Pharmacokinetics of antithrombin concentrate during autologous hematopoietic stem cell transplantation.
Antithrombin is a naturally-occurring anticoagulant protein. Congenital deficiency of this protein predisposes to thrombotic complications. Acquired deficiency of antithrombin occurs in a variety of clinical circumstances, including hematopoietic stem cell transplantation (HSCT), and is associated with multiorgan failure and death in these situations. Normalization of antithrombin levels by infusion of concentrates of this protein has been found to be beneficial in many of these situations, but has not been routinely used in HSCT. Before antithrombin concentrates can be widely recommended in HSCT, its pharmacokinetics at various phases of the transplant process must be defined to allow estimation of the proper dose and dosing interval. To this end, the recovery and half-life of antithrombin concentrate was determined prior to and 7, 14 and 28 days after beginning the preparative regimen in nine patients with lymphoma undergoing HSCT. The recovery of the infused material was constant during the transplant hospitalization, averaging 2.0% per unit/kg. The half-life, however, dropped significantly during the latter half of the transplant procedure. The half-lives pre-chemotherapy and on day 7 were similar and averaged 20.4 h. On days 14 and 21 the the half-lives were significantly lower at 12.2 and 15.5 h, respectively. The drop in half-life during the transplant process will require antithrombin concentrate to be given more frequently during this time to maintain constant antithrombin levels.
Haire
W D
WD
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-3330, USA.
Stephens
L C
LC
Kotulak
G D
GD
Ruby
E I
EI
Gordon
B G
BG
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000991:Antithrombins / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000628:therapy; D008297:Male; D014182:Transplantation, Autologous
D000991:Antithrombins