Reduction in thrombus formation by PG-1 F(ab')2, an anti-guinea pig platelet glycoprotein Ib monoclonal antibody.
We have recently demonstrated that intraperitoneal injection into guinea pigs of F(ab')2 fragments of PG-1, a murine monoclonal antibody recognizing the guinea pig homologue of human platelet glycoprotein Ib, produces virtually complete functional block of the platelet von Willebrand factor receptor without inducing a hemorrhagic state. To assess the ability of this antibody to protect against thrombosis resulting from laser-induced injury to mesenteric small arteries, we injected guinea pigs with either PG-1 F(ab')2 (2.3 mg/kg) or with buffer alone 24 hours before study. For each animal, four mesenteric vessels were studied consecutively for 15 minutes each. The number of thrombi, time to first thrombus, and time to embolization of first thrombi were recorded. In the control animals most individual vessels had three to four thrombi, whereas in the antibody-treated animals, vessels most frequently had only a single thrombus or even none at all. The mean number of thrombi per vessel in the antibody-treated animals (1.125) was significantly lower than the mean in the control animals (3.40), with p less than 0.001. However, there was no significant difference between groups with respect to time to first thrombus after laser injury. Detachment of thrombi in the control animals occurred in an easily recordable, discrete fashion, with 75% of first thrombi embolizing in less than 5 minutes. In the antibody-treated animals, gradual dissolution rather than discrete detachment was typically observed. In 31% of the vessels studied in these animals, no embolus occurred; for the remaining vessels only 9% of thrombi were observed to embolize within 5 minutes of their formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Miller
J L
JL
Department of Pathology, SUNY Health Science Center 13210.
Thiam-Cisse
M
M
Drouet
L O
LO
D000818:Animals; D000911:Antibodies, Monoclonal; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic; D006168:Guinea Pigs; D006487:Hemostasis / Q000187:drug effects*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D013927:Thrombosis / Q000503:physiopathology / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C028254:von Willebrand factor receptor