Differential Effects of Hirudin and Heparin on the Whole Blood Clot Formation, ACT Machine Cardiac Cath Lab ICU Critical Care ICCU LMWH PTCA

A-535 2002

Differential Effects of Hirudin and Heparin on the Whole Blood Clot Formation

Jaime Torres, M.D.; Nobukazu Sato, M.D.; Kenichi A. Tanaka, M.D.; Fania Szlam, M.M.S.; Jerrold H. Levy, M.D. Anesthesiology, Emory University School of Medicine, Atlanta, Georgia

Introduction: Although heparin (Hep) is widely used for anticoagulation during cardiac or vascular surgery, some patients may suffer from serious complications such as heparin-induced thrombocytopenia. Recombinant hirudin (rHir), a direct thrombin inhibitor, is used as a heparin alternative1, 2. However, the effects of rHir on the whole blood clot formation is not completely understood. Therefore, we designed a study to compare the effects of rHir and Hep using the Sonoclot, a viscoelastic coagulation monitor. Methods: After institutional approval and informed consent, 5 healthy volunteers were included in this protocol. Blood samples were collected into tubes containing 3.2 % sodium citrate. Using celite-cuvetts, Sonoclot signature analyses (Sienco Inc, Wheat Ridge, CO) were performed with 0.4 mL recalcified blood samples, to which beef lung Hep (American Pharmaceutical Partners, Los Angels, CA), or rHir (Aventis Pharma, Germany) was added to achieve the following final concentrations; Hep; 1 u/mL, 3 u/mL; rHir; 1 μg/mL, 1.5 μg/mL. The concentrations of rHir reflect the levels needed to achieve anticoagulation during vascular procedures. Sonoclot activated clotting time (ACT) and clot rate (CR) were obtained from Sonoclot analyzer, with CR describing the initial rate of fibrin formation induced by thrombin. Hematocrit and platelet count were also measured. Data were compared by one-sample or paired t-test. P<0.05 was considered significant. All values are expressed as mean±SE. Results: Hematocrit and platelet counts were within normal ranges. Prolongations of SCTs were comparable at Hep 1 u/mL and rHir 1 μg/mL, and at Hep 3 u/mL and rHir 1.5 μg/mL, respectively. However, rHir did not reduce CRs at these levels, whereas Hep effectively did. (Table) Conclusion: rHir and Hep suppress thrombin activation and delay fibrin formation as reflected by similar prolongation of SCTs. However, once fibrin strands start to form, clot gel formation is not effectively suppressed by rHir at 1 and 1.5 μg/mL. Higher doses of rHir is required for more effective thrombin suppression. Sonoclot analyzer enables to monitor the rate of actual clot formation (CR), which is beyond the endpoint of clotting time (ACT). This may be potentially useful for titrating anticoagulants more effectively based on individual responses. References: 1)Anesth Analg 2000; 90: 292-298. 2) Anesth Analg 2001; 92: 344-346. Anesthesiology 2002; 96: A535

Control Hep 1u/ml Hep 3u/ml rHir 1mcg/ml rHir 1.5mcg/ml SCT (seconds) 178±4 459±42* 646±94* 446±44* 543±86* Clot Rate (U/min) 19.2±2.2 4.8±0.9* 2.4±0.3* 16.4±1.0 17.3±3.0 SCT and Clot Rate * p<0.05 compared with control. For more information please visit: www.lifediagnostica.com