Spontaneous heparin-induced thrombocytopenia (HIT) with potential thrombosis is a rare anti–platelet factor 4 (PF4) disorder that is a known complication of total knee arthroplasty despite the absence of heparin exposure. Spontaneous HIT resembles autoimmune HIT, a severe form of this disorder that features both heparin-dependent and heparin-independent platelet-activating properties.

A 60-year-old male patient was admitted on the 34th day post-total hip arthroplasty,  after total hip arthroplasty with saddle pulmonary embolus and extensive bilateral lower-limb deep vein thromboses. He was receiving postoperative prophylaxis with aspirin. The platelet count was 19,000 per cubic millimeter. An evaluation for hypercoagulability showed antibodies of IgG class against PF4–polyanion by chemiluminescence immunoassay. Serotonin-release assay indicated a platelet-activating anti–PF4–polyanion disorder. The absence of heparin exposure was documented in the patient’s chart, and no mention of heparin appeared in the operative note. No arterial or central lines had been placed intraoperatively, nor had any stock heparin flushes been used that would not appear in these records. The patient’s only known lifetime heparin exposure occurred during a percutaneous coronary intervention that was performed 3 years earlier without the development of HIT.

Bivalirudin anticoagulation was initiated, followed the next day by two doses of intravenous immune globulin (IVIG), administered 24 hours apart; anticoagulation was transitioned to apixaban, with a temporary increase in dose owing to a decrease in the platelet count. The platelet count normalized over several weeks. No recurrence of thrombosis was noted at the last follow-up on day 225. In order to investigate the presence of anti-PF4 antibodies with heparin-independent platelet-activating properties, a sample of the patient's plasma was referred to the McMaster Platelet Immunology Laboratory. These findings indicated the production of heparin-independent platelet-activating antibodies. Furthermore, the patient's antibodies against PF4–polyanion were investigated by fluid-phase ELISA, which confirmed greater binding against PF4–heparin than PF4 alone. This finding was consistent with the presence of autoimmune HIT.

A hypothesis for the development of spontaneous HIT after total knee arthroplasty is the abrupt release of an accumulation of polyanions after tourniquet removal that could have activity analogous to that of heparin, in which polyanions cause conformational changes in PF4 that permit binding to HIT antibodies.