[Oral anticoagulants, dextran or low-dose subcutaneous heparin: which drug should be used for prevention of deep venous thrombosis in patients undergoing surgery?].
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Biomedical subjects
Publications and source records attributed to M Verstraete.
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The metabolism of human antithrombin III (heparin cofactor) was studied in four control subjects, in four subjects with peripheral obliterative arterial disease, in six patients with recent venous thrombosis and in one patient with clinically severe haemophilia A. The labelled antithrombin III has a high specific activity (5.75 units/mg) and displayed a single band on SDS-polyacrylamide gel electrophoresis. On Sephadex G-100 gel filtration the labelled material eluted in the same position as the antithrombin III activity in plasma. Crossed immunoelectrophoresis of a mixture of fresh plasma and labelled antithrombin III against a specific antiserum, revealed a single precipitin line in which radioactivity was concentrated. The changes in electrophoretic mobility of both the plasma antithrombin III and the labelled material following the addition of heparin to the mixture or following coagulation were identical. The purified antithrombin III behaved as a homogeneous protein in the turnover experiments. The plasma radioactivity data were approximated by a sum of two exponential terms and the metabolism of antithrombin III represented by a two compartment mammillary model. Results in the control subjects were as follows: plasma antithrombin III concentration 19.6 +/- 2.3 mg/100 ml; intravascular fraction 0.45 +/- 0.05; fractional catabolic rate 0.55 +/- 0.02 of the plasma pool per day; half-life of the plasma radioactivity 2.83 +/- 0.26 days. Circulating large molecular weight degradation products of labelled antithrombin III could not be detected by Sephadex G-100 gel filtration. No significant differences in these parameters were found in the patients with peripheral arterial insufficiency. The turnover rate of antithrombin III was normal in the patient with haemophilia A. In three patients with venous thrombosis not treated with heparin, the turnover of labelled antithrombin III was in the normal range. In three patients with venous thrombosis, treated with heparin, the plasma radioactivity half-life was significantly shortened (2.13 +/- 0.08 days) and the fractional catabolic rate increased (0.75 +/- 0.05) of the plasma pool per day). In one of these patients, the labelled antithrombin III had been incubated with an equimolar amount of heparin prior to injection. In this patient the plasma radioactivity half-life was in the same range as in the other two patients (2.15 days).
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Plasma fibrinolytic activity, as measured by the fibrin-plate method, is enhanced after a single intravenous administration of 40 mg of furosemide. This effect becomes evident within 30 min and a peak response is attained 6 h after i.v. administration. On successive administration of furosemide, the fibrinolytic effect persists and the second peak becomes manifest again after 6 h. Following the parenteral administration of furosemide there is an initial decrease of urinary urokinase excretion which returns to a normal level after 3 to 6 h. Possible mechanisms which may explain the enhanced fibrinolytic activity after furosemide administration are discussed.
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Notwithstanding the large number of clinical trials, most of them designed and performed according to the requirements of modern clinical pharmacology, only a few firm clinical recommendations on drugs affecting platelet function in the prevention of arterial or venous thrombosis can be made at present. There is no good evidence for the clinical effectiveness of aspirin or any other drug affecting platelet function in patients with peripheral arterial occlusion or after vascular grafting. In cerebrovascular disease there is reasonable evidence that the administration of sulfinpyrazone can significantly reduce cerebral ischemia or mortality, but similar trials performed with aspirin, dipyridamole or clofibrate failed to reveal a significant difference in favor of the experimental treatment. Patients with angina only were shown to benefit from treatment with clofibrate, but prospective trials with dipyridamole or aspirin in the primary or secondary prevention of myocardial infarction did not reveal a significant reduction in morbidity or mortality in the experimental group. Use of a combination of the latter two drugs did, however, reveal a reduction in morbidity and mortality. In patients with prosthetic heart valves, there is firm evidence that dipyridamole and sulfinpyrazone therapy can normalize decreased platelet survival, an effect which has been shown to correlate well with the incidence of thromboembolism. Provided further trials lead to confirmatory conclusions, drugs inhibiting platelet function associated or not with oral anticoagulants may constitute an ideal prophylaxis in patients with a substitute valve. There is still much uncertainty as to whether dipyridamole, given in addition to conventional treatment, benefits patients with membranous or mesangiocapillary glomerulonephritis. The same holds for drugs inhibiting platelet function after kidney or heart transplantation in man. Only scanty reports are available on the usefulness of drugs affecting platelet function in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. Three different types of antiplatelet drugs are available for the prevention of postoperative deep vein thrombosis: dextran, oral drugs also affecting platelet function and heparin administered subcutaneously in small doses. In orthopedic surgery dextran 70 administered before and every second day after surgery was the drug showing the most convincing reduction in the incidence of phlebographically proved deep vein thrombosis. Major orthopedic surgery is precisely the type of surgery in which the effectiveness of small dose heparin is much in doubt and in which the effectiveness of aspirin and dipyridamole is still to be confirmed. In general surgery, use of a combination of 1 g aspirin and 0.225 g dipyridamole daily was shown to offer approximately the same level of protection as small doses of heparin, land these two forms of prevention seem to offer a greater degree of protection than dextran...
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