The fibrinolytic potential of the normal primate following the generation of thrombin in vivo.
Parameters of the fibrinolytic system were studied in a primate model where the generation of thrombin was promoted in vivo. The procoagulant stimulus used was a combination of human factor Xa in combination with phosphatidylcholine/phosphatidylserine lipid vesicles (PCPS) as the source of coagulant active phospholipid. The dosage of each component was formulated to provide a gradation of thrombin generating potential assessed prior to in vivo study in an in vitro clotting assay. These ranged from 25.25-36.60 pMole/kg (factor Xa) and 18.85-56.30 nMole/kg (PCPS). In each case, the ratio of the dose of factor Xa/PCPS was maintained at 0.65 (pMole factor Xa/nMole PCPS). Individual dosage combinations producing recalcification clotting times in vitro of 15, 20, 25 and 30 s were used in detailed in vivo studies. Previous studies in dogs had confirmed the thrombin generating potential of factor Xa/PCPS infusions and demonstrated an associated activation of protein C and increased fibrinolytic activity. This has now been extensively characterized in the chimpanzee as follows: 10 min after the infusion of the highest dose (36.6 pMole factor Xa/56.3 nMole PCPS kg bodyweight), the level of circulating t-PA had risen to 900 ng/ml (antigen), 885 IU/ml (functional). Dosage was observed with the lowest dose of 12.25 pMole factor Xa and 18.85 nMole PCPS being associated with relatively minor increases in circulating t-PA activity. There were no changes in u-PA at any dosage during the full time course of the experimental period (90 min). Plasminogen activation was also apparent with alpha-2 antiplasmin levels falling to 30-40% of pre-infusion levels at the highest dosages.(ABSTRACT TRUNCATED AT 250 WORDS)
Giles
A R
AR
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
Nesheim
M E
ME
Herring
S W
SW
Hoogendoorn
H
H
Stump
D C
DC
Heldebrant
C M
CM
D000818:Animals; D001780:Blood Coagulation Tests; D015951:Factor Xa; D005342:Fibrinolysis / Q000502:physiology*; D002679:Pan troglodytes / Q000097:blood*; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D015849:Plasminogen Inactivators / Q000032:analysis; D012016:Reference Values; D013917:Thrombin / Q000096:biosynthesis*
D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D015849:Plasminogen Inactivators; D013917:Thrombin; D015951:Factor Xa