Risk Factors for Venous Thromboembolism of THA and TKA
Risk Factors for Venous Thromboembolism of THA and TKA
We conducted a systematic review on risk factors for VTE of total joint arthroplasty including THA and TKA relating to the demographic characteristics of patients, clinical conditions and so forth. Articles published in recent ten years (2003–2013) were included with data of more than 1,150,000 patients. We presented all potential factors studied in at least one paper, and confirmed the risk directions of all factors examined in at least three papers by using "risk factor" "protective factor" and "controversial factor" as conclusions. In this systematic review of 54 high evidence level papers, six confirmed VTE risk factors for THA and seven for TKA were found (see Table 10).
TKA surgery were associated with higher risk of VTE than that of THA. The better postoperative exercising of THA patients could be a reason, but the inner mechanism has not been studied and is still unclear. We suggested surgeons and physicians to give closer attention to TKA patients in monitoring of VTE.
Older age, female gender, higher BMI and bilateral surgery were found to be VTE risk factors for both THA and TKA. However, the conclusions about age and BMI apply only to particular groups of patients. Age > 75 (vs. age < 75) as well as age > 70 (vs. age < 50) proved to be a risk factor supported by some papers. As for BMI, only those with BMI >30 can be taken as high VTE risk patients. Patients with higher BMI are always associated bad hemodynamics condition which may induce the thrombogenesis. Female gender and bilateral surgery were found to be a risk factor respectively. The procoagulant function of female hormone and coagulant-response following the bilateral surgery are possible explanations.
VTE history seems to be a potential VTE risk factor with high probability. Surprisingly we found the risk to be significant only in TKA patients but not in THA patients. The medical record bias of VTE history may account for this result. The relationship between VTE history and VTE after THA/TKA deserves further and refined research.
Cemented fixation of TKA compared to cementless was found to be a risk factor for VTE in our study. Considering the inconsistent results of other studies additional research is necessary before more definite conclusions can be drawn.
Longer surgery time was found to be a VTE risk factor for both two kinds of arthroplasty surgeries of low limb. An operation lasting more than 2 hours may increase the VTE risk, probably because of multiple surgical effects on the blood vascular system such as the endothelial injuries and hypercoagulable state. However, more studies focusing on the relation between operating time and VTE rate are still needed.
Chemoprophylaxis and mechanical/physical thromboprophylaxis which have been widely used already are widely known "VTE protective factors". A variety of comparisons between different thromboprophylaxes have been included into our systematic review (see Table 9). Enoxaparin and newly-developed direct Factor Xa inhibitors have shown great superiority to LMWH (not containing and containing enoxaparin respectively). In addition, earlier mobilization achieved at either of the three time point (see "Result" section of this article) was reported with a significant decreased risk for VTE of TKA, confirmed by several articles. These conclusions undoubtedly convince us of the reasonability of thromboprophylaxis using.
Several limitations of this systematic review bear further comments as follows:
In this way, the listed risk factors and protective factors of this study can only be seen as a lookup table rather than a final conclusion. Each particular potential factor need to be examined in further researches.
Doctors are nowadays facing a great challenge in preventing of VTE for total joint arthroplasty. A stratification system of VTE risk and appropriate thromboprophylaxis schemes based on risk classification which suit the circumstance of each patient are in urgent need.
Common situation is that the risk of VTE decreases accompanied with the increasing risk of bleeding when drugs were used, as a result of the dose-effect relationship of most drugs including those newly developed ones, e.g. direct factor-Xa inhibitor like TAK-442 and partial factor-VII inhibitor like TB-402 Weitz et al. have conducted chemoprophylaxis based on their own risk classification systems, and found VTE as well as bleeding in the "high risk" group treated with high dose drugs. It implicates that the particular dose of a drug is not enough for some patients in VTE preventing but too strong for others.
Optimal VTE prevention has not been achieved, partly because of the roughness of the existing risk stratification system. Therefore, risk stratification systems need improvement. However, there is even not any VTE risk stratification system for total joint arthroplasty, despite of the "Caprini score" which is not especially for THA and TKA, to our knowledge. Further research may clarify the real VTE risk factors and develop a risk stratification system. In this way, stronger thromboprophylaxes can be given to patients of confirmed VTE risk, rather than misused to become risk factors for bleeding.
Discussion
We conducted a systematic review on risk factors for VTE of total joint arthroplasty including THA and TKA relating to the demographic characteristics of patients, clinical conditions and so forth. Articles published in recent ten years (2003–2013) were included with data of more than 1,150,000 patients. We presented all potential factors studied in at least one paper, and confirmed the risk directions of all factors examined in at least three papers by using "risk factor" "protective factor" and "controversial factor" as conclusions. In this systematic review of 54 high evidence level papers, six confirmed VTE risk factors for THA and seven for TKA were found (see Table 10).
TKA surgery were associated with higher risk of VTE than that of THA. The better postoperative exercising of THA patients could be a reason, but the inner mechanism has not been studied and is still unclear. We suggested surgeons and physicians to give closer attention to TKA patients in monitoring of VTE.
Older age, female gender, higher BMI and bilateral surgery were found to be VTE risk factors for both THA and TKA. However, the conclusions about age and BMI apply only to particular groups of patients. Age > 75 (vs. age < 75) as well as age > 70 (vs. age < 50) proved to be a risk factor supported by some papers. As for BMI, only those with BMI >30 can be taken as high VTE risk patients. Patients with higher BMI are always associated bad hemodynamics condition which may induce the thrombogenesis. Female gender and bilateral surgery were found to be a risk factor respectively. The procoagulant function of female hormone and coagulant-response following the bilateral surgery are possible explanations.
VTE history seems to be a potential VTE risk factor with high probability. Surprisingly we found the risk to be significant only in TKA patients but not in THA patients. The medical record bias of VTE history may account for this result. The relationship between VTE history and VTE after THA/TKA deserves further and refined research.
Cemented fixation of TKA compared to cementless was found to be a risk factor for VTE in our study. Considering the inconsistent results of other studies additional research is necessary before more definite conclusions can be drawn.
Longer surgery time was found to be a VTE risk factor for both two kinds of arthroplasty surgeries of low limb. An operation lasting more than 2 hours may increase the VTE risk, probably because of multiple surgical effects on the blood vascular system such as the endothelial injuries and hypercoagulable state. However, more studies focusing on the relation between operating time and VTE rate are still needed.
Chemoprophylaxis and mechanical/physical thromboprophylaxis which have been widely used already are widely known "VTE protective factors". A variety of comparisons between different thromboprophylaxes have been included into our systematic review (see Table 9). Enoxaparin and newly-developed direct Factor Xa inhibitors have shown great superiority to LMWH (not containing and containing enoxaparin respectively). In addition, earlier mobilization achieved at either of the three time point (see "Result" section of this article) was reported with a significant decreased risk for VTE of TKA, confirmed by several articles. These conclusions undoubtedly convince us of the reasonability of thromboprophylaxis using.
Several limitations of this systematic review bear further comments as follows:
Definition inconsistency of "VTE" across the included papers, e.g. symptomatic or venography-proven (estimated magnitude of bias: low; effects on study results: unknown);
Limitation on number of available papers for each potential factor (estimated magnitude of bias: moderate; effects on study results: difficulty in assessing particular factors);
Selection bias of our review (only level-Iand level-II evidence were included, therefore some risk factors examined in lower level studies like case–control studies were excluded inherently) and publishing bias favoring statistically significant results (estimated magnitude of bias: moderate; effects on study results: neglect of some risk factors);
Confounders that have not been adjusted in studies included, e.g. mutual effects between BMI and metabolic diseases, older age and postoperative immobility (estimated magnitude of bias: moderate; effects on study results: confounding of risk factors).
In this way, the listed risk factors and protective factors of this study can only be seen as a lookup table rather than a final conclusion. Each particular potential factor need to be examined in further researches.
Doctors are nowadays facing a great challenge in preventing of VTE for total joint arthroplasty. A stratification system of VTE risk and appropriate thromboprophylaxis schemes based on risk classification which suit the circumstance of each patient are in urgent need.
Common situation is that the risk of VTE decreases accompanied with the increasing risk of bleeding when drugs were used, as a result of the dose-effect relationship of most drugs including those newly developed ones, e.g. direct factor-Xa inhibitor like TAK-442 and partial factor-VII inhibitor like TB-402 Weitz et al. have conducted chemoprophylaxis based on their own risk classification systems, and found VTE as well as bleeding in the "high risk" group treated with high dose drugs. It implicates that the particular dose of a drug is not enough for some patients in VTE preventing but too strong for others.
Optimal VTE prevention has not been achieved, partly because of the roughness of the existing risk stratification system. Therefore, risk stratification systems need improvement. However, there is even not any VTE risk stratification system for total joint arthroplasty, despite of the "Caprini score" which is not especially for THA and TKA, to our knowledge. Further research may clarify the real VTE risk factors and develop a risk stratification system. In this way, stronger thromboprophylaxes can be given to patients of confirmed VTE risk, rather than misused to become risk factors for bleeding.
