P0248HEPARIN-INDUCED THROMBOCYTOPENIA (HIT): A POSSIBLE CAUSE OF VENOUS THROMBOEMBOLISM IN ACTIVE SYSTEMIC VASCULITIS

Abstract

Abstract Background and Aims Increased incidence of venous thromboembolism in active phase of vasculitis has been found by several authors. Examining large cohorts of patients, the underlying mechanisms still remain unclear. Patients with active vasculitis are not rarely exposed to heparin mainly because of dialysis, plasmafiltration or ECMO. In the high inflammatory context of active vasculitis, as in major surgery, heparin exposure could promote the formation of anti-PF4/heparin antibodies and induce HIT. Method Description of cases with active vasculitis and HIT observed in our cohort of ANCA-associated vasculitis patients from 1994 to 2019. Review of cases reported in the literature. Results We observed 18 patients with systemic vasculitis and HIT (10 M and 8 F, median age: 69.5 yo). Fourteen had ANCA antibodies, one patient had both ANCA and anti-GBM antibodies (double positive), two had positive anti-GBM antibodies, one had negative ANCA and anti-GBM antibodies. Among 15 patients with positive ANCAs, 13 had anti-MPO antibodies and 2 anti-PR3 antibodies (Fig. 1). All patients were exposed to heparin, 10 because of plasmafiltration and dialysis, 8 for dialysis alone. Mean platelet count nadir was 76100/mm3 (range 23000-197000/mm3). In all patients PF4–heparin antibody immunoassay was strongly positive (optical density >1 in 13 patients). The most frequent manifestations were thrombocytopenia and repeated clotting of the extracorporeal circuit and dialyzer with thrombosis of the hemodialysis catheter (6/18 patients). Four patients developed deep vein thrombosis almost invariably in the site of the hemodialysis catheter. Pulmonary embolism was observed in only one patient (Fig. 2). To our knowledge, only 11 cases of HIT in patients with vasculitis have been reported in literature (Table I). Detailed data are available for 7 patients (6 M and 1 F, median age 69.6 yo). Three patients had anti-PR3 antibodies, 2 anti-MPO antibodies, 1 both ANCA anti-MPO and anti-GBM antibodies (double positive), 1 only anti-GBM antibodies. Mean platelet count nadir was 45625/mm3 (range 17000-131000/mm3). Three out of 11 patients developed repeated clotting of the extracorporeal circuit and dialyzer, 2 patients had deep vein thrombosis in the site of the hemodialysis catheter, and one patient had also leukopenia and subarachnoid hemorrhage. Six patients were asymptomatic and developed only thrombocytopenia. Conclusion When patients with active systemic vasculitis develop venous thromboembolism and thrombocytopenia after exposure to heparin, or repeated coagulation of the extracorporeal circuit and dialyzer or plasma-filter, HIT should be included in the possible differential diagnosis, and Platelet factor 4–heparin antibody tests should be performed.