Patient with recurrent HIT after heparin reexposure (patient 17). (A) First episode of HIT (1998). (B) Second episode of HIT after intraoperative heparin rechallenge (2009). The patient’s platelet count rose transiently on 2 occasions after administration of high-dose intravenous IgG. (C) Timing of anti-PF4/heparin seroconversion after heparin rechallenge. Both the EIA-IgG and SRA became positive on day 6; IgM seroconversion occurred on day 7. Reactivity in the EIA in the presence of high heparin (100 IU/mL) is shown by the open circles; thus, the increase in IgM levels was not inhibited by high heparin, whereas the increase in IgG levels and reactivity in the SRA were inhibited by high heparin. (D) Assessment of heparin- and fondaparinux-dependent platelet activation in the presence of patient serum. Strong serum-induced platelet activation (≥80% serotonin release) was observed in the absence of heparin (0 IU/mL) using neat and 1/8 diluted serum; strong heparin-dependent platelet activation was shown by the increase in serotonin release at 0.3 IU/mL UFH, compared with 0 IU/mL UFH, at higher dilutions of patient serum (1/16, 1/32, 1/64, 1/128). The absence of fondaparinux-dependent platelet activation argues against fondaparinux cross-reactivity as an explanation for the patient’s persisting thrombocytopenia. Fonda, fondaparinux; IV, intravenous; PE, pulmonary embolism; US, ultrasound.