The decreased sFLT-1/PlGF ratio in almost all patients suggest that the proangio-and anti-angiogenic system is shifted towards to proangiogenic state, providing evidence that patients with hemoglobinopathies even in the steady phase have altered angiogenic state and low-grade inflammation. The results are in accordance to those published earlier for SCD (Blood, 2008;112:856-865.), where the authors demonstrated that PlGF levels were intrinsically elevated due to the increased red cell turnover and may contribute to inflammation and PHT seen in the disease.

Disclosures:

No relevant conflicts of interest to declare.