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Biomedical subjects

J Hirsh

Publications and source records attributed to J Hirsh.

At least 289 records · Page 16Linked to original sources
PubMed1989

Antithrombotic and bleeding effects of glycosaminoglycans with different degrees of sulphation.

We recently reported that the in vitro anticoagulant activities of dermatan sulphate and heparan sulphate were improved with increased sulphation. In this study we determined how the degree of sulphation of glycosaminoglycans influences their antithrombotic and bleeding effects in vivo. We compared the antithrombotic effects of each glycosaminoglycan by measuring their ability to inhibit experimentally-induced thrombus formation in rabbit jugular veins. The bleeding effect of each glycosaminoglycan was measured by comparing their ability to increase the amount of 51Cr-blood lost from five standardized cuts in rabbit ears. Increased sulphation only improved the antithrombotic effects of dermatan sulphate and heparan sulphate. In contrast, increased sulphation enhanced the blood loss associated with all the glycosaminoglycans evaluated. We conclude that the antithrombotic effects of heparan sulphate and dermatan sulphate can be enhanced by increased sulphation, but that the improved antithrombotic effects are compromised by the concomitant increase in bleeding side-effects.

Animals↗
PubMed1989

Effects of dermatan sulfate and heparin on inhibition of thrombus growth in vivo.

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.

Animals↗
PubMed1989

Anticoagulants during pregnancy.

Anticoagulant therapy during pregnancy is problematic because both heparin and oral anticoagulants can potentially produce adverse maternal and fetal effects. Reviewing the relevant literature makes it clear that heparin is safer for the fetus than are oral anticoagulants. For the prophylaxis and treatment of venous thromboembolic disease in pregnant patients, heparin is the preferred anticoagulant because its efficacy and safety are established. However, because the efficacy of heparin in preventing systemic embolism in patients with prosthetic heart valves is not established, either adjusted-dose heparin or a combination of heparin and oral anticoagulants can be used.

Abnormalities, Drug-Induced↗
PubMed1989

Prevention of venous thrombosis in patients undergoing major orthopaedic surgical procedures.

A summary of the relative effectiveness of the various prophylactic approaches is shown in Table 13. From this it can be seen that for studies comparing active prophylaxis with no prophylaxis, aspirin was relatively ineffective, while dextran, oral anticoagulants and low dose heparin were approximately equally effective, each being associated with a risk reduction of approximately 50 per cent. Low dose heparin and DHE showed a risk reduction of 52 per cent in one study, while LMWH showed a risk reduction of 72 per cent.

Anticoagulants↗
PubMed1989

Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control.

In a randomized trial of neurosurgical patients, groups wearing graduated compression stockings alone (group 1) or graduated compression stockings plus intermittent pneumatic compression (IPC) (group 2) were compared with an untreated control group in the prevention of deep vein thrombosis (DVT). In both active treatment groups, the graduated compression stockings were continued for 14 days or until hospital discharge, if earlier. In group 2, IPC was continued for seven days. All patients underwent DVT surveillance with iodine 125-labeled fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became abnormal. Deep vein thrombosis occurred in seven (8.8%) of 80 patients in group 1, in seven (9.0%) of 78 patients in group 2, and in 16 (19.8%) of 81 patients in the control group. The observed differences among these rates are statistically significant. The results of this study indicate that graduated compression stockings alone or in combination with IPC are effective methods of preventing DVT in neurosurgical patients.

Clinical Trials as Topic↗
PubMed1989

A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip.

A randomized trial was carried out with 194 patients to compare the effectiveness of sodium warfarin or aspirin with that of placebo in the prevention of venous thromboembolism after surgery for fractured hip. Prophylaxis was commenced postoperatively and continued for 21 days or until patient discharge, whichever was earlier. All patients underwent surveillance with iodine 125-fibrinogen leg scanning and impedance plethysmography, with subsequent venography. Venous thromboembolism occurred in 13 patients (20.0%) in the warfarin group, 27 patients (40.9%) in the aspirin group, and 29 patients (46.0%) in the placebo group. Proximal vein thrombosis or pulmonary embolism occurred in 6 patients (9.2%) in the warfarin group, 7 patients (10.6%) in the aspirin group, and 19 patients (30.2%) in the placebo group. The results of this study show that sodium warfarin therapy is safe and effective in preventing thromboembolic complications in patients undergoing surgery for fractured hip, and that aspirin therapy is an equally safe and effective method for preventing proximal vein thrombosis or pulmonary embolism.

Adult↗
PubMed1989

Detection of previous proximal venous thrombosis with Doppler ultrasonography and photoplethysmography.

To evaluate the reliability of two noninvasive tests, the photoplethysmograph (PPG) and venous Doppler ultrasound, in determining the presence or absence of previous proximal deep vein thrombosis (DVT), we performed a blinded retrospective cohort study of patients with objectively confirmed (DVT+) or refuted (DVT-) previous episodes of suspected DVT. Twenty-nine of 33 DVT+ patients had abnormal PPG and/or reflux by venous Doppler ultrasound, whereas 39 of 49 DVT- patients had normal PPG and no Doppler reflux (sensitivity, 88%; specificity, 80%). Of 33 DVT+ patients, 20 had abnormal Doppler results (sensitivity, 61%), in contrast to 46 of 49 DVT- patients with normal results (specificity, 94%). Moreover, 23 of 33 DVT+ patients showed abnormal PPG results (sensitivity, 70%), whereas 40 of 49 DVT- patients had normal PPG (specificity, 82%). Based on our findings, the presence of Doppler reflux is specific for previous proximal DVT, whereas a combination of normal PPG and Doppler ultrasound is reliable for excluding previous proximal DVT. Abnormal PPG with normal Doppler ultrasound does not reliably predict the presence or absence of previous DVT. However, this occurred in only 16 of 82 patients. Therefore, the combination of PPG and venous Doppler ultrasound can reliably predict the presence or absence of previous proximal DVT in most patients.

Female↗
PubMed1989

Intermittent compression units for the postphlebitic syndrome. A pilot study.

The postphlebitic syndrome is a common affliction with limited therapeutic options. Patients who fail to respond to treatment with graded elastic compression stockings often develop a chronic pain syndrome manifested by intractable pain and swelling. Because lymphedema, a condition also associated with leg pain and swelling, has been successfully treated by intermittent compressive therapy with an extremity pump, we conducted a pilot study of compressive therapy in patients with severe postphlebitic syndrome. All five patients studied had dramatic improvement in symptoms and functional status without side effects. Although a large randomized trial is needed to properly evaluate compressive therapy, it appears to be very effective in selected patients.

Adult↗
PubMed1989

Heparin therapy during pregnancy. Risks to the fetus and mother.

The true maternal and fetal risks of heparin therapy during pregnancy are unknown, because most published studies are small and do not report consecutively treated patients. In order to address these issues, we performed a retrospective cohort study of 100 pregnancies in 77 women treated with heparin during pregnancy. In 98 pregnancies heparin therapy was given for the prevention or treatment of venous thromboembolism; in the remaining 2, because of prosthetic heart valves. The rates of prematurity, abortions, stillbirths, neonatal deaths, and congenital abnormalities were similar to those in the normal population. There were two bleeding episodes and no symptomatic thrombotic episodes associated with heparin therapy. We conclude that maternal heparin therapy is safe for the fetus and is associated with an acceptable bleeding rate and a low rate of thrombotic recurrence in the mother.

Abnormalities, Drug-Induced↗
PubMed1988

Heparin clearance and ex vivo recovery in newborn piglets and adult pigs.

The newborn infant requires more heparin per kg body weight than the adult to achieve similar heparin plasma levels. Possible mechanisms include altered heparin pharmacokinetics and/or a decreased expression of anticoagulant activity of heparin in new-born plasma because of low levels of antithrombin III (AT-III). We measured the pharmacokinetics and the anticoagulant activity of heparin in the pig (AT-III level: 100%), in the piglet (levels of AT-III: 50% of adult) and the piglet given exogenous porcine AT-III. All pigs were bolused with 125I-heparin (25 or 100 units/kg) and blood samples collected for the measurement of 125I-radioactivity, and antifactor Xa activity. The half-life of 125I-heparin was dose-dependent and similar in pigs and piglets; however, the volume of distribution was greater in the newborn resulting in an increased total clearance compared to the pig. The anti-factor Xa activity disappeared earlier in the piglet than in the pig. Both the kinetics and the absolute recovery of anti-factor Xa activity were normalized to pig values (after correction for different volumes of distribution) when the piglets were infused with exogenous AT-III. Thus apparent heparin resistance of the newborn is due to both an increased volume of distribution and the low AT-III level which limits the measurement of the anticoagulant activity of heparin in conventional anti-factor Xa assays.

Aging↗