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OBJECTIVES: Venous thromboembolism (VTE) is a well-established complication after many orthopaedic injuries, such as hip and lower limb fractures. The use of direct oral anticoagulants (DOACs, previously termed novel oral anticoagulants) is well-established as thromboprophylaxis after major elective orthopaedic surgery, but not in the nonelective setting. The aim of this study was to investigate the effectiveness and safety of DOACs after nonelective lower limb fracture surgery. DATA SOURCES: A systematic literature search of the MEDLINE, EMBASE, CINAHL, and CENTRAL databases was conducted. No limitation was placed on publication date, with only manuscripts printed in English were eligible. STUDY SELECTION: Included studies were either randomized controlled trials or prospective and retrospective comparative studies. Included studies compared DOACs to conventional methods of thromboprophylaxis in the postoperative period after surgical management of lower limb fractures. DATA EXTRACTION: Outcomes included VTE, bleeding, wound complications, mortality, and adverse events. Eight studies met inclusion criteria, of which 7 compared direct factor Xa inhibitors (XaIs) with conventional VTE prophylaxis and one study compared a direct thrombin inhibitor with conventional VTE prophylaxis. DATA SYNTHESIS: Revman 5.3 (Nordic Cochrane Centre, Denmark) was used to complete the meta-analysis and generate forest plots. CONCLUSIONS: XaIs were shown to have lower rates of deep vein thrombosis (Odds ratio 0.59; 95% confidence interval, 0.46-0.76; P < 0.0001) and less pharmacologically attributable adverse events (Odds ratio 0.62; 95% confidence interval, 0.46-0.82; P = 0.0007). There was difference between DOACs and conventional VTE prophylaxis regarding mortality, PE, symptomatic deep vein thrombosis, or bleeding events. The results generally support the use of DOACs for VTE prophylaxis after nonelective lower limb fracture surgery, such after hip fracture. The results more strongly support the use of XaIs; however, more evidence is needed to fully assess DOACs' role in clinical practice. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Introduction The management of patients with a hip fracture is affected by the use of oral anticoagulants. A cross-sectional analysis was undertaken to investigate health outcome differences in those anticoagulated compared to those not anticoagulated. Methods Patients aged 50 years and over presenting to a large university hospital with hip fractures were identified from the service registry. Patient characteristics and health outcomes between those not anticoagulated were compared with those anticoagulated (warfarin and direct oral anticoagulants, DOAC). Results 200/2307 (9%) patients were anticoagulated. 84% were on warfarin, and the rest a DOAC. Compared to those anticoagulated, there was a higher prevalence of dementia (25% vs. 18%, p = 0.02) and a lower prevalence of cardiovascular disease (54% vs. 78%, p p p p = 0.04) and heart failure (1% vs. 5%, p Conclusion There was no statistically significant difference in health outcomes between those anticoagulated and those not after adjusting for patient characteristics. It was feasible to avoid significant delay in hip fracture surgery in those anticoagulated.

We present final results of a study comparing teriparatide 20 μg every day (QD) with risedronate 35 mg once per week (QW) started within 2 weeks after surgery for a pertrochanteric hip fracture. Patients with BMD T-score ≤ -2.0 and 25OHD ≥9.2 ng/mL were randomized to receive 26-week double-dummy treatment plus calcium and vitamin D, followed by 52-week open-label treatment with the same assigned active drug. Primary endpoint was change from baseline in lumbar spine (LS) BMD at 78 weeks. Secondary and exploratory endpoints were change in BMD at the proximal femur, function, hip pain (Charnley score and 100 mm Visual Analog Scale [VAS]), quality of life (Short Form-36), radiology outcomes, and safety. Data were analyzed with mixed models for repeated measures (MMRM) and logistic regression. Totally, 224 patients were randomized; 171 (teriparatide: 86) contributed to the efficacy analyses (mean ± SD age: 77 ± 7.7 years, 77% females). Mean baseline LS, femoral neck (FN), and total hip (TH) T-scores were -2.16, -2.63, and -2.51, respectively. At 78 weeks, BMD increased significantly more with teriparatide compared to risedronate at the LS (+11.08% versus +6.45%; p < 0.001) and FN (+1.96% versus -1.19%; p = 0.003), with no significant between-group difference in TH BMD. Timed up-and-go (TUG) test was significantly faster with teriparatide at 6, 12, 18, and 26 weeks (differences: -3.2 to -5.9 s; p = 0.045 for overall difference). Hip pain during TUG test by 100 mm VAS was significantly lower with teriparatide at 18 weeks (adjusted difference: -11.3 mm, p = 0.033; -10.0 and -9.3 mm at 12 and 26 weeks, respectively; p = 0.079 for overall difference). Other secondary and exploratory outcomes were not different. Teriparatide group showed two new hip fractures versus seven with risedronate (p = 0.171) and more frequent hypercalcemia and hyperuricemia. In conclusion, 78-week treatment with teriparatide showed significantly greater increases in LS and FN BMD, less pain, and a faster TUG test versus risedronate. © 2016 American Society for Bone and Mineral Research.

BACKGROUND: Traditionally, distal radius fractures (DRFs) have been described using eponyms, e.g. Colles, Smith, Barton, Chauffeur. During the last half of the 20th century several classification systems for DRF have emerged. We evaluated the inter- and intra-observer agreement of the AO/OTA, Frykman and Older classification systems.METHODS: Four observers, an intern, an orthopaedic registrar, an orthopaedic consultant and a radiology consultant, independently evaluated DRF radiograms and classified the fractures according to the AO/OTA, Frykman and Older classification systems. After an interval of 6 months, radiograms of 30 randomly chosen patients were re-evaluated by the same observers.RESULTS: Radiograms of 573 DRF patients were evaluated in the study. The inter-observer reliability of the AO/OTA fracture types (A, B and C) was 'weak' (kappa = 0.45). The agreement dropped to 'minimal' (kappa = 0.24) regarding the AO/OTA groups (A2, A3, B1, B2, B3, C1, C2 and C3). The reliability of the Frykman classification system was 'weak' (kappa = 0.41), and we observed the lowest inter-observer reliability for the Older classification system (kappa = 0.10). The kappa values for the intra-observer reproducibility of the AO/OTA fracture types (A, B and C) ranged from 0.58 to 0.87. For the AO/OTA groups (A2, A3, B1, B2, B3, C1, C2 and C3) the reproducibility was lower ranging from 'minimal' to 'weak'. The intra-observer reproducibility of the Frykman system was 'weak' to 'moderate' and even worse for the Older classification system.CONCLUSION: Based on these findings the AO/OTA classification system seems to be most reliable for routine use, however, with lower kappa values concerning the agreement for the groups. The Frykman and Older classification systems cannot be recommended because of less convincing results.

We examined possible associations between different red blood cell (RBC) transfusion strategies, overall quality of life (OQoL), and recovery of activities of daily living (ADL) in operated frail elderly hip fracture patients, and the possibility that OQoL was related to ADL recovery.A prospective, assessor-blinded, randomized controlled trial was carried out among 157 elderly residents (≥65 years) from nursing homes and sheltered housing facilities with Mini-Mental State Examination scores ≥5 points. Patients were assigned to either a restrictive RBC transfusion strategy [hemoglobin (Hb) 9.7 g/dL, 6 mmol/L] or a liberal strategy (Hb 11.3 g/dL, 7 mmol/L) during the first 30 days after surgery. An interview-based questionnaire, the depression list (DL) assessing OQoL, and the modified Barthel Index (MBI) assessing ADL performance, were conducted on day 30 and 1 year after hip fracture surgery. Sum-scores of DL, MBI, and their changes from day 30 until 1 year (expressing recovery) were compared between RBC transfusion groups. Possible associations between changes of DL and MBI sum-scores were tested for across total patient population.There was no association between OQoL and RBC transfusion strategies on day 30 or at 1 year. The DL sum-score changes were similar for both groups, (ie, 1.06 points) [95% confidence interval (CI) -0.62, 2.76)] P = .21. The MBI sum-scores increased at 1 year following the liberal transfusion strategy (ie, by 6.86 points) (95% CI 0.41, 13.3) P = .03. Recoveries of OQoL and ADL were associated: β = -0.06 (95% CI -0.11, -0.01) P = .02.According to our Hb threshold criteria, OQoL and RBC transfusion strategies for frail elderly hip fracture patients are not associated. However, for survivors with less severe dementia, ADL recovery after 1 year is greater following a liberal transfusion strategy than a restrictive strategy. OQoL progress and ADL recovery were associated.

Background: Radiographic fracture classification helps with research on prognosis and treatment. AO/OTA classification into fracture type has shown to be reliable, but further classification of fractures into subgroups reduces the interobserver agreement and takes a considerable amount of practice and experience in order to master. Questions/purposes: We assessed: (1) differences between more and less experienced trauma surgeons based on hip fractures treated per year, years of experience, and the percentage of their time dedicated to trauma, (2) differences in the interobserver agreement between classification into fracture type, group, and subgroup, and (3) differences in the interobserver agreement when assessing fracture stability compared to classifying fractures into type, group and subgroup. Methods: This study used the Science of Variation Group to measure factors associated with variation in interobserver agreement on classification of proximal femur fractures according to the AO/OTA classification on radiographs. We selected 30 anteroposterior radiographs from 1061 patients aged 55 years or older with an isolated fracture of the proximal femur, with a spectrum of fracture types proportional to the full database. To measure the interobserver agreement the Fleiss’ kappa was determined and bootstrapping (resamples = 1000) was used to calculate the standard error, z statistic, and 95% confidence intervals. We compared the Kappa values of surgeons with more experience to less experienced surgeons. Results: There were no statistically significant differences in the Kappa values on each classification level (type, group, subgroup) between more and less experienced surgeons. When all surgeons were combined into one group, the interobserver reliability was the greatest for classifying the fractures into type (kappa, 0.90; 95% CI, 0.83 to 0.97; p < 0.001), reflecting almost perfect agreement. When comparing the kappa values between classes (type, group, subgroup), we found statistically significant differences between each class. Substantial agreement was found in the clinically relevant groups stable/unstable trochanteric, displaced/non-displaced femoral neck, and femoral head fractures (kappa, 0.60; 95% CI, 0.53 to 0.67, p < 0.001). Conclusions: This study adds to a growing body of evidence that relatively simple distinctions are more reliable and that this is independent of surgeon experience.

Background and purpose — Hip fracture (HF) in frail elderly patients is associated with poor physical recovery and death. There is often postoperative blood loss and the hemoglobin (Hb) threshold f...

BACKGROUND: Volar plating of unstable distal radius fractures (DRF) has become the favoured treatment. The complication rates vary from 3 to 36%. The purpose of the study was to estimate the complication rate of volar plating of DRF and its association with AO/OTA fracture type, surgeon experience and type of volar plate.METHODS: Retrospectively, all patients treated with volar plating of a DRF between February 2009 and June 2013 at Aarhus University Hospital, Denmark were included. AO/OTA fracture type, surgeon experience (1st year, 2nd-5th year resident or consultant), type of plate (VariAx(®), Acu-Loc(®)) and complications were extracted from the electronic medical records. Complications were categorized as carpal tunnel syndrome, other sensibility issues, tendon complications including irritation and rupture, deep infections, complex regional pain syndrome and unidentified DRUJ or scapholunar problems. Reoperations including hardware removal were also charted.RESULTS: 576 patients with a median age of 63 (min: 15; max: 87) were included. 78% were female and the mean observation time was 3.2 years (min: 2.0; max: 5.4). 78% (n=451) of the patients were treated with VariAx(®) and 22% (n=125) with Acu-Loc(®). The overall complication rate was 14.6% (95% CI 11.8-17.7) including carpal tunnel syndrome or change in sensibility in 5.2% and tendon complications in 4.7%. Five flexor tendon ruptures and 12 extensor tendon ruptures were observed. The reoperation rate was 10.4% including 41 cases of hardware removal. A statistically significant association between AO/OTA fracture type C and complications was found. No statistically significant association between complication rate and surgeon experience and type of plate was observed.CONCLUSION: The majority of DRF patients treated with a volar plate suffer no complications. However, the overall complication rate of 14.6% is substantial. Intra-articular fractures, e.g. AO/OTA-type 23C1-3, had significantly higher complication rates. Neither surgeon experience, nor type of volar plate was able to predict complications.

Introduction We have recently reported that increased levels of urine prothrombin fragment 1 + 2 reflected radiologically verified deep vein thrombosis. In this study we evaluated whether urine prothrombin fragment 1 + 2 was associated with pulmonary embolism in non-selected patients. Materials and methods Patients with clinical suspected pulmonary embolism were interviewed on comorbidities and medications. Urine was collected from each patient before radiological examination and snap frozen until analysed on urine prothrombin fragment 1 + 2 with an ELISA kit. Imaging of the pulmonary arteries were conducted with contrast enhanced computer tomography. Results Pulmonary embolism was diagnosed in 44/197 patients. Non-significantly higher urine prothrombin fragment 1 + 2 levels were found in non-selected patients with pulmonary embolism vs. those without ( p = 0.324). Significantly higher urine prothrombin fragment 1 + 2 levels were found in the pulmonary embolism positive patients without comorbidities (n = 13) compared to the control group (n = 28) ( p = 0.009). The calculated sensitivity, specificity and negative predictive value using the lowest detectable urine prothrombin fragment 1 + 2 level was 82%, 34% and 87%, respectively. Conclusions There was no significant urine prothrombin fragment 1 + 2 level difference in patients with and without pulmonary embolism. In non-comorbide pulmonary embolism positive patients the urine prothrombin fragment 1 + 2 levels were significantly higher compared to the control group. The negative predictive value found in this study indicates that uF1 + 2 has the potential to identify patients with a low risk of PE.

Loss of contact between radial head fracture fragments is strongly associated with other elbow or forearm injuries. If this finding has adequate interobserver reliability, it could help examiners identify and treat associated ligament injuries and fractures (eg, forearm interosseous ligament injury or elbow dislocation). (1) What is the interobserver agreement on radiographic loss of contact between radial head fracture fragments? (2) Are there factors associated with the observer such as location of practice or subspecialization that increase interobserver reliability? Fully trained practicing orthopaedic and trauma surgeons from around the world evaluated 27 anteroposterior and lateral radiographs of radial head fractures on a web-based platform for the following characteristics: (1) loss of contact between at least one radial head fracture fragment and the remaining radial head and neck; (2) a gap between fragments of 2 mm or greater; (3) anticipated fracture instability (mobility) on operative exposure; (4) anticipated associated ligament injuries; and (5) recommendation for treatment. Agreement among observers was measured using the multirater kappa measure. Kappas for various observer characteristics were compared using 95% confidence intervals. The overall interobserver agreement was moderate (range, 0.49-0.55) for each question except associated ligament injury, which was fair (0.33). Shoulder and elbow surgeons had substantial agreement (range, 0.51-0.61) in many areas, but kappas were generally in the moderate range (0.41-0.59) based on number of years in practice, radial head fractures treated per year, and trainee supervision. Radiographic signs of radial head fracture instability such as loss of contact have moderate reliability. This characteristic seems clinically useful, because loss of contact between at least one radial head fracture fragment and the remaining radial head and neck is strongly associated with associated ligament injury or other fractures. Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence

The appearance of prothrombin fragment 1 + 2 (F1 + 2) in urine has been associated with postoperative hypercoagulability and thromboembolism. We wanted to assess if F1 + 2 was released in urine (uF1 + 2) in patients with procoagulant disorders, and if higher levels were found in patients with radiological verified deep vein thrombosis (DVT).Consecutive patients were interviewed on comorbidities and medications. An unselected total cohort (n = 534) and a control cohort (n = 177) were analysed. A urine sample (10 ml) was collected and snap frozen before levels of uF1 + 2 were measured with an ELISA kit. Visualisation of DVT was done with compression ultrasound, supplied with venography when feasible. All patients were followed up for 3-6 months.DVT was diagnosed in 108/534 patients. Statistical significant higher uF1 + 2 levels were found in patients with DVT (p0.001), in DVT positive patients with ongoing malignancy (p = 0.034) and in pregnant women compared to the control cohort (p0.001). Non-significant increased urine concentrations were found in DVT positive vs. DVT negative patients with infections and traumas.Levels of uF1 + 2 was associated with DVT both in the total cohort and in the control cohort as well as in most patients with coexisting conditions.

Item does not contain fulltext PURPOSE: Surgical costs are under scrutiny and surgeons are being held increasingly responsible for cost containment. In some instances, implants are the largest component of total procedure cost, yet previous studies reveal that surgeons' knowledge of implant prices is poor. Our study aims to (1) understand drivers behind implant selection and (2) assess whether educating surgeons about implant costs affects implant selection. METHODS: We surveyed 226 orthopedic surgeons across 6 continents. The survey presented 8 clinical cases of upper extremity fractures with history, radiographs, and implant options. Surgeons were randomized to receive either a version with each implant's average selling price ("price-aware" group), or a version without prices ("price-naive" group). Surgeons selected a surgical implant and ranked factors affecting implant choice. Descriptive statistics and univariate, multivariable, and subgroup analyses were performed. RESULTS: For cases offering implants within the same class (eg, volar locking plates), price-awareness reduced implant cost by 9% to 11%. When offered different models of distal radius volar locking plates, 25% of price-naive surgeons selected the most expensive plate compared with only 7% of price-aware surgeons. For cases offering different classes of implants (eg, plate vs external fixator), there was no difference in implant choice between price-aware and price-naive surgeons. Familiarity with the implant was the most common reason for choosing an implant in both groups (35% vs 46%). Price-aware surgeons were more likely to rank cost as a factor (29% vs 21%). CONCLUSIONS: Price awareness significantly influences surgeons' choice of a specific model within the same implant class. Merely including prices with a list of implants leads surgeons to select less expensive implants. This implies that an untapped opportunity exists to reduce surgical expenditures simply by enhancing surgeons' cost awareness. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analyses I.

To investigate whether a liberal blood transfusion strategy [Hb levels ≥11.3 g/dL (7 mmol/L)] reduces the risk of postoperative delirium (POD) on day 10, among nursing home residents with hip fracture, compared to a restrictive transfusion strategy [Hb levels ≥9.7 g/dL (6 mmol/L)]. Furthermore, to investigate whether POD influences mortality within 90 days after hip surgery. This is a post hoc analysis based on The TRIFE - a randomized controlled trial. Frail anemic patients from the Orthopedic Surgical Ward at Aarhus University Hospital were enrolled consecutively between January 18, 2010 and June 6, 2013. These patients (aged ≥65 years) had been admitted from nursing homes for unilateral hip fracture surgery. After surgery, 179 patients were included in this study. On the first day of hospitalization, all enrolled patients were examined for cognitive impairment (assessed by MMSE) and delirium (assessed by CAM). Delirium was also assessed on the tenth postoperative day. The prevalence of delirium was 10 % in patients allocated to a liberal blood transfusion strategy (LB) and 21 % in the group with a restrictive blood transfusion strategy (RB). LB prevents development of delirium on day 10, compared to RB, odds ratio 0.41 (95 % CI 0.17–0.96), p = 0.04. Development of POD on day 10 increased the risk of 90-day death, hazard ratio 3.14 (95 % CI 1.72–5.78), p

Udgivelsesdato: 2009-Apr The new oral, antithrombotic drug rivaroxaban is a direct factor Xa inhibitor, which can restrict thrombin generation both in vitro and in vivo. It has a predictable dose-dependent pharmacokinetic and pharmacodynamic profile and is well tolerated. In patients undergoing total hip or knee arthroplasty, rivaroxaban, 10 mg once daily started 6 - 8 h after the operation, had a significantly better antithrombotic efficacy and a comparable safety when compared with enoxaparin. Furthermore in all studies performed the drug had no adverse influence on the liver function in comparison with enoxaparin. In conclusion, rivaroxaban is a potent and safe new compound for antithrombotic prophylaxis in orthopaedic surgery.

Udgivelsesdato: 2009-Nov Venous thromboembolism (VTE) and the consequent morbidity and mortality associated with this condition continue to be a problem following orthopaedic surgery. The vast majority of patients undergoing orthopaedic surgery receive some form of thromboprophylaxis. However, the use of inappropriate thromboprophylaxis is an important factor which may explain why the clinical burden of VTE is still considerable. Barriers to the use of appropriate thromboprophylaxis include the belief by some surgeons that pharmacological thromboprophylaxis increases the risk of bleeding and the asymptomatic nature of deep vein thrombosis. In addition, in patients at risk of VTE, thromboprophylaxis should be given beyond the standard duration recommended in international or national guidelines, and many surgeons have concerns about adherence and adverse events in the outpatient setting. Furthermore, currently available anticoagulants have drawbacks, including the need for monitoring, or a subcutaneous route of administration. The introduction and implementation of multi-faceted and integrated approaches to thromboprophylaxis could improve adherence with current guidelines, extend appropriate thromboprophylaxis according to risk factors, and improve patient outcomes in this setting. In addition, the development of new anticoagulants with more convenient administration regimens and no need for monitoring may help to achieve these objectives.

Background: There is a clinical need for novel oral anticoagulants with predictable pharmacokinetics and pharmacodynamics. Rivaroxaban is an oral direct Factor Xa (FXa) inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. This analysis was performed to characterize the population pharmacokinetics and pharmacodynamics of rivaroxaban in patients participating in two phase II, double-blind, randomized, active-comparator-controlled studies of twice-daily rivaroxaban for the prevention of venous thromboembolism after total hip- or knee-replacement surgery. Methods: Sparse blood samples were taken from all patients participating in the studies (n = 1009). In addition, a subset of patients in the hip study (n = 36) underwent full profiling. Rivaroxaban plasma concentrations, FXa activity and the prothrombin time were determined. Nonlinear mixed-effects modelling was used to model the population pharmacokinetics and pharmacodynamics of rivaroxaban. Results: An oral one-compartment model described the population pharmacokinetics of rivaroxaban well. On the first postoperative day only, categorization of patients as slow or fast absorbers as a tool to address variability in absorption improved the fit of the model. Clearance of rivaroxaban was lower and more variable on the first postoperative day, and so time was factored into the model. Overall, the only major difference between the models for the hip study and the knee study was that clearance was 26% lower in the knee study, resulting in approximately 30% higher exposure. Residual variability in the models was moderate (37% and 34% in the hip and knee studies, respectively). Plasma concentrations of rivaroxaban increased dose dependently. Pharmacokinetic parameters that were estimated using the models agreed closely with results from full-profile patients in the hip study, demonstrating that rivaroxaban pharmacokinetics are predictable. The pharmacokinetics of rivaroxaban were affected by expected covariates: age affected clearance in the hip study only, haematocrit (on the first postoperative day only) and gender affected clearance in the knee study only, and renal function affected clearance in both studies. Bodyweight affected the volume of distribution in both studies. However, the effects of covariates on the pharmacokinetics of rivaroxaban were generally small, and predictions of ‘extreme’ case scenarios suggested that fixed dosing of rivaroxaban was likely to be possible. FXa activity and the prothrombin time were both affected by surgery, probably because of perioperative bleeding and intravenous administration of fluids; therefore, time was included in the pharmacodynamic models. In both studies, FXa activity correlated with rivaroxaban plasma concentrations following a maximum effect model, whereas prothrombin time prolongation correlated following a linear model with intercept. The slope of the prothrombin time prolongation correlation was 3.2 seconds/(100 μg/L) in the hip study and 4.2 seconds/(100 μg/L) in the knee study. Both pharmacodynamic models in both studies demonstrated low residual variability of approximately 10%. Conclusion: This population analysis in patients undergoing major orthopaedic surgery demonstrated that rivaroxaban has predictable, dose-dependent pharmacokinetics that were well described by an oral one-compartment model and affected by expected covariates. Rivaroxaban exposure could be assessed using the prothrombin time, if necessary, but not the international normalized ratio. The findings suggested that fixed dosing of rivaroxaban may be possible in patients undergoing major orthopaedic surgery.

SummaryRivaroxaban (Xarelto®) is an oral, direct factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. The aim was to compare the population pharmacokinetics (PK) and pharmacodynamics (PD) of twice-daily (bid) and once-daily (od) rivaroxaban in patients undergoing total hip replacement (THR). Blood samples were collected from patients enrolled in two phase IIb, dose-ranging studies undertaken to investigate rivaroxaban for thromboprophylaxis after THR. A sparse sampling technique was used and the samples were pooled for PK and PD analysis, which used non-linear mixed effect modelling. Rivaroxaban PK (samples from 758 patients) were well described by an oral, one-compartment model; age and renal function influenced clearance, and body surface area affected volume of distribution. When comparing the same total daily doses, maximum plasma concentrations of rivaroxaban were higher and minimum plasma concentrations were lower with od dosing, compared with bid dosing; however, the 90% intervals overlapped. The area under the plasma concentration–time curve was 18–30% higher in the od than in the bid study. Prothrombin time in seconds (samples from 1181 patients) correlated with rivaroxaban plasma concentrations in a linear fashion in both studies. In conclusion, the PK and PD of rivaroxaban were predictable when given either bid or od. These findings, along with the suggested efficacy and safety of rivaroxaban in the phase II studies, relative to enoxaparin, supported the selection of a convenient, once-daily 10 mg rivaroxaban dose for investigation in phase III studies.

BACKGROUND: Osteoporosis drugs might affect fracture-healing. We therefore studied the effects of teriparatide in comparison with risedronate on recovery after pertrochanteric hip fractures.METHODS: The study was a randomized, multicenter, active-controlled, 78-week trial comparing teriparatide (20 μg/day) with risedronate (35 mg/week) initiated within 2 weeks after fixation of a low-trauma pertrochanteric hip fracture (AO/OTA 31-A1 or 31-A2). The main inclusion criteria were a bone mineral density T-score of ≤-2.0 and 25-OH-vitamin D of ≥9.2 ng/mL. During the first 26 weeks, patients received study medication with oral or injectable placebo plus calcium and vitamin D in a double-blinded fashion. Secondary (Timed Up-and-Go [TUG] test, hip pain, Short Form [SF]-36 health status, and safety) and exploratory (radiographic outcomes and ability to walk) 26-week end points are reported.RESULTS: Of the 224 patients who were randomized, 171 (86 teriparatide, 85 risedronate) were included in the analysis. The mean age was 77 ± 8 years, 77% were female, and 26% had a prior history of low-trauma fracture. The teriparatide group completed the TUG test in a shorter time at 6, 12, 18, and 26 weeks (differences of -5.7, -4.4, -3.1, and -3.1 seconds, respectively; p = 0.021 for the overall difference). They also reported less pain on a visual analog scale immediately after the TUG test at 12 and 18 weeks (adjusted absolute differences of 10.6 and 11.9 mm, respectively; p < 0.05). There were no significant between-group differences in the SF-36 score, Charnley hip pain score, ability to walk, or use of walking aids during follow-up. Radiographic healing at 6, 12, and 26 weeks, mechanical failure of the implant (teriparatide, 7; risedronate, 8), loss of reduction (teriparatide, 2; risedronate, 4), and nonunion (0 cases) were not significantly different. Mild hypercalcemia and hyperuricemia were more frequent with teriparatide.CONCLUSIONS: Teriparatide was associated with less pain and a shorter time to complete the TUG test between 6 and 26 weeks compared with risedronate. Other fracture-recovery outcomes were similar. The results should be interpreted with caution as these were secondary end points.LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Tibial plateau fracture classification systems have limited interobserver reliability and new systems emerge. The purpose of this study was to compare the reliability of the Luo classification and the Schatzker classification for two-dimensional computed tomography (2DCT) and to study the effect of adding three-dimensional computed tomography (3DCT). Eighty-one observers, orthopedic surgeons and residents, were randomized to either 2DCT or 2D- and 3DCT evaluation of a spectrum of 15 complex tibial plateau fractures using web-based platforms in order to classify according to the Schatzker and according to Luo's Three Column classification. Reliability was calculated with the use of Siegel and Castellan's multirater kappa measure. Kappa values were interpreted according to the categorical rating by Landis and Koch. Overall interobserver reliability of the Schatzker classification was significantly better compared to the Luo classification (kSchatzker=0.32 and kLuo=0.28, P=0.021), however, 'fair' for both fracture classification systems. For the Schatzker classification observers agreed significantly better on 2DCT compared to 2D- and 3DCT (k2DCT=0.37 and k2D+3DCT=0.29, P

Prothrombin fragment 1+2 measured in spot urine (uF1+2) is an indicator of thrombin generation. We examined whether measured levels of uF1+2 can be used to differentiate between patients who do and do not acquire sustained coagulation activation after total hip arthroplasty (THA).We performed two separate studies in patients undergoing THA. Study 1 was a prospective pilot study aiming to roughly estimate the extent of pre- and postoperative fluctuations in the uF1+2 concentration. Study 2 was a larger prospective cohort study aiming to verify the findings of Study 1 and to examine the association between the uF1+2 concentrations and risk of vascular thrombotic complications (VTC) or death. Finally, we sought to define a cut-off concentration value that could be used to identify patients with a sustained uF1+2 elevation after the first postoperative week. The urine samples were analysed by ELISA. In both studies thromboprophylaxis was used for at least 7 days after the operation.The operative trauma resulted in elevation of the uF1+2 level in all patients compared with the preoperative level and levels in the healthy volunteers. Ten out of 113 patients (8.8%) in the second study suffered VTC or death, assumed to be caused by a coagulation problem. Analysis of variance revealed the following statistically significant associations: pre- vs. postoperative log uF1+2 levels (P0.0001), log uF1+2 levels comparing patients with and without events (P=0.004); and the individual log uF1+2 levels (P0.0001). A cut-off value of uF1+2 concentration between 0.3 and 0.5 nmol/l had a sensitivity and a negative predictive value between100% and 90%, and specificity between 45% and 63% and overall accuracy between 50% and 65%. This value was obtained by the analysis of a receiver operating characteristic curve with the purpose of identifying patients with sustained coagulation activation on day 5 after operation.Our studies suggest that measured levels of uF1+2 can be potentially used to assess the individual risk of VTC after THA and to test for non-invasive detection of sustained coagulation activation.

Introduction Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention of thromboembolic disorders. The aim of this study was to demonstrate proof-of-principle for rivaroxaban. Materials and methods This was an open-label, dose-escalation study to assess the efficacy and safety of rivaroxaban, relative to enoxaparin, for the prevention of venous thromboembolism (VTE) after total hip replacement surgery. Patients were randomized in a 3:1 ratio to rivaroxaban (2.5, 5, 10, 20 and 30 mg twice daily [bid] or 30 mg once daily [od] starting 6–8 h after surgery) or enoxaparin (40 mg od starting the evening before surgery). Therapy continued until mandatory bilateral venography was performed 5–9 days after surgery. Results A total of 625 patients received therapy, of whom 466 patients were eligible for the per-protocol efficacy analysis. The primary efficacy endpoint – deep vein thrombosis (DVT), pulmonary embolism (PE) or all-cause mortality – occurred in 22.2%, 23.8%, 20.0%, 10.2%, 17.4%, 15.1% and 16.8% of patients receiving rivaroxaban 2.5, 5, 10, 20, 30 mg bid, 30 mg od and enoxaparin, respectively. The dose-response relationship with rivaroxaban for the primary efficacy endpoint was not statistically significant ( p = 0.0504), although major VTE (proximal DVT, PE and VTE-related death) decreased dose dependently with rivaroxaban ( p = 0.0108). Major, post-operative bleeding increased dose dependently with rivaroxaban ( p = 0.0008), occurring in 0–10.8% of patients, compared with 0% in patients receiving enoxaparin. Conclusions This study demonstrated proof-of-principle for rivaroxaban for the prevention of VTE after total hip replacement surgery.

SummaryRivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N=722), and one in patients undergoing total knee replacement (TKR; N=621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5–9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1–24.4% of per-protocol patients receiving rivaroxaban 5–60 mg, and 27.8% receiving enoxaparin (n=914). There was a flat dose response relationship between rivaroxaban and total VTE (p=0.39). Major bleeding (safety population, n=1,317) increased dose-dependently with rivaroxaban (p

Cost-effectiveness information can help health-system participants make decisions about diagnostic or therapeutic innovations that are more expensive but incrementally safe and effective. However, these analyses cannot help decide whether a less expensive approach is "sufficient" and funds ought to be allocated to other medical issues entirely. At present, formulary committees are commonly determining that medications are "mostly equivalent" in efficacy and safety and choosing individual medications or classes of medications based on cost. Clinicians may not agree with these decisions and will need to understand their rationale. For prophylaxis of venous thromboembolism after hip and knee replacement and hip fracture surgery, many preventive modalities are available with different safety and efficacy profiles and different costs. It is possible to list the important safety and efficacy outcomes of prophylaxis, estimate their incidences and costs, and "model" comparisons of one modality vs another, in order to help decide whether one is preferable.

Summary. Background: The selective antithrombotic fondaparinux is more effective than the low-molecular-weight heparin enoxaparin for prevention of venous thromboembolism (deep-vein thrombosis [DVT] or pulmonary embolism) in patients undergoing major orthopedic surgery, but its cost-effectiveness is undetermined. Objectives: To evaluate the cost-effectiveness of fondaparinux relative to enoxaparin as prophylaxis against venous thromboembolism (VTE) for patients undergoing total hip replacement, total knee replacement or hip fracture surgery in the UK. Patients/methods: A decision analysis model was created simulating the impact of fondaparinux and enoxaparin on patient outcomes and costs over various time points up to 5 years following surgery. The main outcome measures were treatment costs per patient and the incidence of clinical VTE and VTE-related deaths. A weighted (combined) cohort reflects the proportion of patients undergoing these procedures in 2000/2001. Results: In the combined cohort, compared with enoxaparin, fondaparinux is expected to produce 20 fewer clinical VTE events and 3.2 fewer VTE-related deaths per 1000 procedures at 5 years. Cost savings at 5 years are £27 per patient with fondaparinux (discounted at 6% per year). In each of the three surgical groups, fondaparinux leads to lower expected costs per patient and to a smaller number of VTE events and VTE-related deaths. Results are sensitive to the price difference between fondaparinux and enoxaparin and variation in the rate of late DVT. The analysis is robust to variations in all other key parameters. Conclusions: Compared with enoxaparin, fondaparinux is more effective and reduces costs to the healthcare system. At current prices, fondaparinux is the recommended strategy in the UK for prophylaxis following major orthopedic surgery.

It is still under debate that red blood cell (RBC) transfusions might increase the risk of healthcare-associated infections after hip fracture surgery. Previously, we found that a liberal RBC transfusion strategy improved survival in nursing home residents. Our aim, therefore, was to investigate whether a more liberal RBC transfusion strategy was associated with a higher infection risk in frail elderly hip fracture patients.Prospective, assessor-blinded, randomized and controlled trial.Orthopedic ward, Geriatric ward, and Hospital-at-home.284 consecutively hospital-admitted elderly with hip fracture from nursing homes or sheltered housing facilities were included.A restrictive RBC transfusion strategy (hemoglobin9.7 g/dL; 6 mmol/L) compared with a liberal strategy (hemoglobin11.3 g/dL; 7 mmol/L) administered within 30 days after surgery.Leukocytes and C-reactive protein (CRP) in repeated blood samples within 30 days, and number of all infections (pneumonia, urinary tract infection, and other infections) within 10 days.88 % of the patients received a RBC transfusion. A median of 1 RBC unit (interquartile range (IQR): 1-2) was transfused for the restrictive strategy group versus 3 RBC units (IQR: 2-5) for the liberal group. Leukocytes and CRP measurements were similar for both groups. Rates of infection were 72 % for the restrictive group compared to 66 % for the liberal group (risk ratio 1.08; 95 % confidence interval 0.93-1.27, p value 0.29).A more liberal RBC transfusion strategy was not associated with higher risk of infection among residents from nursing homes or sheltered housing undergoing hip fracture surgery.

This is a review of a double-blind, prospective study comparing the thromboprophylactic efficacy and safety of two different prophylactic regimens of a low molecular weight heparin (tinzaparin) in 250 consecutive patients (aged < or 18) undergoing primary elective hip arthroplasty. Regimen 1: 75 U anti-Xa/kg BW (actual range 63 to 91) once daily started 12 hours before operation; and regimen 2: 50 U anti-Xa/kg BW (actual range 41 to 71) once daily started 2 hours before operation. Both regimens were administered in a weight-adjusted fashion and were continued for 7 days after operation or until full mobilization. Efficacy was evaluated by occurrence of postoperative deep vein thrombosis (DVT) diagnosed by bilateral ascending phlebography on day 7 +/- 2 after operation, and the venograms were evaluated in an assessor blind fashion by a panel of three expert radiologists. Safety was evaluated by the amount of blood lost and transfusion requirements during and after the operation; all bleeding complications, reoperations, adverse events and deaths were observed during the study. A 3-month follow-up on survival and occurrence of thromboembolism was performed on all randomized patients. The result was a significantly better protective effect against proximal DVT by regimen 1 compared with regimen 2. This was achieved with improved safety in terms of a significantly decreased need for blood transfusions during operation and fewer wound complications in the postoperative period in favor of regimen 1. Therefore, tinzaparin administered in a dosage of 75 U anti-Xa/kg BW 12 hours before surgery is significantly more protective against proximal DVT and safer than the standard regimen of 50 U anti-Xa/kg BW started 2 hours before surgery in patients undergoing primary elective hip arthroplasty.

The aim of this study was to compare the efficacy and safety of prolonged (35 days) thromboprophylaxis with a standard length (7 days) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty. The study was multicentre, randomised, double-blind, and prospective with two groups. Following seven days on a standard length regimen of dalteparin (5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery), patients were randomized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days. Efficacy was evaluated at the end of the study (day 35) in all patients with bilateral ascending phlebography to detect deep vein thrombosis. Bleeding complications and other adverse events were registered throughout the study period. Three hundred consecutive patients agreed to participate before the operation: 281 were finally randomised and 215 completed the study; two patients died before randomisation; 17 developed deep vein thrombosis; none developed pulmonary embolism; and five of 113 patients (4.4%, 95% CI 1-10%) developed deep vein thrombosis in the dalteparin group, compared with 12 of 102 (11.8%; 95% CI 6-20%) in the placebo group (p=0.039). Deep vein thrombosis in the proximal veins was diagnosed in one patient (0.9%; 95% CI 0-5%) in the dalteparin group, and in five (5.0%; 95% CI 2-11%) in the placebo group (p=0.076). Major bleeding was observed in one patient in the placebo group; minor bleeding complications and adverse events were equally distributed between the groups. We concluded that prolonged (35 days) thrombo prophylaxis with dalteparin is more effective than a standard length (7 days) regimen without increased risk of bleeding complications or other adverse events.

Purpose To address the null hypothesis that surgeons shown radiographs of little finger metacarpal neck fractures with measured fracture angulation would recommend surgery as often as surgeons shown unmarked radiographs. Methods Members of the Science of Variation Group, an international collaboration of fully trained orthopedic and trauma surgeons, were asked to review 20 little finger metacarpal neck fracture cases, which included a vignette and 3 high-quality radiographs. Members were then randomized to review radiographs with or without measured fracture angulation on the lateral view and select operative or nonoperative management. Results Surgeons shown radiographs with measured angulation were more likely to recommend surgery, and there was less variability among these surgeons, particularly for fractures with less angular deformity. Conclusions Measured fracture angulation has a small but significant influence on treatment recommendations for little finger metacarpal neck fractures. Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved

Patients undergoing arthroplastic surgery of the lower limbs and those with multiple injuries have a high risk of thromboembolism. Enoxaparin is a highly effective antithrombotic drug that is well tolerated and without the need for monitoring. Numerous controlled trials in these patient groups have demonstrated enoxaparin to be at least as effective as heparin in reducing the occurrence of deep vein thrombosis while showing a tendency towards lower risk of bleeding complications; therefore, enoxaparin is recommended as thromboprophylaxis in patients undergoing major hip or knee surgery or suffering from multiple trauma.

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

Purpose To address the factors that surgeons use to decide between 2 options for treatment when the evidence is inconclusive. Methods We tested the null hypothesis that the factors surgeons use do not vary by training, demographics, and practice. A total of 337 surgeons rated the importance of 7 factors when deciding between treatment and following the natural history of the disease and 12 factors when deciding between 2 operative treatments using a 5-point Likert scale between "very important" and "very unimportant." Results According to the percentages of statements rated very important or somewhat important, the most popular factors influencing recommendations when evidence is inconclusive between treatment and following the natural course of the illness were "works in my hands," "familiarity with the treatment," and "what my mentor taught me." The most important factors when evidence shows no difference between 2 surgeries were "fewer complications," "quicker recovery," "burns fewer bridges," "works in my hands" and "familiarity with the procedure." Europeans rated "works in my hands" and "cheapest/most resourceful" of significantly greater importance and "what others are doing," "highest reimbursement," and "shorter procedure" of significantly lower importance than surgeons in the United States. Observers with fewer than 10 years in independent practice rated "what my mentor taught me," "what others are doing" and "highest reimbursement" of significantly lower importance compared to observers with 10 or more years in independent practice. Conclusions Surgeons deciding between 2 treatment options, when the evidence is inconclusive, fall back to factors that relate to their perspective and reflect their culture and circumstances, more so than factors related to the patient's perspective, although this may be different for younger surgeons. Clinical relevance Hand surgeons might benefit from consensus fallback preferences when evidence is inconclusive. It is possible that falling back to personal comfort makes us vulnerable to unhelpful commercial and societal influences.

Objective: The purpose of this study was to document the uF1 + 2 excretion in elderly patients during and after a hip fracture (HF). Methods: The study was a prospective pilot study. Spot urine samples were collected immediately after admission and every morning until surgery. After surgery, urine samples were collected on days 1, 5, 7, 14, and at follow-up on day 90 (±10). Results: A total of 24 women and 7 men with HF completed the study. The median uF1 + 2 level was significantly increased on the day of admission relative to the median level at follow-up. Maximum levels were seen on day 1 with a decreasing tendency until follow-up. Patients treated with a hemiarthroplasty had higher median uF1 + 2 levels on all days compared with patients treated with osteosynthesis. Conclusion: A substantial coagulation activity, indicated by high median levels of uF1 + 2, was seen at admission and during the first week after HF.

Summary Arthroscopy of the knee has always been associated with a low risk of complications, including thromboembolism. Therefore, few studies have been concerned with the matter. We present two case reports and a review of the available literature concerning thromboembolic complications after arthroscopy.

Venography is the key diagnostic method of screening for deep venous thrombosis in clinical prophylaxis studies. Although the venographic technique is standardized the outcome is subject to variation for several reasons. The different methodological pitfalls are presented as well as their consequences for the final results of prophylaxis studies, and it is discussed how variations can be minimized.

In a prospective study including 16 patients with multiple trauma and head injury and 14 patients with isolated head injury we measured plasma levels of prothrombin fragment 1 and 2 (F1 + 2) and thrombin/antithrombin III complex (TAT) on admission and on days 1, 2, 3, and 7 after the incident. On admission, all patients had values of F1 + 2 and TAT above the reference range. Admission levels of both F1 + 2 and TAT were significantly higher compared with levels on the following days. Admission levels of F1 + 2 was significantly correlated to the Injury Severity Score. TAT was higher in patients with multiple trauma than in patients with isolated head injury and were significantly correlated to the Injury Severity Score on admission and on day 3. Levels of F1 + 2 were significantly lower on day 1 in four patients with post-traumatic pulmonary dysfunction compared with patients without pulmonary dysfunction. With respect to levels of TAT, no differences were detected between patients with and without pulmonary dysfunction.

Extended thromboprophylaxis is vital in patients undergoing total hip arthroplasty (THA) because of the prolonged risk of venous thromboembolism (VTE). Despite evidence that extended prophylaxis can reduce the incidence of symptomatic VTE in this high-risk patient population and the evidence-based guideline recommendations, a large proportion of patients still do not receive an adequate duration of thromboprophylaxis. This is partly due to the limitations of conventional anticoagulants, such as the subcutaneous route of administration or the requirement for routine coagulation monitoring and dose adjustment. New oral anticoagulants (such as the direct thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitor rivaroxaban) could address the current unmet need. Phase III clinical studies in VTE prevention in patients undergoing THA and total knee arthroplasty (TKA) showed that dabigatran etexilate was non-inferior to the EU regimen of enoxaparin, but did not achieve non-inferiority to the US regimen of enoxaparin. In contrast, rivaroxaban demonstrated superiority to both enoxaparin regimens for the prevention of VTE after THA and TKA, without a significant increase in major bleeding rates. Their convenient, once-daily, fixed dosing, with no need for routine coagulation monitoring, could facilitate adherence to evidence-based guideline recommendations of extended thromboprophylaxis after THA.

In a prospective randomized study heptest, thrombinantithrombin complexes (TAT), D-dimer, and t-PA:ag were analysed pre-and postoperatively in 206 consecutive patients undergoing hip arthroplasty during thromboprophylaxis with either a LMW heparin (Enoxaparin) or Dextran 70. Deep vein thrombosis (DVT) developed in 6 of 102 (6%) Enoxaparin and in 21 of 104 (20%) Dextran patients diagnosed by bilateral phlebography. In the Enoxaparin group heptest showed a significant increase from the pre- to the postoperative level opposed to a significant decrease in the Dextran group. Postoperative levels of TAT, D-dimer, and t-PA:ag were significantly increased in both groups, however, TAT was significantly higher in patients in the Dextran group than in the Enoxaparin patients. D-dimer was significantly higher in Dextran patients with DVT postoperatively compared with patients without DVT. No differences concerning TAT or t-PA:ag were observed between patients with and without DVT in any of the groups.

Summary. Background: Prothrombin fragment 1 + 2 is excreted in urine (uF1 + 2) as a result of thrombin generation and, therefore, may be a useful marker of coagulation status. Objectives: To assess uF1 + 2 levels after total hip replacement (THR) in patients with venous thromboembolism (VTE) and bleeding events. Patients/methods: This study was conducted in parallel with a prospective, dose-finding study evaluating the efficacy and safety of different doses of rivaroxaban (Xarelto®, Bayer HealthCare AG, Wuppertal, Germany) for thromboprophylaxis, relative to enoxaparin. Deep vein thrombosis was diagnosed by mandatory venography performed 5–9 days after THR, or earlier if symptomatic. Symptomatic pulmonary embolism was diagnosed by objective testing. Bleeding complications were registered and stratified into major bleeding, clinically relevant, non-major bleeding, and minor bleeding, using predefined criteria. Results: Eighty-four patients had a VTE and 57 patients had a bleeding event (n = 722). Significantly higher median uF1 + 2 levels were observed in the VTE group on day 3 after THR (P = 0.03), compared with control. Median uF1 + 2 levels were lower in the bleeding group on day 3 after THR (P = 0.005) and on the day of venography (P = 0.36), compared with control. Comparisons between the VTE and bleeding groups showed significantly lower median uF1 + 2 levels in the bleeding group on day 3 after THR and on the day of venography (P

In a randomized doubled-blind placebo-controlled study, plasma levels of thrombin-antithrombin-III (TAT) and factor VIII activity (VIII:C) were measured pre-operatively and on days 1, 3, 5 and 7 post-operatively in 70 consecutive patients undergoing total hip replacement. Patients received either a subcutaneous injection of low-molecular-weight heparin (LMWH) or placebo once daily. Post-operative deep vein thrombosis (DVT) was diagnosed by bilateral phlebography. The levels of TAT and VIII:C both increased significantly after operation and were not significantly influenced by LMWH. Thirty-three patients in whom post-operative DVT developed had a significantly lower level of VIII:C on day 7, compared with patients without DVT.

In a prospective, randomized controlled study, tissue plasminogen activator (t-PA) and tissue plasminogen activator antigen (t-PA:ag) were measured pre- and postoperatively in 40 consecutive patients undergoing total hip replacement. Patients received either a subcutaneous injection of low molecular weight heparin or placebo once daily. Deep vein thrombosis was diagnosed by bilateral phlebography. Patients who developed postoperative thromboembolic complications had significantly lower preoperative t-PA activity levels than patients who did not develop such complications. No difference was observed between the two groups with respect to t-PA:ag. Thromboprophylaxis with low molecular weight heparin did not cause any significant changes in t-PA activity and t-PA:ag. This study in high risk patients indicates that impaired fibrinolysis may be associated with development of thromboembolic complications after operation.