February 5, 2002

Heparin induced thrombocytopenia with thrombosis (HITT) type II is a life-threatening complication of heparin therapy that most often occurs after 5 – 10 days of exposure to heparin. HITT is produced by an antiheparin immunoglobulin (Ig) G in plasma that binds to repeating antigenic determinants of heparin and to the platelet surface epitopes, resulting in platelet activation and aggregation. The platelets are progressively consumed in the formation of disseminated thromboses and embolism, which can result in limb and organ ischemia.

Anticoagulation is a big problem for patients with HITT type II being prepared for cardiac surgery with cardiopulmonary bypass (CPB). Systemic anticoagulation is required for CPB and heparin is the preferred anticoagulant. The FDA has approved recombinant hirudin (r-hirudin or Lepirudin) for anticoagulation in patients with document HITT type II. Hirudin, a highly specific thrombin inhibitor, can be used as the anticoagulant for CPB, but the appropriate dose to be given and how the anticoagulant effect of hirudin should be monitored are not fully standardized.

Monitoring of the anticoagulant effect during surgery may be performed with the ecarin clotting time (ECT), which is a point of care test measured on the Thrombolytic Assessment System (Pharmanetics, Research Triangle Park, NC). Ecarin is a metalloproteinase from snake venom that activates prothrombin to meizothrombin. Hirudin complexes with meizothrombin; thus, the clotting time is prolonged with increasing amounts of hirudin. Prior to CPB, an in-vitro titration of hirudin using the patient’s blood is performed to develop a titration curve for the ECT test’s response to various hirudin concentrations. The ECT is measured periodically during CPB to ensure that an appropriate anticoagulant effect is maintained. Rather than the usual FDA clearance, the ECT cartridge has a humane device exemption; as a result, certain procedures must be in place in order to use the test clinically.

Patients with laboratory confirmed HIT II who need cardiac surgery with cardiopulmonary bypass using hirudin anticoagulation are difficult cases. They require extensive perioperative preparation and cooperation between anesthesia, surgical, hematology and laboratory personnel to be successfully accomplished.