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Biomedical subjects

J Hirsh

Publications and source records attributed to J Hirsh.

At least 235 records · Page 13Linked to original sources
PubMed1992

Overview of low molecular weight heparins and heparinoids: basic and clinical aspects.

Low molecular weight heparins (LMWHs) are fragments derived by enzymatic or chemical depolymerization of standard heparin (SH). They are approximately one-third the size of SH, with a mean molecular weight of 4,000 to 6,000. LMWHs produce less bleeding for equivalent antithrombotic effects than SH in experimental animals. Clinically LMWHs exhibit different pharmacokinetics than SH; they have much better bioavailability at low doses, a longer half life than SH and clearance pattern which is dose independent. In addition, LMWHs have a more predictable dose response than SH. These differences in pharmacokinetic properties occur because in contrast to SH, LMWHs show minimal binding to endothelium and plasma proteins. Clinical trials have demonstrated that LMWHs are effective and safe for the prevention and treatment of venous thromboembolism. In patients having orthopaedic surgery, LMWHs are more effective than low dose SH, more effective than dextran or warfarin. They are also more effective than SH in preventing venous thrombosis in stroke patients and those suffering spinal injury. In addition, recent studies suggest that LMWHs administered by subcutaneous injection in fixed weight-adjusted doses are at least as effective and safe as adjusted dose SH given by continuous intravenous infusion for the treatment of venous thrombosis.

Animals↗
PubMed1991

Stroke prevention in nonvalvular atrial fibrillation.

There has been considerable uncertainty about the best way to prevent stroke in patients with nonvalvular atrial fibrillation. Recent studies have suggested that low-dose warfarin therapy, in addition to producing fewer bleeding complications, may be as effective as higher-dose therapy in preventing thromboembolic events. Four large, prospective, randomized trials have examined the risks and benefits of warfarin therapy for stroke prophylaxis in patients with nonvalvular atrial fibrillation. All four studies showed a substantially reduced incidence of stroke and a low incidence of significant bleeding in patients treated with warfarin. One of these studies also showed that aspirin reduced the incidence of stroke. The benefits associated with long-term low-dose warfarin therapy appear to exceed the risks for serious bleeding in most patients with atrial fibrillation. Aspirin may be a viable therapeutic option for patients who are unable to take warfarin or for those in subgroups at a low risk for stroke.

Aspirin↗
PubMed1991

The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study.

In order to determine whether an association exists between antiphospholipid antibodies (APLA) and thromboembolic events in patients with systemic lupus erythematosus (SLE), we performed a cross-sectional study of consecutive unselected SLE patients. The occurrence of previous thromboembolic events was determined by investigators blinded to the APLA status of the patients by critical review of objective tests that had been performed at the time of symptomatic presentation and by performing venous Doppler ultrasound of the legs to elicit venous reflux as an indication of previous venous thrombosis. The presence of APLA was determined by coagulation assays for the lupus anticoagulant (LA) using five tests with well-defined control ranges and by ELISA assay for anticardiolipin antibodies (ACLA). These tests were measured on two separate occasions. The results of the study demonstrate a statistically significant association between persistently abnormal ACLA assays and thromboembolic events and a non-significant trend between persistently abnormal LA and thromboembolic events. Transient abnormalities of LA and ACLA were less strongly associated with thromboembolic events. We conclude that in patients with SLE, there is a significant association between thromboembolism and APLA.

Autoantibodies↗
PubMed1991

Heparin.

Explore the source record for details and available documents.

Coronary Disease↗
PubMed1991

Standard and low molecular weight heparin have no effect on tissue plasminogen activator induced plasma clot lysis or fibrinogenolysis.

Although heparin is often given as an adjunct to tissue plasminogen activator (t-PA), the effect of heparin on t-PA induced fibrin(ogen)olysis is controversial. To address this controversy, we examined the effects of standard and low molecular weight heparin (enoxaparine) on both t-PA induced clot lysis and t-PA mediated fibrinogenolysis in a human plasma system. Accordingly, 125I-labeled fibrin clots were incubated in t-PA containing citrated plasma in the presence or absence of these glycosaminoglycans, and the extent of thrombolysis was determined by measuring residual radioactivity of the clots, while B beta 1-42 levels were used as a specific index of fibrinogenolysis. Over a wide range of t-PA concentrations (0.1 to 1.6 micrograms/ml), neither heparin nor enoxaparine influences either t-PA induced clot lysis or t-PA mediated B beta 1-42 generation. These findings suggest that either agent could be used as an adjunct to t-PA without compromising either the thrombolytic potential of t-PA or its clot-selectivity.

Drug Interactions↗
PubMed1991

Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin.

OBJECTIVE: To determine the relative efficacy and safety of low molecular weight (LMW) heparin (Enoxaparin) compared with standard calcium heparin for the prevention of postoperative deep vein thrombosis in patients undergoing elective hip surgery. DESIGN: A double-blind, randomized, controlled trial. PATIENTS: Six hundred sixty-five consecutive patients undergoing hip replacement at five participating hospitals. INTERVENTIONS: Patients received either fixed-dose LMW heparin, 30 mg subcutaneously twice daily, or fixed-dose standard calcium heparin, 7500 units subcutaneously twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge if sooner. MEASUREMENTS: All patients had postoperative I-125-fibrinogen leg scanning and impedance plethysmography. If results of one or both tests were positive, then venography was done. Otherwise, venography was done between day 10 and day 14, or sooner if the patient was ready for discharge. RESULTS: Evaluable venograms were obtained in 258 of the 333 patients randomly assigned to receive LMW heparin and in 263 of the 332 patients assigned to receive calcium heparin. For patients with evaluable venograms, thrombosis was detected in 50 patients (19.4%) who received LMW heparin compared with 61 patients (23.2%) who received standard heparin (difference, -3.8%; 95% CI, -11.1% to 3.6%) (P greater than 0.2). Proximal deep vein thrombosis was detected in 5.4% of the patients receiving LMW heparin and in 6.5% of the patients receiving standard heparin (difference, -1.1%; CI, - 5.2% to 3.3%) (P greater than 0.2). For the entire group of 665 patients, venous thrombosis occurred in 17.1% given LMW heparin and in 19.0% given standard heparin. Hemorrhagic complications occurred in 31 patients (9.3%) given standard heparin and in 17 patients (5.1%) given LMW heparin (difference, 4.2%; CI, 0.3% to 8.2%) (P = 0.035). The relative risk reduction was 45%. The rate of major bleeding in the standard heparin group was 5.7% compared with 3.3% in the LMW heparin group (difference, 2.4%; CI, -1.0% to 5.4%) (P = 0.13). The relative risk reduction was 42%. CONCLUSION: Low molecular weight heparin is significantly less hemorrhagic than standard unfractionated heparin; the difference in the rate of deep vein thrombosis, although not statistically significant (P greater than 0.2), favors the use of LMW heparin.

Adult↗
PubMed1991

Heparin as an adjunctive treatment after thrombolytic therapy for acute myocardial infarction.

The rationale for considering heparin therapy as an adjunct to thrombolytic treatment for patients with acute myocardial infarction is to prevent rethrombosis after successful thrombolysis. The risk of reocclusion is high immediately after thrombolysis because blood flowing through the newly opened coronary artery is exposed to thrombin bound to fibrin in the residual thrombus. Clinical studies of patients with venous thrombosis and acute myocardial infarction indicate that there is a relation between the anticoagulant response to heparin and clinical efficacy and that the concept of a therapeutic heparin level is valid. Subcutaneous doses of approximately 15,000 U twice a day fail to provide an adequate anticoagulant response at 24 hours in the majority of patients, whereas intravenous administration of a bolus of 5,000 U followed by continuous infusion of 30,000 U per 24 hours produces an adequate anticoagulant response at 24 hours in approximately 80% of patients. Studies of patients with myocardial infarction who received streptokinase showed a significant beneficial effect on mortality when 12,500 U of heparin was administered subcutaneously 2 times per day. In contrast, the single largest study evaluating heparin 12,500 U administered subcutaneously 2 times per day as an adjunct to recombinant tissue-type plasminogen activator (rt-PA) treatment did not show a beneficial effect on mortality. However, studies using full-dose intravenous heparin therapy demonstrated that heparin improves patency after coronary thrombolysis with rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A critical review of the relationship between impaired fibrinolysis and myocardial infarction.

To explore the relationship between impaired fibrinolysis and myocardial infarction, we conducted a literature search and reviewed the published data. The results indicate that myocardial infarction has a significant influence on fibrinolytic activity and that impaired fibrinolysis is more frequent in patients who have had a myocardial infarction than in healthy control subjects. Prospective cohort studies indicate that tests for global fibrinolytic activity are not of prognostic value for first or recurrent myocardial infarction. However, high levels of plasminogen activator inhibitor and low levels of tissue plasminogen activator activity were associated with an increased risk of reinfarction in survivors of a first myocardial infarction. Whether this relationship between impaired fibrinolysis and reinfarction is causal or coincidental is unclear. There is evidence that impairment of fibrinolytic activity is more marked in patients with myocardial infarction who have minimal coronary atherosclerosis than in those who have marked atherosclerosis, suggesting that impaired fibrinolytic activity might be of pathogenetic importance in this small subgroup of patients.

Cohort Studies↗
PubMed1991

Rationale for development of low-molecular-weight heparins and their clinical potential in the prevention of postoperative venous thrombosis.

Interest in low-molecular-weight heparins (LMWHs) as potential antithrombotic agents was stimulated by two observations in the mid-1970s and early 1980s. The first was finding that LMWH fractions prepared from unfractionated heparin (UFH) progressively lost their ability to prolong the activated partial thromboplastin time (APTT) while retaining their ability to inhibit Factor Xa. The second was the observation that LMWHs prepared by chemical depolarization of UFH are antithrombotic in experimental animal models but produce less microvascular bleeding in experimental models for an equivalent antithrombotic effect than the UFH from which they are derived. Subsequently, it was shown that LMWHs inhibit platelet function and impair vascular permeability less than standard heparin and that LMWHs have a longer biological half-life than standard heparin. A number of LMWHs have been evaluated in clinical trials in general and orthopedic surgery and in the treatment of venous thrombosis. LMWHs are highly effective in orthopedic surgery, where they appear to be more effective than standard heparin. LMWHs have also been shown to be either as effective or more effective than UFH in preventing postoperative thrombosis following general surgery. In preliminary studies, LMWHs appear to be as effective as standard heparin in the treatment of venous thrombosis, but larger studies are required using clinically relevant outcome measures.

Heparin, Low-Molecular-Weight↗