Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.
BACKGROUND
Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding.


METHODS
Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay.


RESULTS
Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]).


CONCLUSIONS
Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.
Genzen
Jonathan R
JR
Department of Laboratory Medicine, Cardiothoracic, Yale University School of Medicine, New Haven, CT, USA. jrg9010@med.cornell
Fareed
Jawed
J
Hoppensteadt
Debra
D
Kurup
Viji
V
Barash
Paul
P
Coady
Michael
M
Wu
Yan Yun
YY
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives; D001778:Blood Coagulation Disorders / Q000097:blood / Q000139:chemically induced; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002648:Child; D016027:Heart Transplantation / Q000009:adverse effects*; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007262:Infusions, Intravenous; D010875:Pipecolic Acids / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced*; D013927:Thrombosis / Q000139:chemically induced*
D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban