PHARMACOKINETICS OF ANTITHROMBIN CONCENTRATE DURING AUTOLOGOUS HEMATOPOIETIC STEM-CELL TRANSPLANTATION

Antithrombin is a naturally-occurring anticoagulant protein. Congenita l deficiency of this protein predisposes to thrombotic complications, Acquired deficiency of antithrombin occurs in a variety of clinical ci rcumstances, including hematopoietic stem cell transplantation (HSCT), and is associated with multiorgan failure and death in these situatio ns, Normalization of antithrombin levels by infusion of concentrates o f this protein has been found to be beneficial in many of these situat ions, but has not been routinely used in HSCT. Before antithrombin con centrates can be widely recommended in HSCT, its pharmacokinetics at v arious phases of the transplant process must be defined to allow estim ation of the proper dose and dosing interval, To this end, the recover y and half-life of antithrombin concentrate was determined prior to an d 7, 14 and 28 days after beginning the preparative regimen in nine pa tients with lymphoma undergoing HSCT. The recovery of the infused mate rial was constant during the transplant hospitalization, averaging 2.0 % per unit/kg. The half-life, however, dropped significantly during th e latter half of the transplant procedure, The half-lives pre-chemothe rapy and on day 7 were similar and averaged 20.4 h. On days 14 and 21 the half-lives were significantly lower at 12.2 and 15.5 h, respective ly. The drop in half-life during the transplant process will require a ntithrombin concentrate to be given more frequently during this time t o maintain constant antithrombin levels.