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Biomedical subjects

A S Gallus

Publications and source records attributed to A S Gallus.

At least 73 records · Page 4Linked to original sources
PubMed1980

Heparin stability: effects of diluent, heparin activity, container, and pH.

The effects have been studied of diluent, heparin activity after dilution, container, and pH on the stability of heparin solutions stored under conditions resembling those present during heparin infusion by intravenous drip or syringe pump. Heparin activity was measured by activated partial thromboplastin time and thrombin clotting time (and, in one set of studies, also by factor Xa inhibitor assay and protamine sulphate neutralisation). Heparin activity was stable for 6 hours regardless of storage conditions. After 24 hours heparin activity was stable when the drug was diluted in 0.9% saline and stored in plastic, but a small loss of activity was observed in several studies after dilution in 5% dextrose or storage in glass. A more extensive comparison confirmed a 3-5% loss in heparin activity over 24 hours after dilution in 5% dextrose. Changing the pH to 3.5 or 10.0 had little effect on storage stability. We conclude that heparin activity in vitro remains stable during short infusions but recommend dilution in 0.9% saline and a plastic container when a heparin solution is infused over 24 hours.

Drug Packaging↗
PubMed1979

Guidelines for the management of oral anticoagulant therapy in patients undergoing surgery.

The management of patients who require surgery while being treated with oral anticoagulants is a difficult balance between the risks of bleeding and those of recurrent thromboembolism. The urgency and the extent and site of surgery are important considerations, as are the strength of the indication for anticoagulants and the degree of anticoagulation. A practical approach is outlined for various situations that may be encountered.

Administration, Oral↗
PubMed1979

Antiplatelet drugs: clinical pharmacology and therapeutic use.

Because platelets are so important in thrombus formation, drugs which inhibit platelet function (the 'antiplatelet drugs') have considerable potential as antithrombotic agents. Among the antiplatelet drugs, only aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine, and clofibrate have had wide clinical trial. Their effects on platelet metabolism differ. Aspirin prevents platelet prostaglandin synthesis by acetylating and irreversibly inactivating platelet prostaglandin synthetase, while sulphinpyrazone is a reversible inhibitor of the same enzyme. Both aspirin and sulphinpyrazone impair the platelet release reaction and reduce platelet aggregation, but neither prevents platelet adhesion to the subendothelium or to foreign surfaces. On the other hand, dipyridamole reduces platelet adhesion as well as aggregation, probably by inhibiting phosphodiesterase and so raising platelet cyclic AMP levels. The effects of hydroxychloroquine and clofibrate have been less well defined. As the antiplatelet drugs form a diverse group of substances with differing effects on platelet function, it is hardly surprising that every potential clinical application of each antiplatelet drug or drug combination has had to be tested separately, and that these drugs have not proved to be equally effective. One or more antiplatelet drugs have now been evaluated in each of the following situations.

Blood Platelets↗
PubMed1976

Prevention of venous thrombosis with small, subcutaneous doses of heparin.

The effect of low-dose heparin prophylaxis on venous thrombosis and bleeding after major elective surgery was studied in a prospective controlled study of 820 patients. The total incidence of venous thrombosis detected with leg-scanning using fibrinogen labeled with radioactive iodine (125I) was reduced from 16.0% in the control group to 4.2% in treated patients. More important, the incidence of popliteal or femoral vein thrombosis was reduced from 2.9% to 1.0%. Prophylaxis resulted in a slight increase in bleeding-minor wound hematoma, mean volume of blood transfused, and a post-operative hematocrit fall in treated patients. However, increased bleeding was clinically minor, and prophylaxis was well tolerated.

Fibrinogen↗
PubMed1976

Prevention of venous thromboembolism.

Of the various prophylactic agents evaluated, four have been found to be effective. These are oral anticoagulants, low-dose heparin, mechanical devices which increase venous blood-flow in the leg, and Dextran. Oral anticoagulants have been shown to be effective in patients having abdominal, thoracic, or hip surgery, when treatment was started either before surgery or in the immediate postoperative period. They have also been shown to be effective in medical patients. The evidence derives from studies which showed that treatment can reduce total mortality, prevents venous thromboembolism detected clinically or at autopsy, and prevents thrombosis diagnosed with venography. On the other hand, the incidence of thrombosis diagnosed by 125I-fibrinogen scanning was not reduced when oral anticoagulants were started just before or just after surgery. This suggests that oral anticoagulant treatment starting in the immediate postoperative period may not prevent formation of the initial thrombotic nidus, but is clinically effective because it prevents extension of the nidus to form a significant thrombus. Bleeding has been a significant complication in almost all studies of surgical patients, and this is the major factor which has prevented widespread use of oral anticoagulant prophylaxis. In addition, the need for careful laboratory monitoring makes this approach inconvenient and adds to its expense. Low-dose heparin has been shown to be effective in general surgical and medical patients, but results have been inconclusive in patients having elective hip surgery, and this approach is probably ineffective in patients with hip fracture. In general surgical patients, low-dose heparin prophylaxis has been shown to prevent pulmonary embolism diagnosed at autopsy examination or with lung scanning, and calf and thigh vein thrombosis diagnosed with 125I-fibrinogen leg-scanning. A slight, but statistically significant, increase in the frequency of wound hematoma and a greater postoperative hematocrit fall have been reported when heparin was given three times daily, but not with the twice daily heparin injection regimen. In these studies, low-dose heparin was given without laboratory control of its anticoagulant effect, so that this prophylactic approach is simple, but the need for subcutaneous injections is a disadvantage of this approach. Results with methods which increase venous blood-flow in the leg have varied, depending on the technic used. Active measures, such as intermittent pneumatic calf compression or peroperative electrical calf muscle stimulation, have been shown to prevent thrombosis detected with 125I-fibrinogen leg-scanning. However, while the evidence suggests that both methods are effective in relatively low risk patients, they may have limited value in the high risk patient who is confined to bed for a long time. These methods are free of side effects and relatively inexpensive, but intermittent calf compression, in particular, is slightly cumbersome...

Abdomen↗
PubMed1976

Heparin kinetics in venous thrombosis and pulmonary embolism.

The response to a standard dose of heparin was studied in 20 patients with venous thromboembolism. The heparin regimen consisted of intravenous injection of 70 units per kg, followed after 90 minutes by a maintenance dose of 400 units per kg per 24 hours given by continuous infusion. Plasma heparin activity and the activated partial thromboplastin time (APTT) were measured at intervals to determine clearance of the initial injection and the response to maintenance dose. Large inter-individual variations were found in the anticoagulant effect and these were due in part to differences in heparin clearance and in part to differences in the APTT response to given amounts of heparin (heparin effect index). The heparin half-life was 63 +/- 15 minutes when plasma heparin activities were used for this calculation and 84 +/- 71.5 minutes when the APTT was used. These results are similar to values previously reported in normal volunteers. Four of the 20 patients had pulmonary embolism and in these heparin half-life was significantly shortened (P less than 0.005).

Adult↗
PubMed1976

Impedance plethysmography using the occlusive cuff technique in the diagnosis of venous thrombosis.

Impedance plethysmography using the cuff technique has been compared with venography in 346 consecutive patients with suspected venous thromboembolism. The limbs were classified according to the venographic results as no thrombosis, proximal (popliteal, femoral, or iliac) vein thrombosis, and calf thrombosis. A discriminant analysis was performed. The impedance plethysmographic result was normal in 386 of 397 limbs which were normal on venography, a specificity of 97%, and abnormal in 124 of 133 limbs which showed proximal vein thrombosis, a sensitivity of 93%. Seventy-three of 88 limbs with calf vein thrombi and a normal impedance plethysmographic result. The sensitivity in 29 limbs with asymptomatic proximal vein thrombosis was 83%. Impedance plethysmography is an accurate method for detecting proximal vein thrombosis but has limitations which include the possibility of false positive results due to arterial insufficiency and muscle tension.

Adolescent↗
PubMed1976

Antithrombotic drugs: part I.

There are three categories of antithrombotic agents: drugs which prevent fibrin fromation (the anticoagulants and defibrinating enzymes), drugs which prevent platelet adhesion or aggregation (the antiplatelet drugs), and thrombolytic drugs which induce fibrin degradation. Clinical studies have now led to a better understanding of the relative value of these drugs in different thrombotic disorders. In addition, knowledge of the mechanism of action of some of these drugs has recently been much advanced. The anticoagulant drugs in clinical use are heparin and the oral anticoagulants. Heparin is a potent inhibitor of several steps on the intrinsic coagulation pathway through its effect on a plasma cofactor, antithrombin III. its action is immediate, but heparin must be given parenterally. Oral anticoagulants act more slowly, by reducing the hepatic synthesis of biologically active factors II, VII, IX and X, but can be given by mouth. Heparin is therefore most suitable for starting anticoagulant treatment, while oral anticoagulants are generally used for prolonged therapy. The value of the anticoagulants as antithrombotic agents has been best assessed by studying their effectiveness in preventing and treating venous thromboembolic disease. Oral anticoagulants have been repeatedly shown to prevent venous thrombosis and pulmonary embolism in patients at high risk of developing these complications. However, the increased risk of postoperative bleeding has prevented their widespread use for this purpose in surgical patients. Recently, the use of low doses of heparin, given subcutaneously before and after surgery, has been shown to markedly reduce the incidence of venous thrombosis and pulmonary embolism (including fatal pulmonary embolism) after major elective abdominal surgery, and to produce only a slight increase of postoperative bleeding. This represents a major advance in anticoagulant prophylaxis of venous thromboembolism insurgical patients. However, low dose heparin prophylasix is relatively ineffective in patients having hip surgery, and has not been evaluated in patients having other types of orthopaidic surgery. There is direct evidence that antocoagulant therapy prevents death and recurrent embolism in patients who have developed pulmonary embolism, and considerable indirect evidence that it prevents pulmonary embolism, and considerable indirect evidence that it prevents pulmonary embolism (and death from pulmonary embolism) in patients who have venous thrombosis. The incidence of further venous thromboembolism or bleeding during treatment appears to be minimised when heparin is given by continuous intravenous infusion in a dose sufficient to produce a moderate, but no excessive, prolongation of a heparin-sensitive, in vitro coagulation test. The tests most commonly used to monitor heparin therapy was based on either the whole blood clotting time or the activated partial thromboplastin time...

Anticoagulants↗
PubMed1976

Antithrombotic drugs: part II.

The defibrinating agent ancrod has had limited clinical trial, but appears to give no advantages over heparin. Intravenous infusion of dextran, a glucose polymer, has been shown to have an antithrombotic effect in many experimental models of thrombosis. However, the evidence that dextran is a clinically valuable antithrombotic drug is conflicting. A number of controlled randomized studies have shown that dextran can prevent postoperative venous thromboembolism when a large volume of dextran 40 or 70 was infused rapidly during and after surgery. However, blood volume expansion during dextran treatment prohibits its use in patients with reduced cardiac reserve, and infrequent though sometimes severe, allergic reactions have been reported. Evidence that dextran is of value for the treatment of venous or arterial thromboembolism comes from uncontrolled studies and is not convincing. Many compounds have been shown to inhibit platelet function in vitro but only five of these drugs have been extensively evaluated as prophylactic or therapeutic antithrombotic agents in man. These are aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine and clofibrate. They have been evaluated mainly in patients with cerebral vascular disorders, coronary artery disease, peripheral artery ischaemia, venous thromboembolism, prosthetic heart valves, and in patients with arteriovenous shunts. The evaluation of the clinical effect of the platelet function suppressing drugs is in its early stages, but they appear to differ from each other in the spectrum of their clinical effectiveness, and they may be more effective in arterial than in venous thromboembolic disorders. Their role in the management of cerebral vascular disease and coronary artery disease is still uncertain, and should be clarified by the results of a number of multi-centre, prospective, randomized studies which are currently in progress. Three types of thrombolytic drugs have been evaluated clinically; the plasminogen activators streptokinase and urokinase, proteolytic enzymes such as plasmin, and agents which increase the level of endogenous plasminogen activator (e.g. anabolic steroids). Of these, the plasminogen activators now have a definite place in clinical practice. The plasminogen activators accelerate the lysis of recent venous thrombi and pulmonary emboli, and of arterial thrombi or emboli. Thrombolytic therapy with these agents should be considered particularly in patients with recent major pulmonary embolism, as lysis of recent emboli is rapid and substantial. It should also be considered in patients with recent extensive venous thrombosis, because total lysis of venous thrombi has been reported to result in long-term preservation of valve function, and is likely to prevent postphlebitic syndrome, though this has not been proven. However, plasminogen activator therapy carries a higher risk of bleeding than heparin treatment...

Anabolic Agents↗
PubMed1975

125-I-labeled fibrinogen scanning. Use in the diagnosis of venous thrombosis.

Venous thrombosis is often asymptomatic in patients in whom major pulmonary embolism develops. When used expectantly, iodine 125-labeled fibrinogen scanning is a very sensitive method for detecting subclinical leg vein thrombi. Fibrinogen scanning is less useful for the diagnosis of established venous thrombosis, but is valuable for detecting extension of venographically diagnosed calf vein thrombosis. The technique is safe if fibrinogen is obtained from carefully screened donors. The limitations of the method include its inability to distinguish between superficial and deep venous thrombi, and its sensitivity to fibrin in hematoma and inflammatory exudates. Though the results agree closely with those of phlebography, scanning seems less reliable for detecting femoral vein than calf vein thrombi and is insensitive to thrombi above the inguinal ligament. Screening for these major thrombi may be improved by combining fibrinogen scanning with impedance plethysmography or ultrasonic examination.

Blood Donors↗