Use of low molecular weight heparin in pregnancy.

In a controlled study of 15 pregnant patients undergoing therapeutic termination of pregnancy, seven received subcutaneously 5,000 anti-FXa units of low molecular weight (LMW) heparin 15 and 3 h prior to the termination, and eight patients acted as controls. Paired maternal and fetal blood samples were taken (before or immediately after the termination) for assay of heparin activity by a chromogenic anti-FXa method sensitive to levels of 0.02 anti-FXa U/ml. LMW heparin was detected in all maternal samples of the test patients but was not detected in any of the fetal samples. The use of LMW heparin as a thromboprophylactic agent was then evaluated in 11 patients who were known to have a severe thromboembolic tendency, had suffered recurrent miscarriages and had responded poorly to conventional anticoagulation (oral anticoagulant, conventional heparin). All patients receiving LMW heparin in thromboprophylactic doses completed uneventful pregnancies and gave birth to healthy babies (three for the first time) without complication. Bone density scans performed in all patients shortly after the delivery showed normal mineral mass. We conclude that LMW heparin does not cross the placental barrier, and in addition offers satisfactory antithrombotic protection for both maternal and placental circulation. In addition, this study provides preliminary data from 11 patients suggesting LMWH may not give rise to maternal osteoporosis, a finding that now needs further investigation.

Congenital thrombophilia among patients with venous thromboembolism.

During a 3-year period we studied 393 adult patients (382 of whom were unrelated) with a history of acute venous thromboembolism. A congenital deficiency state known to predispose to thrombosis was found in 27.2%. Of these, most were due to deficiencies of protein C (9.2%), protein S (7.6%), antithrombin III (5%) or to increased plasma PAI-1 concentration (3.1%) which, in the absence of any known factor that predisposes towards thrombosis, results in a diminished fibrinolytic activity. There was a characteristic pattern between the age of onset (mean 34 years) of thrombosis and individual protein deficiency. Thrombosis appeared spontaneously in 73% of cases with recurrence in 80%. In contrast, in the remaining unrelated patients, 138 (35.1%) in whom venous thromboembolism was secondary and occurred at a mean age of 43 years, and in the other 140 (35.6%) who suffered thromboembolism spontaneously at a later age (mean age 55), there was no permanent protein deficiency state or alteration in fibrinolytic activity and thrombosis recurrence was lower (53.6% and 20.7% respectively). Of the 393 patients, deep vein thrombosis was the most common manifestation; however, in congenital thrombophilia, thrombosis of visceral vessels and Raynaud's syndrome (6%) were also detected.

Thrombo-embolic prophylaxis in total knee replacement. Evaluation of the A-V Impulse System.

We performed a prospective randomised controlled trial of a new mechanical method of prophylaxis for venous thrombo-embolism in 60 patients undergoing knee replacement surgery. The method uses the A-V Impulse System to produce cyclical compression of the venous reservoir of the foot. The overall incidence of deep-vein thrombosis was 68.7% in patients receiving no prophylaxis and 50% in those using the device. The difference was not significant. There was, however, a reduction of the extent of thrombosis in the treated group. There were 13 major calf-vein thrombi and six proximal-vein thrombi in the control group compared with only five major calf-vein thrombi in the treated group. This difference was significant (p = 0.014). No patient developed clinical features of a pulmonary embolism.

Surgical outpatient practices--a time for change?

Outpatient services are becoming increasingly overburdened and delays for appointments are commonplace. The recent NHS reforms have laid down stricter guidelines on waiting times for hospital services and reorganisation of healthcare provision is necessary in order to meet some of these recommendations. The outpatient service is a case in need. Open access referral for minor cases, endoscopy and vascular assessment, for example, may help to utilise more usefully consultations for new referrals. Follow-up in outpatient clinics should become rationalised with clear objectives being made for investigation and reintervention. The long-term follow-up of patients should rest with their general practitioners. Recommendations have been made for a consultant-based service and more patients are expecting to be seen by a consultant. Until an expansion in consultant numbers is forthcoming patients will continue to experience delays in their management. The current service has scope for improvement and some suggestions are made in this paper.

Thoracoabdominal total gastrectomy in the management of adenocarcinoma of the cardia. Is it worth it?

A series of 47 consecutive patients with adenocarcinoma of the gastric cardia presenting between 1982 and 1987 have been reviewed. Of these, 38 patients were eligible for surgery (operability rate of 80.85%) but only 25 patients underwent potentially curative resection (resection rate of 65.7%). The disease was extensive at the time of operation, with only two patients (8%) having node negative tumours. The mean hospital stay for patients undergoing resection was 21 days. There were 15 major complications in 10 patients undergoing resection, but a zero 30-day mortality rate. The prognosis of those patients undergoing radical resection remains dismal. No patient survived longer than 30 months, 80% were dead within 1 year. Tumour recurrence and metastases were documented in 13 patients (52%). In the unresectable group there were two deaths from intubation (9%). The mean hospital stay for this group of patients was 12 days. The mean duration of survival in the group was 5.4 months, 70% of patients dying within 6 months and 95% dead within 1 year. The value of radical surgery in patients with adenocarcinoma of the gastric cardia is questioned.

Elective versus ruptured abdominal aortic aneurysm repair: a 1-year cost-effectiveness analysis.

Abdominal aortic aneurysm (AAA) is a life-threatening condition with an overall mortality of 80%. It predominantly affects men 65-74 years of age and is caused by focal distension of the main blood vessel in the abdomen. Most patients go undetected until their aneurysm ruptures. Controversy surrounds the most appropriate form of screening for AAA. Currently, screening is only carried out selectively in patients with peripheral vascular disease. Some patients have their AAA detected incidentally, whilst ultrasound examination of the abdomen is carried out for other indications. These patients have the opportunity to undergo surveillance or elective surgery. The mortality rate of emergency surgical intervention following rupture (50%) is far worse in comparison to that of patients undergoing planned intervention under specialist vascular surgeons (5%). Despite improvements in outcomes from elective intervention for AAA as a result of specialisation, the overall mortality from this condition remains very high (80%) as the commonest presentation of an AAA is rupture. Screening all men aged 65-74 years is considered too costly in the current economic climate. However the cost difference between elective repair and emergency repair of AAA must be considered given that the outcome from elective AAA repair is far superior to that following ruptured AAA repair. Our objective was to retrospectively collect costs and outcomes of elective and emergency AAA repair in order to carry out a cost-effectiveness analysis. Four multiprofessional teams in accident and emergency, operation theatres, intensive care, and surgical wards at the Kent and Canterbury Hospital were selected from health-care professionals including doctors, managers, nurses, and clerical staff with the purpose of obtaining costs. Detailed cost data collection sheets were prepared to calculate costs, which included staff costs, consumables including drugs, intravenous fluids, equipment, investigations, laundry, catering, and stationery. An inventory of costs per item was obtained, and the total cost was calculated from the number of items used. Outcomes were measured in terms of survival. The total costs of emergency AAA repair were pounds sterling 96,700.69, with a cost per life saved of pounds sterling 24,175.17. The total cost of elective AAA repair was pounds sterling 76,583.22, with a cost per life saved of pounds sterling 5,470.23. Emergency intervention for AAA was found to cost five times more than a planned intervention per life saved per year.

Effect of low molecular weight heparin on intimal hyperplasia.

Intimal hyperplasia is a significant cause of vascular graft failure. To investigate the potential uses of low molecular weight heparins (LMWHs) as prophylactic agents against graft thrombosis in humans, the anti-proliferative effects of a regimen of subcutaneous LMWH have been studied in an experimental model. Aortic intimal hyperplasia was created in 30 New Zealand White rabbits by endothelial denudation using an embolectomy balloon catheter technique. Three groups of ten animals were randomized to act as controls or to be treated with subcutaneous LMWH once or twice daily for 4 weeks. At 4 weeks all animals were killed and the aortas were harvested for analysis. The degree of intimal hyperplasia was measured using a computerized image analysis system and was expressed as an intimal:medial area ratio and also as percentage luminal reduction. A 60 per cent reduction in the degree of intimal hyperplasia was seen following treatment with LMWH. Heparin-treated animals had considerably less luminal reduction (daily LMWH 8 per cent and twice-daily LMWH 10 per cent) compared with untreated controls (26 per cent) (P less than 0.001). There was a similar difference seen in the intima:media area ratios, daily LMWH 0.38, and twice-daily LMWH 0.44, versus controls, 1.11 (P less than 0.001). In an experimental model, subcutaneous LMWH therapy effectively inhibits intimal hyperplasia.

Septic arthritis of the knee: complication of intra-arterial thrombolytic therapy.

A case of septic arthritis of the knee complicating intra-arterial thrombolysis is reported. Septic complications following the use of intravascular catheters are usually relatively minor. This serious case and the discussion that arises highlights the need for shortening the duration of intravascular thrombolysis regimes.

The effect of low molecular weight heparin on intimal hyperplasia in vein grafts.

Intimal hyperplasia due to smooth muscle cell proliferation is a well recognised cause of vascular graft failure. In experimental studies heparin and its low molecular weight derivatives can inhibit this proliferative response. This study examines the effect of subcutaneous low molecular weight heparin (LMWH) therapy on intimal hyperplasia in a model of arterial vein grafting. Twenty-four New Zealand White rabbits underwent interposition vein grafting of the carotid artery. Animals were randomly assigned to a control or treated group. Treated animals received 60 anti Xa units/kg of subcutaneous LMWH daily for 1 month. Animals were then sacrificed, graft patency assessed and the vessels then harvested for analysis of intimal hyperplasia. Intimal hyperplasia in carotid arteries and vein grafts was measured using a computerised image analysis system and was expressed as an intimal:medial area ratio. A statistically significant reduction in the degree of intimal hyperplasia seen in the arterial component of the distal anastomoses of carotid vein grafts was achieved using subcutaneous LMWH [Control 0.44 (0.37-0.55): LMWH 0.27 (0-0.37) p < 0.05]. There was no difference in the degree of intimal hyperplasia seen in the vein grafts themselves. [Control 0.21 (0-0.54): LMWH 0.23 (0-0.72)]. This study suggests that subcutaneous LMWH can inhibit the development of intimal hyperplasia in arteries undergoing vascular grafting but does not influence intimal hyperplasia within vein grafts. This has important implications for the further evaluation of antithrombotic agents following vascular surgery.

Intra-operative antithrombotic therapy with low molecular weight heparin in aortic surgery. How should heparin be administered?

This prospective study evaluates, for the first time, the efficacy of heparinisation with low molecular weight heparin (LMWH) in aortic surgery and identifies the most effective route of administration for heparin. Sixteen patients undergoing abdominal aortic grafting for aneurysmal and occlusive disease were studied. They were randomised to receive 10,000 anti Xa units of LMWH either intravenously or directly into the aorta before or after aortic cross-clamping. Serial venous blood samples and a paired arterial sample from the superficial femoral artery were taken for the estimation of systemic and lower limb heparin activity. All three methods of administration gave therapeutic levels of heparin in the systemic and lower limb circulation. Intravenous and aortic administration before clamping resulted in significantly higher systemic levels when compared with aortic injection after clamping (p less than 0.05 Mann-Whitney U test). Intra-aortic administration resulted in a significantly higher heparin activity in the lower limb when compared with the intravenous route (p less than 0.05). No patient developed distal thrombosis. This study demonstrates that the most effective way of giving heparin in aortic surgery is by direct injection into the aorta. Administration of LMWH after cross-clamping results in less systemic activity which may help to reduce any haemorrhagic side effects.