Nonadherence in Outpatient Thromboprophylaxis after Major Orthopedic Surgery: A Systematic Review

After Major Orthopedic Surgery: A Systematic Review

Thomas Wilke; Sabrina Müller


Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(6):691-700. 

In This Article

Abstract and Introduction


The necessity for extended medication-based thromboprophylaxis after hip/knee-replacement surgery (major orthopedic surgery) has been acknowledged in international guidelines. In this article, we review and critically appraise the literature regarding patients' nonadherence (NA) in outpatient thromboprophylaxis after major orthopedic surgery. We conducted a systematic literature review. All studies published since 1990 and that were found to report research about NA in outpatient thrombosis prophylaxis after major orthopedic surgery were included. Only six relevant contributions could be identified. All these studies dealt with parenteral low-molecular-weight heparins or fondaparinux prophylaxis. The extent of NA (defined as existing when a patient fails to take the prescribed medication on at least 1 day) ranged from 13 to 37%. In one large German survey, patients who were nonadherent missed between 38 and 43% of their outpatient low-molecular-weight heparin injections. Subjective factors can play a role in increasing NA; such factors include a lack of knowledge of or having no fear concerning thrombosis in general and a lack of specific knowledge regarding measures to prevent it, as well as a negative evaluation of injections as the form of therapy application. Waiting times between acute in-hospital treatment and admission to rehabilitation clinics, as well as abstention from stationary rehabilitation programs, form objective adherence barriers. Therefore, NA is a phenomenon influenced by subjective patient-related factors as well as objective, care-provision structural factors. Current trends in patient care (e.g., shorter hospital stays and lengthened ambulant care) are likely to increase both the number of nonadherent patients and the extent of NA, if the current state of knowledge proves an accurate predictor of the future. At present, it appears that between one and two of every five patients are not adherent when parenteral prophylaxis is used. Whether or not new oral anticoagulation alternatives will be capable of improving the situation remains open for future research.


The necessity for extended thromboprophylaxis after hip/knee-replacement surgery (major orthopedic surgery) is well documented.[1–4] Not all, but most of the publications show the cost–effectiveness of an extended thrombosis prophylaxis. Consequently, thromboprophylaxis has been acknowledged in international guidelines,[5] although the evidence concerning its cost–effectiveness is stronger in the case of total hip-replacement surgery than it is concerning total knee-replacement surgery.[6–9] In terms of medication-based thromboprophylaxis, current American College of Chest Physicians (ACCP) guidelines recommend thromboprophylaxis for at least 10 days (evidence: grade 1A) but preferably for up to 35 days (evidence: grade 1A for total hip arthroplasty surgery, grade 2B for total knee arthroplasty surgery[5]).

In principle, medication-based thrombosis prophylaxis can be conducted with different medications and in a variety of care-provision contexts. The most important medicine classes are low-molecular-weight heparins (LMWHs), unfractionated heparins and warfarin.[10] In addition, fondaparinux and recently introduced new oral anticoagulants such as the direct thrombin inhibitor dabigatran etexilate and the factor Xa inhibitor rivaroxaban are available; the latter two agents are potentially easier to administer (oral application, no anticoagulation tests required).[11] These two new anticoagulants are reportedly as effective as LMWHs[12–15] but may be more cost effective.[16] Furthermore, patient preference analysis shows that patients have a clear preference for oral thromboprophylaxis, especially in an outpatient setting.[17]

As a rule, a thrombosis prophylaxis medicine is administrated by an at least daily injection (unfractionated/LMWHs/fondaparinux) or daily tablet(s)/capsule(s) (warfarin, dabigatran and rivaroxaban). As hip- and knee-replacement surgery normally takes place in a stationary environment, the first prophylaxis (which can begin on the day preceding or succeeding the operation, as alternatives to starting on the day of the operation) takes place in the acute treatment hospital.[5] Depending on the length of time spent in stationary treatment, this leads to the first 4–15 days of prophylaxis being conducted in the acute treatment hospital. Following the acute treatment phase, there are, in principle, ten treatment path options (Figure 1; light shaded areas indicate outpatient thromboprophylaxis). In theory, and depending on the care provision situation, patients either proceed directly or after a few days to stationary or ambulant rehabilitation centers, or receive no rehabilitation. With the exception of the days that may be spent in stationary rehabilitation, the ambulant thrombosis prophylaxis begins directly in the post-acute phase. On the basis of clinical and economic developments in numerous countries, it can be observed that there is a clear trend toward shorter acute hospitalization of patients after major orthopedic surgery. This is likely to increase the importance of outpatient thromboprophylaxis.[18] A study based on German patients has shown that for approximately 90% of patients, ambulant thrombosis prophylaxis is already part of their prophylaxis cycle.[19]

Figure 1.

All theoretically possible patient pathways in terms of thromboprophylaxis.
Duration of pathway steps may differ between countries and patients.
PRP (if such prophylaxis is necessary).
Light shaded areads indicate outpatient thrombosis prophylaxis.
PRP: Post-rehabilitation prophylaxis.

The objective of this article is to systematically review the literature regarding nonadherence (NA) in outpatient medication-based thromboprophylaxis after orthopedic surgery. Specifically, the existing evidence regarding the percentage of patients showing any degree of NA, the extent of NA (missed prophylaxis days) and reasons explaining patients' NA are reviewed.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.