Treatment of Experimental Venous Stasis Model in Rats by Heparin and a Very Low Molecular Weight Heparin Fragment. Relationship to Plasmatic Heparin Activity

Abstract

In this work we investigated the possible relationship between plasmatic activity and antithrombotic activity of a Low Molecular Weight Heparin Fragment (CY222, Choay-Paris) compared with Heparin (Hep). A randomized administration of both test drugs was carried out on 198 rats receiving 4 different dosages (4,2,1 or 0.5 mg/Kg b.w.) or a placebo solution (normal saline). A ligature of the inferior vena cava was performed on rats at T = OH and test drugs were administered subcutaneously at T - 2H. Blood and thrombus samples were taken at T = 6H. For all the tests the Heparin level was computed from a standard curve made up of known amounts of the 3 rd STANDARD HEPARIN (W.H.O.).The statistical study between plasmatic and antithrombotic activities was conducted in 2 steps: 1°) search for linear statistical correlation (correlation factor R, independence test T)For Hep: Thrombin Clotting Time: R = −0.26, T = 0.38, p<0.01; APTT: R = −0.28, T = −2.56, p<0.01; Anti-Xa (chromogenic method CBS 31.39):R = 0.48, T = −4.70, p<0.01; Anti-Xa (Hepaclot, Stago):R = −0.35 T = −3.24, p<0.01; Anti-Xa (Heptest, Haemachem, INC): R = −0.36, T = −3.21, p<0.01; Anti-IIa (chromogenic method CBS 34.47): R = −0.32, T = -2.84, pCO.Ol; For CY222: Anti-Xa (chromogenic method): R = −0.23, T = −1.80, p=0.07; Anti-IIa (chromogenic method): R = −0.26, T = −2.07, p<0.05; 2°) a multivariate regression between thrombus weight (mg) and the plasmatic activity of both the test drugs: For Hep Anti-Xa (chromogenic method): F = 14.56 For CY222 Anti-IIa (chromogenic method): F = 14.40 and Anti-Xa (chromogenic method): F = 5.96.In conclusion, we observe a statistical correlation between Anti-IIa activity and thrombus regression. These parameters may use in human Low Molecular Weight Heparin therapy.