A fatal low-molecular-weight heparin-associated thrombocytopenia after hip surgery: Possible usefulness of PF4-heparin ELISA test

In 37 patients undergoing total hip replacement, a prophylactic treatment by a low-molecular-weight heparin (LMWH) was conducted for 2 weeks. They belonged to a group of 499 patients included in a multicenter clinically controlled trial comparing two LMWHs. Blood was collected 1 day before surgery (D-1) and at D+1 or D+2 and D+5 or D+6 as well as D+10 through D+14 after surgery for determinations of platelets counts and anti-Xa. Bilateral venography was performed between D+10 and D+14. A fatal heparin-associated-thrombocytopenia (HAT) occurred on D+9 in one patient and was associated with a positive platelet aggregation test. This finding was confirmed with a recent ELISA test which evidenced a high concentration of PF4-heparin dependent antibodies 72 h before the detection of thrombocytopenia. This led us to study retrospectively PF4-heparin ELISA results by testing the plasma samples of 36 other surgical patients treated under the same conditions and during the same period (four measurements per patient). Among these patients, seven had a venous thrombotic event as a treatment failure. Although some authors claimed that some post-operative thromboses may be facilitated by the presence of heparin-dependent antibodies associated with or without thrombocytopenia, no thrombocytopenia and no positive PF4-heparin ELISA test was observed in this group. Out of the 144 tests performed in these 36 patients for the detection of PF4-heparin complexes dependent antibodies, 15 results were borderline in ten patients and three results in two patients were positive. No relation was evidenced between a positive ELISA test and the occurrence of venous thrombosis. This study points out the possible usefulness of the PF4-heparin ELISA test for HAT-antibodies detection. A daily platelet count in a postoperative patient under heparin therapy, showing thrombocytopenia associated with the detection of heparin-dependent antibodies could allow an earlier and more reliable diagnosis of HAT.