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Orgaran (Org 10172): its pharmacological profile in experimental models
1Organon Scientific Development Group, Oss, The Netherlands.
Haemostasis
|January 1, 1992
Summary
Orgaran, a glycosaminoglycan mixture, shows potent antithrombotic activity with a high anti-factor Xa to anti-thrombin ratio. It effectively prevents venous thrombosis extension with less bleeding risk than heparin.
Area of Science:
- Biochemistry
- Pharmacology
- Thrombosis Research
Background:
- Orgaran is a glycosaminoglycan mixture derived from animal mucosa, containing heparan, dermatan, and chondroitin sulfate.
- A small fraction of Orgaran's heparan sulfate exhibits high affinity for antithrombin III (AT III).
- Orgaran is distinct from heparin and low-molecular-weight heparins, lacking heparin or its fragments.
Purpose of the Study:
- To characterize the anticoagulant and antithrombotic properties of Orgaran.
- To compare Orgaran's efficacy and safety profile with heparin and low-molecular-weight heparins.
- To elucidate the mechanisms underlying Orgaran's antithrombotic activity.
Main Methods:
- In vitro assays to measure inhibition of factor Xa and thrombin.
- Assessment of antithrombin III (AT III) and heparin cofactor II (HC-II) involvement.
- In vivo experimental models to evaluate antithrombotic efficacy and bleeding enhancement.
- Studies on platelet function and degranulation.
Main Results:
- Orgaran significantly catalyzes the inactivation of factor Xa and thrombin.
- It exhibits a higher anti-factor Xa/anti-IIa ratio compared to heparin and LMWHs.
- Orgaran demonstrates potent antithrombotic effects, comparable to heparin, particularly in preventing venous thrombosis extension, with reduced bleeding risk and minimal impact on platelet function.
Conclusions:
- Orgaran possesses significant anticoagulant and antithrombotic properties mediated by AT III and HC-II.
- Its high anti-Xa/anti-IIa ratio and favorable safety profile (less bleeding, preserved platelet function) suggest potential therapeutic advantages over heparin.
- Orgaran is a promising therapeutic agent for preventing and treating thrombotic events.