title: Spontaneous heparin-induced thrombocytopenia syndrome: 2 new cases and a proposal for defining this disorder.
abstract: The existence of spontaneous heparin-induced thrombocytopenia (HIT) syndrome (or autoimmune HIT), defined as a transient prothrombotic thrombocytopenic disorder without proximate heparin exposure serologically indistinguishable from HIT, is controversial. We describe 2 new cases presenting with thrombotic stroke/thrombocytopenia: one following shoulder hemi-arthroplasty (performed without heparin) and the other presenting to the emergency room without prior hospitalization, heparin exposure, or preceding infection. Both patients tested strongly positive for anti-platelet factor 4 (PF4)/heparin immunoglobulin (Ig)G in 2 different immunoassays and in the platelet serotonin-release assay. Crucially, both patients' sera also caused strong (>80%) serotonin release in the absence of heparin, a serologic feature characteristic of delayed-onset HIT (ie, where heparin use precedes HIT but is not required for subsequent development or worsening of thrombocytopenia). We propose that a rigorous definition of spontaneous HIT syndrome should include otherwise unexplained thrombocytopenia/thrombosis without proximate heparin exposure and with anti-PF4/heparin IgG antibodies that cause strong in vitro platelet activation even in the absence of heparin.
authors.affiliation: Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada;
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.affiliation: Department of Medicine, and.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Basciano
authors.affiliation: Division of Interventional Neuroradiology, Department of Neurosurgery, Weill Cornell Medical Center, New York, NY; and.
authors.forename: Jared
authors.initials: J
authors.lastname: Knopman
authors.affiliation: Ken and Ruth Davee Department of Neurology and Clinical Neurological Sciences, Feinberg School of Medicine of Northwestern University, Chicago, IL.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bernstein
mesh_terms: D000906:Antibodies / Q000009:adverse effects; D000925:Anticoagulants / Q000009:adverse effects*; D003937:Diagnosis, Differential; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008875:Middle Aged; D013577:Syndrome; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis*
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D006493:Heparin