Partial reversal of low molecular weight heparin (PK 10169) anti-Xa activity by protamine sulfate: in vitro and in vivo study during cardiac surgery with extracorporeal circulation.
Neutralization of a low molecular weight (LMW) heparin fraction by protamine sulfate was evaluated in vitro and in vivo. Anti-Xa and anti-IIa activities were measured by amidolytic and coagulation methods (activated partial thromboplastin time, APTT). Fifteen patients (4 males and 11 females) underwent surgery with extracorporeal circulation. In vitro, anti-Xa and anti-IIa activities and APTT of unfractionated heparin were neutralized with a protamine/heparin (P/H) gravimetric ratio of 1.6, 1.33 and about 2, respectively. Anti-IIa activity and APTT induced by PK 10169 were completely corrected at a P/H ratio of 1 and 2, respectively, while anti-Xa activity was incompletely neutralized at a ratio of 5. In vivo, in 9 patients who did not receive intravenous protamine sulfate, a good correlation was found between doses of PK 10169 infused, anti-IIa plasma level and blood loss. In 3 patients who were treated prophylactically with protamine, bleeding was normal or only slightly increased. In 3 patients who received protamine because of hemorrhage, mean anti-Xa and anti-IIa were 2.3 and 0.54 U before and 1.32-0.06 U after neutralization. Bleeding was stopped by a second dose of protamine in 1 patient, but blood loss was abnormal in the other patients. However, a correlation between bleeding and anti-Xa or anti-IIa activities was not clearly evident.
Massonnet-Castel
S
S
Pelissier
E
E
Bara
L
L
Terrier
E
E
Abry
B
B
Guibourt
P
P
Swanson
J
J
Jaulmes
B
B
Carpentier
A
A
Samama
M
M
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D005112:Extracorporeal Circulation; D005170:Factor X / Q000037:antagonists & inhibitors*; D015951:Factor Xa; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006494:Heparin Antagonists; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D011479:Protamines / Q000494:pharmacology*
D006494:Heparin Antagonists; D011479:Protamines; D005170:Factor X; D006493:Heparin; D015951:Factor Xa