Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial.

OBJECTIVES: To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. DESIGN: Prospective randomised double blind multicenter study. MATERIALS AND METHODS: Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. RESULTS: At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. CONCLUSIONS: In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.

Long-term prognosis for patients with chronic leg ulcers: a prospective cohort study.

OBJECTIVES: To assess the long-term prognosis of leg ulcers. DESIGN: A 5 year prospective cohort study. MATERIALS: A random sample of 382 patients with open leg ulcers (foot ulcers included) treated in the community. METHODS: Interim analyses were made at 15 months (arterial ulcers) and at 20 months (varicose ulcers). Long-term healing was assessed at 54 months by a postal questionnaire. Five year survival was assessed by official population registries. RESULTS: At 54 months 212 patients (55%) were still alive, of whom 124 (58%) had healed their ulcers, 80 (38%) had open ulcers and eight (4%) were amputated. The healing was worst for patients with venous ulcers, only 44% had healed their original ulcers without recurrence. The 5 year survival was 52%, significantly lower than for age- and sex-matched controls (68%) (p = 0.0002). Patients with venous ulcers had a survival not significantly different from controls and patients with arterial or other aetiologies had a doubled risk of death. Diabetic patients had a lower survival than non-diabetics (p < 0.05) and controls (p < 0.0001), but the healing prognosis was not significantly different. CONCLUSION: Only patients with non-venous ulcers have a higher mortality than expected. The long-term healing prognosis for leg ulcer patients is poor and worst for patients with venous ulcers.

The prevalence of chronic lower-limb ulceration has been underestimated: results of a validated population questionnaire.

A validated population questionnaire was used to survey 12,000 randomly selected inhabitants, aged 50-89 years, in two defined regions of Sweden. The sample included 7 per cent of the total population in the age interval. Overall response rate was 91 per cent. Open ulcers were reported by 306 subjects and 143 (47 per cent) agreed to be examined. The false-positive response rate was high (43 per cent). The observed point prevalence of open leg ulcers was 0.63 (95 per cent confidence interval 0.54-0.72) per cent of the total population. The overall prevalence of leg ulcer history (open plus healed) in the population was estimated to be around 2 per cent and the ratio of open: previous ulcers was 1:2. This study shows a point prevalence more than double that expected, indicating a high rate of self treatment. Assessments of leg ulcer prevalence through the health care system, without knowledge of the rate of self care, measure only the workload of health care professionals. The problem of leg ulcers has generally been underestimated.

Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients.

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 XaI 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 XaI 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 XaI 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 XaI 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 and non-venous leg ulcers: clinical history and appearance in a population study.

In a defined Swedish population of 270,800, all patients with current chronic leg ulcers (827) were identified and a random sample of 382 studied in detail. Ulcers of primarily venous cause comprised 54 per cent of the total, giving a point prevalence of 0.16 per cent (95 per cent confidence interval 0.15-0.18 per cent). Half of all patients experienced their first ulcer episode before the age of 65 years, a greater proportion (61 per cent, P < 0.0001) in the subgroup with venous ulcers. The median duration of ulcer diathesis was significantly longer in patients with venous than in those with non-venous lesions (13.4 versus 2.5 years, P < 0.001). About half the patients with venous and non-venous ulcers had had their current lesion for longer than 1 year. Venous ulcers were more often recurrent than those of non-venous type (72 versus 45 per cent of patients, P < 0.0001). Patients with venous ulcers had a significantly higher body mass index (P < 0.001). The number of dressing changes performed per week was 1100 per 100,000 population. The predictive value of 'classical' clinical indicators of venous ulcer did not exceed 0.76. To increase the accuracy of diagnosis of venous ulcer, clinical examination should be combined with non-invasive 'objective' haemodynamic assessment of the venous circulation.

High prevalence of diabetes in chronic leg ulcer patients: a cross-sectional population study.

In a cross-sectional survey, designed to detect all patients with current chronic leg ulcers, 27% of the patients had diabetes mellitus. The outcome for the 104 examined diabetic patients has been evaluated and compared with the 278 nondiabetic patients. The purpose was to establish the prevalence of leg ulcers among diabetic patients and to assess potential causes. The point prevalence was calculated by extrapolating the leg ulcer frequency to the total diabetic population in the studied area. The point prevalence for active leg ulcers (including foot ulcers) in diabetic patients was 3.5% (95% CI 2.8-4.2). Ulcers above the malleoli were almost as common as foot ulcers. Peripheral vascular disease was present in 67% of all ulcerated legs in patients with diabetes compared to 42% in nondiabetic patients (p < 0.001). In 72% of foot ulcers in diabetic patients arterial impairment was judged to be a contributing aetiological factor and in nondiabetic patients 45% (p < 0.001). Ulcers solely attributed to possible neuropathy were less common (15%). Ulcers with multifactorial causes were common above the malleoli. This survey has given the size of the problem and indicates macroangiopathy to be the dominating factor responsible for slow or nonhealing ulcers in diabetic patients. Objective assessment of arterial circulation is mandatory and signs of arterial impairment require consultation with a vascular surgeon.

Leg ulcer etiology--a cross sectional population study.

Three hundred eighty-two patients with active leg ulcers were clinically examined after random selection out of a population of 827 patients identified within a previous cross-sectional population survey. Bidirectional Doppler ultrasonography was used for objective assessment of arterial and venous circulation. The purpose was to register causative factors and the etiologic spectrum. Venous insufficiency was present in 332 (72%) of 463 legs with active ulceration; deep insufficiency occurred in 176 (38%), and purely superficial insufficiency was present in 156 (34%). Ankle/brachial index was 0.9 or less in 185 (40%) of ulcerated legs. Venous insufficiency was the dominating causative factor in 250 legs (54%), of which 60% was the result of deep venous insufficiency. Arterial insufficiency was judged to be the possible dominating factor in 12%, and 6% showed clearly ischemic ulcers. Mixed ulcers with combined arterial and venous insufficiency were found to be common as were patients with diabetes and arterial impairment. In 10% of the legs a multifactorial origin was present, and in 10% no venous or arterial impairment was detectable. Thus after classification of causes 40% of all ulcerated legs showed potentially surgically curable circulatory disturbances. It is necessary to objectively assess all patients with chronic leg ulcers to be able to detect patients with potentially surgically curable disease.

Chronic leg ulcers: an underestimated problem in primary health care among elderly patients.

STUDY OBJECTIVE: The aim was to establish leg ulcer point prevalence, basal patient characteristics, and level of caretaking. DESIGN: The study was a postal cross sectional survey. The validity was ensured by examining a randomly selected sample of reported patients. Responding health care officials were asked to report all patients with an open wound below knee (including foot ulcer) which did not heal or was supposed to heal within a six week period after onset of ulceration. Response rate was 92%. SETTING: Inpatient and outpatient care in hospitals, community health care, and private nursing homes within Skaraborg county, with a population of 270,800. PARTICIPANTS: 827 individual patients were found with active leg ulcers, 526 women and 301 men. MEASUREMENTS AND MAIN RESULTS: Age adjusted sex ratio of ulcer patients was 1:1.4 (M:F). The median age was 78 years for women and 76 for men; 700 patients (85%) were older than 64 years. The point prevalence for active leg ulcers was 3.0/1000 total population. District nurses provided care for 680 patients (82%), 106 (13%) were in hospital care, and 41 (5%) were managed by outpatient departments. CONCLUSIONS: There has been an underestimation of the leg ulcer problem among elderly patients, especially men. With an expected increasing number of elderly people it is important that this problem is recognised and measures taken to improve the primary care of these patients.

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.

Late symptoms after pregnancy-related deep vein thrombosis.

Thromboembolism during pregnancy is a rare complication with a potential fatal outcome. Very little is known about long-term effects and therefore 104 women with thrombosis during pregnancy or puerperium were identified and their subjective complaints were assessed in a questionnaire. All had their thrombosis diagnosed by objective methods and the median follow-up time was 11 years. In spite of anticoagulant treatment only 22% were without complaints; 4% had ulceration, all occurring in the group with thrombosis during pregnancy. Significantly more women who had had their thrombosis during pregnancy used compression bandages than those who had their thrombosis during puerperium. The severity of the symptoms increased with the increasing number of thromboses. Anticoagulant therapy of the acute episode does not appear to alter the degree of long-term handicap in the lower limbs.

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.

Secondary aortoenteric fistulas--an analysis of 42 cases.

Secondary aortoenteric fistulas are seen with an increasing frequency which parallels the expansion of reconstructive vascular surgery. During a 12-year period 42 cases have been collected from the hospitals, which perform most of the vascular surgery in Sweden (0.7% of vascular operations). Twenty-five were seen after operation for aortic aneurysm, 15 for aortoiliac occlusive disease, one after renal artery ligation (as a part of reconstruction for renovascular hypertension) and one after operation for an iliac pseudoaneurysm. The frequency of complications during and after the primary operation was high. The interval between operation and onset of fistula symptoms was significantly shorter if there had been infectious complications, the median interval was 32 months, the longest being 10 years. The most important symptom was gastrointestinal haemorrhage, consisting of several small bleeds often combined with septic complications. A large number of negative investigations usually preceded the final diagnosis which was made at exploratory laparotomy. After surgery for the fistula the frequency of complications and mortality, were very high. Mortality was 58%, the most common cause of death being a blow out of the aortic stump. Of those leaving hospital, several further operations were performed with a high mortality. Recurrence of the fistula occurred in 16 out of 34 patients who survived surgery. At follow-up (12-74 months after fistula closure) seven patients were still alive.

Late venous function in the leg after deep venous thrombosis occurring in relation to pregnancy.

The frequency of deep venous insufficiency was investigated in 23 patients 3-10 years (mean 7 years) after they had developed an objectively diagnosed deep venous thrombosis (DVT) during pregnancy or the first week after delivery. Investigations included clinical examination, listing of symptoms and plethysmography, venous pressure and Doppler ultrasound. At follow-up there were clinical signs or symptoms of venous insufficiency in 35% of the legs with earlier DVT but in none of the non-thrombosed contralateral legs. Objective evidence of venous insufficiency was present in 15 (65%) of the legs with earlier DVT and in only five (22%) of the non-thrombosed legs. The differences between thrombosed and non-thrombosed legs are statistically significant. There was no correlation between objectively measured venous insufficiency and extent of the DVT. It is concluded that a DVT during pregnancy often leads to venous insufficiency and the risk seems to be higher than after DVT occurring in other groups of patients.

Venous function after fracture of the lower extremity. A 9-year follow-up of 150 cases.

One hundred and fifty patients were examined 8-10 years after a fracture of the lower limb to evaluate whether the frequency of deep venous insufficiency (DVI) was influenced by the type of fracture. The evaluation included clinical examination, subjective complaints, venous pressure, plethysmography and doppler sonography. Symptoms and signs of DVI were more common in the fractured than in the uninjured limbs, while objectively diagnosed DVI did not differ between the groups. Only minor differences were present in the development of DVI between limbs with various types of fracture (hip fractures were not included in the study). High age and incompetence of the popliteal valves were more important in the development of DVI than the earlier fracture. The frequency of objectively measured DVI in the fractured limbs was 35 per cent and in the uninjured limbs 30 per cent.

Venous function five to eight years after clinically suspected deep venous thrombosis.

One hundred and fifty-four patients, who had been subjected to phlebography 5-8 years previously because of clinical suspicion of deep venous thrombosis (DVT), were investigated to evaluate the frequency of deep venous insufficiency (DVI). The evaluation included clinical examination, registration of subjective complaints and objective measurements with plethysmography, venous pressure and Doppler ultrasound. DVT had been present in 75 legs. There were no statistically significant differences between legs with and without earlier DVT apart from more venous outflow obstruction in the former. DVI was as common after calf vein thrombosis as after more proximal DVT. DVI was more frequent in elderly patients and in patients with a history of previous DVI or DVT. The sufficiency of the popliteal vein seemed to be of great importance in the development of DVI. More than one third of legs without DVT had developed DVI at follow-up.

Deep venous insufficiency after postoperative thrombosis diagnosed with 125I-labelled fibrinogen uptake test.

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 legs 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.

Postoperative haemostatic changes in patients given thromboembolic prophylaxis with dextran 70--alone, or in combination with dihydroergotamine.

Haemostatic changes were studied in 107 patients undergoing elective general and urologic surgery or hip replacement. All patients received dextran 70 and half of them, randomly chosen, were also given dihydroergotamine. Blood samples were taken before operation and on the fourth postoperative day. In all patients increases in factor VIII:C, VIII:R Ag and fibrinogen were noted, and decreases in thrombin time, antithrombin III and alpha 2-macroglobulin. In patients undergoing hip replacement, alpha 2-antiplasmin (measured amidolytically) also increased. No major intergroup differences were noted. Comparison between elective hip patients given general anaesthesia and those given epidural analgesia revealed no major differences in haemostatic response. From our findings it would appear that the coagulation and fibrinolytic systems remain unaffected by dihydroergotamine.

After-exercise thermography compared to strain-gauge plethysmography and venous pressure measurements to detect deep venous insufficiency.

After-exercise thermography (AET) has been claimed to be a means of detecting deep venous insufficiency. The question was studied in 167 patients four to five years after major surgery. The tests af follow-up included AET, strain-gauge plethysmography and venous pressure measurements in addition to clinical examination and a questionnaire concerning history, symptoms etc. No correlation was found between abnormal AET and objective manifestations of deep venous insufficiency.

Venous function in the leg after postoperative thrombosis diagnosed with 125I-fibrinogen uptake test.

The 125I-fibrinogen uptake test (FUT) has been widely used in the past decade to detect postoperative thrombosis. FUT has been shown to correlate well with phlebography, and positive FUT is associated with a high frequency of pulmonary embolism. The long-term venous function of the leg after FUT-detected postoperative thrombosis, however, is inadequately documented. In 179 patients who had been studied after operation with FUT, a follow-up evaluation of FUT as an indicator of risk for development of deep venous insufficiency was made four to five years later. The patients replied to a questionnaire, were clinically examined, and underwent venous strain-gauge plethysmography, venous pressure measurement, and, in some cases, phlebography. No statistically significant differences were found in any of the parameters between legs that had been FUT-positive and those that were FUT-negative at the time of the operation. The frequency of deep venous insufficiency thus was equal in FUT-positive and FUT-negative legs. It was also independent of the site of FUT-detected thrombus in the leg.

Lung complications after elective hip surgery.

A total of 350 patients undergoing elective hip surgery were retrospectively studied as regards pulmonary complications. The study is based on the findings of pre- and postoperative chest X-rays and of pulmonary perfusion scintigrams. Twenty-seven per cent of the patients had pulmonary complications of some kind. Twelve per cent had a change in the postoperative as compared to the preoperative X-ray, though most of the changes were minute. In 15.4 per cent there were scintigraphic signs of pulmonary embolism and of these 30 per cent of the patients had symptoms of pulmonary infectious disease. Two patients died from pulmonary embolism. The study shows a low frequency of serious pulmonary complications after elective hip surgery.