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


Using the described search terms, 4194 contributions were identified. However, a more refined analysis showed that only six papers were concerned with the theme NA in outpatient prophylaxis following major surgery (Figure 3 & Table 1). Based on the six criteria defined in the methods section of this paper, the six remaining identified papers can be classified as follows:

  • Medicine class: with one exception (fondaparinux),[25] all articles concern themselves with LMWHs as a class of medicine. All studies analyze the adherence of patients using daily subcutaneous prophylaxis injections;

  • Routine care NA measurement: only two studies measure NA in the routine care context.[19,25] In two further study designs, the prophylaxis treatment as such was not influenced but a study bias exists because the patients were obviously influenced at the beginning by being informed in detail about the goals of the study;[26,27]

  • NA measurement concept: the majority of the studies use self reports. Only one study does not do so.[28] The self-report questionnaires employed differ substantially and range from those including direct questions regarding possible NA to studies using indirect questions in the NA context. Indirect questions are characterized by not directly mentioning the missing of injections, but concentrating on the context surrounding the medical procedure and gradually narrowing the area of investigation.[19] Only three studies use multiple indicator concepts,[19,25,29] as is recommended by current adherence research;

  • Analyzed thromboprophylaxis period: in two studies, the length of observed thromboprophylaxis is not specified.[25,26] In three further studies, the observed thromboprophylaxis ranges from 10 to 21 days (proportion of outpatient thromboprophylaxis is not specified).[27–29] Only one study distinguishes between inpatient and outpatient prophylaxis; the average outpatient prophylaxis treatment length in this study was 10.9 days based on patients with any need for outpatient prophylaxis;[19]

  • Measurement of the NA extent in days: only one study measures the number of NA days;[19]

  • Recording of NA reasons: possible NA causes capable of providing starting points for possible adherence intervention have only been analyzed in two studies.[19,27]

Figure 3.

Consort-like chart showing how the analyzed publications were chosen from a keyword search in the databases MEDLINE and EMBASE.
EMBASE: Excerpta Medica Database; MEDLINE: Medical Literature Analysis and Retrieval System Online.

Based on the six studies summarized in this review, in those studies that most closely reflect routine context NA and used multi-indicator NA measurement concepts, the extent of NA (defined as a patient who missed at least 1 day of medication) ranged from 13 to 37%. Regarding the extent of NA – measured by noninjection days – only one large German survey came to a conclusion; the patients studied failed to take their injections for an average of between 5.9 and 6.4 days (based on 15.4 and 14.8 outpatient prophylaxis days for the NA patients subgroup in different NA scenarios), and this was between 38 and 43% of the total length of outpatient prophylaxis.[19] A scenario analysis in this study showed that if the NA threshold is raised to 2 noninjection days, the NA level falls by 4.7%, but at the same time, the number of NA days per NA patient increases by more than 3 days (>30%) over the total length of the ambulant prophylaxis for those patients.[19]

In the adherence research context, subjective factors increasing NA and that are primarily considered a part of intentional NA are:[101] a lack of knowledge regarding thrombosis and protection against it, missing anxiety about thrombosis and a negative evaluation of injection as a form of application.[19] Objective adherence barriers appear to be long ambulant waiting times between acute treatment and stationary rehabilitation, as well as the decision to forego stationary rehabilitation treatment altogether.[19,101]

The authors of this article were partly responsible for the conduction of one of the studies listed in Table 1.[19] The data collected during this study allow a detailed overview of the NA rates in alternative care-provision situations (Figure 4). It becomes clear that there exists a higher relative NA risk during the course of ambulant rehabilitation compared with the linking and prophylaxis periods after any rehabilitation.[19] This higher NA risk corresponds to an above-average number of NA days. Therefore, from a NA perspective, the most critical patient care provision pathway – also in regard to its dangerous relationship to the clinical evidence concerning the necessity for thrombosis prophylaxis – is the ambulant prophylaxis that follows, in short, the acute treatment phase.

Figure 4.

Nonadherence rates in different prophylaxis pathways. NA rates for patients belonging to the different pathways are shown, and the length of NA (measured both in the number of missed prophylaxis days and as a percentage of the whole length of outpatient prophylaxis) is presented.
Patients who directly admitted NA or a syringe surplus were identified.
NA: Nonadherence.
Adapted from [19].


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