chondroitin and Thrombophlebitis

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

Platelet aggregation, lipoprotein lipase activity, coagulation parameters and routine blood chemistry were measured in a randomised study of 21 surgical patients before, immediately after and 3 months after operation. Sodium heparin 5000 IU was given subcutaneously to 11 patients every 12 hours for 7 days, the first injection 2 hours preoperatively; 10 patients received a semi-synthetic heparin analogue (SSHA 75 mg) in the same manner. The groups were sex and age matched. No conclusive changes were found in platelet aggregation. The increase in lipoprotein lipase activity in SSHA patients 2 hours after injection was significantly greater than in heparin patients. Neither of the two drugs induced significant changes in coagulation parameters or routine blood chemistry. The results indicate a difference in the effect on lipoprotein lipase release between heparin and SSHA at the used dosage schedules.

Topics: Aged; Anticoagulants; Blood Coagulation Tests; Chondroitin; Chondroitin Sulfates; Female; Heparin; Humans; Lipoprotein Lipase; Male; Platelet Aggregation; Postoperative Complications; Thrombophlebitis

To test the possibility that different doses of heparin or other sulfated polysaccharides are required to inhibit thrombosis initiated by different stimuli, we compared the effects of heparin (HEP), pentosan polysulfate (SP54) and dermatan sulfate (DS) on the inhibition of thrombus formation induced by either I) tissue thromboplastin; II) thrombin; or III) factor Xa. Inhibition of thrombus formation induced by the stimuli was measured in a rabbit jugular vein hypercoagulation/stasis model. First, we determined the minimum dose of each sulfated polysaccharide which inhibited tissue thromboplastin-induced thrombus formation by approximately 75%, and then compared the relative effectiveness of this dose to prevent thrombus formation initiated with the other two stimuli. HEP and SP54 were less effective when thrombin was the thrombogenic stimulus, while DS was more effective. HEP was the most effective agent when factor Xa was the stimulus. We conclude that the antithrombotic effectiveness of a given dose of a sulfated polysaccharide may vary depending on the stimulus which initiates thrombus formation.

Topics: Animals; Chondroitin; Dermatan Sulfate; Factor Xa; Female; Fibrinolytic Agents; Heparin; Male; Pentosan Sulfuric Polyester; Polysaccharides; Rabbits; Serine Proteinase Inhibitors; Thrombin; Thrombophlebitis; Thromboplastin

The effects of dermatan sulfate and heparin on inhibition of fibrin accretion onto existing thrombi as related to their ex vivo anticoagulant activity and abilities to inhibit increased prothrombin clearance induced by thrombi were investigated. Our results indicate that for equivalent anti-thrombin activities, dermatan sulfate is a more effective inhibitor of fibrin accretion onto existing thrombi than is heparin. These observations raise the possibility that in some clinical conditions dermatan sulfate, rather than heparin, may be a better antithrombotic agent of choice. This beneficial effect of dermatan sulfate appears to be unrelated to anti-factor Xa activity either endogenous to dermatan sulfate itself (which is unlikely since it does not catalyze factor Xa inhibition) or to anti-factor Xa activity associated with other glycosaminoglycans released into the circulation following dermatan sulfate administration since this activity is less than that associated with heparin treatment. It is more likely that dermatan sulfate mediates this beneficial effect by more effectively inhibiting thrombin within a thrombus than can heparin. This possibility is supported by the ability of dermatan sulfate to normalize prothrombin consumption in animals with existing thrombi.

Topics: Animals; Chondroitin; Dermatan Sulfate; Factor Xa; Female; Fibrin; Heparin; Kinetics; Male; Prothrombin; Rabbits; Serine Proteinase Inhibitors; Thrombin; Thrombophlebitis

It has been suggested that glycosaminoglycans (GAG) such as heparan sulphate (HS), dermatan sulphate (DS), chondroitin-4-sulphate and chondroitin-6-sulphate contribute to the nonthrombogenic properties of the vascular wall. We have investigated the potential role of DS and HS as antithrombotic agents in an experimental model of stasis-induced venous thrombosis in rats. We utilized a range of doses of both DS and HS (0.25-4 mg/kg BW) to test both their antithrombotic activity and potential bleeding effects. The results were evaluated with reference to an unfractionated heparin (0.5-2 mg/kg BW). We report that the antithrombotic activity of DS is not related to its anticoagulant activity as measured by the activated partial thromboplastin time (APTT), thrombin time (TT) and anti-Xa tests. The dose of DS which was able to inhibit thrombus formation by 70% did not prolong the bleeding time measured using two techniques (template and tail transection); in contrast, with HS a prolongation of both times could clearly be seen. On the other hand, standard unfractionated heparin, at a dose which is equipotent to that of DS in preventing thrombus formation, significantly prolonged the bleeding time. These results suggest that DS may be a useful antithrombotic agent with a lower haemorrhagic effect than heparin, unlike HS which expresses a haemorrhagic risk similar to heparin.

Topics: Animals; Bleeding Time; Chondroitin; Dermatan Sulfate; Heparitin Sulfate; Male; Rats; Rats, Inbred Strains; Thrombophlebitis; Vena Cava, Inferior

In this study, the anticoagulant and antithrombotic properties of unfractionated heparin (UFH) and dermatan sulphate (DS) were compared. The ability of UFH and DS to impair thrombin generation in vitro and in ex vivo plasma samples was also studied. DS has minimal anticoagulant activity by conventional assays but impairs thrombin generation both in vitro and in ex vivo plasma samples. However, thrombin generation could not be suppressed below about 35% of control values at all doses of DS studied. While this was sufficient to impair experimental venous thrombosis during 10 minutes' stasis, DS was ineffective in preventing thrombosis following 20 minutes' stasis in doses up to 1.25 mg/kg. In contrast, 1 microgram/ml of UFH completely suppressed thrombin generation in vitro, and 150 micrograms/kg prevented thrombogenesis over a period of 20 minutes' stasis. Neither drug prolonged the bleeding time (BT) at effective antithrombotic doses, but 2.5 mg/kg UFH significantly increased the BT, whereas DS did not. While DS has antithrombotic activity, it is less effective than UFH in inhibiting thrombin generation, and as an antithrombotic agent.

Topics: Animals; Anticoagulants; Chondroitin; Dermatan Sulfate; Fibrinolytic Agents; Heparin; Humans; In Vitro Techniques; Rabbits; Thrombin; Thrombophlebitis

Deep vein thrombosis in the leg and pelvis was seen in a 26-year old woman during the seventh month of pregnancy. 20 days after initial administration of heparin sodium, a local, markedly progressing erythema and induration was observed at the subcutaneous injection sites. The same cutaneous reactions occurred after application of heparin calcium. Following oral anticoagulation treatment with phenprocoumon, the patient was treated towards the end of pregnancy and directly post partum with a low-molecular semisynthetic heparin analogue without any side effects. The skin test again showed good tolerance of another heparin analogue and a low-molecular heparin.

Topics: Adult; Anticoagulants; Chondroitin; Chondroitin Sulfates; Drug Eruptions; Female; Heparin; Humans; Leg; Pelvis; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Trimester, Third; Thrombophlebitis