Heparin-Induced Thrombocytopenia Antibody Is More Common in Patients with Active Bacterial Infections

Abstract 4678

Heparin mobilizes and binds to platelet factor 4 (PF4), forming a heparin-PF4 complex on the platelet surface. Rarely, IgG antibodies recognize and bind to the immune complex, causing platelet activation and thrombin generation, resulting in heparin induced thrombocytopenia (HIT). There is evidence that PF4 has a role in antibacterial host defense and can concurrently prime the immune system with IgG antibodies that can cross-react with the heparin-PF4 complex (Krauel et al, Blood 2011). In the setting of a bacterial infection, the PF4 molecules interact with the bacterial cell wall and induce antibody production. These antibodies are able to recognize any bacteria coated in PF4, resulting in phagocytosis. In the setting of heparin, this antibody can cross react with the heparin-PF4 complex and result in HIT. In vitro studies suggest that E. coli, S. pneumo, and S. aureus coated in PF4 cross-react with human heparin induced anti-PF4/heparin antibodies.

We have collected a database of patients being tested for HIT at our institution and performed a retrospective analysis of the incidence of bacterial infections. We hypothesize that patients who have a bacterial infection will be more likely to develop HIT due to anti-bacterial antibodies that cross-react with the heparin-PF4 complex. We collected culture data from 54 patients with positive HIT antibody by ELISA and 178 patients with negative HIT antibody. The incidence of positive cultures and active infections in described in table 1. In the HIT negative patients, 61/178 (34.3%) had positive cultures, compared to 28/54 (51.9%) in the HIT positive patients (p=0.0198). Given that there is data to support E. coli, S. pneumo, and S. aureus-induced antibody cross-reactivity, we performed a subgroup analysis of the incidence of these specific bacterial infection in HIT positive and negative patients (33.3% versus 19.7%, p=0.0357). There is a statistically significant difference noted in the active infections, subgroup analysis, as well presence of any positive cultures in the HIT positive patients as compared to the HIT negative patients.

This data supports that in the setting of active infection, particularly with E. coli, S. pneumo, and S. aureus, HIT antibody results should be carefully evaluated. Patients with positive cultures are likely to have thrombocytopenia from infection or sepsis, regardless of the presence of a HIT antibody. Thus, additional factors, such as the patient's 4T score and the presence of thrombosis should be considered prior to initiating treatment for HIT.