chondroitin and Hemorrhage

The prophylactic effect of a semisynthetic heparin analogue (SSHA) on deep vein thrombosis was investigated in a prospective double-blind multicentre trial. 440 major general surgical and gynaecological patients were randomized to one of three treatment groups: 50 mg SSHA, 37.5 mg SSHA and 5000 units sodium heparin subcutaneously 12-hourly. Deep venous thrombosis (DVT) was diagnosed with the fibrinogen uptake test and verified with phlebography. Bleeding complications and other side-effects were carefully monitored. There were no significant differences between the three treatment groups of patients in age, sex, type of operation or risk factors. A DVT was diagnosed in 16 patients (12 per cent) in the SSHA 50 mg group, in 21 patients (15 per cent) in the SSHA 37.5 mg group and 21 patients (14 per cent) in the heparin-treated group. No significant differences were found in the number of patients who bled unexpectedly in the postoperative period, required transfusion or developed wound haematomas. Blood loss at operation was similar in all three groups. Three pulmonary emboli were diagnosed by pulmonary scintigraphy, one in each group.

Topics: Adult; Aged; Anticoagulants; Chondroitin; Chondroitin Sulfates; Double-Blind Method; Female; Hemorrhage; Heparin; Humans; Intraoperative Complications; Male; Middle Aged; Postoperative Complications; Prospective Studies; Random Allocation; Risk; Surgical Procedures, Operative; Thrombophlebitis

Topics: Animals; Blood Coagulation Tests; Chondroitin; Dermatan Sulfate; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparin; Heparitin Sulfate; Male; Rabbits; Thrombosis

Heparin and dermatan sulphate are effective antithrombotic agents but the clinical use of heparin is complicated by haemorrhage. The haemorrhagic effect of dermatan sulphate is unknown. In this study we compared the antithrombotic, haemorrhagic and anticoagulant effects of heparin and dermatan sulphate in rabbits. The antithrombotic effect was measured as prevention of venous thrombus formation. The haemorrhagic effect was measured as 51Cr-blood loss from standardized cuts in rabbit ears. The anticoagulant effect was measured as changes in the APTT, TCT and circulating anti-factor Xa level, and the formation of 125I-thrombin/inhibitor complexes ex vivo. The effect of heparin and dermatan sulphate on collagen-induced platelet aggregation was measured ex vivo. Maximal antithrombotic effects of heparin and dermatan sulphate were achieved with 70 and 500 micrograms/kg respectively. A 20-fold increase in heparin dose caused an 8-fold increase in blood loss and higher doses (40- and 80-fold increases) caused further dose-related increases in blood loss (13- and 35-fold increases respectively). In contrast, a 20- to 40-fold increase in the antithrombotic dose of dermatan sulphate did not increase blood loss and an 80-fold dose increase caused only a 7-fold increase in blood loss. There was no relationship between the antithrombotic and haemorrhagic effects of either heparin or dermatan sulphate and their anticoagulant activities. In contrast, there was a relationship between the dose-related enhancement of blood loss by these glycosaminoglycans and the inhibition of collagen-induced platelet aggregation ex vivo. These results suggest that dermatan sulphate is less haemorrhagic than heparin at equivalent antithrombotic doses, and that the haemorrhagic effect is associated with a glycosaminoglycan-induced platelet defect.

Topics: Animals; Blood Coagulation; Chondroitin; Dermatan Sulfate; Dose-Response Relationship, Drug; Factor X; Factor Xa; Hemorrhage; Heparin; Platelet Aggregation; Rabbits; Thrombosis

Topics: Animals; Bone Marrow; Chondroitin; Erythropoiesis; Hematocrit; Hemorrhage; Indium; Mononuclear Phagocyte System; Rabbits; Radioisotopes

Topics: Abnormalities, Drug-Induced; Age Factors; Animals; Basement Membrane; Chondroitin; Female; Fetus; Graft Rejection; Hemorrhage; Heparin; Histocompatibility; Immunosuppressive Agents; Male; Mice; Mice, Inbred Strains; Placenta; Pregnancy; Skin; Skin Transplantation; Sulfates; Time Factors; Transplantation Immunology; Transplantation, Homologous; Trophoblasts

Topics: Abnormalities, Drug-Induced; Alkaline Phosphatase; Autoradiography; Blood Chemical Analysis; Body Weight; Bone and Bones; Cartilage; Cartilage, Articular; Chondroitin; Dextran Sulfate; Dextrans; Fractures, Bone; Guinea Pigs; Hemorrhage; Heparin; Osteoporosis; Pathology; Pharmacology; Rabbits; Rats; Research; Sulfur Isotopes; Toxicology; Wound Healing