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132 Thrombolytic effect of pentosan poly-sulphate in animals
58
POSTERS A8: Heparins
131
EFFECT OF ORG 10172 ON FIBRINOLYTIC PARAMETERS FOLLOWING HIP JOINT SURGERY J. A. Conkie. F. McCall. I. D Walker. 1. F. Davidson.’ Department of Haematology. Royal Infirmary. Glasgow. Scotland. A number of reports have suggested that heparin and its low mokcular weight derivatives possess profibrinolytic properties which may contribute to the clinical effectiveness of these compounds. In a randomised, open, group comparison of the heparinoid. ORG 10172. for the prophylaxis of deep venous thrombosis following elective hip-joint surgery. serial blood samples were taken before and during I I days after surgery (or until patient withdrawal from the study). and the levels of fibrinolytic components were determined. Patients admitted to the study received one of three dosage regimes (two injections S.C. daily) or were assigned to a control group: at present, the findings are described for 9. I I and 8 patients from regimes I. 2 and 3. along with a placebo group of 14 patients. Among the parameters measured were euglobulin fibrinolytic activity (EFA) by a fibrin plate method. and TPA. PAI and anti-Xa levels by amidolytic methods.
132
THROMBOLYTIC EFFECT OF PENTOSAN POLY-SULPHATE IN ANIMALS K.-M. Sedlarik and H.-P. Kl&king Experimental Surgery, University of Groningen, The Netherlands and Institute of Pharmacology and Toxicology, Medical Academy Erfurt, GDR To demonstrate the thrombolytic effect of pentosan polysulphatestudies were carried out on a rabbit model of a radiolabelled jugular vein thrombus. At an initial dose of 5 mg/kg followed by infusion of 2.5 mg/kg/h for 3 hours, pentosan polysulphate produced partial thrombolysis corresponding to a loss of abt. 30 % of thrombus-attached 125 I-activity. Control thrombi showed no significant loss of radioactivity with a nominal end lysi?s of 2.5 %. Infusion of pentosan polysulphate after the initial dose to maintain a nearly constant plasma
Ffbrinolysrs @ Longman
(1988) 2, Supp. I. 58-62 Group UK Ltd 1988
I
The post-operative ‘Iibrinolytic shut-down’ following major surgery was confirmed in all groups by an immediate fall in EFA. reaching a minimum on the 2nd post-op. day. This was accompanied by a transient rise in PAI levels which peaked on the 1st post-op. day. while the TPA changes were more variable. The anti-Xa levels achieved by these patients generally reflected the allocated dosage regimes, the maximum levels achieved being 0.14. 0.17 and 0.18 snti-Xa U/ml. When the fibrinolytic parameters were compared between the control group and each of the treated groups at corresponding time points after surgery. no significant differences were found among the groups for EFA. TPA or PAL These suggest that this LMW heparinoid. ORG 10172. has no influence on the endogenous components of the Iibrinolytic pathway in patients following major hip surgery.
concentration level does obviously not enhance the rate of thrombolysis. Similar results were obtained with other plasminogen activator-releasing substances in vivo. In this model, streptokinase causes an almost complete thrombolysis.
POSTERS A8: Heparins
131
EFFECT OF ORG 10172 ON FIBRINOLYTIC PARAMETERS FOLLOWING HIP JOINT SURGERY J. A. Conkie. F. McCall. I. D Walker. 1. F. Davidson.’ Department of Haematology. Royal Infirmary. Glasgow. Scotland. A number of reports have suggested that heparin and its low mokcular weight derivatives possess profibrinolytic properties which may contribute to the clinical effectiveness of these compounds. In a randomised, open, group comparison of the heparinoid. ORG 10172. for the prophylaxis of deep venous thrombosis following elective hip-joint surgery. serial blood samples were taken before and during I I days after surgery (or until patient withdrawal from the study). and the levels of fibrinolytic components were determined. Patients admitted to the study received one of three dosage regimes (two injections S.C. daily) or were assigned to a control group: at present, the findings are described for 9. I I and 8 patients from regimes I. 2 and 3. along with a placebo group of 14 patients. Among the parameters measured were euglobulin fibrinolytic activity (EFA) by a fibrin plate method. and TPA. PAI and anti-Xa levels by amidolytic methods.
132
THROMBOLYTIC EFFECT OF PENTOSAN POLY-SULPHATE IN ANIMALS K.-M. Sedlarik and H.-P. Kl&king Experimental Surgery, University of Groningen, The Netherlands and Institute of Pharmacology and Toxicology, Medical Academy Erfurt, GDR To demonstrate the thrombolytic effect of pentosan polysulphatestudies were carried out on a rabbit model of a radiolabelled jugular vein thrombus. At an initial dose of 5 mg/kg followed by infusion of 2.5 mg/kg/h for 3 hours, pentosan polysulphate produced partial thrombolysis corresponding to a loss of abt. 30 % of thrombus-attached 125 I-activity. Control thrombi showed no significant loss of radioactivity with a nominal end lysi?s of 2.5 %. Infusion of pentosan polysulphate after the initial dose to maintain a nearly constant plasma
Ffbrinolysrs @ Longman
(1988) 2, Supp. I. 58-62 Group UK Ltd 1988
I
The post-operative ‘Iibrinolytic shut-down’ following major surgery was confirmed in all groups by an immediate fall in EFA. reaching a minimum on the 2nd post-op. day. This was accompanied by a transient rise in PAI levels which peaked on the 1st post-op. day. while the TPA changes were more variable. The anti-Xa levels achieved by these patients generally reflected the allocated dosage regimes, the maximum levels achieved being 0.14. 0.17 and 0.18 snti-Xa U/ml. When the fibrinolytic parameters were compared between the control group and each of the treated groups at corresponding time points after surgery. no significant differences were found among the groups for EFA. TPA or PAL These suggest that this LMW heparinoid. ORG 10172. has no influence on the endogenous components of the Iibrinolytic pathway in patients following major hip surgery.
concentration level does obviously not enhance the rate of thrombolysis. Similar results were obtained with other plasminogen activator-releasing substances in vivo. In this model, streptokinase causes an almost complete thrombolysis.