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Thirty-three patients with acute iliofemoral thrombosis were randomly assigned to three treatment groups in a pilot dose-ranging study of thrombolytic therapy in deep vein thrombosis. One group received tissue culture urokinase in a dose of 2,200 I.U./kg/hr, and a second group in a dose of 1,100 I.U./kg/hr following a loading dose of 4,400 I.U./kg given in ten min. Urokinase was administered for 12 hr periods, alternating with 12 hr periods of heparin. A third group received an initial dose of 250,000 I.U. of streptokinase in 20 min, followed by 100,000 I.U./hr. Treatment of all patients continued for three days. At the end of this period little improvement, evaluated by "blinded" interpretation of pre- and post-treatment phlebograms, was found in five out of ten of the higher-dose urokinase patients, seven out of eleven of lower-dosage urokinase patients, and six out of ten of streptokinase patients. Optional treatment for another three days showed little further improvement of urokinase-patients and moderate further improvement in the streptokinase-patients. Neither of the 2 dosage schemes at intermittent application of urokinase appeared to be advantageous. Urokinase treated patients experienced fewer adverse reactions.

The efficacy of dextran-40 infusions or low-dose heparin or xantinol-nicotinate administration in preventing postoperative thromboembolic complications has been investigated in a prospective, controlled, randomised trial as part of an international multicentre trial. 382 patients over the age of forty years undergoing elective major general surgery were investigated; 100 had a complete protocol in the control, 94 in the heparin, 92 in the dextran, and 32 in the xantinol-nicotinate group. 31 patients died: 13 in the control group, 10 in the heparin group, 6 in the dextran group, and 2 in the xantinol-nicotinate group. In 4 controls, 6 in the heparin group, and 1 in the dextran group the cause of death was acute pulmonary embolism. 4 further controls, 1 in the heparin group, and 2 in the dextran group had emboli found at necropsy, which either contributed to the deaths or were incidental findings. The distribution of pulmonary emboli in this study did not show the difference between the control and the heparin group reported in the multicentre trial. The 125I-fibrinogen test was done in all patients. The frequency of isotopic deep-vein thrombosis was 36-0% in the controls, 12-8% in the heparin group, 21-7% in the dextran group, and 40-6% in the xantinol-nicotinate group. The difference between the controls and the heparin groups was highly significant and between the control and the dextran group, probably significant. There were significantly more side-effects in the heparin group than in the dextran group.

Clotting tests based upon the activated partial thromboplastin time are disturbed by heparin. This brief communication shows that Factor XII clotting activity in plasma samples heparinized in vitro and in vivo can be measured accurately by means of an aPTT-test using congenitally deficient substrate plasma when the plasma dilution buffer contains hexadimethrine bromide (Polybrene), 15 mg/L. This method of neutralizing heparin obviates more complicated procedures such as heparin adsorption to anion exchange resins.

If blood for monitoring of heparin therapy is collected through indwelling catheters it may be contaminated by exogenous heparin. A prospective study comparing thrombin times in plasma obtained by venipuncture and by collection through heparin perfused catheters showed that 26 out of 77 catheter samples were contaminated. In 16 of these 26 cases, overestimation of the heparin effect would have led to incorrect dosage recommendations. It is concluded that blood for laboratory monitoring of heparin treatment should be collected by venipuncture.

Three laboratory methods for monitoring heparin treatment have been compared using 63 plasma samples: the thrombin time, the activated partial thromboplastin time, and the measurement of the heparin concentration using a chromogenic substrate. A good correlation was found between the methods. However, the intensity of anticoagulation was identical in only 27 of the 63 samples (43%) when the thrombin time and the activated partial thromboplastin time were compared. Fully discordant results were recorded for four samples (6%). The thrombin time was found to be more closely related to the plasma heparin concentration than was the activated partial thromboplastin time. Both antithrombin-III activity and immunologic levels were lower in the group with strong heparinization. It is suggested that the thrombin time is a good and safe method for monitoring heparin treatment.

1. The effectiveness of 3 X 5000 IU s. c. heparin daily (starting preoperatively) for the prevention of postoperative deep vein thrombosis was evaluated in a prospective, controlled, randomized study including general surgical and urological patients. 125I-fibrinogen test was performed daily in all patients. 2. 178 patients fulfilled the conditions of the protocol. 35.8% of the 95 patients in the control group developed deep vein thrombosis, but only 13.3% of 83 subjects in the heparin group did so. The difference is statistically highly significant (p less than 0.001). 3. The vast majority of all thrombi in both groups appeared before the 3rd postoperative day. 4. With 1 exception, all deep vein thrombi in the heparin group started in the mid-calf region. In the control group 5 deep thrombi originated in the popliteal vein. 5. Heparin displays a better effect in males (n = 34; p less than 0.01) than in females (n = 49; p less than 0.025). 6. In patients undergoing surgery for malignant disease heparin does not reduce the incidence of deep vein thrombosis. 7. Heparin is far more effective in patients under 60 years of age than in those over 60 (p less than 0.005). 8. Heparin is more effective in obese patients than in those of normal body build. 9. Heparin prophylaxis also reduces the incidence of deep vein thrombosis in patients who exhibit predisposing factors. In patients of the control group with preexisting disease of the venous system, there were significantly more deep vein thrombi (p less than 0.01) than in those without predisposing factors. 10. In the heparin group 29% of all thrombin time determinations show a definite prolongation of more than 26 sec (normal value 15 sec). 11. In 14 patients (=16.9%) of the heparin group, 21 side effects or complications were seen. Bleeding complications were the main problem, comprising 5 wound hematomas and hematomas at the injection site, 4 postoperative bleeding episodes and 2 reoperations. There were no complications in the control group. 12. According to the results of 10 well controlled studies, there is no doubt that in general surgery small doses of subcutaneous heparin, commencing preoperatively, do reduce the incidence of postoperative deep vein thrombosis to a significant degree. However, whether this form of prophylaxis is also effective in patients with fractures of the hip and in elective hip surgery cannot, on the evidence available, be decided. In the fields of gynecological surgery and urology as well, more data are needed before this form of heparin prophylaxis can be recommended.