Experience with a new percutaneous port system, Percuseal, for intravenous injection in patients with haemophilia, von Willebrand disease and severe alpha1-antitrypsin deficiency.

We have implanted a new port system (Percuseal) in altogether 13 patients with haemophilia A, B, von Willebrand disease and alpha1-antitrypsin deficiency in order to facilitate venous access. The Percuseal system differs from subcutaneous ports, such as Port-a-Cath, in that the upper part of the device protrudes above the skin. In this way, the patient can easily puncture the port membrane under the guidance of his eyes without penetrating the skin. In the present study cohort, a number of complications occurred. These were mainly caused by repeated local infections (in five patients), which made it necessary to replace the ports in three of the patients and to permanently remove the ports as the first option in two of the patients. In one patient, the port was removed because of inconvenience when doing physical exercise. In one additional patient, a severe systemic infection occurred, causing spondylitis. Despite the high infection rate, most patients considered the device very convenient to use. Because of the side-effects seen in our study, the Percuseal port in its present form is not to be recommended for regular use. A reconstruction of the port, making it smaller and giving it an antibacteriostatic cap, may possibly make this kind of port system a feasible alternative to use in order to improve pharmacoeconomics in the prophylactic treatment of haemophilia and patients with alpha1-antitrypsin deficiency.

Interleukin-1 receptor antagonist is detectable in human carotid artery plaques and is related to triglyceride levels and Chlamydia pneumoniae IgA antibodies.

OBJECTIVES: To investigate whether the interleukin-1 receptor antagonist (Il-1ra) and interleukin-1beta (Il-1beta) can be detected in human carotid artery tissue, and whether their presence is related to evidence of Chlamydia pneumoniae infection, risk factors for atherosclerosis, and clinical data. SETTING: Departments of Vascular Diseases and Surgical Pathophysiology, University Hospital, Malmö, Sweden. SUBJECTS: A total of 66 patients undergoing carotid endarterectomy (median age 74, range 53-89 years, 26 women). Il-1beta and Il-1ra were studied in carotid artery plaques and in Il-1ra in serum. RESULTS: Interleukin-1 receptor antagonist was detected in mononuclear cells in plaques from 37/66 (56%) patients. Patients with Il-1ra in plaques showed higher [2.04 (1.70-3.14) mmol x L(-1) vs. 1.69 (1.09-1.99) mmol x L(-1); P < 0.05] serum(s-)triglyceride(tg) levels, and a higher frequency of IgA seropositivity for C. pneumoniae (76% vs. 52%; P < 0.05) than those without. S-Il-1ra levels correlated with s-tg levels (r=0.38; P=0.047). There were no differences between patients with and without Il-1ra in plaques concerning s-Il-1ra, blood(b-)haemoglobin or leucocyte count, s-cholesterol, b-glucose, blood pressure, IgG seropositivity for C. pneumoniae, prevalence of neurological symptoms preceding operation, smoking, or diabetes mellitus. There were no differences in frequency of Il-1ra in plaques or in s-Il-1ra levels between patients with symptomatic and asymptomatic stenosis, between smokers and nonsmokers, or between diabetic and nondiabetic patients. Il-1beta was not detected in plaques in the current study. CONCLUSION: Interleukin-1 receptor antagonist can be detected in human atherosclerotic carotid artery plaques, and is related to s-triglyceride levels and IgA seropositivity for C. pneumoniae, but not to prevalence of neurological symptoms related to embolization.

Predictors of carotid endarterectomy in middle-aged individuals.

The objective was to investigate which screening variables in a population study predicted carotid endarterectomy. Among 793 carotid endarterectomies performed at Malmö University Hospital between 1991 and 1998, 85 patients (14 females) were identified that had participated in a population screening between 1974 and 1991. Median time from screening to operation was 16 years (range 6-26 years). Screening variables were compared with corresponding values from the background screening population (n = 33261). As operated patients were older than the background population at screening (49 [37-60] vs. 46 [26-61] years; p < 0.0001), comparisons were age-adjusted. Operated patients had higher systolic blood pressure (SBP; 130 [126-133] vs. 125 [125-125] mmHg; p < 0.01), serum total cholesterol (6.1 [5.9-6.3] vs. 5.7 [5.7-5.7] mmol/l; p < 0.0001), serum triglyceride (1.4 [1.3-1.6] vs. 1.1 [1.1-1.1] mmol/l; p < 0.0001), serum glutamic acid transferase (0.46 [0.40-0.53] vs. 0.40 [0.40-0.41] microkat/l; p < 0.05), and plasma fibrinogen (3.77 [3.42-4.16] vs. 3.35 [3.30-3.41] mmol/l; p < 0.05) levels, a lower 120-min insulin/glucose ratio at an oral glucose tolerance test (OGTT; 0.48 [0.38-0.58] vs. 0.60 [0.59-0.61]; p < 0.05) and forced vital lung capacity (3.7 [3.6-3.9] vs. 3.9 [3.9-4.0] l/min; p < 0.05), and a higher prevalence of smoking at screening (68% vs. 45%; p < 0.0001). Smoking, SBP, serum total cholesterol, and the 120-min insulin/glucose ratio remained independent predictors for carotid surgery in multivariate analysis. No differences existed among patients operated on because of symptomatic and asymptomatic stenosis. In conclusion, increased SBP and total cholesterol, lower 2-h insulin/glucose ratio at an OGTT, and smoking predict carotid surgery at long-term follow-up.

Thromboprophylaxis with low-molecular-weight heparin: economic considerations.

Postoperative thromboembolic events are a major cost factor for every healthcare system. Although thromboprophylaxis carries its own costs, the application of a thromboprophylactic regimen is cost-effective in most instances, at least in high-risk patients. A regimen of general postoperative prevention of deep vein thrombosis is always more cost-effective than surveillance programmes with treatment after diagnosis, and is almost always more cost-effective than no prophylaxis. For patients with a high risk of postoperative thromboembolism, such as after orthopaedic surgery, low-molecular-weight heparins have a rather clear advantage over prophylaxis with unfractionated heparin and warfarin, also in terms of cost- effectiveness. With regard to moderate-risk patients, such as after general surgery, the economic benefits are less clear. However, since the results of economic analyses are heavily dependent on the healthcare system, and since there are methodological difficulties and uncertainties connected with the analyses, the implications are difficult -- if not impossible -- to generalize. There is an urgent need for further prospective studies, which should be performed with defined economic variables a priori and in close cooperation with health economists.

Location of postoperative deep vein thrombosis in relation to age and survival.

The aim of the study was to determine the effect on long-term survival of the location of DVT in relation to age groups and side of operation. 1310 patients undergoing total hip arthroplasty and who participated in one of 7 randomized, prospective clinical trials with thromboprophylaxis were included in this analysis. A trend analysis showed that the incidence of proximal and distal DVT increased significantly with age (p<0.05). In patients older than 64 years of age the relative risk of death was non-significantly higher when proximal DVT was present compared to patients without DVT and the relative risk of death was non-significantly higher in patients older than 74 years of age when distal thrombi was present compared to patients without DVT. The test for trend showed an increase with age in the incidence of both ipsi- and contralateral DVT; the increase was significant in patients with contralateral DVT (p<0.05). The relative risk of death was higher (of borderline significance) in patients older than 74 years of age with contralateral DVT.In conclusion, the pattern of location of asymptomatic deep vein thrombosis changes with increasing age. The location of asymptomatic and treated DVT has no significant influence on long-term survival.

Comparison of the cost of preventing postoperative deep vein thrombosis with either unfractionated or low molecular weight heparin.

The relative costs were analysed of (1) no prophylaxis against deep vein thrombosis (DVT), (2) selective treatment of DVT after confirmation of diagnosis, (3) general prophylaxis with standard low-dose unfractionated heparin and (4) general prophylaxis with low molecular weight heparin (LMWH) in patients undergoing elective general abdominal surgery or elective hip surgery. The mean calculated costs per patient undergoing general abdominal surgery were: Swedish crowns (SEK) 1950 for no prophylaxis, SEK 5710 for selective treatment of DVT, SEK 735 for prophylaxis with unfractionated heparin and SEK 665 for prophylaxis with LMWH. The corresponding costs for hip surgery were SEK 3930, SEK 10790, SEK 1730 and SEK 1390 respectively. Thus, the least expensive management strategy in patients undergoing elective general abdominal or hip surgery would appear to be general prophylaxis with either unfractionated heparin or LMWH. Furthermore, general prophylaxis with LMWH would appear to be more cost-effective than general prophylaxis with unfractionated heparin.

Accuracy of duplex sonography before carotid endarterectomy--a comparison with angiography.

OBJECTIVES: The aim of this prospective study was to contribute to the evaluation of the reliability of Duplex sonography (DS) before carotid endarterectomy (CEA). DESIGN: The study was performed prospectively in a university hospital setting. METHODS: Eighty-one consecutive patients aged 49-83 years were examined with DS and carotid angiography (CAG) before CEA. The results of the DS were judged as either confident, or CAG was assessed to be necessary preoperatively. The results from the DS and the CAG were then compared. RESULTS: DS was judged as confident in 148 of the 162 arteries examined. In none of these 148 arteries did CAG change patient management in any way, and the agreement between DS and CAG was good. In the remaining 14 arteries CAG was judged necessary, in 11 arteries because DS assessed the internal carotid artery (ICA) as occluded, which was confirmed by CAG in 10 arteries. In three arteries the reason was poor quality of the DS, however these three arteries were correctly assessed as severely diseased. CONCLUSIONS: This study confirms that DS alone is sufficient in the preoperative evaluation before CEA, provided that CAG is performed whenever DS shows occlusion of the ICA, or when the quality of the DS is poor.

Thromboprophylaxis with a low molecular weight heparin (tinzaparin) in emergency abdominal surgery. A double-blind multicenter trial.

In this prospective randomized double-blind study the thromboprophylactic effect of postoperative low molecular weight heparin (tinzaparin) was compared with placebo in 80 patients undergoing emergency abdominal surgery. The fibrinogen uptake test was used but because of withdrawal of the labelled fibrinogen from the market the calculated number of patients was not reached. However, this is one of the few studies in emergency abdominal surgery we thought it important to report. The frequency of deep vein thrombosis was reduced with prophylaxis from 22% (95% conf. intervall 11-38%) to 8% (2-21%), a risk reduction of 65%, which is however not significant. Together with data from the few previously published studies it can be concluded that patients undergoing emergency abdominal surgery seem to benefit from prophylaxis, which should be instituted either before operation or at latest 24 hours after. The exact prophylactic relation between pre- and post-operative start would, however, require a separate, randomized study.

Survival in patients undergoing total hip arthroplasty in relation to thromboprophylaxis with low molecular weight heparin: a long-term follow-up study.

The aim of the study was to determine the long-term survival in patients undergoing total hip arthroplasty in relation to type of perioperatively administered thromboprophylaxis. Patients from seven randomized controlled trials of the effect of thromboprophylaxis on development of early thromboembolic complications after total hip arthroplasty were included in a follow-up analysis with death as the end-point. There was no difference in survival between groups receiving active thromboprophylaxis, but there was a general trend towards a better survival in the 3 placebo groups compared with low molecular weight heparin (LMWH), (RR: 1.53; C.I.: 1.04-2.25). There was a significant excess of cardiovascular deaths in the LMWH groups (RR: 2.48; CI: 1.45-4.24). Long-term prospective studies should be performed to assess the long-term effect of various thromboprophylactic regimens on morbidity and mortality after total hip arthoplasty.

Intraplaque haemorrhage at carotid artery surgery--a predictor of cardiovascular mortality.

OBJECTIVE: To ascertain whether carotid intraplaque haemorrhage (IH) in patients undergoing carotid artery surgery is a predictor of increased cardiac mortality over a 5.5 year follow-up. DESIGN AND SUBJECTS: Carotid artery plaques were obtained at surgery from 47 consecutive patients (41 men, six women), median age 67 (range 48-81) years, with symptoms of carotid transient ischaemic attacks (TIAs) or carotid territory minor stroke. As determined at preoperative angiography, the degree of stenosis was 50-99%. Specimens were classified histologically as manifesting severe atherosclerosis, fibrous plaque, IH, or residual IH debris. SETTING: Medical Angiology and Vascular Surgery Units, Malmö General Hospital. INTERVENTION: Carotid endarterectomy. MAIN OUTCOME MEASURE: Correlation between mortality and IH. RESULTS: At follow-up after 5.5 years, mortality was 28% (13/47) overall, 92% (12/13) in the IH subgroup [of stroke (n = 1) or myocardial infarction (n = 11)], but only 3% (1/34), of pancreatic cancer, in the non-IH subgroup (P = 0.0001). Mortality was also significantly higher in the severe atherosclerosis than in the fibrous plaque subgroup, 39% (12/31) vs. 6% (1/16) (P = 0.044), but not significantly increased in any other subgroup (fibrous plaque, residual IH, TIA, minor stroke, or acetylsalicylic acid or anticoagulant treatment). No correlation existed between IH or death and haemoglobin value or platelet count. CONCLUSIONS: Evidence of recent IH seen at carotid artery surgery may be a marker of cardiovascular mortality. As IH was also found in a post-mortem control subgroup, the difference may be due to abnormality in blood components (e.g., coagulation factors) or impaired vessel-wall healing capacity (e.g. endothelial dysfunction).

Study of the interaction of dextran and enoxaparin on haemostasis in humans.

The effect on haemostatic variables by dextran 70, enoxaparin and their combinations, given in doses of 500 ml i.v. and 40 mg s.c. respectively, was studied in a randomised cross-over fashion in twelve healthy male volunteers. Antifactor-IIa activity, antifactor-Xa activity, APTT, factor VIII, vWF, bleeding time and blood counts were analysed over a 24-h period. Dextran alone did not affect antifactor-IIa activity and antifactor-Xa activity. No difference in antifactor-IIa and antifactor-Xa activity was found for Amax, tmax, AUC0-8 h and AUC0-24 h in the groups treated with enoxaparin or the combination of enoxaparin and dextran. Only minor changes in APTT were observed without statistical significance between the treatment groups. Factor VIII did not change significantly in the three treatment groups. However, vWF was significantly reduced in the dextran and the dextran/enoxaparin group (p = 0.046 and 0.01 respectively) but no difference was found between the two groups. Bleeding time was not significantly increased four hours after administration of the test substances and no difference was found between the individual treatment groups. Our findings indicate that dextran can be combined with enoxaparin, when used in thromboprophylactic doses, without increased risk for bleeding.

Effect of low molecular weight heparin, dextran and their combinations on experimental venous thrombosis in rabbits.

An experimental model based on the combination of endothelial damage and flow reduction was used to induce jugular vein thrombosis in rabbits. The effect on thrombosis of a low molecular weight heparin (LMWH [Fragmin]), dextran 70, placebo and their combination was studied in a double-blind fashion with actual doses used in clinical thromboprophylaxis. Saline and polygeline were used as placebo in the control group. Four groups with 120 isolated vein segments in 60 animals were studied for presence of thrombus formation, occlusive thrombi and thrombus weights. Dextran reduced the thrombus weights (p = 0.048) and the formation of occlusive thrombi (p = 0.01), but not the formation of thrombi when compared with the placebo control group. Similarly, LMWH reduced the thrombus weights (p = 0.046), the formation of thrombi (p = 0.007) and occlusive thrombi (p = 0.0001). Compared with the LMWH group the group treated with the combination of LMWH and dextran was found to reduce the frequency of occlusive thrombi (p = 0.03) and numerically, but not significantly, further reduce the overall frequency of thrombosis (p = 0.18) and thrombus weights (p = 0.11). The results are consistent with an augmentation of the antithrombotic effect of LMWH by dextran 70. The need for further evaluation of the combined efficacy of LMWH and dextran is apparent from this study.

[Cost-effectiveness of the prevention of postoperative thromboembolism]. / Die Kosteneffektivität in der Prävention postoperativer Thromboembolien.

Awareness of cost-effectiveness aspects has become increasingly important within the health care sector in times of constrained resources. Health economics deal with methods of making choices under conditions of uncertainty and provide models for decision making. A key question is to compare alternative strategies. Within the field of prophylaxis against venous thromboembolism general thromboprophylaxis is cost-effective provided that the frequency of deep vein thrombosis is higher than 10%. Diagnostic screening and selective treatment of detected thrombosis is always the least cost-effective alternative. Although detailed analyses are still lacking it seems as if the use of low molecular weight heparins is more cost-effective than unfractionated low dose heparin. Besides saving lives by preventing fatal pulmonary embolism an adequate thromboprophylaxis also will provide monetary savings.

Natural history of patients with unoperated atherosclerotic carotid artery disease--results from a retrospective study.

The natural history of carotid artery disease was studied in a retrospective study of 609 angiograms performed during 1969-1979 on patients who had subsequently not been operated on. The indication for angiography differed, but was aimed at clarifying suspected cerebrovascular events. 578 patients could be followed-up after a median time of 10.4 years (0-22). The median survival time after angiography was 9.7 years for the 355 men and 12.8 years for the 223 women (p = 0.0099). Internal carotid stenosis of > 50% was seen in 9.0% (bilaterally in 2.2%), a stenosis > 75% in 4.5% (bilaterally in 0.9%) and occlusion in 9% (bilaterally in 0.7%). Ulceration was present in 10.7% (bilaterally in 1.6%). 26.5% of the patients had a cerebrovascular event during follow-up, of which 31.4% had transient ischaemic attack or amaurosis fugax. Survival was not influenced by the degree of stenosis, but presence of arteriosclerotic carotid artery disease significantly reduced the median survival time from 11 to 3 years. The main cause of death for men was myocardial infarction (27.7%) and for women a cerebrovascular event (27.8%), a significant difference. From this study, in selected patients it can be concluded that the annual frequency of cerebrovascular events was low, approaching frequencies reported in asymptomatic patients. The cause of death differed between men and women, with more cardiac deaths among men and more cerebrovascular deaths among women.

Cost/benefit aspects on thromboprophylaxis.

Several studies have shown thromboprophylaxis of any kind to be more cost-effective than no prophylaxis or general diagnostic surveillance and selective treatment. Little has been written on low molecular weight heparins from the cost-effectiveness point of view. This preliminary study shows low molecular weight heparin to be more cost-effective than standard low-dose heparin in most situations of prophylaxis.

Thromboprophylaxis in emergency surgery.

Except for hip fracture surgery, emergency surgery has been only exceptionally studied concerning thromboprophylaxis. There are, however, several reasons to believe the frequency to be fairly high and that the patient group would be in need of prophylaxis. This paper discusses various emergency situations and also gives the design for an ongoing controlled study on the effect of postoperative start of thromboprophylaxis with low molecular weight heparin in emergency abdominal surgery.