Cost effectiveness of low-molecular weight heparin versus warfarin following hip replacement surgery

Little information is available on the efficacy of low-molecular-weight heparin (enoxaparin) versus warfarin for treatment of deep vein thrombosis and pulmonary embolism following hip replacement surgery. Still less is known of the comparative cost effectiveness of these two therapies. A retrospective study was done on 56 patients who underwent elective hip surgery at an urban medical center between 1991 and 1996. All patients received enoxaparin or warfarin for purposes of thromboprophylaxis. An analysis of medication cost, therapy, laboratory monitoring, and bleeding events of the two antithrombolytic agents was undertaken. Total savings with enoxaparin averaged $1253 per patient, or $137,886 over the study period. The incidence of deep vein thrombosis or pulmonary embolism was 0% with enoxaparin and 3% with warfarin. These data indicate that enoxaparin is a more cost-effective and efficacious regimen for thromboprophylaxis following hip replacement surgery than warfarin.     

Vestibular hypersensitivity to clicks is characteristic of the Tullio phenomenon

OBJECTIVES: This study evaluated the cost-effectiveness of a smoking cessation and relapse-prevention program for hospitalized adult smokers from the perspective of an implementing hospital. It is an economic analysis of a two-group, controlled clinical trial in two acute care hospitals owned by a large group-model health maintenance organization. The intervention included a 20-minute bedside counseling session with an experienced health counselor, a 12-minute video, self-help materials, and one or two follow-up calls. METHODS: Outcome measures were incremental cost (above usual care) per quit attributable to the intervention and incremental cost per discounted life-year saved attributable to the intervention. RESULTS: Cost of the research intervention was $159 per smoker, and incremental cost per incremental quit was $3,697. Incremental cost per incremental discounted life-year saved ranged between $1,691 and $7,444, much less than most other routine medical procedures. Replication scenarios suggest that, with realistic implementation assumptions, total intervention costs would decline significantly and incremental cost per incremental discounted life-year saved would be reduced by more than 90%, to approximately $380. CONCLUSIONS: Providing brief smoking cessation advice to hospitalized smokers is relatively inexpensive, cost-effective, and should become a part of the standard of inpatient care.     

A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications associated with total knee arthroplasty. The American College of Chest Physicians recommends twice-daily, fixed-dose low-molecular-weight heparin (LMWH) as routine prophylaxis in this patient population. This study represents a cost analysis of ardeparin and enoxaparin, the two LMWHs currently available for this indication in the United States. Costs for treating DVT, PE, and major bleeding episodes were derived from values reported in the literature. Both ardeparin and enoxaparin were found to produce significant cost savings when used routinely as DVT prophylaxis after knee replacement surgery compared with no prophylaxis. Based on the currently available data, enoxaparin 40 mg once daily appears to be the least costly LMWH for routine pharmacoprophylaxis of DVT in patients undergoing knee replacement surgery.     

Screening for major deep vein thrombosis in seriously injured patients: a prospective study

The purpose of the study is to determine the prevalence of acute deep venous thrombosis (DVT) in severely injured trauma patients, to investigate the cost effectiveness of a noninvasive surveillance program, and to assess the merit of current methods of prophylaxis against DVT. One hundred and forty-eight patients (295 limbs) with a mean age of 36.5 years, mean trauma score of 13.3, mean injury severity score of 22.4 with predominantly blunt injuries (88.5%), were part of the study. The mean length of stay was 17.6 days. Venous duplex scans (VDS) were performed on inpatients on days 2-5, day 11, and day 30 following admission. Sequential compression device and/or subcutaneous heparin was used in 99% of patients with compliance being monitored by trauma nurse clinicians. A total of 272 VDS were performed with total charges of $111,520. DVT was found by VDS or venography in eight limbs (2.7%) of six patients (4%), our of the limbs being symptomatic. Two additional patients had pulmonary embolism, both with normal VDS. Routine serial VDS in severely injured patients who undergo aggressive prophylaxis against DVT is not cost effective and therefore not justified.     

Pneumatic sequential compression reduces the risk of deep vein thrombosis in stroke patients

OBJECTIVE: To determine if pneumatic sequential compression devices (SCDs) combined with subcutaneous heparin and antiembolic hose reduce the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in stroke patients. BACKGROUND: DVTs and PEs are serious complications among hospitalized stroke patients. Subcutaneous heparin and SCDs have both been used to prevent DVT. It is not known if SCDs combined with subcutaneous heparin can improve the protection afforded by heparin alone. METHODS: The study group was comprised of nonhemorrhagic stroke patients admitted to the neurology service from October 1988 through June 1996. From October 1988 through April 1991 (233 patients), and during February 1993 (16 patients), patients received 5,000 U subcutaneous heparin twice daily and antiembolic hose. From June 1991 through January 1993 and from March 1993 through June 1996 (432 patients) all nonambulatory stroke patients had SCDs applied to both legs in addition to subcutaneous heparin and antiembolic hose. RESULTS: Twenty-three of 249 patients (9.2%; 21 of 233 and two of 16 patients) treated with heparin alone developed DVT and six patients (2.4%) developed PE (six of 233 and zero of 16). Half the PE cases (three of six) were fatal and all PEs were in patients with DVT. Eighty-three of the 249 patients were nonambulatory. Twenty-two of the 23 DVTs and all the PEs developed in nonambulatory patients. Only one DVT (0.23%) and no PEs occurred among the 432 patients (148 nonambulatory) treated with SCDs as well as heparin. The addition of SCDs resulted in more than a 40-fold reduction in the risk of DVT. CONCLUSIONS: Nonambulatory stroke patients have an increased risk for DVT and PE. Adding SCDs to treatment with subcutaneous heparin and antiembolic hose reduced the risks of DVTs and PEs. SCDs should be considered for adjunctive DVT prophylaxis in nonambulatory stroke patients.     

Management of deep vein thrombosis of the lower extremity in pregnancy: a challenging dilemma

This study reviews our experience in the management of deep vein thrombosis (DVT) of the lower extremity during pregnancy and analyzes the outcome of various treatment alternatives, including conventional full-dose heparin therapy and Greenfield filter insertion. Twenty-four patients treated over an 8-year period were reviewed. Fifteen patients were treated with conventional full-dose intravenous heparin therapy for 5 to 10 days, followed by subcutaneous low-dose heparin until labor, and continued for 6 weeks postpartum (Group A); Eleven patients had Greenfield filters inserted, followed by the same low-dose subcutaneous heparin regimen (Group B). There were 18 femoral or iliofemoral, 5 femoropopliteal, and 1 popliteal and below-knee DVT. The indications for Greenfield filter insertion included two patients in Group A (one with pulmonary embolism, despite adequate heparin therapy, and one with significant bleeding). Nine other patients had prophylactic indications: two for free-floating iliofemoral DVT, three with iliofemoral DVT (occurring just 1-2 weeks before labor), and four with femoropopliteal DVT. There were three immediate major complications (pulmonary embolism, bleeding, or death) in Group A; two with pulmonary embolism, one of which was fatal, and one with significant bleeding (3 of 15 patients; 20%). No major complications occurred in Group B. On long-term follow-up (mean, 61 months), 4 of 12 patients (33%) in Group A had significant leg swelling, with partial resolution of DVT in 2 patients and venous occlusion in 2 patients by duplex ultrasound. This is in contrast to 3 of 11 patients (27%) in Group B with significant leg swelling. There was no fetal morbidity or mortality in either group. Conventional full-dose heparin therapy for DVT of the lower extremity in pregnancy can carry significant morbidity and mortality. Greenfield filters may be used safely in some of these patients.     

Meta-analysis of effectiveness of intermittent pneumatic compression devices with a comparison of thigh-high to knee-high sleeves

This meta-analysis used all original articles from 1966 to June 1996 that fit the preset inclusion criteria to examine the clinical effectiveness of intermittent pneumatic compression (IPC) devices in preventing deep vein thrombosis (DVT) and pulmonary embolism and to compare the results of knee-high sleeves to thigh-high sleeves. IPC devices decreased the relative risk of DVT by 62 per cent when compared with placebo, 47 per cent compared with graduated compression stockings, and 48 per cent compared with mini-dose heparin. IPC devices significantly decreased the relative risk of DVT compared with placebo in high-risk patients such as neurosurgery and major orthopedic surgery patients and in modest risk patients such as general surgery patients. In major orthopedic surgery patients, the incidence of DVT was similar for IPC- and warfarin-treated patients; however, IPC was significantly better than warfarin at decreasing the incidence of calf only DVT, whereas warfarin seemed to be better at decreasing proximal DVT. IPC devices are effective in decreasing the incidence of DVT in patients at moderate to high risk and are probably more efficacious than graduated compression stockings or mini-dose heparin; however, IPC devices are not protective against pulmonary embolism. The data directly comparing the various methods of compression (knee-high versus thigh-high sleeves and graded-sequential versus uniform compression) are sparse and conflicting.     

Comparison of sequential compression devices and foot pumps for prophylaxis of deep venous thrombosis in high-risk trauma patients

Multiple-trauma patients are at increased risk for deep venous thrombosis (DVT) but are also at increased risk of bleeding, and the use of heparin may be contraindicated. Sequential pneumatic compression devices (SCDs) are an alternative for DVT prophylaxis. However, lower extremity fracture or soft tissue injury may preclude their use. In these circumstances, foot pumps (FPs) are often substituted, yet little clinical data exist to support their use. We identified 184 consecutive high-risk trauma patients who received DVT prophylaxis with compression devices. We reviewed demographic data, mechanism of injury, Injury Severity Score, injury pattern, and method of prophylaxis. Generally, SCDs were preferred, but FPs were substituted in patients with lower extremity injuries. Occurrences of DVT or pulmonary embolism were also noted. Patients surviving less than 48 hours were excluded. SCDs were used in 118 patients (64%) and FPs in 66 patients (34%). There were no differences in age, Injury Severity Score, or presence of shock on admission. As expected, FP patients were more likely to have lower extremity fractures (65 vs 26%; P < 0.05) and were also more likely to have associated pelvic fracture (59 vs 25%; P < 0.05) and chest injury (61 vs 26%, P < 0.05). There was no difference in the incidence of head injury, although SCD patients had more severe head injuries (Glasgow Coma Score, 7.9 vs 10.5; P < 0.05). The overall incidence of DVT was 5.4 per cent (10 of 184), with no differences between the two groups (SCD 7% vs FP 3%). Three patients had a pulmonary embolism (FP, two; SCD, one), none of which were fatal. Compression devices provide adequate DVT prophylaxis with a low failure rate (3-8%) and no device-related complications. FPs appear to be a reasonable alternative in the high-risk trauma patient when lower extremity fractures precludes use of SCD.     

Deep venous thrombosis: incidence on admission to a brain injury rehabilitation program

OBJECTIVE: To determine the incidence of deep venous thrombosis (DVT) in brain injured individuals at time of admission to a brain injury (BI) rehabilitation program. DESIGN: Prospective study, sequential case series. SETTING: University tertiary care BI rehabilitation center. DATA SET: Eighty-two traumatic brain injury (TBI) and 71 atraumatic brain injury (ABI) patients were consecutively admitted to our BI unit over a 12-month period and screened within 24 hours of admission for a lower extremity DVT with color flow duplex Doppler ultrasonography. All patients had been prophylaxed with either subcutaneous heparin anticoagulation therapy or intermittent compression devices, and all patients were within 2 months of the original BI. MAIN OUTCOME MEASURES: Evidence of intrinsic venous occlusion by duplex Doppler. RESULTS: DVTs were detected and treated prior to rehabilitation admission in three patients (2%), and these persisted at rehabilitation admission. New DVTs were detected at time of rehabilitation admission in 17 patients (11%). All were occult DVTs; none of the 17 patients had clinical findings indicative of acute DVT. No significant differences were noted in the TBI group when age, highest 24-hour Glasgow Coma Scale score, length of acute hospitalization, type of DVT prophylaxis, or presence of an extremity fracture were compared for individuals with and without DVT. No significant differences were noted in the ABI group when age, length of acute hospitalization, and type of DVT prophylaxis were compared for individuals with and without DVT. CONCLUSION: The overall incidence of DVTs was 13% and the incidence of occult DVT was 11%. Individuals with TBI had an overall incidence of DVTs of 20% and an occult DVT incidence of 18%. Individuals with ABI had an overall incidence of DVT's of 6% and an occult DVT incidence of 4%. These findings indicate the importance of baseline screening for DVT in this patient population.     

A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group

BACKGROUND: The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS: Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS: At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS: In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.     

The delivery of oxygen by a venturi T piece

Thromboembolic events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) are very uncommon in the pediatric age group; even more rare is the white clot syndrome. We present the case of a 13-year-old girl who presented with no known risk factors for thromboembolic disease or cardiopulmonary complaints, yet was found to have extensive lower extremity DVT and PE. This patient also suffered the rare but potentially devastating complication of heparin therapy referred to as the white clot syndrome, resulting in amputation of the lower extremity. Greater awareness of both thromboembolic disease in children and the white clot syndrome may lessen the morbidity and mortality associated with these entities.     

The cost effectiveness of alpha interferon in the treatment of chronic active hepatitis C

OBJECTIVE: To model the costs and effects of alpha interferon in the treatment of chronic active hepatitis C. DESIGN: A Markov modelling process to simulate the costs and outcomes in hypothetical cohorts of patients treated with and without alpha interferon. OUTCOME MEASURES: Costs per life saved and per life-year gained. RESULTS: On the basis of assumptions formulated about the disease processes and response to treatment, treatment with alpha interferon results in a discounted cost per life-year gained of $33,230 in patients with cirrhosis at the start of treatment and $71,950 in patients without advanced liver disease. The result is sensitive to the assumptions made about the long term effectiveness of alpha interferon. CONCLUSIONS: Alpha interferon is an expensive drug. Its effectiveness is clouded by uncertainty about the long term impact of the drug on the natural history of the disease. If adopted, its use should be monitored to allow the long term cost effectiveness of the drug to be evaluated properly.     

Advanced HIV infection treated with zidovudine monotherapy: lifetime values of absolute cost-effectiveness as a pharmacoeconomic reference for future studies evaluating antiretroviral combination treatments. The Osservatorio SIFO sui Farmaci

OBJECTIVE: This study was undertaken to evaluate the cost and the effectiveness of zidovudine monotherapy in patients with advanced HIV infection and to derive preliminary data on the cost-effectiveness of the triple treatment with saquinavir plus zalcitabine plus zidovudine compared with zidovudine alone. DESIGN: We used a combined method of survival analysis utilizing both the quality-adjusted time without symptoms or toxicity (Q-TWIST) method and the Gompertz approach. This combined method was applied to assess the absolute cost-effectiveness and cost-utility ratios of zidovudine monotherapy and to perform a preliminary incremental cost-effectiveness comparison of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone. The clinical material used in our study was derived from two reports on the treatment of advanced HIV infection. Data of lifetime costs of HIV infection were obtained from published information. RESULTS: In patients with advanced HIV infection treated with zidovudine monotherapy, lifetime survival was 252.1 discounted person-years per 100 patients. Using an average lifetime cost of $93,000 (discounted) per individual, the absolute ratio of cost-effectiveness for zidovudine monotherapy was $36,980 per life-year, while the absolute cost-utility ratio was $47,112 per quality-adjusted life-year. In the comparative analysis of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone, our calculations showed that the administration of the triple treatment can have an "average" cost-effectiveness, provided that mean lifetime survival per patient (discounted) is improved to at least 3.68 years (with an average survival gain of at least 14 mo per patient). CONCLUSIONS: The values of absolute cost-effectiveness and cost-utility ratios for zidovudine monotherapy are a useful reference point for further pharmacoeconomic studies in the area of antiretroviral drugs.     

Cost-effectiveness of hepatitis A vaccination in healthcare workers

OBJECTIVE: To study the cost-effectiveness of vaccination for hepatitis A. SETTING: Hypothetical analysis of students currently enrolled in medical school in the United States. METHOD: A Markov-based model was developed using data from the literature, actual hospital costs, and an annual discount rate of 5%. The incidence rate was based on the lowest annual rate for the US population during the past decade. RESULTS: Over the lifetimes of students currently in medical school, the model estimated that there would be 286 hepatitis A cases with four deaths and 107 lost years of life. With routine vaccination, these numbers would decrease to 17, 0.3, and 6, respectively. The costs per life-year saved and quality adjusted life-year saved were $58,000 and $47,000, respectively. Serologic screening prior to vaccination was less cost-effective than universal vaccination. If the incidence of hepatitis A was underestimated by a factor of 5, the cost per life-year saved would decrease to $5,500. If the incidence of hepatitis was underestimated by a factor of 10, vaccination would result in a net cost savings. CONCLUSION: We conclude that the cost per life-year saved by routine hepatitis A vaccination was similar to many other standard medical modalities. For routine vaccination of medical students to be cost-saving, the incidence rate for hepatitis A must be at least 10 times higher than the rate presently reported for the general population. Serological screening prior to vaccination was not cost-effective.     

Assessment of outpatient treatment of deep-vein thrombosis with low-molecular-weight heparin

BACKGROUND: Low-molecular-weight (LMW) heparins are safe and effective for out-of-hospital treatment of acute deep-vein thrombosis (DVT) in a clinical trial setting. We examined the efficacy, safety, and feasibility of home treatment with LMW heparin of consecutive eligible patients with acute DVT in a routine care setting. In addition, we report our experience with patient compliance, acceptance, and satisfaction. METHODS: We performed a prospective cohort study of consecutive patients presenting to 2 thromboembolism clinics in a large Ontario city. Eligible patients were treated with LMW heparin for a minimum of 5 days and with long-term warfarin sodium. Outcomes included the incidences of bleeding and recurrence of DVT and pulmonary embolism and patient satisfaction as determined by a questionnaire. RESULTS: One hundred thirteen patients with objectively confirmed DVT underwent screening; 89 patients were treated at home with LMW heparin. During the study, 1 patient died of a combination of pulmonary embolism and major bleeding, another patient required admission to the hospital for bleeding, and 5 patients with active malignant disease had recurrent DVT. Of the patients who completed the satisfaction questionnaire, 75 (91%) of 82 were pleased with home treatment; 44 (70%) of 63 felt comfortable self-injecting the LMW heparin; and 71 (92%) of 77 were satisfied with the support and instruction they received during the outpatient treatment. CONCLUSIONS: Outpatient treatment of DVT with LMW heparin is safe, effective, and feasible for most patients and is associated with a high degree of patient satisfaction.     

Deep venous thrombosis: epidemiologic, diagnostic and therapeutic aspects

Deep vein thrombosis (DVT) has a high social and economic cost disease being its prevalence in the general population elevated and producing possibly fatal (pulmonary embolism) or disabling (post-thrombotic syndrome) complications. Thus, it appears of great importance to know the epidemiological and clinical characteristics of DVT in order to perform the best diagnosis, therapy and prophylaxis. The study population is composed by 146 patients (84 males and 62 females, mean age 60.9 +/- 15.3 years, range 19.92 years), arrived in our Vascular Echography Laboratory with the clinical suspect of DVT confirmed by means of echo color Doppler. The most frequent clinical signs were skin hyperthermia in 118 patients (80.8%) and edema in 116 patients (79.5%), while the most common symptom was pain, 89 patients (61.0%). Eleven patients (7.5%) were asymptomatic. The echo criteria utilized were direct thrombus visualization, vessel diameter higher than the contralateral, reduced or absent vessel wall ability to be compressed, reduced or absent color Doppler venous flow, lack or reduction of respiratory flow modulation, visualization of collateral circulation. DVT was located in 131 patients (89.7%) in inferior limbs (proximal in 122 patients, isolated distal in 9 patients), in 14 patients (9.6%) in superior limbs and in 3 patients (2.1%) in the internal jugular vein. In 130 patients a risk factor or a predisposing condition was identified: secondary DVT; in 16 patients the DVT was considered idiopathic. The most frequent risk factors were: previous surgery 28.1%, immobilization 19.9% trauma 17.1%, tumors 9.6%. A hypercoagulation was detected in 4 patients: antithrombin III deficit in 2, post-splenectomy thrombocytosis in 1 and antiphospholipid antibodies syndrome in the last one. The Pisa territory epidemiologic data showed a male 0.51 and female 0.38/1000 subject/year DVT incidence, with significantly higher values in older than 45-54 males and 55-64 females. One hundred and thirty one patients were treated with 5-11 day heparin infusion and thereafter with warfarin at least for 6 months, 1 year or indefinitely depending on thromboembolic risk. Six patients with distal DVT and 9 patients with hemorrhagic risk were treated with subcutaneous calcic or low weight heparin. In 1 patient with a mobile thrombus judged as at very high risk of embolization, a caval filter was positioned. Anticoagulant therapy complications were: 2 minor bleedings, 1 alopecia, 1 thrombocytopenia. Two patients died for neoplastic complications. Fifty-seven patients completed a 6-month follow-up and were submitted to a control each study that evidenced: total recanalization in 15 (26.3%), partial recanalization in 25 (43.9%) and no recanalization in 17 patients (29.8%). In 6 patients there was a DVT relapse and in 9 pulmonary embolization: almost all these patients were in the partial recanalization group.     

Increased kidney xanthine oxidoreductase activity in salt-induced experimental hypertension

OBJECTIVES: To assess the efficacy and safety of low molecular weight heparin (LMWH) as deep venous thrombosis (DVT) prophylaxis following total knee arthroplasty. DATA SOURCES: Medline 1986 to June 1997, Embase, and manufacturers were used to identify randomized controlled trials. REVIEW METHODS: Trials included were randomized studies of LMWH with routine radiological screening for DVT. Placebo or active controls were included. Two reviewers independently screened trials for inclusion, and assessed their quality. Pooled relative risk estimates of DVT and proximal DVT rates were calculated using a DerSimonian and Laird random effects model. Sensitivity of the results to the type of control used and the quality of the trial was assessed. RESULTS: The relative risk of DVT for a patient given LMWH is 0.73 (95% CI 0.66 to 0.80) when compared with patients treated with adjusted dose heparin or warfarin controls. The relative risk for proximal DVT is 0.58 (95% CI 0.38 to 0.90). The relative risk of pulmonary emboli in the LMWH group was 0.55 (95% C.I. 0.20 to 1.57). No excess of bleeding was recorded in the LMWH group. CONCLUSIONS: Low molecular weight heparin is more efficacious than either adjusted dose heparin or adjusted dose warfarin, when used to prevent DVT and proximal DVT following total knee arthroplasty.     

The problem of the asbestos induced laryngeal carcinoma

A course of small doses of heparin given subcutaneously before and after elective operations has been reported to reduce the incidence of deep venous thrombosis and pulmonary embolism in general surgical patients. To test the safety of mini-dose heparin for neurosurgical patients, mini-dose heparin was used for 150 adult patients undergoing elective neurosurgical procedures. No operative complications were thought to be related to heparin administration. Postoperatively, there were four wound seromas, two hematomas, and one non-fatal pulmonary embolus. Seven patients died postoperatively, of whom five had no evidence of pulmonary embolus. Although no conclusions were drawn as to the effectiveness of mini-dose heparin in preventing deep venous thrombosis or pulmonary emboli, it was believed that the method could be used safely and without fear of increased intracranial or intraspinal bleeding for neurosurgical patients.     

Evaluation of enoxaparin given before and after operation to prevent venous thromboembolism during digestive surgery: play-the-winner designed study

A total of 316 patients were included in a play-the-winner (PTW) designed study comparing the safety of enoxaparin started preoperatively versus postoperatively as prophylaxis against venous thromboembolism for digestive surgery. In a PTW-designed study the treatment of any next patient depends on the outcome of the previous patient. If successful, the next patient receives the same treatment, if not, the comparative regimen is given. Excessive bleeding according to specified criteria, severe adverse reactions, clinically detected deep venous thrombosis (DVT), or pulmonary embolism (PE) were criteria for classification as "loser." The PTW design allocates most patients to the superior treatment. The main variable in PTW studies is the number of consecutive patients receiving the same treatment. In this study 163 patients were allocated to postoperatively started and 153 to preoperatively started prophylaxis with enoxaparin. The frequency of "winners" was found to be 82.8% and 78.4% in the post- and preoperatively treated groups, respectively. No significant differences were found between the groups with regard to frequency of "winners" or the number of consecutive patients before change of treatment. The percentile of survival distribution did not detect superiority of any group. Prophylaxis against postoperative venous thromboembolism for digestive surgery using enoxaparin can safely be started preoperatively.     

Low molecular weight heparin and unfractionated heparin for prevention of thrombo-embolism in general surgery: a meta-analysis of randomised clinical trials

Low molecular weight heparin (LMWH), unfractionated heparin (UFH) and warfarin were compared with respect to efficacy and safety in the prevention of thrombo-embolism in general surgery. Meta-analysis (MA) with a priori definition of the MA protocol was used to combine the results from randomised trials with patients who underwent general surgery and deep-vein thrombosis (DVT) prophylaxis with LMWH, UFH or warfarin. Forty-four studies were identified for assessment and 33 were included, however, none for warfarin. For efficacy (DVT and pulmonary embolism) and major bleeding, no significant difference between the LMWH- and UFH-treated groups was demonstrated. The relative risk of minor bleedings for LMWH versus UFH was 0.75 (0.64-0.88; 95% confidence interval) and is significant (p < 0.05). Within the limitations of the MA, LMWH and UFH did not differ significantly in terms of prevention of thrombo-embolism, but LMWH had a significantly better safety profile. On this basis, LMWH may be preferable to UFH in the prevention of thrombo-embolism in general surgery.