We identified subjects with a scheduled orthopedic hip or knee arthroplasty and tested them for aPL prior to surgery and after surgery and found that the prevalence of aPL positivity preoperatively was 44% compared to 3 to 10% in the general population [18
]. This marked difference in rate may be attributed to the fact that patients undergoing joint replacement surgery tend to be elderly and there is an associated increase in aPL antibodies with advancing age and the medications and diseases that are often concomitant with advancing age.
Additionally, the incidence of aPL in this study is higher than that found by Bedair et al. [14
] in people undergoing joint replacement surgery who were selected because they are at increased risk for VTE. The differences in rates between these two studies suggested that the expression of aPL is independent of existing risk for VTE and possibly heterogeneous in different populations. Further studies are needed to determine what populations (if any) have an associated increased incidence of VTE associated with the presence or development of aPL. Bedair et al. did not report VTE complications in their study.
Although rare, thromboembolic events occur as a result of arthroplasty in spite of aggressive thromboprophylaxis, and these events cause significant morbidity and mortality. The contribution of aPL in this process, if any, remains controversial. Some evidence suggests that positivity is associated with VTE [13
], while others found no such association [19
]. Further research is needed to determine if there is a subset of patients for whom these antibodies are thrombogenic, if there are subtypes of these antibodies that are more thrombogenic or a combination of these factors.
All subjects who remained antibody negative postoperatively received LMWH, and all of the subjects who were on warfarin developed aPL. Evidence suggests that neither warfarin nor LMWH therapy interferes with the dilute Russell's venom viper time (DRVVT) [17
Perhaps LMWH, by some unknown mechanism, prevents the development of antibodies to protein bound phospholipids and therefore affords some degree of protection from an otherwise thrombogenic complication of orthopedic surgery. Support for a protective effect of heparin is given by recent observation that heparin prevents the development of preeclampsia in mice [22
]. Further research into this explanation is needed, including investigating this association in a larger population and elucidation of potential mechanisms.
Two (2%) study subjects developed deep vein thrombosis within 90 days postoperatively in this cohort; this finding is consistent with current literature [8
]. Although no conclusions may be drawn from this study alone, the fact that about 1.5% of the population undergoing joint replacement can be expected to develop VTE is evidence that a subset of patients exists for whom VTE continues to be a concern. Among the risk factors that should be investigated in this group are aPL.
It is important to note that while no one can dispute the increased margin of safety that aggressive anticoagulation has brought to these procedures, thromboprophylaxis is not without risk. Identifying risk strata for VTE may mean that thromboprophylaxis can be tailored accordingly to balance prevention of VTE with the concerns associated with thromboprophylaxis.
The results of this study into aPL development in subjects undergoing knee or hip arthroplasty are hypothesis-generating. To expand these findings, future studies should investigate a larger population, measure all participants prospectively with prolonged followup, measure aPL later in the postoperative period, and correlate aPL results with clinical outcomes. Elucidation of the association between aPL antibodies and VTE in the context of arthroplasty procedures may help identify a subgroup of patients at high risk for development of VTE who would benefit from more aggressive thromboprophylaxis.