heparitin-sulfate and Cerebrovascular-Disorders

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

To compare the baseline National Institutes of Health Stroke Scale (NIHSS) score and the Trial of Org 10172 in Acute Stroke Treatment (TOAST) stroke subtype as predictors of outcomes at 7 days and 3 months after ischemic stroke.. Using data collected from 1,281 patients enrolled in a clinical trial, subtype of stroke was categorized using the TOAST classification, and neurologic impairment at baseline was quantified using the NIHSS. Outcomes were assessed at 7 days and 3 months using the Barthel Index (BI) and the Glasgow Outcome Scale (GOS). An outcome was rated as excellent if the GOS score was 1 and the BI was 19 or 20 (scale of 0 to 20). Analyses were adjusted for age, sex, race, and history of previous stroke.. The baseline NIHSS score strongly predicted outcome, with one additional point on the NIHSS decreasing the likelihood of excellent outcomes at 7 days by 24% and at 3 months by 17%. At 3 months, excellent outcomes were noted in 46% of patients with NIHSS scores of 7 to 10 and in 23% of patients with scores of 11 to 15. After multivariate adjustment, lacunar stroke had an odds ratio of 3.1 (95% CI, 1.5 to 6.4) for an excellent outcome at 3 months.. The NIHSS score strongly predicts the likelihood of a patient's recovery after stroke. A score of > or =16 forecasts a high probability of death or severe disability whereas a score of < or =6 forecasts a good recovery. Only the TOAST subtype of lacunar stroke predicts outcomes independent of the NIHSS score.

Topics: Anticoagulants; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Female; Follow-Up Studies; Glasgow Coma Scale; Heparitin Sulfate; Humans; Male; National Institutes of Health (U.S.); Probability; Time Factors; Trauma Severity Indices; Treatment Outcome; United States

While previous studies suggest that the peak time period for the occurrence of ischemic stroke is in the mid- to late-morning hours, detailed information pertaining to circadian variations among the various stroke subtypes has been limited. The purpose of our study was to define the circadian patterns of symptom onset in an acute stroke trial with an established system for stroke subtype classification.. An analysis was conducted on 1272 patients enrolled in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) study. All patients had a documented time of stroke symptom onset, and all stroke subtype determinations were made by a single rater.. The Greatest portion of atherothrombotic strokes (25.7%), cardioembolic strokes (30.5%), and strokes of other/unknown mechanism (27.1%) occurred between 6:01 AM and 12:00 noon. The greatest portion of lacunar strokes (31.6%) were present on awakening. More than one half of the infarcts in this series were either present on awakening or occurred in the mid- to late-morning hours. The correlation between stroke subtype and time of symptom onset did not reach statistical significance (P=0.07, Pearson's chi(2) method).. Although there is a trend for clustering of ischemic stroke in the morning hours, there is insufficient specificity to predict with any reasonable likelihood the stroke subtype according to the circadian pattern of symptom onset.

Topics: Anticoagulants; Brain Ischemia; Cerebrovascular Disorders; Chondroitin Sulfates; Circadian Rhythm; Dermatan Sulfate; Forecasting; Heparitin Sulfate; Humans

TOAST is a multicenter, randomized, placebo-controlled clinical trial testing the usefulness of a new antithrombotic drug in improving the outcome of persons with acute ischemic stroke. Until recently, no clinical trial testing a treatment for ischemic stroke had demonstrated efficacy in outcome. Design problems of previously conducted trials with inconclusive results may partly explain their failures. During the design of TOAST, the investigators addressed several issues so the trial could test the treatment accurately. We report the strategies used in designing, implementing, and coordinating the trial.

Topics: Adult; Aged; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Fibrinolytic Agents; Heparitin Sulfate; Humans; Male; Middle Aged; Research Design; Treatment Outcome

Aim of our study was to compare heparan sulphate and acetylsalicylic acid (ASA) in the secondary prevention of cerebrovascular events. Eighty patients with recent episodes of RIA or minor stroke of atherothrombotic origin were randomized in two groups of 40, one treated with heparan sulphate and the other with ASA. The two groups were homogeneous for age, sex, clinical history and type of events qualifying for enrollment. After a 6-month follow-up no difference was found in fatal or non fatal vascular events. The incidence of adverse reactions was significantly lower in the heparan sulphate group. All the patients showed a trend towards improvement in cognitive functioning, but a significant improvement in attentional functions was observed only in the heparan sulphate group. As hypothesis, it may be supposed that such clinical results depend on a better perfusion of inner watershed cerebral areas.

Topics: Aged; Aged, 80 and over; Aspirin; Cerebrovascular Disorders; Female; Fibrinolytic Agents; Follow-Up Studies; Heparitin Sulfate; Humans; Ischemic Attack, Transient; Male

In a double-blind, randomised trial Org 10172 low-molecular-weight (LMW) heparinoid was compared with placebo in the prevention of deep-vein thrombosis in patients with acute thrombotic stroke. Prophylaxis was started within 7 days of the onset of stroke with a loading dose of 1000 anti-factor-Xa units intravenously followed by a fixed dose of 750 anti-factor-Xa units twice a day subcutaneously; it was continued for 14 days or until hospital discharge, if earlier. 50 patients were randomised to receive Org 10172 and 25 to receive placebo. All patients underwent surveillance with I125-fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became positive. Venous thrombosis occurred in 2 of 50 patients (4.0%) given Org 10172 and 7 of 25 patients (28.0%) given placebo (p = 0.005); the corresponding rates of proximal-vein thrombosis were 0% and 16%, respectively (p = 0.01). There was one major haemorrhage in the Org 10172 group and one minor bleed in the placebo group.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Chondroitin Sulfates; Clinical Trials as Topic; Dermatan Sulfate; Female; Fibrinolytic Agents; Follow-Up Studies; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Radiography; Random Allocation; Thrombosis; Time Factors

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

We evaluated the safety and possible efficacy of large doses of the heparinoid ORG 10172 in 57 patients with acute or progressing ischemic stroke. Patients received a loading bolus of the drug followed by a maintenance intravenous infusion for 7 days. The plasma level of ORG 10172 was monitored by the degree of inhibition of coagulation factor Xa. In general, the drug was well tolerated and few hemorrhagic complications occurred. Two patients with large cardioembolic hemispheric strokes had intracranial hemorrhagic complications. Most patients improved during treatment. By 3 months after the stroke, 37 patients (65%) had a favorable outcome (minimal or no residual disability). This study suggests that high-dose intravenous infusions of ORG 10172 can be safely given to patients with acute ischemic stroke.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Ischemia; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparitin Sulfate; Humans; Injections, Intravenous; Middle Aged; Pilot Projects

An intravenous infusion of a low molecular weight heparinoid, with a reduced risk of hemorrhage, may be an alternative to heparin in the management of acute ischemic stroke. To evaluate this hypothesis, we studied the safety of the heparinoid, ORG 10172, in a dose-escalation study in 26 patients. The drug was administered as a loading bolus followed by a 7-day infusion in five rates with target anti-factor Xa levels from 0.2 to 1.0 U/ml. The drug was well tolerated; no major bleeding complications or thrombocytopenia occurred. There were no deaths or hemorrhagic transformation of cerebral infarctions. The results indicate that ORG 10172 at doses to achieve a level of 1.0 U/ml or less may be used safely in management of acute cerebral infarction.

Topics: Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Female; Glycosaminoglycans; Hemorrhage; Heparinoids; Heparitin Sulfate; Humans; Male; Middle Aged; Molecular Weight

A new heparinoid, Org 10172, was given to five patients with hemorrhagic stroke with thromboembolic complications. Treatment did not cause progression of cerebral bleeding, and thrombotic processes were inhibited. No side effects were encountered.

Topics: Aged; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Female; Fibrinolytic Agents; Glycosaminoglycans; Heparitin Sulfate; Humans; Male; Middle Aged; Thromboembolism