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

الملخص EN

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.