Purpose: Patients with cardiovascular disorders frequently need anticoagulation for diagnostic studies, surgical procedures, and therapy. Heparin-induced thrombocytopenia is a relatively common complication of heparin therapy that can result in thrombosis and subsequent limb loss or death, necessitating use of alternative anticoagulants. Methods: Two patients who needed cardiac surgery had thrombocytopenia induced by exposure to heparin and heparin-coated tubing. Several assays were examined for their ability to monitor intraoperative anticoagulation of a factor Xa inhibitor, danaparoid sodium. Results: In vitro, celite and kaolin activated clotting times and activated partial thromboplastin time were prolonged linearly in the presence of increasing concentrations of danaparoid sodium. Aprotinin did not alter the linearity of the response but did alter its slope. In vivo, activated clotting times and activated partial thromboplastin time were insensitive to clinically significant changes in danaparoid sodium plasma levels during cardiopulmonary bypass. Correction in activated partial thromboplastin time lagged 2 hours behind clinically important changes in anti-factor Xa levels. Only anti-factor Xa levels were adequate to monitor intraoperative danaparoid sodium levels. Conclusion: Anticoagulation for cardiopulmonary bypass can be successfully performed with danaparoid sodium and intraoperative anti-factor Xa monitoring. (J Vasc Surg 1998;27:568-75.)