Pentosan Polysulfate and Heparin Exhibit Comparable Interactions with Platelet Factor 4, Suggesting a Potential Risk of Thrombocytopenia

Nizzolo S, Zanzoni S, Holthoff HP, Girasole M, Gruber R, Lenhart D, Yates E, Guerrini M, Bertini S · ACS Omega

PPS binds platelet factor 4 (KD 27.8 nM for the whole product, tighter with longer chains) and forms complexes that the HIT-mimicking antibody KKO recognises, with the complex size and charge behaviour sitting between low-molecular-weight and unfractionated heparin and rising with molecular weight; in the immunoassay PPS's antigenicity was closer to unfractionated heparin than to low-molecular-weight heparin, and fondaparinux formed none — a mechanistic basis for HIT-like reactions that the authors say warrants platelet monitoring with parenteral dosing.

Population

PPS, its size-separated fractions, and heparins characterized against platelet factor 4

Intervention

Biophysical binding and immunoassay studies of PPS–PF4 complexes

Comparator

Unfractionated and low-molecular-weight heparins

Limitations

Biophysical and immunoassay work, not clinical events, and in-vitro antibody binding does not strictly predict HIT; two authors are employees of bene PharmaChem, which supplied the PPS, though the paper declares no competing financial interest.