David Bergqvist

Venous thromboembolism (VTE) in Europe - The number of VTE events and associated morbidity and mortality

Venous thromboembolism (VTE) is often asymptomatic, mis-diagnosed, and unrecognized at death, and there is a lack of routine postmortem examinations. These factors are thought to result in marked underestimates ofVTE incidence. The objective of our study was to estimate the total burden of VTE within the European Union (EU) per annum. An epidemiological model was constructed to estimate the number of community- and hospital-acquired incidents and recurrent cases (attack rate) of nonfatal VTE and VTE-related deaths, as well as incident and prevalent cases of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (PH) occurring in the EU per annum. Individual models were developed for six EU countries. The models were populated with data from published literature and, where necessary, expert opinions. The findings were tested using probabilistic sensitivity analyses. The estimated total number of symptomaticVTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715 (404,664-538,189) cases of deep-vein thrombosis, 295,982 (242,450-360,363) cases of pulmonary embolism (PE), and 370,012 (300,193-483,108) VTE-related deaths. Of these deaths, an estimated 27,473 (7%) were diagnosed as being antemortem; 126,145 (34%) were sudden fatal PE, and 217,394 (59%) followed undiagnosed PE. Almost three-quarters of all VTE-related deaths were from hospital-acquired VTE. VTE is a major health problem in the EU, with over one million VTE events or deaths per annum in the six countries examined. Given the availability of effective VTE prophylaxis, many of these events and deaths could have been prevented. These results have important implications for the allocation of healthcare resources.

Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high‐risk abdominal surgery

The aim of this study was to assess whether the synthetic factor Xa inhibitor fondaparinux reduced the risk of venous thromboembolism more efficiently than the low molecular weight heparin dalteparin in patients undergoing major abdominal surgery.

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.

Incidence and Clinical Presentation of Bowel Ischaemia After Aortoiliac Surgery--2930 Operations from a Population-based Registry in Sweden*

OBJECTIVES To study the incidence and clinical presentation of intestinal ischaemia after aortoiliac/femoral surgery, and to validate a vascular registry concerning a serious complication. DESIGN AND SETTING In the Swedish Vascular Registry (SWEDVASC) the outcome and complications of all vascular procedures are registered prospectively. MATERIALS AND METHODS All 2930 patients operated in 1987-93 were analysed for notified complications. A 5% random sample of all patients and a 20% random sample of fatal cases were analysed for un-notified complications. Of 415 requested patient records 413 were analysed. RESULTS The estimated incidence of bowel ischaemia was 2.8%. Among patients operated on for a ruptured aneurysm in shock it was 7.3%. Of the 63 patients with intestinal ischaemia only 15 presented with early passage of bloody stools. In 60 patients (95%) the lesion affected the left colon within the reach of a sigmoidoscope. Bowel ischemia was unnotified only in fatal cases, the estimated un-notified complication rate was 0.7%. CONCLUSIONS The incidence in this study on unselected patients did not differ from previous reports from specialised centres. Diagnosis is difficult and justifies a high index of suspicion and early use of sigmoidoscopy. The validity of the SWEDVASC registry was confirmed by a high report-rate for this complication.

Incidence and prevalence of abdominal aortic aneurysms, estimated by necropsy studies and population screening by ultrasound.

Incidence and prevalence of abdominal aortic aneurysms, estimated by necropsy studies and population screening by ultrasound.

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.

Risk Factors for Intestinal Ischaemia after Aortoiliac Surgery: a Combined Cohort and Case-control Study of 2824 Operations

OBJECTIVE To identify risk factors for intestinal ischaemia after aortoiliac surgery. MATERIALS AND METHODS Among 2824 patients operated on during 1987-93 and registered prospectively in the Swedish Vascular Registry, 62 cases of postoperative intestinal ischaemia were identified. They were compared with the remaining 2762 patients through the registry and with a random sample of 127 controls through patient records. Multivariate analysis was performed. RESULTS Patients in shock operated on for ruptured aneurysms were at greatest risk of developing postoperative intestinal ischaemia. Excluding patients in shock, operation for aneurysmal disease and for occlusive disease carried the same risk. Renal disease, emergency surgery, age, type of hospital, aortobifemoral graft, operating time, cross-clamping time and ligation of one or both internal iliac arteries were independent risk factors. CONCLUSIONS Patient-related haemodynamic risk factors together with surgical skill and decision making defines the risk for this serious complication.

Intestinal ischemia -- the basics.

Introduction: In this review the physiology of the intestinal circulation of importance for the understanding of intestinal ischemia is briefly outlined. Perspectives: The potential threat of massive intestinal vasoconstriction causing nonocclusive intestinal ischemia is discussed, as is the clinical importance of the reperfusion component of the ischemic injury. The clinical causes of intestinal ischemia are outlined. The delay in the usual clinical diagnostic process and its severe consequences are emphasized. Emphasis is made to discuss the special situation with sigmoid gangrene following surgery for ruptured aortic aneurysm. Laparotomy upon clinical suspicion of intestinal ischemia is generally recommended. The various therapeutic surgical measures available if diagnosis is made before massive intestinal gangrene are discussed.

A Prospective Comparison of Duplex Ultrasonography, Captopril Renography, MRA, and CTA in Assessing Renal Artery Stenosis

Purpose: To prospectively compare the diagnostic accuracy of duplex ultrasonography, captopril renography, computed tomography angiography (CTA), and 3D Gd magnetic resonance angiography (MRA) in diagnosing hemodynamically significant renal artery stenosis (RAS). Material and Methods: The standard of reference was measurement of transstenotic pressure gradient. Fifty-eight hypertensive patients with suspicion of RAS were evaluated, when possible, by all five techniques. Sensitivity and specificity to detect RAS were compared for each technique on both a patient and kidney basis. Discrepancies were evaluated separately and classified as borderline, method dependent, or operator dependent. Results: The prevalence of RAS was 77%. The sensitivity/specificity of ultrasonography, captopril renography, CTA, and MRA in detecting kidneys with RAS was 73/71%, 52/63%, 94/62%, and 93/91%, respectively. Ultrasonography had a significantly lower sensitivity than CTA and MRA (P<0.001) but higher than captopril renography (P = 0.013). Borderline RAS was the main cause for discrepancies. Conclusion: MRA and CTA were significantly better than duplex ultrasonography and captopril renography in detecting hemodynamically significant RAS. The ultrasonography criteria for RAS based on the evaluation of renal peak systolic velocity and renal/aortic ratio are questionable. Captopril renography cannot be recommended for assessing RAS.

Safety assessment of new antithrombotic agents: Lessons from the EXTEND study on ximelagatran ☆

BACKGROUND Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.