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Thromb Haemost 1994; 71(05): 663-669
DOI: 10.1055/s-0038-1642500
Review Article
Schattauer GmbH Stuttgart

Aprotinin Could Promote Arterial Thrombosis in Pigs: a Prospective Randomized, Blind Study

Ch M Samama
1   The Département d’Anesthésie, Hôpital Pitié, Paris, France
,
E Mazoyer
2   INSERM U 353, Institut des Vaisseaux et du Sang, Paris, France
,
P Bruneval
3   Département d’Anatomo-Pathologie, Hôpital Broussais, Paris, France
,
P Ciostek
2   INSERM U 353, Institut des Vaisseaux et du Sang, Paris, France
,
Ph Bonnin
4   Laboratoire d’Explorations fonctionnelles, Hôpital Lariboisière, Paris, France
,
M Bonneau
5   N.N.R.A, Jouy-en-Josas, France
,
J Roussi
2   INSERM U 353, Institut des Vaisseaux et du Sang, Paris, France
,
O Bailliart
4   Laboratoire d’Explorations fonctionnelles, Hôpital Lariboisière, Paris, France
,
G Pignaud
2   INSERM U 353, Institut des Vaisseaux et du Sang, Paris, France
,
P Viars
1   The Département d’Anesthésie, Hôpital Pitié, Paris, France
,
J P Caen
2   INSERM U 353, Institut des Vaisseaux et du Sang, Paris, France
,
L O Drouet
2   INSERM U 353, Institut des Vaisseaux et du Sang, Paris, France
› Author Affiliations
Further Information

Publication History

Received 07 September 1992

Accepted after revision 17 January 1994

Publication Date:
06 July 2018 (online)

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Summary

Haemostatic properties of aprotinin could be associated with an increased risk of thrombosis. A randomized, blinded study was conducted to consider the potential thrombogenicity of aprotinin, using the Fobs’ model on femoral arteries in 12 pigs. The flow variations were measured by a pulsed Doppler in anaesthetised animals. Ear immersion bleeding time was performed. During the first part of the study, a stenosis was performed successively on both femoral arteries, each for a period of 30 min, without prior injury, to assess the integrity of the vessel, and to check that the arteries did not develop cyclic flow reductions (CFR), permanent cessation of flow (PCF) or partial thrombosis, when a stenosis is applied. Then the clamp was released and a bolus of placebo (saline), or aprotinin (4 millions KIU, followed by a continuous infusion of 1 million KIU · h−1), was administered. At the end of the bolus, the second part of the study began. Stenosis was applied to the arteries. If CRF, PCF, or partial thrombosis were observed without prior injury then the infused drug (aprotinin or saline) was considered a prothrombotic drug, and the opposite artery was studied. For each animal, right and left femoral artery segments were fixed and studied (morphologic study). Eighteen arteries were studied. In the aprotinin group, 6 arteries out of 8 developed an unexpected thrombosis, as compared with only 2 out of 10 arteries in the control group (p = 0.02). The morphologic study confirmed the occurrence of thrombosis in 4 out of 7 arteries in the aprotinin group, as compared with only 1 out of 9 in the control group. The ear immersion bleeding time was not different in either group. No difference could be demonstrated with regard to the values of activated partial thromboplastin time, prothrombin time and fibrinogen.

Aprotinin may have promoted the development of thrombosis in the pig.

 

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