chondroitin-sulfates and Thrombophlebitis

Topics: Brain Ischemia; Chondroitin Sulfates; Clinical Trials as Topic; Cost-Benefit Analysis; Dalteparin; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; MEDLINE; Thrombophlebitis

Topics: Chondroitin Sulfates; Dermatan Sulfate; Dextrans; Drug Administration Schedule; Drug Combinations; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Pulmonary Embolism; Thromboembolism; Thrombophlebitis

Besides low molecular weight heparins (LMWHs) a number of new antithrombotic agents have been evaluated mainly in the prevention of deep vein thrombosis (DVT) and, to a lesser extent, in the treatment of established DVT. They include the Pentasaccharide, a synthetic ultra LMWH, Dermatan Sulphate, a glycosaminoglycan which activates heparin cofactor II, Orgaran, a mixture of Heparan and of Dermatan Sulphate, Hirulog and Hirudin, two direct thrombin inhibitors. The efficacy and safety of these compounds have been studied in comparison with a placebo or with unfractionated heparin but not with LMWH which is considered as a gold standard for these clinical indications. It is thus difficult at present to appreciate the advantages of these new antithrombotic agents over conventional LMWH therapy.

Topics: Anticoagulants; Antithrombin III; Binding Sites; Chondroitin Sulfates; Clinical Trials as Topic; Dermatan Sulfate; Drug Evaluation, Preclinical; Factor Xa Inhibitors; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Multicenter Studies as Topic; Oligosaccharides; Postoperative Complications; Pulmonary Embolism; Recurrence; Thrombin; Thrombophlebitis

This review covers experimental and clinical experiences with transplantation of allogeneic veins processed by slow rate cooling with 2.5% (W/V) chondroitin sulfate and 1 M dimethylsulfoxide. These results are contrasted with the results obtained using dimethylsulfoxide alone. The short-term patency of experimental autologous (100%) and allogeneic (70-100%) cryopreserved veins may be attributed to the combination of "no-touch" procurement techniques employing the smooth muscle relaxant papaverine, the chondroitin sulfate preservation method, and recipient therapy. Explanted autografts retain many cell and tissue functions. In contrast, explanted allografts demonstrate short-term loss of endothelial cells and smooth muscle function, both of which subsequently return. Clinically there have been positive short-term correlations between good initial runoff from the graft site and 1-year patency (68-74%) and limb salvage (94%) rates. In contrast, grafts with poor initial runoff, composite grafts, or grafts requiring secondary reconstruction resulted in lower 1-year patency (40-44%) and limb salvage (64%) rates. More experience, larger study groups, and longer follow-up are necessary to evaluate the clinical performance of chondroitin sulfate-preserved grafts. In the meantime, chondroitin sulfate-preserved veins are reserved for coronary artery bypass or peripheral bypass patients in the absence of suitable autologous vessels.

Topics: Animals; Chondroitin Sulfates; Cryopreservation; Cryoprotective Agents; Dimethyl Sulfoxide; Humans; Immunosuppression Therapy; Platelet Aggregation Inhibitors; Thrombophlebitis; Transplantation, Autologous; Transplantation, Homologous; Veins

Venous thrombo-embolism is a common complication in patients with acute ischaemic stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been evaluated for the prevention of deep vein thrombosis in patients with acute ischaemic stroke in two studies. In a double-blind study, 75 patients were randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The corresponding rates for proximal deep vein thrombosis were 0 and 16%, respectively (p = 0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. In the second study, the safety and efficacy of Orgaran was compared with unfractionated heparin in the prevention of deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients with marked lower limb paralysis secondary to stroke were randomized to receive Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12-hourly or unfractionated heparin (42 patients) in a dose of 5,000 units subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p = 0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%, respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Glycosaminoglycans; Hemiplegia; Heparin; Heparinoids; Heparitin Sulfate; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Thrombophlebitis

Topics: Animals; Anticoagulants; Blood Coagulation; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Drug Evaluation, Preclinical; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Incidence; Mammals; Molecular Weight; Platelet Aggregation; Postoperative Complications; Rabbits; Renal Dialysis; Thrombocytopenia; Thrombophlebitis; Thrombosis

Type II of heparin-associated thrombocytopenia (HAT) is well known, but the cardinal symptom, thrombocytopenia, is rarely adequately considered. Serious and potential lethal complications such as pulmonary embolism, cerebral stroke, or limb gangrene are often falsely regarded as insufficient anticoagulation. Guided diagnosis and therapy are of vital importance for the patient's outcome. Based on the experience of patients with HAT Type II treated in the intensive care unit, a diagnostic and therapeutic approach to the cardinal symptom thrombocytopenia is presented. A recently developed heparin-induced platelet activation assay (HIPAA) seems to be a highly sensitive laboratory test. The first therapeutic principle in case of presumed and diagnosed HAT is the cessation of unfractioned or low-molecular-weight heparins. ORG 10172 (Orgaran), a low-sulfated heparinoid with a low cross-reactivity (10%) to heparins, can be regarded as the most effective anticoagulant in patients with HAT Type II.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arterial Occlusive Diseases; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Female; Gangrene; Heparin; Heparitin Sulfate; Humans; Middle Aged; Phenprocoumon; Platelet Activation; Platelet Aggregation; Platelet Count; Pulmonary Embolism; Recurrence; Systemic Inflammatory Response Syndrome; Thrombocytopenia; Thromboembolism; Thrombophlebitis

A multicentre, double-blind, randomized study was performed in 179 patients with acute ischaemic stroke resulting in limb paresis. The purpose was to compare the safety and efficacy of Org 10172 (1250 anti-Xa Units s.c. once daily) and heparin sodium (5000 IU s.c. twice daily) in preventing deep-vein thrombosis (DVT). Prophylaxis started within 72 hours of the onset of stroke and continued for at least 9 days. To detect DVT, patients underwent a daily 125I-fibrinogen leg scanning which, if found positive, was followed by venography. A first computed tomography scan of the brain was performed at screening to rule out cerebral haemorrhage and a second at cessation of treatment to detect any haemorrhagic transformations. At the 2-3-months' follow-up period the patients were examined for signs and symptoms of DVT or pulmonary embolism. On an intention-to-treat analysis, DVT occurred in 14.6% of patients receiving Org 10172 and in 19.8% of those receiving heparin during the treatment period (p = 0.392, NS). Pulmonary embolism was diagnosed in one patient in each group. Major conversion to a symptomatic haemorrhagic brain infarct was found in one patient in each group. Death occurred in 13.5% of patients treated with Org 10172 and in 6.7% of patients treated with heparin (p = 0.135, NS). Deaths were mainly related to pulmonary infection and cerebral oedema, thus considered to be due directly to the clinical status of the patients. 1250 anti-Xa Units of Org 10172 once daily is both safe and as effective as 5000 IU of heparin sodium twice daily given for DVT prophylaxis in patients with acute ischaemic stroke of recent onset.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Humans; Injections, Subcutaneous; Male; Thrombophlebitis; Treatment Outcome

This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. "Intent to treat" analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy ("compliant patients") were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Elective Surgical Procedures; Female; Gastrointestinal Neoplasms; Glycosaminoglycans; Hematologic Tests; Hemorrhage; Heparinoids; Heparitin Sulfate; Humans; Lung Neoplasms; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis

Two studies evaluating the effect of Orgaran prophylaxis on the incidence of postoperative thrombosis in hip fracture surgery are reported. In one Scandinavian study, dextran was used in the comparative group, and in the US study, warfarin was used. In both, Orgaran was significantly more effective in reducing the frequency of deep vein thrombosis without producing an increase in bleeding complications or other side effects.

Topics: Aged; Aged, 80 and over; Chondroitin Sulfates; Dermatan Sulfate; Dextrans; Female; Glycosaminoglycans; Hemorrhage; Heparinoids; Heparitin Sulfate; Hip Fractures; Humans; Incidence; Male; Postoperative Complications; Pulmonary Embolism; Scandinavian and Nordic Countries; Single-Blind Method; Thrombophlebitis; United States; Warfarin

Topics: Chondroitin Sulfates; Dermatan Sulfate; Dihydroergotamine; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Hip Prosthesis; Humans; Incidence; Pulmonary Embolism; Single-Blind Method; Thrombophlebitis; Treatment Outcome

Venous thrombo-embolism is a common complication in patients with acute ischaemic stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been evaluated for the prevention of deep vein thrombosis in patients with acute ischaemic stroke in two studies. In a double-blind study, 75 patients were randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The corresponding rates for proximal deep vein thrombosis were 0 and 16%, respectively (p = 0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. In the second study, the safety and efficacy of Orgaran was compared with unfractionated heparin in the prevention of deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients with marked lower limb paralysis secondary to stroke were randomized to receive Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12-hourly or unfractionated heparin (42 patients) in a dose of 5,000 units subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p = 0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%, respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Glycosaminoglycans; Hemiplegia; Heparin; Heparinoids; Heparitin Sulfate; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Thrombophlebitis

In a prospective, randomized, assessor-blind multicentre study two antithrombotic subcutaneous regimens were compared in patients undergoing total hip replacement. Group 1 (154 patients) received 750 anti-Xa units of a new low molecular weight heparinoid (Lomoparan) subcutaneously twice a day and group 2 (155 patients) received 5000 units heparin and 0.5 mg dihydroergotamine (heparin-DHE 5000) twice a day. The incidence of deep vein thrombosis, assessed by routine bilateral venography on day 10 (+/- 1), was 17 and 32 per cent in groups 1 and 2 respectively (risk reduction 47 per cent; P = 0.007). One patient in each group developed a symptomatic pulmonary embolism confirmed by lung scanning. Major bleeding complications occurred in one patient in each group and no significant difference was observed between the two groups with respect to minor bleeding complications. Subcutaneous Lomoparan appears to be as safe as heparin-DHE 5000 at the above doses with regard to bleeding complications, and is more efficacious with respect to venous thrombosis.

Topics: Aged; Blood Loss, Surgical; Chondroitin Sulfates; Dermatan Sulfate; Dihydroergotamine; Drug Combinations; Female; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hip Prosthesis; Humans; Male; Prospective Studies; Thromboembolism; Thrombophlebitis

To compare the relative safety and efficacy of a low-molecular-weight heparinoid (ORG 10172) with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke.. Double-blind randomized trial.. Seven Canadian university-affiliated hospitals.. Eighty-seven patients with acute ischemic stroke resulting in lower-limb paresis.. Patients received either low-molecular-weight heparinoid, 750 anti-factor Xa units twice daily, or unfractionated heparin, 5000 units subcutaneously twice daily. Treatment was continued for 14 days or until hospital discharge if sooner.. Deep vein thrombosis was diagnosed using 125I-labeled fibrinogen leg scanning and impedance plethysmography. Venography was indicated if either test was positive. Overt hemorrhage, major or minor, was assessed clinically.. Venous thrombosis occurred in four patients (9%) given low-molecular-weight heparinoid and in 13 patients (31%) given heparin (relative risk reduction, 71%; 95% CI, 16% to 93%. The corresponding rates for proximal vein thrombosis were 4% and 12%, respectively (relative risk reduction, 63%; P greater than 0.2). The incidence of hemorrhage was 2% in both groups.. Low-molecular-weight heparinoid, given in a fixed dose of 750 anti-factor Xa units subcutaneously twice daily, is more effective than subcutaneous low-dose heparin for the prevention of deep vein thrombosis in patients with acute ischemic stroke.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antithrombin III; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Fibrinolytic Agents; Follow-Up Studies; Glycosaminoglycans; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Thrombophlebitis

We assessed the safety and efficacy of the novel low molecular weight heparinoid Lomoparan (Org 10172) for the prevention of deep-vein thrombosis in patients undergoing elective total hip replacement in a randomized, placebo-controlled, double-blind trial in 197 consecutive patients. The heparinoid (750 anti-factor Xa-units, s.c., b.i.d.) was administered to 97 patients and 99 patients received placebo. Study medication was started preoperatively and continued for 10 days. Efficacy was assessed by bilateral phlebography at day 10, postoperatively. The incidence of deep-vein thrombosis was 56.6% and 15.5% respectively in the placebo and heparinoid treated patients (incidence reduction: 74%; P less than 0.001). This reduction was observed both for proximal-vein thrombosis (25% to 8%; P less than 0.005) and isolated calf-vein thrombosis (31% to 7%; P less than 0.001). No major hemorrhage was observed. The number of red-cell units transfused and drain-fluid loss were comparable for the two study groups. Six patients in the heparinoid group and none in the control group developed minor wound hematomas (P less than 0.05). During an 8-week post-discharge follow-up period three patients with a normal venogram at day 10 developed clinically apparent venous thromboembolism, which was confirmed by objective testing. All three patients belonged to the heparinoid-treated group. We conclude that 750 anti-factor Xa units Org 10172 s.c. twice daily starting preoperatively is safe and effectively reduces early deep-vein thrombosis following elective total hip replacement. Further studies on the incidence of post-discharge thromboembolism are required.

Topics: Aged; Blood Loss, Surgical; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Glycosaminoglycans; Heparitin Sulfate; Hip Prosthesis; Humans; Male; Middle Aged; Safety; Thrombophlebitis

In a randomized, prospective trial, a low-molecular-weight heparinoid (Org 10172 [Lomoparan]) was compared with warfarin for efficacy and safety in preventing deep-vein thrombosis in 263 patients who had an operatively treated fracture of the hip. One group of patients received Org 10172 in a dose of 750 units subcutaneously every twelve hours until the ninth postoperative day; on the seventh postoperative day, warfarin was added to the regimen. The other group received only warfarin. Both drugs were begun preoperatively, immediately after the admission evaluation. In the patients who received warfarin, the desired prothrombin time was one and one-half times the control level. Deep-vein thrombosis was detected by 125I-fibrinogen scanning and impedance plethysmography and was confirmed by phlebography and compression ultrasonography. Deep-vein thrombosis was found in nine (7 per cent) of the 132 patients who received Org 10172 and in twenty-eight (21 per cent) of the 131 patients who received warfarin (p less than 0.001). Adverse reactions were not significantly different in the two groups. Major bleeding complications occurred in eight patients in the Org-10172 group, only four of whom were receiving the drug at the time of bleeding, and in five patients who were receiving warfarin (not significant). There was no difference in intraoperative loss of blood or in requirements for transfusion. We concluded that the low-molecular-weight heparinoid Org 10172 is a safe, convenient, effective antithrombotic agent for the prevention of venous thrombosis after an operation for fracture of the hip.

Topics: Aged; Aged, 80 and over; Blood Loss, Surgical; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparinoids; Heparitin Sulfate; Hip Fractures; Humans; Iodine Radioisotopes; Male; Middle Aged; Molecular Weight; Plethysmography; Postoperative Complications; Prevalence; Prospective Studies; Risk Factors; Thrombophlebitis; Warfarin

A prospective, randomized, assessor-blind trial has been undertaken to compare the thromboprophylactic effect and safety of the heparinoid Org 10172 (a mixture of low molecular-weight sulfated glycosaminoglycuronides) and dextran 70 in patients operated on for hip fracture. Prestudy biostatistical calculations led to the need for 260 patients. Three hundred eight patients were randomized and 19 were excluded after randomization, the majority because of postponed surgery. Analyses were made on the 289 patients on an intention-to-treat basis, as well as on the 247 patients given correct prophylaxis. Diagnosis of deep vein thrombosis was based on bilateral ascending phlebography on postoperative days 10 through 12. The frequency of deep vein thrombosis on an intention-to-treat basis was 10% in the Org 10172 group and 30% in the dextran 70 group and, on the basis of correct prophylaxis, 12% and 31%, respectively, both differences being significant (p less than 0.001). Two-month mortality rates were equal in the groups. Three fatal pulmonary emboli were seen in the dextran group. Significantly more patients in the dextran group received postoperative transfusions; no other differences in various hemorrhagic parameters were seen. Thus it can be concluded that Org 10172 has a significantly better thromboprophylactic effect than does dextran in patients with hip fractures without significant side effects.

Topics: Aged; Aged, 80 and over; Chondroitin Sulfates; Dermatan Sulfate; Dextrans; Female; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparitin Sulfate; Hip Fractures; Humans; Male; Single-Blind Method; Thrombophlebitis

We have measured the effects of Org 10172 (a mixture of naturally occurring glycosaminoglycans derived from hog intestinal mucosa) on blood loss after transurethral prostatectomy (TURP), using doses which are likely to prevent postoperative venous thrombosis (VT). 48 patients entered a double-blind randomised pilot study: 18 were given subcutaneous (sc) injections of a placebo and 30 received sc Org 10172 (750 anti-Xa units/day, 500 units twice daily (bid), or 750 units bid, starting just before TURP and continued until discharge; 10 patients per group). No Org 10172 regimen increased peroperative blood loss but all caused a similar trend towards increased urinary bleeding after surgery. Since there was no apparent dose effect gradient, it was decided to pool the data from all three dosing blocks: this analysis showed that Org 10172 increased geometric mean blood loss during the first 2 days after surgery from 10.4 gm hemoglobin (Hgb; range = 3.2-71) to 20.5 gm Hgb (range = 1.9-147) (p = .005), an effect which retained its significance after allowing for two other major determinants of postoperative bleeding, the weight of prostate resected and the length of surgery, and also when pooling was restricted to the twice daily Org 10172 injection groups and their corresponding controls. Bleeding was not severe, but our results indicate a need for caution when considering the use of Org 10172 in this setting.

Topics: Aged; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Glycosaminoglycans; Hematuria; Hemorrhage; Heparinoids; Heparitin Sulfate; Humans; Male; Middle Aged; Prostatectomy; Randomized Controlled Trials as Topic; Thrombophlebitis; Urologic Diseases

The potential antithrombotic effect of a new low molecular weight heparinoid, Org 10172, was examined in a randomized, double-blind, placebo-controlled, dose-ranging pilot study of the prevention of deep venous thrombosis (DVT) in 45 high-risk patients having major thoracic or abdominal surgery for cancer. Org 10172 was given in doses of 500, 750 or 1000 U bd subcutaneously. DVT occurred in 9 of 14 patients given placebo and in 4 of 11 patients given 500 U bd but in none of the 20 patients given 750 or 1000 U bd. Operative blood loss and post-operative bleeding were not significantly different between the groups but one patient given 1000 U bd had major post-operative bleeding. Average mid-interval and trough plasma anti-Xa levels reached 0.26 and 0.20 U/ml respectively following the highest dose. It is concluded that Org 10172 is a potentially useful antithrombotic agent and that the effective and safe dose appears to be between 500 and 1000 U bd for prevention of DVT in high-risk patients.

Topics: Aged; Aged, 80 and over; Chondroitin Sulfates; Dermatan Sulfate; Factor X; Factor Xa; Female; Glycosaminoglycans; Hemorrhage; Heparitin Sulfate; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Pilot Projects; Research Design; Thoracic Surgery; 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

Mechanical properties of the vein wall are determined by extracellular matrix components, including glycosaminoglycans (GAGs). The aim of the study was to evaluate the activity of enzymes involved in GAGs degradation pathway in the wall of varicose veins and varicose veins complicated by thrombophlebitis, when compared to the wall of normal ones.. Normal, varicose veins and varicose veins complicated by thrombophlebitis were collected during surgical treatment of 10 patients. Activities of endoglycosidases, sulphatases and exoglycosidases were assessed according to colorimetric methods.. Activities of neutral endoglycosidases degrading chondroitin-4-sulphate (C4S) and heparan sulphate (HS) were decreased, whereas activities of neutral endoglycosidases degrading dermatan sulphate and hyaluronic acid were increased in varicose veins and varicose veins complicated by thrombophlebitis. Activities of acidic endoglycosidases degrading C4S and HS were decreased in varicose veins and varicose veins complicated by thrombophlebitis, whereas activity of acidic endoglycosidases degrading chondroitin-6-sulphate was decreased only in varicose veins complicated by thrombophlebitis. Furthermore increased activities of arylosulphatase B, beta-N-acetylhexosaminidase and alpha-L-iduronidase were demonstrated in varicose veins, as well as in varicose veins complicated by thrombophlebitis.. Changed activities of GAGs-degrading enzymes may contribute to previously reported changes in the content and molecular differentiation of GAGs in the wall of varicose veins that may play a role in the disease pathogenesis.

Topics: Adult; beta-N-Acetylhexosaminidases; Chondroitin Sulfates; Colorimetry; Dermatan Sulfate; Female; Glycosaminoglycans; Glycoside Hydrolases; Heparitin Sulfate; Humans; Hyaluronic Acid; Iduronidase; Male; N-Acetylgalactosamine-4-Sulfatase; Saphenous Vein; Sulfatases; Thrombophlebitis; Varicose Veins

Topics: Adult; Antithrombin III; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Heparitin Sulfate; Humans; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombocytopenia; Thrombophlebitis; Ultrasonography, Doppler

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Recombinant Proteins; Thrombocytopenia; Thrombophlebitis

Heparin-induced thrombocytopenia is an immuno-mediated life-threatening side effect of heparin therapy which poses difficulties in diagnosis and major therapeutic problems. Heparin must be instantly discontinued. We describe the case of a 60-year-old male patient with type II heparin-induced thrombocytopenia, complicated by progressive deep venous thrombosis and pulmonary embolism. He failed to improve when therapy was continued with a low molecular weight heparin (Fragmin) and high doses of intravenous immunoglobulins were administered. The test for heparin-dependent platelet aggregation was positive for unfractionated heparin and low molecular weight heparin, but negative for the heparinoid Org 10172. During subsequent anticoagulant therapy with Org 10172 for seven days the number of platelets increased rapidly and the patient recovered. Nine months later Org 10172 was used again in this patient for thrombosis prophylaxis without any adverse effects. In patients with heparin-induced thrombocytopenia requiring immediately acting anticoagulant therapy, Org 10172 can be considered as an effective alternative drug to unfractionated and low molecular weight heparins.

Topics: Anticoagulants; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Dose-Response Relationship, Drug; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Infusions, Intravenous; Male; Middle Aged; Platelet Aggregation; Pulmonary Embolism; Thrombocytopenia; Thrombophlebitis

Venous thromboembolism is a common complication in patients with acute thrombotic stroke. Estimates of the frequency of deep vein thrombosis (DVT) in untreated patients range from 20 to 75%. This wide range reported depends on the methods used to detect DVT and, importantly, on the degree of lower limb paralysis. Most thrombi occur in the paralyzed limbs in which the frequency ranges from 60 to 75%. Of these thrombi, 25% occur in the proximal segment and present a high risk for pulmonary embolism. Indeed, pulmonary embolism is the third most common cause of death in stroke patients and occurs in 1 to 2% of patients who do not receive prophylaxis. A number of methods of preventing DVT have been shown to be safe and effective in stroke patients. These include low-dose heparin, low-molecular-weight heparin, and a heparinoid. Of these, the data with the heparinoid danaparoid provide the most solid evidence for efficacy, and in comparative trials it has been shown to be more effective than heparin.

Topics: Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Randomized Controlled Trials as Topic; Thrombophlebitis

Topics: Abdomen; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Randomized Controlled Trials as Topic; Thrombocytopenia; Thrombophlebitis

A 15-year-old boy developed deep vein thrombosis of the right leg 9 days after appendectomy. In spite of three courses of thrombolysis with streptokinase and effective heparinization the thrombosis progressed with additional occlusion of the left iliac vein. Although platelet counts were constantly normal, heparin-associated thrombocytopenia was suspected as the cause of the new venous occlusions. This diagnosis was confirmed by detecting heparin-associated antibodies with the heparin-induced platelet activation test. Therapy was instituted replacing heparin by the low molecular weight heparinoid Orgaran. Bilateral recanalization occurred within 6 days.. Heparin-associated thrombocytopenia must be considered if thrombosis occurs or progresses despite effective heparinization even in the absence of thrombocytopenia.

Topics: Adolescent; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Humans; Male; Platelet Activation; Thrombocytopenia; Thrombophlebitis

Deep vein thrombosis of the right leg occurred in a 77-year-old woman after percutaneous cardiac catheterization via the right femoral vein, performed to assess mitral valve disease with atrial fibrillation. She thereupon received intravenous heparin (1,000 IU/h; partial thromboplastin time 60-70s). 13 days later she developed a transient incomplete right brachiofacial hemiparesis with motor aphasia. Transthoracic echocardiography revealed a fresh left atrial thrombus. Platelet count fell from initially normal levels to 20 x 10(9)/l. Because type II heparin-associated thrombocytopenia was suspected heparin administration was discontinued and phenprocoumon administered. Heparin-dependent antibodies were demonstrated with the heparin-induced platelet activation test. Cross reactions occurred in vitro against all low-molecular heparins and heparinoid ORG 10172. The platelet count had become normal 17 days later, the leg veins had recanalized and the intraatrial thrombus had become much smaller. The patient declined cardiac surgery and was discharged on the 41st hospital day in satisfactory general condition on maintenance anticoagulant dosage.

Topics: Aged; Antibodies; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Chondroitin Sulfates; Coronary Thrombosis; Dermatan Sulfate; Echocardiography; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Mitral Valve Stenosis; Partial Thromboplastin Time; Phenprocoumon; Platelet Count; Thrombocytopenia; Thrombophlebitis

Topics: Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Terminology as Topic; Thrombophlebitis

Heparin-associated thrombocytopenia (HAT) type II, a severe side effect of heparin therapy, is thought to be induced by an immunological mechanism. By crossreactivity studies we have demonstrated that sera of patients with HAT type II activate platelets in vitro not only after the addition of heparin but also after addition of a chemically polysulphated chondroitin-like substance, Arteparon, used for treatment of degenerative joint disease. In addition here, we describe a patient who developed deep venous thrombosis and pulmonary embolism following administration of Arteparon and typical HAT type II with thrombocytopenia, 36 h after the first administration of heparin. This patient had never received heparin, but had repeatedly been treated with Arteparon for degenerative joint disease. We conclude that this patient had been presensitized by Arteparon, as indicated by his clinical course. In vitro studies again confirm crossreactivity between heparin and Arteparon.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Cross Reactions; Drug Hypersensitivity; Glycosaminoglycans; Heparin; Humans; Male; Middle Aged; Pulmonary Embolism; Thrombocytopenia; Thrombophlebitis

Topics: Aged; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparin; Heparitin Sulfate; Humans; Thrombocytopenia; 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

The pharmacological profile of Org 10172, a mixture of sulphated glycosaminoglycorunans derived from hog intestinal mucosa, has been assessed in experimental thrombosis and bleeding models in rats and compared with heparin USP. Org 10172 inhibited thrombus formation in arterio-venous shunts dose dependently, the dose required for 50% inhibition (ID50) of thrombus formation was 40 anti-Xa units/kg i.v. The ID50 for heparin USP was 70 anti-Xa units/kg i.v. Org 10172 hardly increased bleeding in doses upto 1600 anti-Xa units/kg i.v., whereas heparin USP dose dependently increased bleeding from 90 anti-Xa units/kg i.v. onwards. The benefit (anti-thrombotic)/risk (bleeding) ratio of Org 10172 was therefore considerably better than that of heparin USP. The improved profile of Org 10172 towards bleeding might be caused by differences in the interaction with blood platelets in comparison with heparin USP. Org 10172 had less effect on the platelet content in thrombi than heparin USP. Org 10172 did not inhibit collagen induced release of serotonin in contrast to heparin USP. Org 10172 inhibited factor Xa induced aggregation of rabbit platelets but only at anti-Xa levels which were fifteen times higher than for heparin USP. In contrast to heparin USP Org 10172 had only a very weak effect on the activated partial thromboplastin time (APTT) ex vivo.

Topics: Animals; Blood Coagulation; Blood Platelets; Chondroitin Sulfates; Dermatan Sulfate; Disease Models, Animal; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Male; Platelet Aggregation; Rabbits; Rats; Rats, Inbred Strains; Thrombophlebitis