Suboptimal effect of a three-factor prothrombin complex concentrate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose.
BACKGROUND
Plasma transfusion is standard therapy for urgent warfarin reversal in the United States. "Four-factor" prothrombin complex concentrate (PCC), available in Europe, has advantages over plasma therapy for warfarin reversal; however, only "three-factor" PCCs (containing relatively low Factor [F]VII) are available in the United States.


METHODS
The efficacy of a three-factor PCC for urgent warfarin reversal was evaluated in 40 patients presenting with supratherapeutic international normalized ratio (ST-INR > 5.0) with bleeding (n = 29) or at high risk for bleeding (n = 11). In 13 patients, pre- and posttherapy vitamin K-dependent factors were assayed. Historical controls (n = 42) treated with plasma alone were used for rate of ST-INR correction comparison.


RESULTS
Treatment with plasma alone (mean, 3.6 units) lowered the INR to less than 3.0 in 63 percent of historical controls. Low-dose (25 U/kg) and high-dose (50 U/kg) PCC alone lowered INR to less than 3.0 in 50 and 43 percent of patients, respectively. Additional transfusion of a small amount of plasma (mean, 2.1 units) increased the rate of achieving an INR of less than 3.0 to 89 and 88 percent for low- and high-dose PCC therapy, respectively. FII, F IX, and FX increments were similar for PCC-treated patients with or without supplemental plasma; FVII was significantly higher in the PCC plus plasma group compared to the PCC-only group (p = 0.001).


CONCLUSIONS
Three-factor PCC does not satisfactorily lower ST-INR due to low FVII content. Infusion of a small amount of plasma increases the likelihood of satisfactory INR lowering.
Holland
Lorne
L
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9073, USA.
Warkentin
Theodore E
TE
Refaai
Majed
M
Crowther
Mark A
MA
Johnston
Marilyn A
MA
Sarode
Ravindra
R
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000506:poisoning*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D004338:Drug Combinations; D062787:Drug Overdose; D005164:Factor IX / Q000627:therapeutic use*; D005167:Factor VII / Q000627:therapeutic use*; D005170:Factor X / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000627:therapeutic use*; D012189:Retrospective Studies; D014859:Warfarin / Q000506:poisoning*
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D004338:Drug Combinations; C025667:prothrombin complex concentrates; D014859:Warfarin; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; C000599051:Profilnine SD