Collagen type III induced ex vivo thrombogenesis in humans. Role of platelets and leukocytes in deposition of fibrin.
Exposure of type III collagen coats on plastic cover slips in parallel-plate perfusion chambers to flowing nonanticoagulated human blood resulted in deposition of platelets and fibrin. Blood was drawn directly from an antecubital vein by an occlusive roller pump over the collagen coats in chambers having flow slits of different dimensions, so that wall shear rates of 100, 650, and 2600 s-1 were obtained at 10 ml/min. Coagulation was minimally activated during the passage of blood from the vein to the chamber as shown by fibrinopeptide A levels of 3.7 ng/ml after 5-minute perfusions. The surface coverage with platelets increased from 18% at 100 s-1 to 59% at 2600 s-1, and the corresponding thrombus volumes increased from 2 to 22 microns 3/microns 2, respectively. This contrasted with the coverage with fibrin on collagen, which decreased from 28% at 100 s-1 to 9% at 2600 s-1. Fibrin deposits on the thrombi covered 6% of the surface irrespective of the shear rate, indicating that some of the deposited platelets accelerated the deposition of fibrin. The type III collagen preparation did not activate factor XII and did not possess tissue factor activity, indicating that the surface itself was not procoagulant. However, a correlation between deposited leukocytes and surface coverage with fibrin was observed (r = 0.78, p less than 0.01), suggesting a role for these cells in the deposition of fibrin. The data demonstrate that thrombogenesis is triggered by pure type III collagen, although the deposition of fibrin is not initiated by the collagen itself but presumably by deposited leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Sakariassen
K S
KS
F. Hoffmann-La Roche Ltd, Pharma Research/CVD, Basle, Switzerland.
Joss
R
R
Muggli
R
R
Kuhn
H
H
Tschopp
T B
TB
Sage
H
H
Baumgartner
H R
HR
D001777:Blood Coagulation / Q000187:drug effects; D001783:Blood Flow Velocity / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology*; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D003094:Collagen / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D066298:In Vitro Techniques; D007962:Leukocytes / Q000502:physiology*; D010477:Perfusion; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology
D002951:Citrates; D005344:Fibrinopeptide A; D019343:Citric Acid; D005337:Fibrin; D003094:Collagen; D013917:Thrombin