Prolonged Thromboprophylaxis Research Articles

Symptomatic venous thromboembolism after femoral vein harvest

The femoral vein is increasingly utilized as a conduit in major arterial and venous reconstruction. However, perioperative complications, especially venous thromboembolism (VTE) associated with femoral vein harvest (FVH), are not well described. The purpose of this study was to determine the incidence and risk factors for the development of symptomatic VTE in patients who undergo FVH. We conducted a retrospective cohort study of all patients who underwent FVH over a 5-year period at a single institution. Patient clinical characteristics, indications for surgery, postoperative venous duplex scans, and computerized tomography scans of the chest were gathered and reviewed from an electronic medical record query. Statistical analysis was performed to determine which factors correlate with development of perioperative complications after FVH. There were 57 patients (53% male; mean age, 62 years) who underwent 58 FVHs. Of the procedures, 53% were performed for arterial reconstruction and 47% for vascular reconstruction after cancer resection (85% portomesenteric reconstruction). Perioperative VTEs were diagnosed in 17 of 58 (29%) FVH procedures. Sixteen ipsilateral deep vein thromboses (DVTs) occurred distal to the FVH site and five (9%) occurred proximal to the FVH site. The incidence of VTE was significantly greater in patients with malignancy (52% vs 10%; P = .001), and 88% of all VTEs in this series were diagnosed in patients with cancer. All DVTs proximal to the FVH site and all DVTs in the contralateral extremity occurred in patients with malignancy. Pulmonary embolism occurred in two patients. No patients developed compartment syndrome or limb loss. Eight patients (14%) required FVH site wound debridement. VTE after FVH occurs more frequently in patients with malignancy. Aggressive and prolonged thromboprophylaxis and routine venous ultrasound surveillance are warranted after FVH in patients with malignancy.

Prevention of Venous Thromboembolism with New Oral Anticoagulants versus Standard Pharmacological Treatment in Acute Medically Ill Patients

Venous thromboembolism (VTE) is a common and potentially avoidable cause of morbidity and mortality in patients hospitalized for acute medical illness. Our objective was to conduct a systematic review of studies that assessed the efficacy and safety of new oral anticoagulant (OAC) drugs versus standard pharmacological drugs and/or placebo in prevention of VTE in acute medically ill patients. PubMed.org and ClinicalTrials.gov databases were searched to identify studies that evaluated the efficacy and safety of a new OAC versus the standard pharmacological treatment and/or placebo in the prevention of VTE in medically ill patients. Relative risks (RR), weighted means and 95% CIs were calculated. Statistical heterogeneity was evaluated using Chi2 and I2 statistics. Two studies were included in the meta-analysis. The primary outcome in both studies was the composite of VTE-related death, symptomatic non-fatal pulmonary embolism (PE), symptomatic deep venous thrombosis (DVT) and asymptomatic proximal DVT. Both studies compared a factor (F)Xa inhibitor with enoxaparin in standard short-term thromboprophylaxis followed by a period where the FXa inhibitor was compared with placebo as prolonged thromboprophylaxis in medically ill patients. The primary major safety outcome in both studies was a composite of treatment-related major bleeding and clinically relevant non-major bleeding. A total of 14 629 patients were randomized. Compared with subjects treated with enoxaparin followed by placebo, the RR of the primary outcome during the prolonged treatment period was 0.79 (95% CI 0.66, 0.94), the RR for the primary outcome during the first short-term treatment period was 1.03 (95% CI 0.81, 1.31). For major bleeding during the prolonged treatment period, the RR was 2.69 (95% CI 1.65, 4.39) for patients treated with an FXa inhibitor compared with enoxaparin/placebo. For major bleeding during the shorter treatment period, the RR was 2.01 (95% CI 1.10, 3.65) in favour of enoxaparin. In acute medically ill patients, prolonged thromboprophylaxis with an oral FXa inhibitor is more protective than regular short-term treatment with enoxaparin. However, treatment with FXa inhibitors is significantly associated with major bleeding, both in long- and short-term treatment compared with enoxaparin.

Time Course of Venous Thromboembolism Events and Influence of Risk Factors in High Risk Medical Patients,

Abstract 4182▪▪This icon denotes a clinically relevant abstract Background:Venous thromboembolism (VTE) prophylaxis has been identified in clinical guidelines as an appropriate strategy for high-risk medical inpatients as it results in reduced VTE events and reduced mortality. However, real life data regarding the timing of VTE events and the relationship between risk factors and VTE in this population is lacking. Further knowledge of the time course of recurrence and influence of risk factors in actual practice may help clinicians determine strategies regarding the frequency of clinical surveillance and the appropriate duration of treatment. Objective:To document the time course of symptomatic VTE events in high-risk medical patients in every day clinical practice and to relate the frequency of risk factors to the likelihood of VTE development. Methods:Charts from 1134 consecutive high-risk medical patients who were hospitalized in the Calgary region and discharged between January and February 2008 were abstracted using standardized case record forms. All hospitals in the region use a common unique patient identifier number, thus enabling the tracking of subsequent patient visits to the emergency room, inpatient admissions or outpatient visits occurring anywhere in the region's acute care system. Any identified patient was followed for a subsequent visit related to VTE.High-risk medical patients were defined as age > 60 years and having at least one of the following risk factors: malignancy, respiratory illness, neurological illness, inflammatory bowel disease, previous VTE, acute infection or heart failure. Records were excluded if the patient was admitted for VTE or to rule out VTE, receiving chronic anticoagulation, experiencing acute coronary syndromes, had a hospital stay ≤ 3 days, was a surgical or orthopedic patient, or pregnant. Data was collected on the timing of VTE related events for up to 100 days post discharge. Results:A total of 989 patients met criteria over the review period. Seventy-four percent (732/989) of all patients received mechanical or pharmacological prophylaxis in hospital. Only 2% (95% CI, 1.6% to 3.6%) of all patients received anticoagulation prophylaxis at discharge. Twenty-one percent of patients in the population studied were identified as requiring medical care for symptoms associated with VTE. Confirmation of VTE by diagnostic testing occurred in 4% (95% CI, 2.7% to 5.2%) while the other 17% (95% CI, 15.0% to 19.8%) had diagnostic tests that were negative or inconclusive.The mean length of time to confirmed first VTE event was 33.5 days. Eighty percent of first events occurred by day 57 and 90% of first VTE events occurred by day 69 post hospital admission. Patients with more than 2 risk factors had a rate of confirmed symptomatic VTE events of 6.1%, increasing to 8.7% for those with more than 3 risk factors while only 2.9% of patients with 2 or less risk factors developed a confirmed VTE. (p=0.015) Conclusion:This study demonstrates that in a real life setting, 6% of those hospitalized medical patients with more than 2 risk factors would develop symptomatic VTE event confirmed by diagnostic testing, increasing to 8.7% for those with more than 3 pre-specified risk factors. The mean time to first VTE event of 33.5 days along with 80% of VTE events occurring by day 57 suggest that more consideration needs to be given to prolonged VTE prophylaxis in this high risk population. The frequency and timing of the VTE events coupled with the results of the EXCLAIM study suggest that this high risk population may benefit from prolonged thromboprophylaxis. Disclosures:Hull:LEO Pharma: Consultancy; sanofi-aventis: Consultancy; Pfizer: Consultancy; Portola: Consultancy; Merck: Consultancy; Bayer: Consultancy; Johnson & Johnson: Consultancy. Merali:LEO Pharma: Consultancy; Genzyme: Consultancy; Boehringer Ingelheim: Consultancy; Abbott: Consultancy; BMS: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; sanofi-aventis: Consultancy; Nycomed: Consultancy; Otsuka: Consultancy. Mills:Pfizer: Consultancy; sanofi-aventis: Research Funding. Komari:sanofi-aventis: Employment.

Practical Viewpoints on the Diagnosis and Management of Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT, type II) is an immune-mediated disorder due to antibodies formed against heparin-platelet factor 4 complexes, usually appearing at days 5 to 14 after initiation of heparin. It is important to recognize HIT because heparin prophylaxis or treatment paradoxically associates with new venous and/or arterial thrombosis. Early clinical suspicion and diagnosis together with proper pharmacotherapy and close laboratory monitoring are the cornerstones for successful management. This includes monitoring of Thrombocytopenia, its Timing to heparin administration, appearance of new Thrombosis or resistance to treatment, and differential diagnosis by exclusion of o Ther causes (the 4T's). Specific attention should be paid to the absence or presence of thrombosis and to tailoring thromboprophylaxis or anticoagulant therapy with a nonheparin alternative. Even in the absence of HIT-associated thrombosis, an active policy for prolonged thromboprophylaxis is demanded. Rapid and reliable assays should be developed for diagnosis and anticoagulation monitoring to secure safe management with nonheparins. Semiquantitative testing for on-call hours should be available and later confirmed as clinically needed. Alternative therapeutic options are available, but because their use is infrequent, experienced coagulation treatment centers should provide guidance in the treatment and in laboratory monitoring. Most of the evidence in HIT is grade IC, and thus the best evidence is provided by clinical experience. New anticoagulants and platelet inhibitors may offer future alternatives in the management of HIT, but the current treatment options provide the best experience and benefit. The joint clinical and laboratory guidelines provided in this article along with two practical case scenarios were prepared by a Nordic expert panel. They will be valuable for hematologists and colleagues who do not routinely encounter HIT.

Prolonged use of thromboprophylaxis may not be necessary in laparoscopic colorectal surgery

Patients undergoing colorectal resections are considered high risk for developing thromboembolic disease. We postulate, however, that the rapid recovery and swift mobilization after laparoscopic resections reduce this risk and that these patients therefore do not need prolonged thromboprophylaxis. This hypothesis was tested in this paper. All patients who underwent laparoscopic colorectal surgery in our Colorectal Surgical Unit in the period from June 1991 until January 2010 were entered into a prospective database. The entire database was reviewed, and incidence of thromboembolic disease and significant bleeding complications were noted. Three thousand, three hundred sixty-four patients were laparoscopically operated on for colorectal disease and were entered in the database. Two thousand, one hundred twenty-seven patients were operated on for benign disease; 1,230, for colorectal cancer, and four, for other malignancies. Two deep venous thromboses were encountered (0.059%), and ten patients had pulmonary embolism (0.30%). The combined venous thromboembolism (VTE) risk for the overall group of patients undergoing laparoscopic colorectal operations is 0.36%. The combined VTE risk was 0.57% (7/1,230) in patients with colorectal cancer and 0.24% (5/2,127) in patients with benign disease (p = 0.118). Bleeding complications occurred in 44 patients (1.3%). In our group, the combined VTE risk for the overall group of patients undergoing laparoscopic colorectal operations is 0.36%. Therefore, we postulate that the prolonged use of thromboprophylaxis is not indicated in the vast majority of patients undergoing laparoscopic colorectal surgery. In particular, patients undergoing laparoscopic resections for benign disease and without other risk factors have such a low VTE risk that prolonged prophylaxis is probably not warranted.

Cost-Effectiveness of Prolonged Thromboprophylaxis After Cancer Surgery

Consensus guidelines recommend prolonged thromboprophylaxis for up to 4 weeks after major abdominopelvic cancer operations. Several factors impede widespread adoption of these guidelines. These include lack of awareness, cost, increased bleeding complications, increased incidence of heparin-induced thrombocytopenia, and poor patient compliance. A cost-effectiveness model was constructed comparing four potential strategies to postdischarge thromboprophylaxis in surgical oncology patients: (1) low-molecular-weight heparin (LMWH) once daily; (2) low-dose unfractionated heparin (LDUH) three times daily; (3) oral aspirin once daily; or (4) no prolonged prophylaxis. Probabilities and costs were estimated on the basis of published literature and average Medicare reimbursement. The decision analysis was conducted from the perspective of the health care system, with the primary end point being cost per patient without venous thromboembolism (VTE). Sensitivity analyses tested the robustness of the results. LDUH was most cost-effective, saving $154 per patient without VTE compared with no prophylaxis. LMWH was not cost-effective, incurring a cost of $230 per patient without VTE compared with no prophylaxis. Aspirin was a viable alternative to LDUH, saving $123 compared with no prophylaxis. When poor compliance was considered, aspirin became the dominant strategy. Sensitivity analyses failed to show any instance where LMWH was cost-effective. In terms of population costs, widespread use of LDUH after discharge would save $30.3 million per year in the United States. Although all chemical prophylaxis is effective in preventing VTE in the outpatient setting after cancer surgery, either LDUH or aspirin are the most cost-effective, depending on patient compliance.

Prolonged thromboprophylaxis with Low Molecular Weight heparin for abdominal or pelvic surgery

Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low-molecular weight heparin (LMWH) administered during the in-hospital period is well documented, but the optimal duration of thromboprophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominal surgery benefit from prolongation of the thromboprophylaxis to 1 month after surgery. No systematic review on prolonged thromboprophylaxis after major abdominal or pelvic surgery has been published. To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 1 month after abdominal or pelvic surgery with thromboprophylaxis administered during the in-hospital period only in preventing late VTE. Electronic searches were performed January 2008 in the Medline, Embase, Lilacs, and the Cochrane Central Register of Controlled Trials. Abstract books from major congresses addressing thromboembolism were hand searched, as were reference lists from studies of relevance. We assessed both randomised and non-randomised controlled clinical trials comparing prolonged thromboprophylaxis with any anti-thrombotic agent with placebo and/or thromboprophylaxis during the admission period only. The patient population in the trials were patients undergoing abdominal or pelvic surgery. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (ascending bilateral venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral CT scan or autopsy). Studies exclusively reporting on clinical diagnosis of VTE, without objective confirmation were excluded. The identification of studies and data extraction were performed by the authors. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcome were defined as bleeding complications and mortality within 3 months after surgery. The search exclusively detected trials evaluating prolonged thromboprophylaxis with LMWH as compared to control or placebo. 133 studies were found in the searches, of which only 4 were found eligible for inclusion, and 129 were excluded. The incidence of overall VTE after major abdominal or pelvic surgery was 14.3% (95% confidence interval 11.2% - 17.8%) in the control group as compared to 6.1% (95% CI 4.0% - 8.7%) in the patients receiving out-of-hospital LMWH. This difference was statistically significant, Peto Odds Ratio 0.41 (95% CI 0.26 -0.63), P < 0.0005. Prolonged thromboprophylaxis with LMWH was also associated with a statistically significant reduction of even the incidence of symptomatic VTE from 1.7% (95% CI 0.8% - 3.4%) in the control group to 0.2 % (95% CI 0.0% - 1.2%) in patients receiving prolonged thromboprophylaxis, Peto Odds ratio 0.22 (95% CI 0.06 -0.80), P = 0.02. The respective incidence of bleeding in the control and LMWH group were 3.7% (95% CI 2.4% -5.5%) and 4.1% (95% CI 2.7% - 6.0%), Peto Odds ratio 1.11 (95% CI 0.62 - 1.97), P = 0.73. There was no significant heterogeneity detected as regards to outcome parameters reported in the included trials. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery.

Prolonged thromboprophylaxis with Dalteparin during immobilization after ankle fracture surgery: A randomized placebo-controlled, double-blind study

Prolonged thromboprophylaxis with Dalteparin during immobilization after ankle fracture surgery: A randomized placebo-controlled, double-blind study

Prolonged thromboprophylaxis with low molecular weight heparin after major abdominal surgery

To analyze the effect of prolonged thromboprophylaxis with low molecular weight heparin in patients undergoing major abdominal surgery. Literature searches in PubMed, EMBASE and Cochrane Database between 1990 and 2006 were conducted to identify trials concerning prolonged thromboprophylaxis in major abdominal surgery. Three randomized controlled trials met the search criteria. They showed that low molecular weight heparin is effective and safe to use as prolonged thromboprophylaxis after major abdominal surgery. Three published randomized studies all show a 50-60% relative risk reduction of late occurring deep venous thrombosis after major abdominal surgery. Evidence for the use of prolonged thromboprophylaxis after major abdominal surgery is emerging, and seems justified in selected high-risk patients, including patients operated on for cancer.

Prolonged thromboprophylaxis with Dalteparin during immobilization after ankle fracture surgery: A randomized placebo-controlled, double-blind study

Background Skeletal trauma and immobilization are well-known risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE). While prophylaxis against thromboembolic complications has become routine after major orthopedic surgery, whether or not prophylaxis after minor surgery and lower limb immobilization is necessary is still under debate.Methods In a double-blind, placebo-controlled study, 272 consecutive patients were randomized to receive either thromboprophylaxis with Dalteparin (n = 136) or placebo (n = 136) for 5 weeks after ankle fracture surgery. All patients received 1 week of initial treatment with Dalteparin before randomization. A unilateral phlebography was performed when the cast was removed.Results The overall incidence of DVT was 21% (95% CI: 13–29%) in the Dalteparin group and 28% (CI: 19– 37%) in the placebo group (risk ratio = 0.8, CI: 0.6–1.1; p = 0.3). The incidence of proximal DVTs was 4% and 3%, respectively. No major bleeding occurred.Interpretation We found no significant difference in the incidence of DVT between the 2 treatment groups and our results do not support prolonged thromboprophylaxis. The overall incidence of DVT was high, reflecting the potential risk of PE and post-thrombotic syndrome after ankle fracture surgery. Most of the DVTs were asymptomatic, however, and were located in distal veins.

Prolonged prophylaxis against venous thromboembolism with enoxaparin in patients undergoing cancer surgery: long-term survival analysis

Objective: ENOXACAN II was a randomized, double-blind trial that showed prolonged (four-week) thromboprophylaxis with enoxaparin to be more effective than and as safe as standard (one-week) thromboprophylaxis in patients undergoing surgery with a curative intent for abdominopelvic cancer. This follow-up study compared long-term, all-cause mortality in both groups. Methods: Survival rates were calculated on the randomized, treated population ( n = 501). The primary efficacy endpoint was survival at one year. An exploratory analysis including survival data up to 44 months was performed. Because some patients were deemed to have undergone palliative as opposed to curative surgery, and there was a significant difference between the treatment groups in the percentage of patients undergoing palliative surgery, the survival analyses were adjusted for the type of surgery performed. Results: When adjusted for type of surgery, there was a trend towards reduced mortality among patients undergoing palliative surgery in the prolonged prophylaxis group (hazard ratio [HR] = 0.598, P = 0.3565) that became more pronounced beyond the pre-specified one year follow-up period (HR = 0.469, P = 0.078). This trend may reflect a beneficial effect of prolonged prophylaxis on survival in the palliative surgery group (one-year survival 65.4 versus 50% for standard prophylaxis). In patients undergoing curative surgery, one-year survival rates were equal in the standard and prolonged prophylaxis groups (93.8 and 93.2%, respectively). Conclusion: Prolonged thromboprophylaxis with enoxaparin may affect long-term survival in palliative surgery for cancer, but further investigation is warranted.

Portal vein thrombosis is a common complication following splenectomy in patients with malignant haematological diseases

Elective laparoscopic splenectomy (LS) is performed with increasing frequency rather than open splenectomy (OS) because of reduced morbidity. LS is feasible also in patients with haematological diseases with splenomegaly, a group that is subject to more postoperative complications, such as bleeding, infections and portal vein thrombosis (PVT). We retrospectively reviewed the medical records of 69 patients splenectomised for haematological diseases during a 5-yr period at a single centre with the aim of comparing the results and complications after LS and OS. Thirty-nine patients underwent LS and 30 OS. The median durations of surgery were 138 and 115 min (ns) in the LS and OS groups respectively. Three conversions (7.7%) from laparoscopic surgery to open surgery were necessary because of bleeding and/or splenomegaly. Thromboembolic complications occurred in totally seven of 69 patients. PVT was diagnosed in five of 37 (13.5%) patients with haematological malignancies (three with indolent lymphoma and two with myeloproliferative disease), one after LS and four after OS. All patients with PVT had splenomegaly and had received thromboembolic prophylaxis with low-molecular-weight heparin of short duration. Two patients were diagnosed with deep vein thromboses in the lower leg. Both had idiopathic thrombocytopenic purpura (ITP) and LS. Patients with malignant haematological diseases and splenomegaly seem to have a high risk of developing PVT after splenectomy why careful observation and prolonged thromboprophylaxis is recommended for these patients. Ultrasonography or computerised tomography should be considered in all patients with abdominal symptoms after splenectomy.

High sensitivity with color duplex sonography in thrombosis screening after ankle fracture surgery.

Phlebography is regarded as the reference standard for diagnosing asymptomatic deep vein thrombosis (DVT) in studies of thromboprophylaxis. However, technical advances with noninvasive color duplex sonography (CDS) have made this procedure an interesting alternative. The objective of the present prospective study was to compare the sensitivity and specificity of CDS with those of phlebography. The first 180 consecutive patients included in a larger randomized trial for prolonged thromboprophylaxis were subject to unilateral CDS and to phlebography after ankle fracture surgery. The patients were examined 6 weeks after surgery, all examinations being evaluated blindly. After patient drop outs and exclusions, 144 patients were left for analysis. Phlebography and CDS examinations were inconclusive or were not completed for 19% of these patients (28/144). DVT was diagnosed by phlebography in 21% (24/116) of the remaining patients. Most of the thrombi were isolated calf DVTs (18/24). In contrast, DVT was diagnosed by CDS in 31% of these patients (36/116): only one case diagnosed by phlebography was missed by CDS. The specificity of CDS is thus 86% and its sensitivity is 96%. The positive predictive value is 64%, and the negative predictive value is 99%. CDS is a safe method for detecting asymptomatic distal DVT. It has a high sensitivity and high negative predictive value, which means that the method is highly reliable to rule out DVT. Our results indicate that CDS could be considered as an alternative method for DVT screening.

Rates of proximal deep vein thrombosis as assessed by compression ultrasonography in patients receiving prolonged thromboprophylaxis with low molecular weight heparin after major orthopedic surgery

Patients undergoing major orthopedic surgery are at an increased risk of thromboembolism even after the acute postoperative phase. Therefore, prolonged thromboprophylaxis is currently recommended and widely used. The length of hospital stay after major orthopedic surgery is steadily decreasing and most patients are transferred to specialized rehabilitation centers in the early postoperative phase. Consequently, thromboprophylaxis is usually given during the rehabilitation period. Previously there have been no systematic studies of how many patients with asymptomatic thrombosis are transferred to a rehabilitation center or how many patients develop deep vein thrombosis (DVT) during rehabilitation. In the present study, 238 patients who had undergone major orthopedic surgery were examined by compression ultrasonography on day 1 or 2 and on day 20 of their rehabilitation phase in order to detect asymptomatic proximal DVT. Sonograms were read centrally with blinding to the clinical course of the patients. All patients received standard thromboprophylaxis during the acute postoperative phase. Prolonged thromboprophylaxis with enoxaparin was given during the rehabilitation phase. The mean duration of thromboprophylaxis was 36.8 days. At admission to the rehabilitation center, proximal DVT was identified in 16 patients (6.7%). New proximal DVT at discharge from the rehabilitation center was identified in 3.2% of patients following prolonged thromboprophylaxis with enoxaparin. In conclusion, a considerable percentage of patients with asymptomatic proximal DVT are transferred to rehabilitation centers following major orthopedic surgery. Using prolonged thromboprophylaxis, new proximal DVTs will still develop during rehabilitation, but at a low rate.

Does prolonged thromboprophylaxis improve outcome in patients undergoing surgery?

Patients undergoing major abdominal surgery, particularly for malignancy, are at increased risk of venous thromboembolism. Haemostatic markers of coagulation are raised for several weeks after surgery. A higher dose of low-molecular-weight heparin than normally used for thromboprophylaxis is effective in preventing post-surgical VTE in patients with cancer with no compromise on bleeding. Four weeks' of thromboprophylaxis with the LMWH dalteparin is significantly more effective than standard (1 week) thromboprophylaxis in preventing proximal DVT. A meta-analysis of studies comparing 4 weeks' with 1 week of thromboprophylaxis showed that prolonged thromboprophylaxis with LMWH following major abdominal surgery for malignancy significantly reduces the risk of late occurring DVT.

Investment in prolonged thromboprophylaxis with dalteparin improves clinical outcomes after hip replacement

Clinical guidelines recommend the use of extended out-of-hospital thromboprophylaxis in patients who have had major arthroplasty. However, the cost-effectiveness of prolonging pharmacological thromboprophylaxis into the out-of-hospital phase following hip replacement surgery remains the subject of considerable debate. This debate centers on the clinical relevance of the 'surrogate' venographic endpoints that have been used in most clinical trials and used to generate some of the cost analyses of thromboprophylaxis. The objective of this study was to estimate, from the payer perspective, the direct medical costs of prolonging the duration of thromboprophylaxis with dalteparin from 1 week to 28-35 days in patients undergoing hip replacement, and to compare these to the costs associated with using 'standard' in-hospital thromboprophylaxis with low-molecular-weight heparin (LMWH) or warfarin. To derive 'best' estimates for rates of clinically and economically relevant thromboembolism associated with hip replacement surgery (i.e. those that would in reality incur management costs), we used data on the prevalence of both symptomatic and asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). These estimates were used in conjunction with diagnostic-related groups (DRG) reimbursement rates and a dalteparin cost model, which assumed home-based self-administration for prolonged thromboprophylaxis, to calculate overall direct medical costs of prolonged vs. in-hospital thromboprophylaxis. The management costs of the strategies evaluated were, to the nearest 1000 Euros: 465 000 Euros for in-hospital prophylaxis with LMWH; 339 000 Euros for in-hospital prophylaxis with warfarin; and 368 000 Euros for prolonged prophylaxis with dalteparin. For every 1000 patients treated, prolonging thromboprophylaxis with dalteparin from 1 to 4-5 weeks will avoid 30 clinical DVTs and 18 PEs at a saving of 2000 Euros per clinical event. Compared with in-hospital warfarin, prolonged thromboprophylaxis with dalteparin will avoid 28 DVTs and four PEs at an incremental cost-effectiveness ratio of 900 Euros per clinical event avoided. We consider that investment in prolonged thromboprophylaxis with dalteparin is justified for the improvement in clinical outcomes produced.

Recent Advances in Venous Thromboembolic Prophylaxis in Major Orthopedic Surgery: A Regional Perspective

Recent Advances in Venous Thromboembolic Prophylaxis in Major Orthopedic Surgery: A Regional Perspective

Preventing thromboembolic complications in cancer patients after surgery: a role for prolonged thromboprophylaxis

Patients undergoing major abdominal surgery for malignancy are at particularly high risk of developing VTE. Extra protection against this can be given to patients with cancer by using a higher dose of LMWH than normally used for prophylaxis, with no increase in bleeding complications. Despite thromboprophylaxis with high-dose LMWH for the first postoperative week, the rate of late VTE is estimated to be between 10% and 20%. A meta-analysis of two studies using dalteparin or enoxaparin has shown that prolonging thromboprophylaxis for a further 3 weeks significantly reduces the risk of late occurring VTE by 62%. Thromboprophylaxis with LMWH for at least one month should be considered in patients undergoing surgery for malignant disease.

Thromboembolic disease in surgery for malignancy-rationale for prolonged thromboprophylaxis.

Patients undergoing surgery for malignancy are at increased risk of initial and recurrent venous thromboembolism (VTE). Several factors have been found to increase the risk of deep vein thrombosis (DVT) in cancer patients both during the first days after the operation and after discharge from hospital. Although, in general, thromboprophylaxis is provided to cancer patients after surgery, the length of time these patients require prophylaxis has not yet been established. Autopsy series, clinical series, and clinical trials indicate that up to about 40% of VTE occurs post discharge. General surgical patients undergoing major abdominal surgery require VTE prophylaxis, and prolonged thromboprophylaxis should be considered in the post-discharge period in high-risk patients, particularly those with cancer. Evidence from studies in general and orthopedic surgery show that prolonged prophylaxis reduces the number of thromboembolic events after discharge from hospital. Prophylaxis should be simple, safe, and effective and should be administered easily to allow continuation of therapy after discharge. Low-molecular-weight heparins are potentially the most suitable agents for long-term thromboprophylaxis in cancer patients.

Cost-Effectiveness of Prolonged Administration of a Low Molecular Weight Heparin for the Prevention of Deep Venous Thrombosis Following Total Hip Replacement

Recently there has been discussion on the value of prolonged thromboprophylaxis after elective hip surgery to prevent thromboembolic complications up to one month. Continuing low molecular weight heparin for one month can significantly reduce the frequency of venographically-proven deep vein thrombosis (DVT). How this will influence health economics has hitherto not been evaluated. Data on costs and effect from a randomized comparison between 10 and 30 days of once daily low molecular weight heparin (enoxaparin) were used in a cost-effectiveness study. Data on treatment costs were based on patients actually treated for DVT within the randomized study. Various sensitivity analyses were performed. In the study both phlebographically detected and clinically manifested venous thromboembolism were registered. By using costs from the health care system in Sweden it could be shown that the cost was 6,075 Swedish Krona (SEK) per phlebographic DVT avoided and 13,184 Swedish Krona (SEK) per clinical DVT avoided. If more than 50% of the patients managed to self-administer the low molecular weight heparin injections, the use of prolonged prophylaxis is cost-effective. Prolonged prophylaxis with the low molecular weight heparin enoxaparin after elective hip arthroplasty is cost-effective provided that at least 50% of the patients can administer the subcutaneous injections themselves.