Dkk3 levels in patients with myeloproliferative neoplasms

Dickkopf-3 (Dkk3) has been proposed as tumor suppressor gene and a marker for tumor blood vessels and has pro-angiogenic properties. Dkk3 is expressed in platelets and megakaryocytes from healthy controls and patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN). The aim of this study is, to find out whether patients with MPN have higher Dkk3 serum levels than normal controls.; We analyzed Dkk3 serum levels with ELISA in patients with newly diagnosed and untreated MPN, including 10 essential thrombocythemia (ET), 10 polycythemia vera (PV), 10 primary meylofibrosis (PMF) and 10 healthy blood donors and correlated these findings with biological and clinical key data and the JAK2-V617F status. Dkk3 levels were corrected to platelet count, Dkk3c, as patients with MPN have higher platelet counts than controls.; As expected, patients with MPN have higher platelet counts than normal controls. Dkk3 serum levels of patients with MPN (5.4 ± 6.1 ng/ml) showed no significant difference compared to normal controls (4.4 ± 3.8 ng/ml). Regarding Dkk3c, a significant difference to controls was found in PV (8.5 ± 8.7 ng/ml; p=0.04), but not in ET and PMF (5.7 ± 3.8 ng/ml; p=0.07 and 2.7 ± 3.6 ng/ml; p=0.9; respectively. Dkk3c correlated with the JAK2-V617F mutational burden (p=0.014, Rho=0.445).; Dkk3 levels corrected to platelet count showed higher levels in PV than normal controls. Elevated Dkk3c level could possibly correlate to platelet activation in PV patients and increased Dkk3 release. Whether this remains a surrogate marker of platelet release or it contributes to the thrombophilic state through its pro-angiogenic properties remains to be shown

Anti-Platelet Factor 4/Heparin Antibody Formation Occurs Endogenously and at Unexpected High Frequency in Polycythemia Vera

Background. Myeloproliferative neoplasms (MPN) encounter thromboses due to multiple known risk factors. Heparin-induced thrombocytopenia (HIT) is a thrombotic syndrome mediated by anti-platelet factor 4 (PF4)/heparin antibodies with undetermined significance for thrombosis in MPN. We hypothesized that anti-PF4/heparin Ab might occur in MPN and promote thrombosis. Methods. Anti-PF4/heparin antibodies were analyzed in 127 MPN patients including 76 PV and 51 ET. Screening, validation testing, and isotype testing of anti-PF4/heparin Ab were correlated with disease characteristics. Results. Anti-PF4/heparin antibodies were detected in 21% of PV and 12% of ET versus 0.3–3% in heparin-exposed patients. Validation testing confirmed anti-PF4/heparin immunoglobulins in 15% of PV and 10% of ET. Isotype testing detected 9.2% IgG and 5.3% IgM in PV and exclusively IgM in ET. IgG-positive PV patients encountered thromboses in 57.1% suggesting anti-PF4/heparin IgG may contribute to higher risk for thrombosis in MPN. Overall, 45% of PV patients experienced thromboses with 11.8% positive for anti-PF4/heparin IgG versus 7.1% in PV without thrombosis. Conclusion. Anti-PF4/heparin antibodies occur endogenously and more frequently in MPN than upon heparin exposure. Thrombotic risk increases in anti-PF4/heparin IgG-positive PV reflecting potential implications and calling for larger, confirmatory cohorts. Anti-PF4/heparin IgG should be assessed upon thrombosis in PV to facilitate avoidance of heparin in anti-PF4/heparin IgG-positive PV