Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin.

A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment (Kabi 2165, Fragmin) for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the fragment was given in the evening before surgery, and thereafter every evening. There were 1002 analyzable patients, 826 having received correct prophylaxis. Sixty three percent of the patients were operated on for malignant diseases. The frequency of DVT was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2 to 5.0%, p = 0.02). In patients with malignancies the reduction was from 11.2 to 6.4% (p = 0.06). The frequency of bleeding was 6.7% among the heparin fragment patients and 2.7% among the patients given conventional heparin (p = 0.01). The corresponding frequencies for patients with malignancies were 3.2 and 2.8%, respectively (p = 0.28). All bleedings were minor and of no clinical significance. Local pain at the injection site was reported significantly less often among patients with the fragment. Twenty patients died, 13 with malignant disease, mortality being the same in the two groups. It is concluded that heparin fragment administered in the evening before surgery and then every evening is a practically acceptable alternative to prevent postoperative DVT in patients undergoing elective abdominal surgery, also when the histology shows malignancy. Thus, the advantages of using LMWH compared with conventional low-dose heparin are simplified administration routines, better thromboprophylactic effect, and less local pain at injection sites. A disadvantage is the slight increase in hemorrhagic side effects, all of minor clinical importance and not seen in patients undergoing surgery for malignancy.

Low molecular weight heparin given the evening before surgery compared with conventional low-dose heparin in prevention of thrombosis.

A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a low molecular weight heparin fragment for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the heparin fragment was given the evening before surgery, and further doses were given thereafter every evening. There were 1002 analysable patients, 826 having received correct prophylaxis. Of these 1002 patients, 64 per cent were operated on for malignant disease. A total of 20 patients died, 10 in each group. The frequency of deep vein thrombosis was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2-5.0 per cent, P = 0.02) [corrected]. The frequency of bleeding was 6.7 per cent among the heparin fragment patients and 2.7 per cent among the patients given conventional heparin (P = 0.01), but all bleeds were of minor degree and there was no difference in the reoperation rate for bleeding, or in the transfusion requirements. Local pain at the injection site was reported significantly less often among patients given the heparin fragment.

Plasminogen activators in human xenografted oro-pharyngeal squamous cell carcinomas.

Specimens of squamous cell carcinomas of the head and neck established as xenografted tumour lines on nude mice were examined by the fibrin slide method for the presence of plasminogen activator(s). The fibrinolytic activity was partly quenched by antibodies against the vessel-related tissue plasminogen activator and partly by antibodies against urokinase. The results indicate that inactive pre-urokinase in tumour tissue is to some degree activated when the tumour tissue is transplanted to the nude mice. In organ culture of the tumours, urokinase of both low and high molecular form was secreted into the medium, but only traces of tissue plasminogen activator. Inhibition of urokinase activity might be an approach to hinder tumour growth.

Atherosclerotic aneurysm of the deep femoral artery. Case report.

Three cases of atherosclerotic aneurysm of the deep femoral artery are described. They demonstrated the differing presentations of atherosclerotic femoral aneurysm, viz. as "asymptomatic" pulsating tumour or with manifestations of distal ischaemia or rapid growth and rupture. A search of the literature revealed 12 cases of atherosclerotic aneurysm in the deep femoral artery, and additionally 11 mentioned in review articles on femoral aneurysm. Notably, five of the 15 (including the 3 here described) cases of deep femoral artery aneurysm presented with rupture, an incidence higher than has been reported for aneurysm of the common or superficial femoral artery. The reason probably is that deep femoral aneurysms are more difficult to diagnose before they have reached a size carrying higher risk of rupture. A more aggressive approach, with operation soon after establishment of the diagnosis, is therefore proposed.

Plasminogen activators in alveolar bone in man.

Plasminogen activators in alveolar bone in man was studied in quenching experiments by a fibrin slide technique with addition of monospecific antibodies against tissue plasminogen activators (t-PA) and urokinase (u-PA). The plasminogen activator activity was quenched in the slides with anti-t-PA. No quenching was observed in the slides with anti-u-PA. This does not exclude the possibility that enzymatically inactive pre-urokinase is present.

Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor.

Fibrinolytic components after venous occlusion and concentrations of tissue plasminogen activator inhibitor were studied in 100 consecutive patients with confirmed recurrent deep vein thrombosis or pulmonary embolism. After 20 minutes of venous occlusion the fibrinolytic response was decreased in 33 patients, as measured both amidolytically with S-2251 and on fibrin plates. Two different mechanisms responsible for the poor fibrinolytic response could be distinguished. Twenty two of the patients in whom the response was poor released normal amounts of tissue plasminogen activator antigen, as assayed by immunoradiometric assay, but had appreciably increased concentrations of tissue plasminogen activator inhibitor. The 11 other patients in whom the response was poor had both low tissue plasminogen activator activities and low tissue plasminogen activator antigen concentrations but normal concentrations of tissue plasminogen activator inhibitor. The results show not only that defective synthesis or release of tissue plasminogen activator may be important in the pathogenesis of venous thrombosis but also that a large group of patients with thrombosis have an increased concentration of the inhibitor to tissue plasminogen activator.

Deep vein thrombosis after renal transplantation: a prospective analysis of frequency and risk factors.

In a prospective study the frequency of deep vein thrombosis during the first 3 weeks after kidney transplantation has been evaluated using the combination of thermography and strain-gauge plethysmography for objective diagnosis. 83 consecutive patients were included, 33 with juvenile diabetes mellitus. The overall frequency of thrombosis was 24.1%, diabetes mellitus being a significant risk factor. No other risk factors were found. The transplant did not influence the venous outflow from the corresponding leg. Plasminogen activator activity in the iliac vein wall at transplantation did not differ between patients with and without thrombosis.

Immunological identification of plasminogen activators in normal and malignant tissues of the oral cavity in man.

Plasminogen-activator activity was examined qualitatively in normal and malignant mucosa of the oral cavity in humans, using an immunological histochemical fibrin slide technique. No fibrinolytic activity was observed in sections of normal mucosa when monospecific antibodies against a melanoma cell activator (anti-MA) were added. Antibodies against urokinase (anti-UK) did not react on the fibrinolytic activity which indicates that the activator is of tissue type. In malignant tissue, fibrinolytic activity was completely blocked by a mixture of anti-MA and anti-UK.

Human ureter, a source of tissue plasminogen activator.

In organ cultures of human ureters, plasminogen activators were released into the medium. Unlike most tissue cultures that release mainly urokinase (UK), the activators released by ureter cultures were predominantly of the tissue-type (t-PA), as shown by radioimmunoassay. Using affinity chromatography it was possible to distinguish two activities. One minor fraction was quenched by antibodies against UK, but not by antibodies against t-PA. The other activity was quenched by antibodies against t-PA, but not by those against UK, and required the presence of fibrin to activate plasminogen. Because of the large amount of t-PA, cells derived from human ureter might well prove to be a useful source of t-PA.

Prostacyclin (PGI2) and plasminogen activator (PA) activity in umbilical vein grafts. An experimental study.

Glutaraldehyde-tanned human umbilical cord vein grafts (Dardik Biograft, Meadox) (HUV) measuring 6 cm in length and 5-6 mm in diameter were placed in the carotid arteries (CA) or jugular veins (JV) of sheep and the anastomoses were made end-to-end. Sections from the anastomotic sites and mid-graft were submitted to prostacyclin (PGI2) (radioimmunoassay) and plasminogen activator, PA, (histochemical) assays. Anastomotic PGI2 production from 6 grafts placed in the CA and removed 10 days later was similar to that of control arteries. The midgraft PGI2 synthesis tended to be less but the difference was not statistically significant. Anastomotic PGI2 from 11 grafts placed in the CA and removed 90 days later was also similar but the midgraft production was significantly less (p less than 0.025). From the distal anastomoses and mid portion of grafts placed in the jugular veins and removed 10 days later PGI2 synthesis was significantly less than that of control veins (p less than 0.025 and p less than 0.005 respectively) but no difference between the proximal anastomosis and control veins was observed. In none of 11 HUV removed on the 10th postoperative day was there any PA in the neointima; however, in 6 out of the 9 HUV removed on the 90th postoperative day, PA was demonstrated in the neointima. In conclusion, PGI2 synthesis similar to that of control vessels but less from the mid-graft regions. Neointima gained the ability to produce plasminogen activator.

Decreased fibrinolytic activity in human atherosclerotic vessels.

Using a semi-quantitative, histochemical fibrin slide technique, plasminogen activator (PA) activity was determined in 65 atherosclerotic arteries obtained from 65 patients during surgery -42 during resection of the infrarenal part of the aorta, and 23 from a leg artery in patients undergoing a below-knee amputation. In 12 of the patients undergoing resection of the aorta, another specimen was obtained from a collateral artery free from atherosclerotic lesions. PA activity in the atherosclerotic aortic specimens was significantly decreased compared with that in collateral arteries, and low PA activity was also found in leg arteries.

Comparison of plasminogen activator activity in human arteries and veins.

Biopsy specimens were obtained from 138 arteries and concomitant veins in different anatomic regions of both healthy subjects and patients undergoing surgery of various kinds. A fibrin slide technique was used to determine plasminogen activator (PA) activity, no significant difference being found between activity in arteries and that in veins, other than in epigastric veins where it was significantly greater. Arterial PA activity was similar in both healthy and uraemic subjects, and was unaffected by uraemia due to diabetes or other renal disorder, and by such factors as age and sex. Correlation between arterial activity and that in concomitant veins was found for all the anatomic regions studied.

Immunological characterisation of plasminogen activators in the human vessel wall.

A histochemical technique was used to identify the activity of the plasminogen activator (PA) in the vessel wall of veins. Antibodies against melanoma cell activator and urokinase (UK), both raised in goats, were mixed into the fibrin film. The PA activity was quenched by the antibodies against melanoma activator but remained unchanged when antibodies against UK, or an IgG preparation of normal goat serum, was mixed in the fibrin film. The results of this study show that the PA activity in the vein vessel wall is immunologically similar to or identical to the PA derived from melanoma cells which has previously been shown to cross-react with the tissue-like PA. No UK-like activity was present in the vessel wall.

Decreased fibrinolytic activity in vessels and ureters of rejecting human kidneys.

Plasminogen activator (PA) activity was determined with a histochemical fibrin slide technique in renal arteries, veins and ureters in 62 transplanted kidneys and again at transplantectomy in 12 transplants who later underwent irreversible rejection. At transplantation PA activity was the same whether the grafts later rejected or not. There was a significantly decreased PA activity in the vessels and ureters in rejected transplants. The role of the fibrinolytic system as a pathogenetic factor in rejected kidneys is discussed.

Influence of major surgery on plasminogen activator activity in superficial hand veins.

In 108 patients the plasminogen activator (PA) activity in superficial hand veins was measured with a fibrin slide technique before and after a major surgical operation. In the early postoperative period the PA activity was significantly decreased and the PA activity did not return to its preoperative value until the 14th postoperative day. The postoperative decrease was more than 0.5 arbitrary unit in 90 patients, resulting in an abnormally low value in 44. Overweight or an operation time of 180 min or more was found to increase the proportion of patients with a postoperative decrease in the PA activity. No sure relationship was demonstrable in the postoperative PA activity between patients with venous thrombosis and those without.

Increased vascular plasminogen activity in patients with pheochromocytoma.

Fibrinolytic and coagulation components were assayed in six patients with pheochromocytoma. Blood samples and a specimen from a superficial hand vein were obtained before, and six months after removal of the tumour. Vascular plasminogen activator (PA) activity in the vein wall was significantly increased in all patients who all had increased concentrations of urinary adrenaline, or noradrenaline, or of both. After adrenalectomy catecholamines were normalized and the PA activity was within normal range in all patients. There were no significant differences in factor VIII, antithrombin III, fibrinolytic activity, plasminogen or inhibitors of the plasminogen activation in plasma.

Comparison of the plasminogen activator activity of superficial hand and foot veins.

The plasminogen activator (PA) activity in superficial hand and foot veins was determined with a fibrin slide technique in 68 patients (46 with and 22 without thrombosis). The activity in the hand veins was identical to that of the foot veins in 57% of the patients and higher in 38%. There was a correlation between activity in hand and foot veins in patients with and without thrombosis. Thus, biopsy specimens from superficial hand veins can be used for assessing the PA activity in patients with leg thrombosis.