Apparent cross‐reactivity of heparin‐dependent platelet antibodies with danaparoid in a PF4 ELISA

A 60‐year‐old previously fit woman presented with deep vein thrombosis. She had a history of 2 pregnancies, no transfusions and a platelet count of 241×10 9 /l. She was treated with intravenous unfractionated heparin and, after 10 days, her platelet count dropped to 30×10 9 /l. The patient had not been previously exposed to heparin. There was no evidence for disseminated intravascular coagulation and a clinical diagnosis of heparin induced thrombocytopenia was made. Heparin was discontinued and danaparoid was administered. Over the next 10 days, her platelet count returned to normal. Laboratory investigation using a solid phase PF4‐heparin ELISA assay (GTI‐PF4) revealed the presence of heparin dependent antibodies. These antibodies were only partially inhibited by the addition of excess heparin (100 & 200iu) which suggested that heparin independent anti‐PF4 antibodies were also present. Substitution of excess danaparoid for heparin in the GTI‐PF4 kit also resulted in partial inhibition of antibody binding and suggested that the antibodies might cross‐react with danaparoid. Investigation using an annexin V flow cytometric assay confirmed the presence of heparin dependent platelet antibodies but the addition of excess heparin completely inhibited antibody binding. There was no evidence that the antibodies were cross‐reactive with danaparoid in the annexin V assay. The clinical outcome in this case suggests that the results of the annexin V assay may provide more accurate information about the cross‐reactivity of heparin dependent antibodies with heparin analogues than solid phase PF4‐heparin ELISA assays.