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Biomedical subjects

J Hirsh

Publications and source records attributed to J Hirsh.

At least 91 records · Page 5Linked to original sources
PubMed1998

Use of antithrombotic agents during pregnancy.

Anticoagulant therapy is indicated during pregnancy for the prevention and treatment of VTE, for the prevention and treatment of systemic embolism in patients with mechanical heart valves, and, in combination with aspirin, for the prevention of pregnancy loss in women with APLA and previous pregnancy losses. Several questions concerning anticoagulant therapy remain unanswered. Oral anticoagulants are fetopathic, but the true risks of the warfarin embryopathy and CNS abnormalities are unknown. There is some evidence that warfarin embryopathy occurs only when oral anticoagulants are administered between the 6th and the 12th weeks of gestation and that oral anticoagulants may not be fetopathic when administered in the first 6 weeks of gestation. Oral anticoagulant therapy should be avoided in the weeks before delivery because of the risk of serious perinatal bleeding caused by the trauma of delivery to the anticoagulated fetus. The safety of aspirin during the first trimester of pregnancy is still a subject of debate. There is a concern about the efficacy of unfractionated heparin in the prevention of arterial embolism in pregnant women with mechanical heart valves. Finally, the role of LMWH and heparinoids and appropriate dosing have still to be determined. Because it is safe for the fetus, heparin is the anticoagulant of choice during pregnancy for situations in which its efficacy is established. The evidence for the efficacy of heparin for the prevention and treatment of VTE disorders during pregnancy is based on level IV studies. There is some doubt that heparin is effective for the prevention of systemic embolism in patients with mechanical heart valves. Low doses of heparin or poorly controlled heparin therapy are not effective in preventing systemic embolism in patients with mechanical heart valves.

Administration, Oral↗
PubMed1998

The occurrence of subsequent malignancy in patients presenting with deep vein thrombosis: results from a historical cohort study.

BACKGROUND: Several studies have reported that patients who present with idiopathic deep vein thrombosis (DVT) have an increased risk of subsequently developing cancer. A clinical trial had previously been conducted examining the optimal duration of oral anticoagulant therapy following initial heparin treatment in patients with proximal DVT. METHODS: A historical cohort study was performed on patients enrolled in the duration of anticoagulant trial. Patients known to have cancer at the time of entry into the trial were excluded. The qualifying DVTs were classified as idiopathic (no known associated risk factors) or secondary without knowledge of subsequent recurrent venous thrombosis or cancer. The patients were then followed for the development of cancer. RESULTS: Thirteen (8.6%) of the 152 patients in the idiopathic cohort subsequently developed cancer compared to eight (7.1%) of 112 patients in the secondary cohort, P = 0.86. Two (5.4%) of 37 patients with recurrent venous thromboembolism and 19 (8.4%) of 227 patients without recurrent thromboembolism developed cancer, P = 0.7. CONCLUSION: Our study did not detect an increased risk of subsequent cancer in patients presenting with idiopathic DVT compared to secondary DVT; nor did we detect an increased incidence of cancer in patients with recurrent venous thromboembolism. Further studies are required prior to pursuing a policy of aggressive screening for cancer in patients with idiopathic venous thromboembolism.

Administration, Oral↗
PubMed1998

The effects of standard and low molecular weight heparin on bone nodule formation in vitro.

Previously, we demonstrated in a rat model of heparin-induced osteoporosis that low molecular weight heparin (LMWH) produces less bone loss than unfractionated heparin, and that only heparin increases osteoclast number and activity. In contrast, both heparin and LMWH were found to decrease osteoblast function to a similar extent, possibly because at the doses tested both agents produced maximal inhibition. To examine the relative effects of heparin and LMWH on osteoblast function more closely we used an in vitro bone nodule assay, together with measurements of alkaline phosphatase (ALP) activity. Both agents inhibited bone nodule formation and ALP activity in a concentration-dependent manner, but 6 to 8-fold higher concentrations of LMWH were required to achieve equivalent effects. The effect of heparin on osteoblast function was both chain-length and negative charge-dependent because the ability of defined heparin fragments to inhibit nodule formation correlated with their molecular weight (r = 0.98), and N-desulfated heparin was less inhibitory than heparin. In contrast, the effect of heparin on osteoblast function was pentasaccharide-independent because heparin with low affinity for antithrombin had similar activity to heparin with high antithrombin activity. These findings help to explain mounting clinical evidence that the risk of osteoporosis is lower with LMWH than with heparin.

Animals↗
PubMed1998

Recent clinical trials in the treatment of venous thromboembolism and unstable angina with low molecular weight heparins.

Low molecular weight heparins (LMWHs) have a more predictable anticoagulant response, better bioavailability when administered by subcutaneous injection, and a longer plasma half-life than unfractionated heparin. Consequently, LMWHs can be administered by subcutaneous injection, once daily, without laboratory monitoring. When used in this way, LMWHS are as safe and effective as unfractionated heparin administered by continuous intravenous infusion with laboratory monitoring for the treatment of venous thrombosis and pulmonary embolism, and at least as safe and effective as unfractionated heparin for the treatment of unstable angina. Three recent studies demonstrated that because of their improved pharmacokinetic properties, LMWHs can be used to treat selected patients with venous thrombosis in the out-of-hospital setting.

Angina, Unstable↗
PubMed1998

A novel antithrombin-heparin covalent complex: antithrombotic and bleeding studies in rabbits.

Heparin has been used extensively for prophylaxis and treatment of deep vein thrombosis. However, heparin has several limitations including a short intravenous half-life, inability to inhibit clot-bound thrombin, and bleeding. We have developed a covalent antithrombin-heparin complex (ATH) that has a longer intravenous half-life and greater anticoagulant activity than heparin. The antithrombotic activity of ATH was tested in a rabbit jugular vein thrombosis treatment model. Administration of ATH caused a 17% reduction in clot weight compared with an increase of 24, 60, 172 and 135% for administration of antithrombin plus heparin, heparin, antithrombin and saline, respectively. Clot weight and fibrin accretion were both significantly lower in the ATH group than in the antithrombin plus heparin group (P < 0.05). The peak anti-factor-Xa activity was fourfold higher in the ATH group than in the antithrombin plus heparin group. Using a rabbit bleeding ear model, there was no significant difference in cumulative blood loss between ATH and antithrombin plus heparin groups, at similar plasma anti-factor-Xa levels. In conclusion, ATH has superior antithrombotic activity and similar bleeding effect compared with heparin on a mass basis. The enhanced antithrombotic activity of ATH may be a result of its increased anticoagulant activity or its longer half life, or both.

Animals↗
PubMed1997

The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis.

OBJECTIVE: To prospectively test the hypothesis that a diagnosis of deep vein thrombosis can be excluded in outpatients who present with clinical indications of deep vein thrombosis and whose results of D-dimer testing and impedance plethysmographic examination on the day of presentation are normal. DESIGN: Prospective cohort study. SETTING: Four university-affiliated hospitals. METHODS: Three hundred ninety-eight consecutive patients with clinical indications of deep vein thrombosis were included in the final analysis. All patients underwent an assessment of pretest probability, bedside D-dimer testing, and impedance plethysmographic examination. In most patients, if the results of D-dimer testing and impedance plethysmographic examination were negative for deep vein thrombosis, anticoagulants were withheld and patients were followed up for 3 months. If the results of one or both tests were abnormal, an examination using venous compression ultrasonography or phlebography was performed. RESULTS: In the majority of patients (69%), the results of D-dimer testing and impedance plethysmographic examination were normal. This combination had a negative predictive value of 98.5% (95% confidence interval, 96.3-99.6) for deep vein thrombosis. CONCLUSION: The results of the D-dimer assay and impedance plethysmographic examination on the day of presentation can be used to treat the majority of outpatients who present with clinical indications of deep vein thrombosis without further testing.

Adult↗
PubMed1997

A histomorphometric comparison of the effects of heparin and low-molecular-weight heparin on cancellous bone in rats.

Long-term heparin treatment causes osteoporosis through, an as yet, undefined mechanism. To investigate this phenomenon and to determine the relative benefits of low-molecular-weight heparin (LMWH) use, we treated rats with once daily subcutaneous injections of either unfractionated heparin (1.0 U/g or 0.5 U/g), the LMWH, Tinzaparin (1.0 U/g or 0.5 U/g), or placebo (saline) for a period of 32 days. The effects on bone were then compared both histomorphometrically and biochemically by measuring urinary type I collagen cross-linked pyridinoline (PYD) and serum alkaline phosphatase, markers of bone resorption and formation, respectively. Histomorphometric analysis of the distal third of the right femur, in the region proximal to the epiphyseal growth plate, demonstrated that both heparin and LMWH decrease cancellous bone volume in a dose-dependent fashion, but that heparin causes significantly more cancellous bone loss than does LMWH. Although both heparin and LMWH decrease osteoblast and osteoid surface to a similar extent, only heparin increases osteoclast surface. In support of these histomorphometric findings, biochemical markers of bone turnover demonstrated that both heparin and LMWH treatment produce a dose-dependent decrease in serum alkaline phosphatase, consistent with reduced bone formation, whereas only heparin causes a transient increase in urinary PYD, consistent with an increase in bone resorption. Based on these observations, we conclude that heparin decreases cancellous bone volume both by decreasing the rate of bone formation and increasing the rate of bone resorption. In contrast, LMWH, causes less osteopenia than heparin because it only decreases the rate of bone formation.

Alkaline Phosphatase↗
PubMed1997

Conserved and sexually dimorphic behavioral responses to biogenic amines in decapitated Drosophila.

A preparation of decapitated Drosophila melanogaster has been used for direct application of drugs to the nerve cord. Serotonin, dopamine, and octopamine stimulate locomotion and grooming, showing distinguishable effects that often are potentiated by addition of the vertebrate monoamine oxidase-inhibitor hydrazaline. Many of the hydrazaline-induced effects are sexually dimorphic, with males showing greater responses than females. Behaviors similar to those induced by dopamine can be induced by application of the vertebrate dopamine D2-like receptor agonist quinpirole, whose effects are also sexually dimorphic. In contrast, vertebrate D2-like and D1-like dopamine antagonists result in akinesic states, and D1-like agonists selectively stimulate grooming. These data indicate that Drosophila nerve cord amine receptors are coupled to reflexive behaviors similar to those stimulated by brain dopamine receptors in vertebrates.

Animals↗
PubMed1997

A comparison of compression ultrasound with color Doppler ultrasound for the diagnosis of symptomless postoperative deep vein thrombosis.

BACKGROUND: Despite advances in primary prophylaxis, venous thromboembolism still occurs in a considerable number of high-risk surgical patients. Screening with conventional ultrasound imaging to detect asymptomatic deep vein thrombosis (DVT) has been suggested as a strategy to improve management of such patients, but it is insufficiently sensitive. We evaluated the ability of color Doppler ultrasound to improve the sensitivity of compression ultrasound in the detection of asymptomatic DVT in high-risk orthopedic patients. METHODS: We prospectively evaluated bilateral compression and color Doppler ultrasound measurements of the entire leg in 204 consecutive patients who underwent elective hip or knee replacement surgery, using contrast venography as the reference test. The sensitivity, specificity, and positive predictive value of the ultrasonography tests were determined. RESULTS: The sensitivity, specificity, and positive predictive value (with 95% confidence intervals [CIs]) of compression ultrasound for the detection of proximal DVT were 60% (39%-81%), 96% (92%-99%), and 71% (48%-89%) respectively. The sensitivity, specificity, and positive predictive value (with 95% CIs) of compression ultrasound for the detection of calf vein thrombosis were 33% (18%-52%), 91% (83%-96%), and 58% (34%-80%), respectively. Color Doppler ultrasonography did not identify any additional proximal or calf vein thrombi to those detected by compression ultrasound alone. The sensitivity for all thrombi was 47% (95% CI, 34%-61%) with a positive predictive value of 65% (95% CI, 48%-79%). CONCLUSIONS: Color Doppler ultrasonography has a moderate to low accuracy for the detection of DVT in patients who have had hip and knee replacement surgery. Color Doppler ultrasonography does not increase the detection rate for asymptomatic DVT over compression ultrasound and thus cannot be recommended as a screening test in this setting.

Hip Prosthesis↗