Low-dose Subcutaneous Heparin Research Articles

Low-Dose Heparin and Deep-Vein Thrombosis after Total Hip Replacement

The effect of subcutaneous low-dose heparin on postoperative deep-vein thrombosis (D.V.T.) (diagnosed by the 125I-labelled fibrinogen test) has been investigated in a trial of 143 patients undergoing the operation of total hip replacement. Two randomized studies were carried out: in one the scanning for D.V.T. was carried out daily for 7 days postoperatively andin the other for 15 days. In both, the incidence of D.V.T. was significantly lower in the heparin-treated patients (P less than 0.005). Bilateral D.V.T. was also prevented (P less than 0.05), through the extension of D.V.T. to the distal veins of the thigh was not significantly reduced. Heparin treatment was, however, followed by a higher incidence of severe postoperative bleeding (P less than 0.02) and wound haematoma formation (P less than 0.005), and the postoperative haemoglobin was significantly lower than in the control group (P less than 0.005). A higher number of transfused blood units was also needed by the heparin treated patients (P less than 0.001).

Plasma heparin levels after low dose subcutaneous heparin in patients undergoing hip replacement.

Plasma heparin levels were measured at 2 and 8 h after 5000 iu of heparin subcutaneously in 43 patients awaiting total hip replacement. At 2 h, 37 patients had plasma levels between 0.05 and 0.15 iu/ml, three patients had more than 0.2 iu/ml, and three had only trace levels. At 8 h, most patients had less than 0.1 iu/ml, and six patients had no detectable plasma heparin. There were no correlations between plasma heparin levels and age, sex, body weight or use of analgesics. Patients with high 2 h plasma heparin levels may bleed at operation, whereas those with very low plasma heparin concentrations may be at risk of post-operative venous thrombosis; it may therefore sometimes be necessary to monitor plasma heparin levels in order to determine the optimal regime in individual cases.

Low-dose perioperative heparin: a survey of its use

Two years ago we discussed the value of various measures, including low-dose subcutaneous heparin, in the prevention of deep-vein thrombosis.1 We concluded that heparin used in this way lowers the incidence of deep-vein thrombosis after most major operations and that it is safe, cheap and simple to administer. Subsequent experience summarised in this issue has confirmed these conclusions. How widely is this treatment now used?

LOW-DOSE SUBCUTANEOUS HEPARIN VERSUS ORAL ANTICOAGULANTS IN THE PREVENTION OF POSTOPERATIVE DEEP-VENOUS THROMBOSIS: A Controlled Clinical Trial

In a controlled clinical trial, using the 125I-fibrinogen test, low-dose subcutaneous heparin was more effective in preventing postoperative deep-venous thrombosis (D.V.T.) than were routine oral anticoagulants. The frequency of thrombosis was 2% (1 out of 50) in the heparin group and 18% (9 out of 50) in the acenocoumarol (nicoumalone) group. This high incidence of thrombosis in patients on oral anticoagulants was unexpected. Earlier reports had shown a significant reduction in clinically evident D.V.T and lethal pulmonary em- bolism found at necropsy. The efficacy of routine oral anticoagulation had not, however, been tested with the help of an objective measure such as the 125I-fibrinogen test. Further investigation comparing these two methods as far as the prevention of lethal pulmonary embolism is concerned is indicated.

EFFECT OF LOW-DOSE HEPARIN ON INCIDENCE OF POSTOPERATIVE PULMONARY EMBOLISM DETECTED BY PHOTOSCANNING

In a double-blind investigation thromboembolic prophylaxis with subcutaneous low-dose heparin was studied in 112 patients admitted for elective major surgery. Pulmonary embolism was diagnosed by photoscanning on the third or fourth day after operation, and plain chest X-rays were taken simultaneously. Deep vein thrombosis (D.V.T.) was detected by the 125I-fibrinogen leg scanning technique. 58 patients were treated with heparin, each receiving 5000 units every 12 hours for 5 days, starting 2-5 hours before operation. In this group 11 patients (19%) had pulmonary embolism and/or D.V.T. Of the 54 patients in the control group 30 (56%) had pulmonary embolism and/or D.V.T. Thus low doses of heparin reduce the incidence of tromboembolism after major surgery.

A DOUBLE-BLIND TRIAL OF LOW DOSES OF SUBCUTANEOUS HEPARIN IN THE PREVENTION OF DEEP-VEIN THROMBOSIS AFTER MYOCARDIAL INFARCTION

A randomised double-blind trial was undertaken in a hundred and fortysix patients with acute myocardial infarction to determine whether low-dose subcutaneous heparin reduced the frequency of deep-venous thrombosis (D.V.T.) in the legs. Low-dose heparin (5000 units 12-hourly) started within 12 hours of the onset of myocardial infarction and continued for 10 days significantly reduced the frequency of D.V.T., diagnosed by the 125I-fibrinogen technique, from 17·2% in the control group to 3·2% in the heparin-treated group. There were no complications of heparin treatment. Since the relation between the prevention of D.V.T., detected with 125I-labelled fibrinogen, and the prevention of pulmonary embolism is uncertain, it would seem reasonable to embark on a larger trial to determine whether the frequency of pulmonary embolism could be reduced with low-dose heparin.

Low-dose subcutaneous heparin in prevention of deep-vein thrombosis

Earlier this year1 we discussed the prevention and treatment of venous thrombosis and concluded that heparin in low dosage seemed the most promising drug for preventing deep-vein thrombosis postoperatively, although the optimum regimen was not yet known. Sharnoff and his associates who began this work 10 years ago claim to have shown that this treatment largely prevents fatal pulmonary embolism.2

LOW-DOSE HEPARIN AFTER MYOCARDIAL INFARCTION

A trial of low-dose subcutaneous heparin in the prevention of deep-vein thrombosis was undertaken in 50 patients with myocardial infarction. The development of lower-limb thrombosis was detected by the radioactive fibrinogen technique in 23% of the patients who received heparin and 29% of the controls. This difference is not significant.

EFFICACY OF LOW DOSES OF HEPARIN IN PREVENTION OF DEEP-VEIN THROMBOSIS AFTER MAJOR SURGERY: A Double-blind, Randomised Trial

In a prospective, double-blind, randomised trial, the prophylactic efficacy of " low-dose " heparin (5000 units subcutaneously begun two hours preoperatively and continued every twelve hours for seven days) was investigated in 78 " high-risk " patients over the age of forty undergoing major surgery. The frequency of deep-vein thrombosis, determined by the 125I-fibrinogen test, was 42% in the control group and 8% in the patients receiving heparin. The difference between these two frequencies was statistically significant (p<0·001). Low-dose subcutaneous heparin has also been given to 183 patients undergoing major surgery and considered to be even more at risk of thrombosis. A low frequency of thrombosis (9·7%), similar to that found in the trial, was detected in 133 consecutive patients undergoing major elective operations. Only in patients with fractures of the femoral neck several hours before heparin could be administered were the results unsatisfactory: 20 (40%) out of 50 consecutive patients with this condition who were investigated developed postoperative thrombosis. In this entire group of 222 patients receiving heparin prophylaxis, pulmonary emboli were recognised clinically in only 1 individual. Heparin could be detected in the plasma by a new assay method, but often not by the thrombin clotting-time or the activated partial thromboplastin-time. At these levels, bleeding was not increased, even during major surgery in elderly patients. A large-scale clinical trial of low-dose heparin prophylaxis in surgical patients is both warranted and feasible.