Pentosan-induced thrombocytopenia: support for an immune complex mechanism

Pentosan polysulphate is a low molecular weight heparinoid that is used as an anticoagulant. Because the drug also has antineoplastic properties, it has been used experimentally at the National Institutes of Health to treat metastatic malignancies. We present the case of a patient who developed thrombocytopenia resembling Type II heparin-induced thrombocytopenia (HIT) during the course of pentosan therapy. The patient's plasma demonstrated platelet reactivity both by aggregometry and 14C-serotonin release in the presence of pentosan. Heparin and other polyanions could substitute for pentosan in aggregation studies. The aggregating activity co-purified with the patient's IgG and was inhibited by pre-incubation with monoclonal antibody (MoAb) to the platelet Fc receptor. To elucidate the relationship between the platelet, the polyanion and the antibody, we measured the binding of 3H-heparin to platelets in the presence of the patient's IgG and found that it was increased 6-fold over binding in the presence of control IgG. Heparin binding was not reduced by MoAb against the Fc receptor. Taken together, these data support a model in which polyanion-antibody complexes attach to the platelet surface by the polyanion and secondarily stimulate the platelet via their Fc termini.