Whole blood anticoagulant effects of Sulodexide as measured by activated clotting time and their neutralization by Protamine sulfate

Objective Porcine mucosal heparin has been conventionally used and still continues to be used in medical and surgical indications. In view of the current shortage of heparin there is a need to develop a suitable alternative. The purpose of this study is to compare the anticoagulant effects of Sulodexide and its protamine neutralization profiles in the activated clotting time (ACT).

Material and Methods Under an IRB approved protocol and following a double-syringe technique, blood was drawn in labeled syringes containing 200 ul of Sulodexide batches 1056,1285,2516.2604,3274,4190 (obtained from Alfa Sigma). In order to study neutralization by protamine sulfate, 200ul of Sulodexide (1056) at a final concentration of 50,25,10 µg/ml, together with 200 ul of protamine sulfate at final concentration of 25ug/ml was placed in a separate set of labeled syringes. After gently mixing the contents of the syringes, ACT was immediately performed and the clotting time recorded in seconds.

Results All 6 different Sulodexide batches showed a concentration-dependent anticoagulant response. At a final concentration of 6.2 µg/ml the ACT response observed was Sulodexide-1056 (189 ± 21 seconds), sulodexide-1285(179 ± 13 sec), sulodexide-2516(191± 9 sec), sulodexide-2604(181± 3 sec), sulodexide-3274 (173 ± 7 sec), sulodexide- 4190 (180± 2sec),compared to a saline control value of 138 ±2 seconds. At a final c concentration of 12.5 µg/ml the ACT response observed was Sulodexide-1056 (240 ± 5 seconds), sulodexide-1285(241 ± 8 sec), sulodexide-2516(253 ± 12 sec), sulodexide-2604(202 ± 5 sec), sulodexide-3274 (235 ± 9 sec), sulodexide- 4190 (221 ± 4 sec),compared to a saline control value of 134 ± 4 seconds. At a final concentration of 50 µg/ml, the ACT response observed was Sulodexide-1056 (451 ± 55 seconds), sulodexide-1285(367 ± 20 sec), sulodexide-2516(373 ± 10 sec), sulodexide-2604(368 ± 17 sec), sulodexide-3274 (377 ± 13 sec), sulodexide- 4190 (375 ± 11 sec),compared to a saline control value of 140 ± 5 seconds.

Conclusion Sulodexide at concentrations of 6.25-50 µg/ml (0.62–5.0 USP/ml) produced comparable anticoagulant effects to heparin which were neutralized by protamine sulfate. These results validate the hypothesis that Sulodexide can be used as a substitute anticoagulant for heparin.

Publikationsverlauf

Artikel online veröffentlicht:
18. Juni 2021