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In order to detect deep vein thrombosis (DVT), 101 patients with acute medical or infectious disorders were examined with the 125I-fibrinogen uptake test. All patients were bedridden on admission and were scanned daily from the second to the eighth day. Thirteen patients developed a positive fibrinogen uptake test. Thus, if a positive test is interpreted as DVT, the incidence of DVT was 13% in our bedridden patients. Of the patients admitted because of heart disease or pneumonia 20% had DVT, but only 4% of those admitted with other diagnoses. Other clinical "risk factors" studied, could not identify patients who developed DVT.

SummaryA multicenter, randomized double-blind study compared in two parallel groups the efficacy and safety of a low molecular weight heparin (LMWH) enoxaparin 20 mg once daily, with unfractionated heparin (UFH) 5000 IU twice daily, administered subcutaneously for 10 days, in the prevention of venous thrombosis disease in 442 hospitalized elderly patients bedridden for an acute medical illness. The main efficacy endpoint was defined as the occurrence of venous thrombosis, diagnosed by a daily fibrinogen uptake test, and/or documented clinical pulmonary embolism.Intention-to-treat analysis of efficacy showed that the incidence of venous thromboembolic events was low: 4.8% (10/207) in the LMWH group (9 episodes of isotopic venous thrombosis and one of scintigraphic pulmonary embolism), and 4.6% (10/216) in the UFH group (10 episodes of isotopic venous thrombosis). The two treatments were equivalent, where equivalence was defined as a maximum difference of 7% between the two groups (p = 0.0005).There were no significant differences in terms of safety between the 216 patients in the LMWH group and the 223 patients in the UFH group who received at least one injection of the randomized treatment. During the study period, 15 patients (3.4%) died (7 in the LMWH group and 8 in the UFH group): 2 sudden deaths, one in each group, including one case in which pulmonary embolism could not be excluded since no autopsy was performed, and 13 others deaths unrelated to the study treatments. Six patients (1.4%) presented a bleeding complication: 2 (0.9%) in the enoxaparin group (one major and one minor hemorrhage), and 4 (1.8%) in the UFH group (2 major and 2 minor hemorrhages).These results indicate that subcutaneous enoxaparin 20 mg once daily for 10 days is as effective and well tolerated as subcutaneous UFH 5000 IU twice daily in the prevention of venous thromboembolic disease in bedridden elderly in-patients presenting an acute medical illness.

Postoperative thromboembolic complications were evaluated in 2578 patients undergoing elective abdominal surgery, all receiving prophylaxis with low molecular weight heparin. A positive fibrinogen uptake test (FUT) developed in 217 patients (8.4%), while 37 patients (1.4%) had major thromboembolism (TE, defined as proximal deep vein thrombosis and/or pulmonary embolism, verified with phlebography, pulmonary scintigraphy or autopsy). In only 14% a positive FUT was associated with a major TE event. In 19% of the patients with major TE the FUT was negative. In multiple logistic regression the independent predictors for major TE were partially different from those for positive FUT. Thirty day mortality was 3.0%. There were significant associations between both positive FUT and major TE on one hand and mortality on the other (relative risks 2.4 and 5.8, respectively). FUT is not a good predictor of major TE. Both positive FUT and major TE indicate a significant risk of postoperative death.

The optimal administration regimens of low molecular weight heparins (LMWHs) have not yet been established. The aim of this study was to compare the efficacy and safety of 2500 and 5000 Xal units of the LMWH dalteparin in patients undergoing elective general surgery for malignant and benign abdominal disease. Prophylaxis was started in the evening before surgery and given once-daily every evening thereafter. The study was designed as a prospective, randomized, double-blind, multicentre trial. Some 66.4 per cent of patients were operated on for a malignant disorder. The primary endpoint was deep vein thrombosis (DVT) detected with the fibrinogen uptake test. Bleeding complications were recorded and classified. Analysis was made both on an intention to treat basis and in patients given correct prophylaxis (86.3 per cent). A total of 2097 patients were randomized and 27 excluded after randomization. A technically correct fibrinogen uptake test was obtained in 1957 patients. The incidence of DVT was significantly lower in patients given 5000 Xal units, this being true for both correct prophylaxis (6.8 versus 13.1 per cent, P < 0.001), on an intention to treat basis (6.6 versus 12.7 per cent, P < 0.001), and in patients with malignant disease (8.5 versus 14.9 per cent, P < 0.001). Sixty-seven patients (3.2 per cent) died within 30 days with no difference between the groups. There were two cases of fatal pulmonary embolism. The frequency of bleeding complications in the whole series was higher in patients randomized to 5000 Xal units (4.7 versus 2.7 per cent, P = 0.02), although this was not the case in those operated on for malignant disease (4.6 versus 3.6 per cent, P not significant). Dalteparin in the dose of 5000 Xal units started in the evening before surgery has a good thromboprophylactic effect in high-risk general surgery at the cost of a small bleeding risk. In patients with malignant disease there was no increased risk of bleeding. The overall frequency of fatal pulmonary embolism with dalteparin is extremely low, even in this high-risk group of patients.

Venous volume (venous capacity) of the calf is low in patients with acute myocardial infarction, who also have a high risk of deep vein thrombosis (DVT). The effect of graduated compression stockings on the venous volume and on the incidence of DVT was therefore studied in 80 patients aged 70 years and above with acute myocardial infarction. Graduated compression stockings were randomly fitted to one leg, the other serving as a control, after which the venous volume was measured by strain gauge plethysmography. The incidence of DVT was measured by the 125I fibrinogen uptake test. Venous volume was significantly higher in legs treated with graduated compression stockings compared to control legs. DVT developed in eight control legs but not in any leg treated with graduated compression stockings (P = 0.003). DVT was also significantly more frequent in women compared to men and the majority of DVT developed in legs with very low venous volume values.

The effects of dihydroergotamine (DHE) on the circulation of the leg during combined epidural and general anaesthesia were studied to determine if DHE would enhance leg blood flow and prevent postoperative deep vein thrombosis in a double-blind trial of 40 elderly female patients subjected to cholecystectomy. Central and big toe temperature, arterial blood pressure, heart rate, calf volume and arterial inflow of the leg by electrical impedance plethysmography and the venous outflow by Doppler method were measured. DHE 0.5 mg subcutaneously reduced the volume of the leg, i.e. increased the electrical impedance, probably due to venous vasoconstriction. Simultaneously the need for etilefrine hydrochloride was reduced. No significant changes in the pulsatile inflow of the leg or the outflow were detected. Deep vein thrombosis (DVT) was detected by fibrinogen uptake test in five patients (three in DHEH and two in the control group) and verified by ascending phlebography in four patients. Intraoperative characteristics in patients with postoperative DVT were tachycardia (P < 0.001), enhanced need for etilefrine (P < 0.01) and a more rapid increase in big toe temperature (P < 0.05) after induction of epidural analgesia, compared with patients without DVT. Femoral vein flow velocity remained at the preinduction level, whereas pulsatile arterial inflow slightly increased. Together with a low basal impendance of the leg, the changes were indicative of a more intense vasodilatation, probably leading to stagnant flow and development of postoperative deep vein thrombosis.

To assess the eficacy and safety of dermatan sulphate (MF 701) in preventing postoperative deep vein thrombosis (DVT), 324 patients aged 40 years or over undergoing elective major general surgical operations were included in a randomized trial comparing MF 701 (100 my intramuscularly once a day) with unfractionated calcium heparin (UFH, 5000 units subcutaneously three times daily). Both treatments were initiated before operation and continued until discharge. In all, 316 patients were included in the analysis (MF 701, 157; UFH, 159). Serial impedance plethysmography was performed in all patients; a 125I-radiolabelled fibrinogen uptake test was added to impedance plethysmography in a randomized subsample of 62 patients (MF 701, 28; UFH, 34). Positivity in either test was confirmed where possible by venography. DVT was diagnosed by venography or, when this could not be performed, by positivity of either impedance plethysmography or fibrinogen uptake test. The incidence of DVT was 3.1 per cent (patients receiving MF 701) and 1.6 per cent (those receiving UFH) in patients undergoing impedance plethysmography alone, and 7.1 and 11.8 per cent, respectively, in those undergoing both impedance plethysmography and fibrinogen uptake test; in neither case was the difference between treatments statistically significant. There were five in-hospital deaths, two in patients receiving MF 701 and three in patients on UFH. The incidence of clinically overt haemorrhage was 5.7 per cent in patienis on MF 701 and 17.6 per cent in those on UFH (P < 0.01). Postoperative transfusions and reoperations due to bleeding were significantly less frequent in patients receiving MF 701. Mortality rates at 3 months were similar for the two treatment groups. Compared with standard prophylaxis using UFH, MF701 showed a similar eficacy with a significantly greater safety.

A total of 1290 patients (Pts) undergoing general surgery were enrolled in a randomized, multicentre double-blind study in order to investigate the efficacy and safety of two different doses of a low molecular weight heparin (LMWH) (Logiparin) for the prevention of deep vein thrombosis. Patients were randomized to either 5,000 IU unfractionated heparin twice daily, 2,500 anti-Xa or 3,500 anti-Xa units of Logiparin once daily. Each treatment was given subcutaneously two hours before surgery and continued for seven to ten days. All coagulation tests were performed blindly in a core laboratory. Blood samples were collected before surgery and then 3 hours after injection on Day 3 and 5 after surgery. Anti-Xa amidolytic activities were significantly higher in the two LMW Heparin groups than in the unfractionated heparin group (mean peak levels +/- s.e.m. on Day 3: 0.097 +/- 0.004; 0.152 +/- 0.004 and 0.034 +/- 0.003 IU respectively). As expected a significant correlation was observed between anti-Xa activity and the dose of LMW Heparin injected. The correlation coefficient was higher when the doses were expressed in anti-Xa units/kg body weight. However, the body weight accounts for only 16% of the interindividual variability of anti-Xa activity. Therefore, there is no clear evidence to suggest that weight-adjusted doses should be recommended when this LMW Heparin is used as prophylactic treatment in general surgery. A weak negative correlation was found between anti-Xa activity and thrombosis as demonstrated by a positive radiolabelled fibrinogen uptake test and confirmed by positive phlebography. No significant correlation was demonstrated between anti-Xa activity and the occurrence of postoperative bleeding.

SummaryBecause the use of radioactive fibrinogen uptake test (FUT) has become questionable both for ethical (risk of virus transmission) and technical (lack of sensitivity) reasons, we investigated the potential value of two alternative methods for screening of asymptomatic deep venous thrombosis following elective digestive surgery: liquid crystal contact thermography (LCCT) and measurement of plasma concentration of D-dimer (DD), as compared with bilateral ascending phlebography. Out of 194 patients, 185 underwent phlebography on the 8th (0-19, median and range) postoperative day. Despite prophylaxis with low-molecular-weight heparin and elastic stockings, DVT was detected on phlebography in 58 legs of 45 patients. Sensitivity of LCCT with respect to the presence of DVT was 55% (n = 184 patients) or 28% (n = 368 legs) with a specificity of 67% and 82%, respectively. These poor performances were obtained despite a good interobserver agreement for the LCCT assessments (overall kappa coefficient of 0.66 between three experts). The most accurate cut-off of DD for discriminating patients with or without DVT was 3,000 pg/1, as determined by ROC curve analysis. Sensitivity of a DD level of more than 3,000 pg/1 for the presence of phlebographically documented DVT on the 8th postoperative day was 89% for a specificity of 48%.Thus, LCCT cannot be used for screening of postoperative, mainly asymptomatic DVT following general surgery. On the other hand, measurement of plasma DD may be useful for initial screening, a negative result (level less than 3,000 pg/1) allowing to exclude DVT (negative predictive value of 93%) and a positive result (positive predictive value of 35%) requiring confirmation by phlebography. This sequential approach might be useful in studies of the efficacy of antithrombotic regimens for prophylaxis of DVT in patients at risk.

SummaryIn a prospective, double-blind, randomized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery. Six hundred and seventy-three patients were randomly allocated to the two prophylaxis groups; 20 of these, however, did not undergo surgery and did not receive any prophylaxis. Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day. Treatment was initiated 2 h preoperatively and continued for 7 to 10 days. The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography. Venous thrombosis was diagnosed in 24 of 323 patients (7.4%) treated with low molecular weight heparin and in 26 of 330 patients (7.9%) treated with low-dose heparin. DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group. During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin. No pulmonary embolism was found in patients treated with low molecular weight heparin. Both prophylactic schemes were well tolerated. Intra-and postoperative blood loss, incidence of wound hematoma, frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group. The results of this trial show that the investigated low molecular weight heparin is at least as effective and safe as low-dose heparin in preventing deep vein thrombosis in patients undergoing elective abdominal surgery.

Plasminogen activator inhibitor (PAI-1) antigen and fibrin/ogen degradation products (FbDP, FgDP) were measured before and 8 days after gynaecological surgery in 50 patients randomly submitted to prophylaxis with low molecular weight heparin (Alfa LMW1-OP 2123, Alfa Wassermann, Bologna, Italy; LMWH group) or standard calcium heparin (CH group). All patients were screened for deep venous thrombosis by the 125I Fibrinogen uptake test. In the CH group, but not in LMWH group, postoperative PAI-1 levels were significantly higher (p

In 1980, unfractionated heparin (UFH) was the established agent for the prophylaxis of venous thromboembolic (VTE) disease in patients undergoing general surgery. VTE prophylaxis was the first indication in which low-molecular-weight heparins (LMWHs) were tested. Approximately 40 trials have demonstrated that LMWHs are at least as effective and safe as UFH. LMWHs exhibit a number of advantages over UFH, including ease of administration, convenient once-daily dosing, and facilitation of outpatient management. The ideal time of administration and the dose of the initial one or two injections of LMWH remain unresolved issues. LMWHs are used with increasing frequency in the treatment of acute deep vein thrombosis (DVT), having been studied in comparison to UFH in 16 major clinical trials. LMWHs are at least as effective as UFH in the prevention of VTE, but higher doses than those used for prophylaxis are required. There is still an ongoing debate about whether the daily dose should be administered in one or two subcutaneous injections. In some recent studies, symptomatic new DVTs or pulmonary emboli (PE) were the primary end points, which had to be verified by objective methods, but such end points may be not be sensitive enough to detect major differences in the efficacy of different LMWHs.

The 125I-fibrinogen test was evaluated as a diagnostic tool for deep vein thrombosis in patients with erysipelas. In the investigated group of 43 patients, several showed an increased uptake that could not be verified by subsequent phlebography. The false positive test may have been caused by the local inflammatory process. The 125I-fibrinogen test seems to be too unspecific to be used for diagnosing deep vein thrombosis in this patient group.

One hundred thirty-four limbs (40% retrieval) were reviewed 14 to 21 years after total hip arthroplasty. Each had been screened for deep vein thrombosis following surgery by the fibrinogen uptake test, with proximal thrombi confirmed venographically. The limbs were assessed for chronic venous insufficiency with a standard clinical grade and photoplethysmography. Clinical chronic venous insufficiency was found in 4 of 36 (12%) limbs without and 11 of 98 (11%) with previous thrombosis (chi-square = .09, P = .77). Clinical chronic venous insufficiency was detected in 9% of limbs (6/67) with calf thrombi, 0% of limbs (0/11) with isolated femoral thrombi, and 25% of limbs (5/20) with calf and femoral thrombi. After photoplethysmographic assessment, only 2 of 98 (2%) cases were thought to be attributable to thrombosis after hip arthroplasty (95% confidence interval, 0.2-7.2). Despite a high incidence of deep vein thrombosis diagnosed on the fibrinogen uptake test after total hip arthroplasty, symptomatic deep chronic venous insufficiency was an unusual outcome 14 to 21 years later.

A randomized open trial was undertaken to compare the antithrombotic efficacy of a low molecular weight heparin (LMWH; Sandoparin) with that of dextran 70 in patients undergoing surgery for hip fracture. One hundred thirteen patients received LMWH once daily subcutaneously at a fixed dosage while 103 patients received intravenous dextran 70. Postoperative deep vein thrombosis (DVT) was assessed by a diagnostic algorithm using the 125Iodine fibrinogen uptake test as screening and Duplex ultrasonography and/or ascending venography as confirming techniques for suspected DVT. The frequency of DVT was significantly lower in the LMWH group than in the dextran group (15.5 versus 32.6%, p less than 0.005). Proximal DVT was rare in both groups (LMWH: 2%, Dextran: 1%). Only one case of fatal fat pulmonary embolism was observed during the 10 day prophylaxis period in a patient receiving Dextran. Three cases of pulmonary embolism occurred later; one fatal event in the dextran group on day 14, and two cases in the LMWH group (one fatal and one non-fatal event) on day 14 and 17, respectively. There was no major bleeding complication in either group. We conclude that the LMWH we used is safe, was well tolerated, and has a significantly better thromboprophylactic effect than dextran 70.

• To assess the incidence, risk factors, and clinical importance of deep vein thrombosis in acute stroke, we studied 70 consecutive patients who underwent hemostasis screening at the time of entry into the study and followed up these patients with serial venous Doppler examinations and the iodine 125-labeled fibrinogen uptake test. Mortality was significantly higher among the 20 patients who developed a deep vein thrombosis, and eight of them had necropsy evidence of pulmonary embolism. Severity of leg paresis and a shortened activated partial thromboplastin time were significantly associated with subsequent deep vein thrombosis with multivariate analysis. Significantly higher levels of fibrinopeptide A were found in patients with postmortem evidence of pulmonary embolism. Deep vein thrombosis is a frequent complication of acute stroke and may influence the prognosis by inducing pulmonary embolism. Our findings allow rapid identification of high-risk patients who may benefit maximally from prophylactic treatment of venous thromboembolism.

An open controlled study was carried out to assess the efficacy and tolerance of a new low molecular weight heparin for the prevention of post-surgical deep vein thrombosis and pulmonary embolism. Forty-five patients undergoing abdominal surgery mainly for neoplasm, gallstones and gastric ulcers were administered 7,500 AXaU of low molecular weight heparin subcutaneously, 2 hours before surgery and once a day for 7 days after. Heparin calcium (15,000 IU subcutaneously per day) was used as a comparison drug in 45 control subjects, matched for age, sex and type of operation. Deep vein thrombosis was identified with clinical parameters, radio-labelled fibrinogen uptake test, echo-doppler and venography; pulmonary embolism with clinical examination, chest X-rays and/or scintigraphy. No episodes of deep vein thrombosis occurred in the low molecular weight heparin-treated patients, whilst there was 1 episode, without pulmonary embolism, in the control group. The consumption of blood and haemoderivatives for transfusions was higher in the heparin calcium group. Only in this group, furthermore, did 5 patients have to suspend antithrombotic treatment due to severe haemorrhages. General tolerance of the two drugs was identical and very good.

255 hip fracture patients were studied by 125I-fibrinogen uptake test and bilateral phlebography. We found the sensitivity of fibrinogen scanning to be 44% for the non-operated limb and 50% for the calves. The predictive value of a negative result was found to be 92% and 93% respectively. We conclude that the use of fibrinogen uptake test as single diagnosticum is not valid and can only be recommended in combination with phlebography when studying patient where the frequency of DVT is expected to be low.

In a double blind randomized trial on 250 patients undergoing elective abdominal surgery the effect of Fragmin was compared with heparin. Patients over 40 years of age except appendectomy and herniotomy were included. The dose of heparin was 5,000 IU b.i.d. whilst Fragmin was given in a dose of 2,500 U once per day and the second injection was a placebo. Prophylaxis started 2 h preoperatively and was maintained for 7 days. The fibrinogen uptake test was used as a screening method for thrombosis which was confirmed by phlebography. 124 patients were in the heparin group and 126 in the Fragmin group. Comparability between groups was found in: age, sex, Broca index, amount and type of risk factors, type of surgery. Thromboembolism was found in 10 cases in each group. Blood transfusions on the postoperative days 1 to 6 were required in 2 Fragmin and in 12 heparin patients. The total amount of blood given during that time was 6 units in the Fragmin and 37 units in the heparin group. These differences were significant.

Despite evidence that prophylaxis against deep-vein thrombosis (DVT) is effective, a large proportion of general surgical patients receive no prophylaxis. To determine the extent to which various prophylactic methods reduce the incidence of postoperative DVT, data from randomised controlled trials of these methods were combined by means of meta-analysis. The rates of DVT diagnosed by the fibrinogen uptake test were: control/no therapy 27.0% (95% confidence limits 21.9%, 32.1%); heparin 9.6% (7.2%, 11.9%); gradient compression stockings 11.1% (5.3%, 16.8%); intermittent pneumatic compression 17.6% (6.1%, 29.1%); heparin plus stockings 6.3% (0%, 17.6%); heparin plus dihydroergotamine 9.9% (6.2%, 13.6%); and stockings plus intermittent pneumatic compression 4.5% (1.1%, 8.0%). These results confirm the value of prophylaxis to reduce the incidence of DVT and suggest that combined treatments may be most effective.

Totally, 150 patients, subjected to total hip arthroplasty, were randomly allocated into three prophylactic groups with either conventional dextran alone or with additional graded compression stockings or with additional preoperative administration of dextran. The overall frequency of deep venous thrombosis (DVT), as studied by radioactive fibrinogen uptake test and ascending phlebography of the operated on thigh was in the conventional dextran group 46 percent, the additional stockinged group 30 percent, and in the additional preoperative dextran group 52 percent. In the stockinged group, there was a lower frequency of DVT in the nonoperated on leg as well as, on an average, about 350 mL less peroperative bleeding as compared with the other two groups. No adverse reaction occurred from dextran administration. Increased and prolonged postoperative administration of dextran decrease the number of femoral DVTs.

The fibrinogen uptake test has proved its efficiency; unfortunately the method is complicated and takes a minimum of 24 to 48 hours. If this delay is acceptable when depicting deep vein thrombosis, it becomes a problem when there is urgency. A test giving a rapid solution and which would allow to follow the evolution in image-form would be very welcome. Our hopes with marked fibrinogen (with Tc 99m) do not seem justified after this preliminary study.

Doppler ultrasound is the preferred screening test in asymptomatic patients with high risk for venous thrombosis. Radiographic phlebography leads to definitive diagnosis in most instances. Radionuclide angiography using 99mTc MAA with delayed images to detect particle entrapment in venous blood clots can be used when radiographic phlebography is contraindicated or impractical. To detect active thrombosis in patients with past venous disease, the serial fibrinogen uptake test is the method of choice. This method is also used to monitor the efficacy of anticoagulation therapy and to detect propagating thrombosis in patients failing to respond to anticoagulation, hopefully before massive lethal pulmonary embolism occurs. Radionuclide methods are contraindicated in pregnant women and children where non invasive methods are preferred. No completely satisfactory test exists for detection of hypogastric vein thrombosis. Among the methods currently being evaluated in the laboratory the ultrasound B-scan imaging, 99mTc MAA uptake test and 99mTc mAA venous scan offer the best possibilities for successful clinical application.

The main plasma fibrinogen species, high molecular weight fibrinogen (HMW, mw. 340,000) and LMW (mw. 305,000), displaying different in vitro properties, were examined as to half-life and incorporation into venous thrombi (DVT). Total plasma fibrinogen and relative amounts of HMW were measured pre- and postoperatively in eighteen patients undergoing total hip arthroplasty, and related to the occurrence of deep vein thrombosis, as determined by the fibrinogen uptake test (FUT). Total fibrinogen and HMW did not disclose significant differences between scan-negative and scan-positive groups. HMW and LMW, prepared from purified fibrinogen, were labelled with I 125 and I 131 , injected simultaneously and the incorporation into thrombi registered by leg-scanning. In 5 patients demonstrating a positive FUT, HMW as well as LMW were incorporated approximately to the same extent. This result implies that neither of these fibrinogen fractions offer any advantage as compared to ordinary fibrinogen when used for FUT. The half-lives of HMW and LMW were calculated from the elimination curves of the plasma clot-radioactivity. In all the surgical patients (n=10) as well as in the two medical DVT-patients and in two healthy volunteers the half-life of LMW was approximately 10% longer than that of HMW.

The value of elevation of the leg and elastic stockings for the prevention of deep vein thrombosis has been studied in two groups of patients using the fibrinogen uptake test for diagnosis. Neither method appears to haw any effect on the incidence of thrombosis.

Thirteen patients are described in whom the results of (125)I fibrinogen uptake testing in life were compared with the postmortem findings in the soleus muscle and in addition with direct radioactive counting of soleus muscle portions. The sensitivity of the (125)I fibrinogen uptake test was found to be approximately half that of direct muscle radioactive counting or histological examination. Some limitations of the technique are discussed.

Twenty-nine patients were operated on with the Charnley hip prosthesis. All the patients were given dextran 70 as thrombosis prophylaxis. Deep vein thrombosis (DVT) was diagnosed in 10 patients with the radioactive fibrinogen uptake test and phlebography. Variables of coagulation and fibrinolysis were studied before and after surgery. Tissue plasminogen activator (t-PA) activity in the plasma without venous occlusion decreased postoperatively, but there was no correlation with DVT. The t-PA activity in venous occlusion plasma was not reduced after surgery. Plasminogen activator inhibitor (PAI-1) levels were raised immediately postoperatively. There was a significant correlation between preoperative PAI-1 activity and development of postoperative DVT (P less than 0.05). Patients developing DVT had higher levels of PAI-1 postoperatively than patients not developing DVT. A defective fibrinolytic system, as defined by high PAI-1 activity, thus predisposed to postoperative DVT.

The [125I]fibrinogen uptake test was modified to give a quick result, and improve sensitivity and specificity in the diagnosis of deep venous thrombosis (DVT). At least 800 counts were recorded at each measuring point. The leg veins were emptied more effectively. Thus the proximal thigh could be evaluated and the influence of varicose veins reduced. The feet and the leg points were measured in a zig-zag order (from side to side) to avoid systematic errors in early diagnosis. The modified test detected 62% of the thrombi 1 h after injection, 82% after 1 day and 95% after 2 days. The method still lacks in specificity; this is unavoidable since fibrin accumulates in various other conditions than DVT. The combination of high sensitivity and low specificity makes the modified test reliable as a screening procedure, but not as an independent method.

In 81 patients with clinically suspected deep vein thrombosis, the diagnostic accuracy of thermography, 99m Tc-plasmin and 99m Tc-fibrinogen uptake tests for detecting and localizing DVT was compared with a routinely used 131 I-FUT and X-ray phlebography as reference method. Sensitivity of these tests for detection of DVT was high (0.86–1.0). 99m Tc-labelled compounds and thermography should be used for detecting rather than for localizing DVT, since sensitivity of these tests was somewhat lower in the thigh. Clinical examination and exclusion of patients with inflammatory processes, hematoma or trauma markedly increases the specificity. Uptake tests with 99m Tc-labelled compounds are fast, reliable and suitable as bedside tests.

In a prospective, double-blind investigation of the prophylaxis of deep vein thrombosis (DVT) in patients undergoing elective major abdominal surgery, 269 patients were randomized into two groups. One hundred and thirty-two patients received a fixed combination of heparin sodium 5000 units plus dihydroergotamine mesylate 0.5 mg (H/DHE) twice a day and 137 patients received a fixed combination of low molecular weight heparin 1500 units plus dihydroergotamine mesylate 0.5 mg (LMWH/DHE) once a day as well as one injection of placebo per day. Treatment was initiated 2 h pre-operatively in both groups and continued for 7–10 days. The frequency of DVT determined by the 125I-labelled fibrinogen uptake test and phlebography was 10.3 per cent in patients receiving H/DHE and 10.4 per cent in those receiving LMWH/DHE. DVT of the femoral vein was detected in four patients of the H/DHE group and in none of the LMWH/DHE group. Intra- and postoperative blood loss did not differ significantly between both groups. Also no difference in the development of wound haematoma and injection site haematoma was found. While intra-operative volume substitution was comparable in both groups, significantly more patients under H/DHE prophylaxis received volume substitution during the postoperative phase. These results show that once-daily prophylaxis with the combination of low molecular weight heparin and dihydroergotamine is equally as effective and as safe as the twice-daily regimen using a combination of unfractionated heparin and dihydroergotamine in patients undergoing elective, major abdominal surgery. The advantages of the once-daily regimen of LMWH/DHE include greater patient acceptance, less nursing time and greater cost effectiveness, provided the new combination can be sold at a cost which maintains this advantage.

The effect of hypobaric spinal anaesthesia or narcotic-halothane-relaxant general anaesthesia on the incidence of postoperative deep vein thrombosis was studied in 140 elective total hip replacements in a prospective randomised manner. Deep vein thrombosis was diagnosed using impedance plethysmography and the 125I fibrinogen uptake test, combined, in selected cases, with ascending contrast venography. The overall incidence of deep vein thrombosis was 20%. Nine patients (13%) developed deep vein thrombosis in the spinal group and nineteen (27%) in the general anaesthetic group (p less than 0.05). The incidences of proximal thrombosis and of bilateral thrombi were also less with spinal anaesthesia than with general anaesthesia. It is concluded that spinal anaesthesia reduces the risks of postoperative thromboembolism in hip replacement surgery. The presence of varicose veins, being a non-smoker and having a low body mass index were associated with an increased incidence of deep vein thrombosis.

The 125I-fibrinogen uptake test was used in rabbits after the production of thrombosis in the marginal ear vein. The uptake was very similar with thrombosis produced by irritants, thrombin as well as with inflammation without thrombosis. The 131I-albumin accumulated under these conditions to the same exten or even more than 125I-fibrinogen. The local increase of permeability seemed to represent the most important factor in the uptake of both 125I-fibrinogen und 131I-albumin.

The operative courses of 294 elective consecutive colorectal resections were reviewed in order to evaluate the morbidity and mortality of postoperative thromboembolic complications. All patients received low-dose heparin prophylaxis. Fifty-seven patients were screened for deep venous thrombosis with the fibrinogen uptake test, and treatment of thromboembolism was started if the diagnosis was established by venography and/or pulmonary scintigraphy. Neither the morbidity nor mortality from clinical thromboembolic complications was lowered in the group of patients who were screened. Rectal surgery seems to carry a higher risk of postoperative thromboembolic complications than colon surgery, and thromboembolic complications are responsible for about half of the postoperative deaths following elective colorectal surgery.

A comparison was made of the incidence of venous thrombophlebitis resulting from the use of a high-osmolality contrast medium (Conray 60%, meglumine iothalamate), and a low-osmolality contrast medium (Niopam 61%, iopamidol). In 20 patients Conray was injected into one leg and Niopam into the other. The incidence of thrombophlebitis was then determined using the iodine-125 fibrinogen uptake test in prospective, randomised, double-blind study. There was significantly less thrombophlebitis with Niopam than with Conray and it is concluded that Niopam is a safer contrast medium for phlebography.

In a randomized, prospective, double-blind multicenter trial, the effect of low-dose conventional heparin (5,000 IU/12 h) was compared to a low molecular weight (LMW) heparin fragment (5,000 antifactor Xa U/24 h). 432 patients 40 years or older undergoing elective abdominal surgery were included, 382 correctly treated. 45% had malignant diseases. The groups did not differ in risk factors. Analysis was made both on the basis of intention to treat and correct prophylaxis. No difference in results between these 2 groups was seen. Deep vein thrombosis (125I-fibrinogen) occurred in 4.3% of the low-dose heparin group and in 6.4 of the LMW heparin group. There was a significant delay in the onset of deep vein thrombosis in the LMW heparin group. Mortality, peroperative blood loss, transfusions or infectious complications did not differ. Hemorrhagic complications occurred significantly more often in the LMW heparin group (11.6%) than in the low-dose heparin group (4.6%). Significantly fewer patients experienced local injection pain in the LMW heparin group. APTT and AT III were similar in both groups, but anti-Xa activity was significantly higher in the LMW heparin group. Single daily LMW heparin injection reduced the frequency of deep vein thrombosis to the same level as low-dose heparin twice daily. The dose or administration interval of LMW heparin in this study caused significantly more bleeding complications.

One hundred and thirty-two elderly patients undergoing emergency hip surgery were randomly allocated to receive subarachnoid block (SAB) or general anaesthesia (GA). Using the 125-I fibrinogen uptake test, deep vein thrombosis was found to occur in 17 of 37 patients in the SAB group and 30 of 39 patients in the GA group (P 0.05). Blood loss was 513 ml (± SEM 44) in the SAB group and 714 ml (± SEM 67) in the GA group (P < 0.01). Hypoxaemia was present preoperatively (mean PaO2 9.2 kPa). Immediately following general anaesthesia, the mean fall in PaO2 was 0.86 kPa compared with preoperative values but only 0.16 kPa following subarachnoid block (P < 0.01). At 24 hours postoperatively the fall in PaO2 was similar in both groups and recovered only slowly during the first week. Twelve patients died, three in the SAB group and nine in the GA group. This difference in mortality was not statistically significant.

A number of newer noninvasive or minimally invasive diagnostic techniques overcome the inaccuracies of clinical diagnosis of venous disease. Among these are Doppler ultrasound; plethysmography, especially the strain-gauge technique; the 125I fibrinogen uptake test; and radionuclide phlebography. Contrast phlebography is still the procedure of choice when diagnostic controversy remains or when facilities for the other techniques are not available.

One hundred and seventy-six patients scheduled for elective major abdominal surgery were randomized to two prophylactic regimens to prevent postoperative thromboembolism. All patients were screened with the 125I-labelled fibrinogen uptake test, and thromboembolism was verified by ascending phlebography and/or perfusion/ventilation lung scintigraphy. In the group of patients receiving low-dose heparin treatment (5000 units twice daily subcutaneously) 12 per cent developed thromboembolic complications. In the other group, where low-dose heparin treatment was supplemented with graded compression stockings only 2 per cent developed thromboembolism. It is concluded that the combination of low-dose heparin and the use of graded compression stockings is superior to heparin alone in preventing thromboembolism following major abdominal surgery.

Methods currently used to diagnose deep vein thrombosis (DVT) include contrast phlebography, the 125I-fibrinogen uptake test, Doppler ultrasound, and impedance plethysmography. Contrast phlebography, considered the "gold standard" for the diagnosis of DVT, provides excellent visualization of the entire deep, muscular, and superficial venous systems.

Postoperative thrombosis detected with the 125I-labelled fibrinogen uptake test (FUT) is frequent. FUT correlates well with phlebography and a positive FUT is associated with high incidence of pulmonary embolism. This study has been performed to evaluate venous function 3–5 years after FUT-detected thrombosis. A follow-up examination was performed in 381 patients who had been studied after operation with FUT. The follow-up included a questionnaire, clinical examination, venous occlusion strain-gauge plethysmography, ambulatory strain-gauge plethysmography, venous pressure examination and, in some cases, Doppler ultrasound examination of venous valve function in the leg. No statistically significant differences were found in any parameters used between legs with and without FUT-detected postoperative thrombosis, except that more FUT-positive logs had an abnormal venous pressure decrease during exercise than FUT-negative legs. The frequency of deep venous insufficiency was equal in FUT-positive and FUT-negative legs. Moreover the frequency of deep venous insufficiency was not affected by the site of the FUT-detected thrombosis or by the different kinds of prophylactics used. The frequency of venous insufficiency was high.

The 125 I-fibrinogen uptake test (FUT) was evaluated in a series of 42 subjects to determine its ability to detect active venous thrombosis. Included were patients with recent active thrombosis, patients with long-standing quiescent venous obstruction, and normal controls. In serial tests, increasing isotope uptake was found to occur only in patients with active thrombophlebitis ( P Five patients with known calf vein thrombosis had increasing FUT results at the upper thigh. Phlebography or technetium scans confirmed propagation of the thrombosis. These results suggest a screening value for the FUT in suspected propagating thrombosis. If results are confirmed by subsequent phlebography, major therapeutic changes such as intensification of anticoagulation or venous interruptions can hopefully be made before potentially lethal pulmonary embolism occurs.

The late venous function after a postoperative FUT-detected thrombosis is unsatisfactorily documented. This study evaluated the venous status of legs with and without FUTdetected postoperative thrombosis four to five years later. Material; 50 patients (30 male, 20 female), mean age 70 years (55-4 years), who were operated on with electiv hip surgery or abdominal surgery. All were screened with FUT to detect thrombosis. 21 patients (28 legs) developed postoperative thrombosis. Methods: At follow up a clinical examination was made and a questionaire answered. Strain-gauge plethysmography and distal ambulatory venous pressure were made as well as After Exercise Thermography (AET). In 17 legs venous pressure measurement could not be performed. Results: The clinical examination and subjective symptoms did not differ between FUT-pos. and FUT-neg. legs. 29% of the FUT-pos. legs and 26% of the FUT-neg. legs had indication of deep venous insufficiency in plethysmographic and/or venous pressure recordings. Five patients with FUT-neg. legs and signs of venous insufficiency at follow-up had had a new operation during the observation time, none had had clinical signs of thrombosis. Nine patients had FUT-pos. thrombosis extending above knee, but only one had deep venous insufficiency at follow-up. AET was pos. in 39/91 legs. Of these 9 legs (24%) were FUT-pos.Conclusion: So far this study, where 250 patients are to be included, has not revealed any difference in follow-up venous function between legs with and without postoperative thrombosis as diagnosed with FUT.

The incidence of pulmonary embolism and deep vein thrombosis was measured in 50 matched pairs of patients undergoing common surgical procedures with preoperative and postoperative ventilation-perfusion lung scans and the fibrinogen uptake test. One patient in each pair was treated with intravenous dextran 70 and pneumatic leggings. The incidence of pulmonary embolism among the treated patients was significantly reduced from 24% to 8%, but the incidence of deep vein thrombosis was not significantly reduced (34% to 24%).

The fibrinogen uptake test has been used to detect deep vein thrombosis after total hip replacement in 90 patients. The upper third of the thigh in each leg was ignored and peripheral leg counting carried out distal to this. The results were directly compared with the findings of venography in the 170 legs of the 90 patients. There was a high false positive rate (30 per cent) with the fibrinogen uptake test which was associated with the presence of knee joint efusion or varicose veins, but not with the site of operation. There was a low false negative rate (less than 5 per cent), and the fibrinogen uptake test, used in this way, may fail to detect a percentage of small thrombi in the wound area that are probably produced by the local trauma of operation. It is considered that the fibrinogen uptake test has a clinical use as a screening test for deep vein thrombosis after hip replacement, but venography is required in the interests of accuracy.