Post‐operative platelet count profile: the most reliable tool for identifying patients with true heparin‐induced thrombocypenia after cardiac surgery

Cardiac surgery with cardiopulmonary bypass (CPB) is a clinical situation that is particularly at risk of heparin-induced thrombocypenia (HIT). IgGantibodies specific toplatelet factor 4/heparin (PF4/H) complexes are responsible for this severe immune complication of heparin treatment as they strongly activate platelets in vivo, thereby inducing thrombocytopenia and thrombosis in some affected patients.DuringCPB, patients receive large amounts of unfractionated heparin (UFH), the most common anticoagulant used in cardiac surgery patients because of its short half-life and easy monitoring that is feasible withactivated clotting timewithin theoperating roomand rapid neutralization with protamine sulphate. Apart from the use of UFH, the risk of immune response to modified PF4 is higher after CPB, because the patient s blood remains in prolonged contact with the artificial surface of the extracorporeal circuit, thus promoting massive platelet activation and the release of granule content and large amounts of platelet factor 4 (PF4). In 1992, Amiral et al. [1] demonstrated that PF4, a tetrameric member of the C-X-C subfamily of chemokines, formed macromolecular complexes with heparin that bound HIT antibodies. These complexes were then identified as inducing the immune response characterized by the development of PF4specific platelet-activating IgG antibodies responsible for HIT. Leukocytes are also stronglyactivatedbyartificial surfaces,with up-regulation of adhesive molecules and secretion of several cytokines, which also could favor the immune response to heparin afterCPB.AfterCBP, platelet-associatedPF4 levels are also likely increased, with large chains of heparin abundant in UFH that are more effective in increasing the antigenicity of PF4, these effects contributing to the higher risk of HIT after cardiac surgery. However, the diagnosis of HIT has always been considered a challenge in this particular clinical situation. Typically, HIT is characterized in most medical and surgical settings by a fall in platelet count > 50% after the initiation of heparin treatment [2]. However, a significant decrease in platelet count usually occurs during cardiopulmonary bypass and is persistent in the first post-operative days in most cardiac surgery patients. Moreover, several other potential causes of thrombocytopenia are often present in critically ill cardiac patients, and previously described clinical scores for evaluating the likelihood of HIT [3,4] cannot easily be applied after CPB. On the other hand, a large proportion of patients develop antibodies to PF4/H complexes post-operatively [5–7] and the specificity and usefulness of PF4-specific immunoassays are therefore low after cardiac surgery. In 1999, we defined the normal changes in platelet count (PC) after cardiopulmonary bypass in a large group of patients who had not developed antibodies to PF4/H complexes in the post-operative period [6]. In addition, we also defined two abnormal patterns of PC evolution possibly associated with HIT [8]. The first pattern (named P1) is biphasic and characterized by a decrease in PC of at least 40% compared with the maximum post-operative value after previous correction of the thrombocytopenia occurring during CPB. The second pattern (P2) is monophasic and defined by persistent thrombocytopenia in days 5–10 post-operatively without any previous correction of PC after CPB.We then, after studying a prospective cohort of cardiac surgery patients, demonstrated that the P1 pattern was specifically related to the development of pathogenic antibodies to PF4/H and effectively detected HIT after cardiopulmonary bypass [8,9]. On the other hand, the clinical significance of pattern P2 remained to be defined. In 2004, Lillo-Le Louët et al. [10] proposed a clinical score for the diagnosis of HIT after CPB that also included PC evolution as Correspondence: Yves Gruel, Department of HaematologyHaemostasis, CHU Trousseau, 37044 Tours Cedex, France. Tel. : +33 2 47 47 46 72; fax: +33 2 47 47 59 04. E-mail: gruel@med.univ-tours.fr Journal of Thrombosis and Haemostasis, 8: 27–29 DOI: 10.1111/j.1538-7836.2009. 03646.x