Category Archives: Complications

The STIC Intra-Compartmental Pressure Monitor System by C2Dx

by Rob Salter, Internal Product Specialist, C2Dx, Inc.

C2Dx is the exclusive manufacturer of the STIC Intra-Compartmental Pressure Monitor System previously supplied by Stryker. The company is led by a team of medical device industry veterans with years of experience providing superior products and service to customers around the globe. Our company is privately held and dedicated to providing world class products and service to healthcare professionals, while driving costs out of the healthcare continuum.

Compartment syndrome is one of the few true orthopedic emergencies and the consequences can be dire. A delay in diagnosis often leads to delayed treatment, causing irreversible muscle damage after 8 hours and irreversible nerve damage after 6 hours. The leading causes of malpractice claims filed against orthopaedic surgeons is missed compartment syndrome. These suits involve 87% delays in diagnosis and 37% delays in treatment, with 65% of total suits won by the plaintiff.

As described, time to diagnosis is one of the most prognostic factors, yet the ambiguity of the clinical signs may lead to delay. Many clinical exam findings are lagging indicators while pain out of proportion is the only leading indicator. Pain has low sensitivity, is considered subjective and on its own, inconclusive. Individual signs have only 13 – 54% sensitivity and 3+ signs are required for 98% sensitivity.

Recognized as the Gold Standard for over 30 years, the STIC Intra-Compartmental Pressure Monitor provides quick and continuous measurements, which adds valuable data to your clinical assessment for a prompt and more informed decision. Results show 94% sensitivity, 98% specificity, and 99% negative predictive value (Duckworth and McQueen, 2019).

Additional benefits of the STIC Monitor System include:

  • Sterile disposables for a simple, rapid set-up
  • Proven accuracy and reliability with strong clinical evidence
  • Hand-held with convenient pre-filled syringe for easy transport
  • Cost effective with a dedicated CPT reimbursement code

Click here to learn more about the STIC Intracompartmental Pressure Monitor System.

Local Antibiotics in Prophylaxis of Surgical Wound Infections

by Laurence E. Dahners, MD

August 22nd, 2009

In 2007 we published an animal study (Yarboro S, Baum E, Dahners L: Locally Administered Antibiotics for Prophylaxis Against Surgical Wound Infection. Journal Bone Joint Surgery 2007 89(5)) documenting that injecting gentamicin into contaminated wounds after closure of the incision results in several orders of magnitude reduction in bacteria counts as opposed to systemic cephalosporins such as are usually given to prophylax against infection. This results in high concentrations in the wound cavity which are not achieved by IV administration and by injecting it after wound closure it is not removed before closure like antibiotic irrigation solutions. It worked significantly better than sustained release pellets at reducing bacterial counts. I have incorporated this into my trauma practice by injecting (80mg gentamicin in 40cc saline, inject enough to fill the wound) a gentamicin solution after the wound is closed and been very pleased with the reduction in the numbers of infections, especially in open fractures. Data that we published in the August 2009 JBJS suggest that systemic cephalosporins and local gentamicin have a large synergistic effect, so I would recommend doing both.

Dr. Dahners is a Professor of Orthopaedic Surgery at the UNC School of Medicine in Chapel Hill, NC, USA.  His clinical focus is on trauma and his research interests are in ligament physiology, ligament healing, ligament growth and contracture, and bone healing and the biomechanics of internal fixation.  You can see his “Pearls” of orthopaedics on

Dr. Dahners et al published “Better Prophylaxis Against Surgical Site Infection with Local as Well as System Antibiotics.  An in Vivo Study” in the August 2009 issue of the Journal of Bone and Joint Surgery.

Stopping Healthcare-Associated Infections

by Barbara Dunn

November 14th, 2009

When someone develops an infection at a hospital or other patient care facility that they did not have prior to treatment, this is referred to as a healthcare-associated (sometimes hospital-acquired) infection (HAI).  According to the World Health Organization (WHO), at any point in time, 1.4 million people worldwide suffer from infections acquired in hospitals.

As part of an ongoing commitment to quality care and infection prevention, nationwide doctors and hospitals are partnering with Kimberly-Clark to deliver continuing education programs on healthcare-associated infection (HAI) prevention to staff and management Whether you’re a healthcare professional, patient, or visitor , the most effective way to keep HAIs down to a minimum is to wash your hands or use an alcohol-based sanitizer.

Please view the informational video at this link.

For more information please go to the Not on My Watch campaign.

Barbara Dunn was born in Jersey City, New Jersey, worked as an interior designer in Manhattan, then moved to Hawaii where she worked for a production company before moving to Arlington and reinventing herself as a PR executive.

Ischemic Optic Neuropathy (ION)

by James W. Ogilvie, MD

Thursday, November 26th, 2009

 Ischemic optic neuropathy (ION) is a disorder than can occur following surgical procedures. There is partial or complete loss of vision as the result of a vascular insult. It has several possible etiologies including thrombosis of the central retinal artery most commonly associated with giant cell arteritis. Direct trauma to the orbit and cortical blindness must also be considered. ION has also been reported with acute non-surgical blood loss and the use of Viagara™. Hippocrates gives an account of someone with acute hematemesis who subsequently lost their sight, perhaps the first report of ION.

The least common and most enigmatic cause of post-operative vision loss is an ischemic episode to the optic nerve heads which are supplied by the short posterior cilliary arteries. The diagnosis of ION is made by fundoscopic examination of the eye in someone who reports a visual field defect following surgery. Emboli in the retinal vessels (posterior ION) can be visualized while in anterior ION (That which occurs anterior to the cribriform plate.) there are no initial diagnostic findings. After several months there is visible atrophy of the optic nerve heads resulting in a pale retina.

Because there may be effective therapies for other causes, it is important to differentiate ION from other etiologies of visual loss. An ophthalmologic consultant can accurately make the diagnosis. To date there is no effective treatment for anterior ION. Many therapeutic trials have been performed including the use of steroids, osmotic agents, hyperbaric oxygen, vasodilators and surgical decompression, all without benefit. There may be some spontaneous improvement in visual fields, but recovery from no light perception is very rare.

The causes of ION are not well understood, but acute blood loss is the most constant finding. ION has been reported with surgery in the supine, sitting and prone position. Prolonged spinal surgery in the prone position is the other commonly reported factor. Long surgical procedures resulting in facial edema when accompanied by hypotension or low hematocrit is often encountered in cases of ION. While atherosclerosis or diabetes may be predisposing factors, the relationship has not been studied in a scholarly fashion and ION has been reported in adolescents undergoing scoliosis surgery.

There is speculation that with acute blood loss there is an idiosyncratic response from released endogenous vasoconstrictors which may cause vasospasm of the short posterior cilliary vessels. It is not a sympathetic nervous system response due to the fact that sympathetic nerves do not supply the short posterior cilliary arteries. There may also be a congenital predisposition to ION due to a reduced ratio of capillary vessels to optic nerve heads. Unfortunately, there are no pre-operative tests to identify those with an increased susceptibility to ION.

Prevention of ION is clearly preferable. Reducing facial edema with the use of the reverse Trendelenburg position, limiting the use of crystalloids for fluid resuscitation and avoiding hypotension or anemia may lessen the incidence of ION.

ION frequently results in a medical liability action. If there are irregularities in the anesthetic record such as prolonged anemia or hypotension, use of large amounts of crystalloid for fluid resuscitation resulting in facial edema or improper patient positioning, the surgical team is often held liable. The issue of informed consent is often raised. What responsibility for discussing visual loss lies with the surgeon and anesthesiologist? There are no absolute answers to this issue, however this question should be settled long before discovery depositions are taken, preferably prior to the surgery itself.

     The guest author of this article for is Dr. James Ogilvie, a board certified orthopaedic surgeon.  He is Professor, Department of Orthopaedic Surgery, at the University of Utah in Salt Lake City and Professor Emeritus, Department of Orthopaedic Surgery, at the University of Minnesota in Minneapolis, MN. He is Staff Surgeon / Attending Staff at Shriners Hospital Intermountain Unit in Salt Lake City.

     A more detailed article on ION by Dr. Ogilvie can be found by clicking on the following link to it in the October 2009 issue of the American Academy of Orthopaedic Surgeons newsletter “AAOS Now”.

Thromboprophylaxis in Orthopaedic Surgery

Richard J. Friedman, MD, FRCSC

Saturday, March 5th, 2011


Venous thromboembolism is a serious complication after total hip or knee surgery and there is a well-established clinical need for thromboprophylaxis. However, in a large number of cases adequate administration of thromboprophylaxis does not seem to occur after total joint arthroplasty. A major challenge in the management of thromboprophylaxis is to balance the benefits of treatment with the risks, including bleeding complications. Another potential barrier to the optimal use of thromboprophylaxis could be the inconvenience of currently available agents. Many surgeons therefore adopt a conservative approach towards thromboprophylaxis. Simplifying therapy with more convenient, efficacious and safe anticoagulants could change attitudes to anticoagulant use, and improve adherence to thromboprophylactic guidelines.


Venous thromboembolism (VTE) is a serious complication after major orthopaedic surgery [1]. The rates of venographic deep vein thrombosis (DVT) and proximal DVT 7 to 14 days after major orthopaedic surgery in patients who receive no thromboprophylaxis are approximately 40% to 60% and 10% to 30%, respectively [1]. The manifestation of DVT is, to some extent, a consequence of bone damage during surgery, when procoagulant debris triggers thrombin generation, resulting in hypercoagulability [2]. In addition to hypercoagulability, the other components of Virchow’s triad of venous stasis and endothelial damage are also thought to play a part in thrombosis [3]. Thus, there is a well-established clinical need for thromboprophylaxis after arthroplasty [1].

A major challenge in the management of anticoagulants is to balance the benefits of treatment with the risks, including bleeding complications. Many surgeons appear concerned about postoperative bleeding and tend to adopt a conservative approach towards the relative risks and benefits of thromboprophylaxis [2]. Consequently, although evidence-based guidelines and recommendations advocate the use of anticoagulants after major orthopaedic surgery, thromboprophylaxis is still used suboptimally [4–6]. However, the evidence that careful prophylaxis administered at an appropriate time after surgery causes surgical bleeding is sparse [7]. In this review, current trends in thromboprophylaxis after orthopaedic surgery in the United States (US) are described. Factors limiting appropriate implementation of thromboprophylaxis regimens are also discussed 

Current Standard of Care

Further to the consensus document developed by the National Institute of Health in 1986 [8], there have been a series of American College of Chest Physicians (ACCP) guidelines published on the use of pharmacological agents for thromboprophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA), last updated in 2008 [1].

In the US, the available options for anticoagulation and thromboprophylaxis after elective THA or TKA are the vitamin K antagonists (VKAs, e.g. warfarin), the low molecular weight heparins [LMWHs]), and fondaparinux (an indirect Factor Xa inhibitor). Each of these options is associated with significant limitations that complicate use in clinical practice. VKAs have been the mainstay of oral anticoagulant therapy for more than 60 years [9]. However, VKAs have unpredictable pharmacokinetics and pharmacodynamics, and significant inter- and intrapatient variability in dose–response relationships. They are associated with multiple drug–drug and food–drug interactions and have a narrow therapeutic window [9]. Regular coagulation monitoring is therefore required to ensure that the international normalized ratio is within the recommended range of 2.0 to 3.0. The heparins are administered subcutaneously, which means patients often require daily appointments or a nurse visit to administer their medication. LMWHs are also associated with the risk of developing heparin-induced thrombocytopenia [10]. Fondaparinux is also administered subcutaneously, and is contraindicated in patients with severe renal impairment and in those that weigh less that 50 kg. In patients over the age of 75 who have undergone THA or TKA, fondaparinux causes an increased risk of bleeding [11].

The timing of initiation of prophylaxis depends upon the type of anticoagulant used. Warfarin therapy is generally initiated prior to surgery because of its delayed onset of action, whereas prophylaxis with LMWH can be started 10–12 hours before or 12–24 hours after surgery. There does not seem to be a clear advantage with either regimen, and both regimens are recommended by the ACCP [1]. Thromboprophylaxis is recommended to continue for at least 10 days after joint replacement surgery, with extended prophylaxis for up to 35 days recommended for those patients undergoing THA surgery and with a suggestion that thromboprophylaxis for up to 35 days could be beneficial for those undergoing TKA [1]. Traditionally, thromboprophylaxis used to continue only until the patient was discharged from hospital [12], despite the fact that this could be a suboptimal duration [13] and the risk of DVT and mortality after discharge is considerable [14, 15]. The median length of stay in US hospitals is now as short as 3 days after THA and 4 days after TKA [16]. A retrospective study of the medical records of 3,778 orthopaedic surgery patients found that 88% were discharged from hospital and prescribed warfarin or acetylsalicylic acid [6].

Suboptimal Utilization of Thromboprophylaxis

Despite the fact that thromboprophylaxis is now recommended for routine use after total joint arthroplasty, it is not always used optimally. Approximately 10% of patients received inadequate in-hospital thromboprophylaxis, and approximately 33% received inadequate post-discharge thromboprophylaxis according to findings from the US Hip and Knee Registry (1996–2001) [17]. An analysis of the data from the multinational Global Orthopaedic Registry (GLORY) to evaluate the compliance of surgeons with the ACCP guidelines for the prevention of VTE showed that only 47% of THA patients and 61% of TKA patients received prophylaxis in accordance with the recommended start time, duration and dose/treatment intensity recommended by the guidelines [16]. Although nearly all patients received prophylaxis on the first day after surgery, more than a quarter did not receive any form of prophylaxis 7 days after surgery [18].


Suboptimal thromboprophylaxis decreases patient outcomes, resulting in many patients remaining at unnecessary risk of thrombosis and its complications [4]. The reasons for lack of compliance with the guidelines may be numerous. They include lack of awareness, poor understanding or disagreement with guidelines (either specifically or as a general concept), resistance to changing established practices, and doubt that a new approach will change outcomes. Established surgeons may also be reluctant to use new anticoagulant regimens because of a fear of increased bleeding risk [17]. Attitudes may also limit a physician’s willingness to follow guidelines. An awareness of the guidelines does not necessarily mean physicians have sufficient knowledge to critically evaluate and apply recommendations [4].

Other potential barriers include the mistaken belief that a small asymptomatic DVT is not important because it cannot cause clinically significant pulmonary embolism (PE) [19], which fortunately is only held by a minority [20]. Due to the often clinically silent nature of VTE, and the low incidence of VTE during the short postoperative hospital stay, the chances of a surgeon witnessing a major DVT or an acute PE are rare [4]. In addition, the trend towards earlier hospital discharge means that many symptomatic events occur after that time [21, 22], and patients are often seen by other specialists when referred back to hospital with a venous thromboembolic event; therefore, surgeons are often unaware of the true incidence of VTE in their patients.

Long-term sequelae of VTE are frequent and often disabling [23]. Recurrent VTE can occur after surgery, although the incidence is less than in other patients groups such as those with cancer [24]. Thrombosis damages the deep venous valves resulting in venous reflux and venous hypertension of the lower limbs. This residual venous obstruction and inflammation are thought to be responsible for the development of post-thrombotic syndrome [25, 26]. Chronic thrombotic pulmonary hypertension, which is associated with considerable morbidity and mortality, occurs in approximately 3–4% of patients over 2 years after a symptomatic PE [27].

Economic Impact of Venous Thromboembolism

The acute and chronic phases of VTE related care have substantial economic consequences [28, 29] that can be effectively modeled [30]. A recent study found the total annual healthcare cost for a VTE ranged from $7,594 to $16,644, depending on the type of event and whether it was a primary or secondary diagnosis. The hospital readmission rates for DVT or PE within 12 months were 5.3% for primary and 14.3% for secondary diagnoses [31]. These data indicate that thromboprophylaxis with anticoagulants should not only be beneficial to patients, but could also be cost effective for the healthcare system [32, 33].

Need for More Convenient Anticoagulants

Another potential barrier to the optimal use of thromboprophylaxis could be the inconvenience of currently available agents [34]. Orthopaedic surgeons and their patients would benefit from an oral anticoagulant that could be administered in fixed doses [35].

Simplifying Therapy

Non-compliance can result in a poor quality of life and increased medical expenditures in managed care. In a study of diabetic patients, total medical costs were approximately $4,500 for patients at 80–100% adherence compared with approximately $8,900 for those at 1–19% adherence [36]. A variety of factors affect non-compliance, but simplifying treatment has been shown to improve adherence in asthma patients [37] and cardiovascular patients given single-pill amlodipine/atorvastatin were found to be approximately three times more likely to achieve adherence over 1 year of follow-up than patients given a two-pill regimen [38]. Similarly, simplifying therapy to a once-daily regimen in virologically suppressed HIV-1-infected patients improved adherence and patient satisfaction [39].

Novel Anticoagulants

Anticoagulants in development are targeting different steps in the coagulation pathway to provide simpler alternatives to currently available anticoagulants. Among these new agents are direct thrombin inhibitors and direct Factor Xa inhibitors [40]. The direct thrombin inhibitor dabigatran etexilate appears an attractive alternative to the current standard of care in patients after THA and TKA [41–44]. It has been granted marketing authorization in the European Union and Canada for the prevention of VTE after THA or TKAThe manufacturer’s recommended dose is 220 mg once daily (starting 1–4 hours after surgery with a single 110 mg capsule) for a total of 28–35 days after THA or a total of 10 days after TKA [45]. Direct Factor Xa inhibitors in development include rivaroxaban, apixaban, edoxaban (DU-176b), and YM150, and of these rivaroxaban is in the most advanced stage of development [46]. Rivaroxaban has shown potential as a once-daily, oral anticoagulant that may be administered in fixed doses for the prevention and treatment of thromboembolic disorders following orthopedic surgery [47–52]. Rivaroxaban is approved in more than 90 countries worldwide, including the European Union and Canada, for the prevention of venous thromboembolism after elective hip or knee replacement surgery in adult patientsA dose of 10 mg once daily (with the initial dose 6–10 hours after surgery, provided that hemostasis has been achievedfor 5 weeks after elective hip arthroplasty or 2 weeks after elective knee arthroplasty is recommended by the manufacturer [53].


The main difference between direct thrombin inhibitors and direct Factor Xa inhibitors is their mechanism of action. They also differ in their pharmacokinetic and pharmacodynamic profiles, such as metabolismFor example, in the case of dabigatran, more than 80% of the systemically available drug is eliminated by renal excretion [54]. Twothirds of administered rivaroxaban is metabolized to inactive metabolites (half of this is eliminated via the kidneys and half via the fecal route), and onethird is excreted as unchanged active drug in the urine [55].



The need to use thromboprophylaxis after major orthopaedic surgery is now becoming well recognized. However, adequate administration of thromboprophylaxis regimens does not seem to occur after total joint arthroplasty in a large number of cases. The reasons for this appear complex, involving surgeons’ poor awareness of the problem of post-surgical thrombosis, their attitudes to guidelines, concerns about causing bleeding, and the complexities of anticoagulation with current agents. Simplifying therapy, such as oncedaily fixed dosing, could change attitudes to anticoagulant use and improve adherence to guidelines. Newly developed, oral, fixed-dose anticoagulants should enable substantial improvement in thromboprophylaxis usage, thereby improving patient outcomes. The primary drawback of the new anticoagulants, particularly those with a long half-life, is the lack of specific antidotes to reverse their anticoagulant effect[56]. Specific antidotes might be needed in particular situations such as for overdose or emergency surgery. However, this may not pertain to dabigatran and rivaroxaban as they have relatively short halflives (12–14 hours and 7–11 hours, respectively) [45, 53]. As off-label prescribing is not uncommon, there is a risk that new anticoagulants licensed for thromboprophylaxis after THA or TKA will be prescribed for unlicensed indications [57]. These current challenges could be overcome by finding specific antidotes and post-approval surveillance of off-label prescribing.


1.         W. H. Geerts, D. Bergqvist, G. F. Pineo, et al., “Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition),” Chest, vol. 133, no. 6 Suppl, pp. 381S–453S, 2008.

2.         O. E. Dahl, D. Bergqvist, “Current controversies in deep vein thrombosis prophylaxis after orthopaedic surgery,” Current Opinion in Pulmonary Medicine, vol. 8, no. 5, pp. 394–397, 2002.

3.         H. M. Zaw, I. C. Osborne, P. N. Pettit, and A. T. Cohen, “Risk factors for venous thromboembolism in orthopedic surgery,” The Israel Medical Association Journal, vol. 4, no. 11, pp. 1040–1042, 2002.

4.         J. A. Caprini, T. M. Hyers, “Compliance with antithrombotic guidelines,” Managed Care, vol. 15, no. 9, pp. 49–66, 2006.

5.         A. K. Kakkar, B. L. Davidson, and S. K. Haas, “Compliance with recommended prophylaxis for venous thromboembolism: improving the use and rate of uptake of clinical practice guidelines,” Journal of Thrombosis and Haemostasis, vol. 2, no. 2, pp. 221–227, 2004.

6.         V. F. Tapson, T. M. Hyers, A. L. Waldo, et al., “Antithrombotic therapy practices in US hospitals in an era of practice guidelines,” Archives of Internal Medicine, vol. 165, no. 13, pp. 1458–1464, 2005.

7.         D. Warwick, O. E. Dahl, and W. D. Fisher, “Orthopaedic thromboprophylaxis: limitations of current guidelines,” The Journal of Bone and Joint Surgery (Proceedings), vol. 90, no. 2, pp. 127–132, 2008.

8.         Prevention of venous thrombosis and pulmonary embolism. NIH Consensus Development, JAMA: The Journal of the American Medical Association, vol. 256, no. 6, pp. 744–749, 1986.

9.         J. Ansell, J. Hirsh, E. Hylek, et al., “Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition),” Chest, vol. 133, no. 6 Suppl, pp. 160S–198S, 2008.

10.       J. Hirsh, T. E. Warkentin, S. G. Shaughnessy, et al., “Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety,” Chest, vol. 119, no. 1 Suppl, pp. 64S–94S, 2001.

11.       Arixtra (fondaparinux sodium)-Prescribing Information,, 2005.

12.       G. Agnelli, G. B. Mancini, and D. Biagini, “The rationale for long-term prophylaxis of venous thromboembolism,” Orthopedics, vol. 23, no. 6 Suppl, pp. s643–s646, 2000.

13.       R. J. Friedman, “Optimal duration of prophylaxis for venous thromboembolism following total hip arthroplasty and total knee arthroplasty,” The Journal of the American Academy of Orthopaedic Surgeons, vol. 15, no. 3, pp. 148–155, 2007.

14.       A. Planes, N. Vochelle, J. Y. Darmon, M. Fagola, M. Bellaud, and Y. Huet, “Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo,” Lancet, vol. 348, no. 9022, pp. 224–228, 1996.

15.       E. Rahme, K. Dasgupta, M. Burman, et al., “Postdischarge thromboprophylaxis and mortality risk after hip-or knee-replacement surgery,” Canadian Medical Association Journal, vol. 178, no. 12, pp. 1545–1554, 2008.

16.       R. J. Friedman, A. S. Gallus, F. D. Cushner, G. Fitzgerald, and F. A. Anderson, Jr., “Physician compliance with guidelines for deep-vein thrombosis prevention in total hip and knee arthroplasty,” Current Medical Research and Opinion, vol. 24, no. 1, pp. 87–97, 2008.

17.       F. A. Anderson, Jr., J. Hirsh, K. White, and R. H. Fitzgerald, Jr., “Temporal trends in prevention of venous thromboembolism following primary total hip or knee arthroplasty 1996-2001: findings from the Hip and Knee Registry,” Chest, vol. 124, no. 6 Suppl, pp. 349S–356S, 2003.

18.       D. Warwick, R. J. Friedman, G. Agnelli, et al., “Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry,” The Journal of Bone and Joint Surgery, vol. 89, no. 6, pp. 799–807, 2007.

19.       O. E. Dahl, “Continuing out-of-hospital prophylaxis following major orthopaedic surgery: what now?,” Haemostasis, vol. 30, no. Suppl 2, pp. 101–105, 2000.

20.       S. Z. Goldhaber, A. G. Turpie, “Prevention of venous thromboembolism among hospitalized medical patients,” Circulation, vol. 111, no. 1, pp. e1–e3, 2005.

21.       C. Kearon, “Duration of venous thromboembolism prophylaxis after surgery,” Chest, vol. 124, no. 6 Suppl, pp. 386S–392S, 2003.

22.       R. H. White, P. S. Romano, H. Zhou, J. Rodrigo, and W. Bargar, “Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty,” Archives of Internal Medicine, vol. 158, no. 14, pp. 1525–1531, 1998.

23.       S. J. McRae, J. S. Ginsberg, “Initial treatment of venous thromboembolism,” Circulation, vol. 110, no. 9 Suppl 1, pp. I3–I9, 2004.

24.       P. Prandoni, A. W. Lensing, A. Cogo, et al., “The long-term clinical course of acute deep venous thrombosis,” Annals of Internal Medicine, vol. 125, no. 1, pp. 1–7, 1996.

25.       C. Kearon, “Natural history of venous thromboembolism,” Circulation, vol. 107, no. 23 Suppl 1, pp. I22–I30, 2003.

26.       S. R. Kahn, J. S. Ginsberg, “Relationship between deep venous thrombosis and the postthrombotic syndrome,” Archives of Internal Medicine, vol. 164, no. 1, pp. 17–26, 2004.

27.       V. Pengo, A. W. Lensing, M. H. Prins, et al., “Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism,” The New England Journal of Medicine, vol. 350, no. 22, pp. 2257–2264, 2004.

28.       J. A. Caprini, M. F. Botteman, J. M. Stephens, et al., “Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States,” Value Health, vol. 6, no. 1, pp. 59–74, 2003.

29.       K. K. Knight, J. Wong, O. Hauch, G. Wygant, D. Aguilar, and J. J. Ofman, “Economic and utilization outcomes associated with choice of treatment for venous thromboembolism in hospitalized patients,” Value Health, vol. 8, no. 3, pp. 191–200, 2005.

30.       S. D. Sullivan, S. R. Kahn, B. L. Davidson, L. Borris, P. Bossuyt, and G. Raskob, “Measuring the outcomes and pharmacoeconomic consequences of venous thromboembolism prophylaxis in major orthopaedic surgery,” Pharmacoeconomics, vol. 21, no. 7, pp. 477–496, 2003.

31.       A. Spyropoulos, “Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations,” Journal of Managed Care Pharmacy, vol. 13, no. 6, pp. 475–486, 2007.

32.       B. Detournay, A. Planes, N. Vochelle, and F. Fagnani, “Cost effectiveness of a low-molecular-weight heparin in prolonged prophylaxis against deep vein thrombosis after total hip replacement,” Pharmacoeconomics, vol. 13, no. 1 Pt 1, pp. 81–89, 1998.

33.       G. Agnelli, M. R. Taliani, and M. Verso, “Building effective prophylaxis of deep vein thrombosis in the outpatient setting,” Blood Coagulation and Fibrinolysis, vol. 10 Suppl 2, pp. S29–S35, 1999.

34.       B. I. Eriksson, D. J. Quinlan, “Oral anticoagulants in development: focus on thromboprophylaxis in patients undergoing orthopaedic surgery,” Drugs, vol. 66, no. 11, pp. 1411–1429, 2006.

35.       J. I. Weitz, “Emerging anticoagulants for the treatment of venous thromboembolism,” Thrombosis and Haemostasis, vol. 96, no. 3, pp. 274–284, 2006.

36.       M. C. Sokol, K. A. McGuigan, R. R. Verbrugge, and R. S. Epstein, “Impact of medication adherence on hospitalization risk and healthcare cost,” Medical Care, vol. 43, no. 6, pp. 521–530, 2005.

37.       A. Gillissen, “Patients adherence in asthma,” Journal of Physiology and Pharmacology, vol. 58, no. Suppl 5, pp. 205–222, 2007.

38.       B. V. Patel, R. S. Leslie, P. Thiebaud, et al., “Adherence with single-pill amlodipine/atorvastatin vs a two-pill regimen,” Vascular Health and Risk Management, vol. 4, no. 3, pp. 673–681, 2008.

39.       B. A. Boyle, D. Jayaweera, M. D. Witt, K. Grimm, J. F. Maa, and D. W. Seekins, “Randomization to once-daily stavudine extended release/lamivudine/efavirenz versus a more frequent regimen improves adherence while maintaining viral suppression,” HIV Clinical Trials, vol. 9, no. 3, pp. 164–176, 2008.

40.       J. Ansell, “Factor Xa or thrombin: is factor Xa a better target?,” Journal of Thrombosis and Haemostasis, vol. 5 Suppl. 1, pp. 60–64, 2007.

41.       B. I. Eriksson, O. E. Dahl, N. Rosencher, et al., “Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial,” Journal of Thrombosis and Haemostasis, vol. 5, no. 11, pp. 2178–2185, 2007.

42.       J. S. Ginsberg, B. L. Davidson, P. C. Comp, et al., “Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery,” Journal of Arthroplasty, vol. 24, no. 1, pp. 1–9, 2009.

43.       B. I. Eriksson, O. E. Dahl, N. Rosencher, et al., “Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial,” Lancet, vol. 370, no. 9591, pp. 949–956, 2007.

44.       B. I. Eriksson, R. Friedman, “Dabigatran Etexilate: Pivotal Trials for Venous Thromboembolism Prophylaxis After Hip or Knee Arthroplasty,” Clinical and Applied Thrombosis/Hemostasis, vol. 15, pp. 25S–31S, 2009.

45.       Dabigatran Summary of Product Characteristics, “Pradaxa®(dabigatran etexilate) Summary of Product Characteristics,”, 2008.

46.       K. A. Bauer, “New anticoagulants,” Current Opinion in Hematology, vol. 15, no. 5, pp. 509–515, 2008.

47.       B. I. Eriksson, L. C. Borris, O. E. Dahl, et al., “A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement,” Circulation, vol. 114, pp. 2374–2381, 2006.

48.       W. Mueck, B. I. Eriksson, K. A. Bauer, et al., “Population pharmacokinetics and pharmacodynamics of rivaroxaban – an oral, direct factor xa inhibitor – in patients undergoing major orthopaedic surgery,” Clinical Pharmacokinetics, vol. 47, no. 3, pp. 203–216, 2008.

49.       B. I. Eriksson, L. C. Borris, R. J. Friedman, et al., “Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty,” The New England Journal of Medicine, vol. 358, no. 26, pp. 2765–2775, 2008.

50.       A. K. Kakkar, B. Brenner, O. E. Dahl, et al., “Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial,” Lancet, vol. 372, pp. 31–39, 2008.

51.       M. R. Lassen, W. Ageno, L. C. Borris, et al., “Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty,” The New England Journal of Medicine, vol. 358, no. 26, pp. 2776–2786, 2008.

52.       A. G. G. Turpie, M. R. Lassen, B. L. Davidson, et al., “Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial,” Lancet, vol. 373, no. 9676, pp. 1673–1680, 2009.

53.       Xarelto® Summary of Product Characteristics,, 2009.

54.       S. Blech, T. Ebner, E. Ludwig-Schwellinger, J. Stangier, and W. Roth, “The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans,” Drug Metabolism and Disposition, vol. 36, no. 2, pp. 386–399, 2008.

55.       C. Weinz, T. Schwarz, D. Kubitza, W. Mueck, and D. Lang, “Metabolism and excretion of rivaroxaban, an oral, direct Factor Xa inhibitor, in rats, dogs and humans,” Drug Metabolism and Disposition, vol. 37, no. 5, pp. 1056–1064, 2009.

56.       J. I. Weitz, J. Hirsh, and M. M. Samama, “New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition),” Chest, vol. 133, no. 6 Suppl, pp. 234S–256S, 2008.

57.       D. C. Radley, S. N. Finkelstein, and R. S. Stafford, “Off-label prescribing among office-based physicians,” Archives of Internal Medicine, vol. 166, no. 9, pp. 1021–1026, 2006.

Dr. Friedman is a Clinical Professor of Orthopaedic Surgery at The Medical University of South Carolina and Chairman of the Department of Orthopaedic Surgery of Roper Hospital, Charleston, SC, USA.  He is a world reknown leader in the prevention of deep vein thrombosis.