Risk Factors for Venous Thromboembolism of THA and TKA

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Risk Factors for Venous Thromboembolism of THA and TKA

Results

Screening Results



We included 54 papers from 226 identified titles, in which about 1,150,000 patients from more than 30 countries and 28 classes of factors were examined. All the included studies were above level-II and 10 of them (19%) were level-I. The NOS results were provided in Table 2. Twenty-eight classes of factors were examined. The overall frequences of studies and reference numbers were collected (see Table 3 and Table 4). We summarize all factors examined by at least one study in Table 4, Table 5, Table 6, Table 7, Table 8 and Table 9, in which the factors were classified into five aspects: demographic factors, clinical factors, laboratory indexes, health care provider-related factors and thromboprophylaxes. The factor examined by at least three articles are qualified to be determined whether it is a "risk factor", a "protective factor" or an "controversial factor" (see Table 10). Factors examined by fewer than three articles were included but not discussed.

The full search screening procedure and results are presented in Figure 1. All but one of the 54 papers have provided quantitative results. We contacted the corresponding author of that article by email and got an article published in his own country (Thailand) with sufficient supplementary data.

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Figure 1.



Flow diagram of manuscript search and selection procedure.

Demographic Factors



Age. Twelve papers - examined age as a risk factor for VTE. Both THA and TKA have got themselves reported in no fewer than eight papers. Of THA, six reported an increased risk for older patients. Of TKA patients, three papers reported older age as a risk factor for VTE.

A total of four papers took "increased age" as the potential factor, while other papers investigated some specific cut-off age values such as 60, 70 ,80 and so on. Seniors older than 70 (vs. <70) or 75(vs. <75) were found with greater VTE risk. However, the above results referring to the specific cut-off age values were constrained by the number of papers.

Gender



Thirteen papers examined gender as a risk factor for VTE. Both THA and TKA have got themselves reported in nine papers. Of THA, two reported an increased risk for female patients while another study found female gender with decreased VTE risk. Of TKA patients, two papers reported female gender as a risk factor for VTE.

BMI



Six papers examined BMI as a risk factor for VTE. Of THA, one paper among the total of three papers reported an increased risk for patients with higher BMI. Of TKA patients, six papers examined BMI and one found it a risk factor. The significant cut-off BMI value of either TKA or THA is 30. Patients with BMI higher than 30 have greater VTE risks than those with BMI less than 25.

Race



One paper examined race as a risk factor for VTE for TKA. The black race was found to be a risk factor while Hispanic race showed no significant difference when compared to the white race. Hispanic race was also investigated in the same paper but found with no significant association with VTE when comparing with the white race.

ASA Physical Status



Three papers examined ASA score as a risk factor for VTE. Three papers for THA and two papers for TKA examined this factor. Consistently, none of these papers reported significant association between ASA score and VTE incidence. Researchers of all the three papers used "ASA = 3 or 4" as the potential factor to compare with "ASA = 1 or 2" but found no significant difference.

Clinical Factors



Underlying Diagnosis. Three papers examined underlying diagnoses, e.g. RA or OA, as risk factors for VTE. One paper described RA as a risk factor for VTE of TKA. In one paper of TKA and another paper of THA, researchers found RA a protective factor compared to OA. No significant association was found when referring to trauma, dysplasia and osteonecrosis.

Comorbidity (Charlson Index)



Three papers examined Charlson comorbidity index as a risk factor and one paper reported an increased risk for VTE of TKA patients. Charlson index is widely used to assess the severity of patients' comorbidities before surgery and higher charlson scores indicate worse conditions. Some reseachers used different cut-off values of charlson index, e.g. "1" "3" to compare with "0" value, while the other one paper used "1 point increase" as the potential risk factor.

Cardiovascular Disease



Ten papers examined cardiovascular diseases as a risk factors for VTE. Heart diseases, cerebrovascular diseases and venous disorders were included in this class. VTE history was found a significant risk factor for THA patients by two in six papers, but with no association with VTE for TKA. Varicose vein was examined by three papers focusing on TKA and turned out to be an controversial factor. The rest of the cardiovascular factors reported by less amount of papers were presented in Table 6.

Respiratory Disease



Respiratory diseases including pulmonary disease and sleep apnea were examined by two papers. Pulmonary disease is found with no association with VTE for either THA or TKA. One from two papers reported an increased risk of VTE for sleep apnea, applicable to both THA and TKA.

Neurological Disease



One paper examined neurological diseases as risk factors of VTE for THA and TKA. No significant association was found between VTE and both the two kinds of surgeries. No detail about the neurological disease type was presented in the paper.

Liver and Kidney Disease



Two papers examined liver and kidney diseases including chronic kidney disease (CKD) as risk factors of VTE. One study found CKD3B a risk factor for THA patients who received enoxaparin as thromboprophylaxis, compared to milder CKDs, e.g. CKD1, CKD2 or CKD3A. In addition, researchers of the above paper have also took "CKD3B" as a potential risk factor for THA patients who received desirudin, but found no significant association between CKD and VTE rate.

Metabolic Disease



Six paper examined metabolic diseases as a risk factors of VTE for THA and TKA. One paper for THA and two papers for TKA found metabolic syndrome with increased VTE risk.

Diabetes mellitus was examined by four studies for both THA and TKA, and showed no significant association with VTE. Risk directions of hypertension, dyslipidemia and gout were presented in Table 6. The influences of confounders among the above metabolic diseases still remain unclear.

Hematological Disease



Two papers examined hematological disease as a risk factor of VTE. One paper focusing on TKA found hematological a VTE risk factor. No details about the specific types of the hematological diseases were presented in the above paper.

Endocrine Disease



Two papers examined endocrine disease as a risk factor of VTE. One paper for THA and two for TKA found no significant association between endocrine disease and VTE. The specific types of the endocrine diseases were not stated except hypothyroid disorder in one article.

Malignancy



Four papers examined malignancy as a potential factor of VTE for THA and TKA but none of them reported a significant association for VTE. Neither the type nor the stage of the malignancy was mentioned in any papers.

Medication (Hormone Replacement/Herbal)



Three papers examined medications including hormone replacement and herbal as risk factors. Hormone replacement showed no significant association with VTE, supported by one paper for THA and three for TKA.

When regarding to herbal therapy, the only one paper fount it with an significantly increased risk. The paper found that the herbal therapy of traditional Thailand medicine can increase VTE risk for TKA patients, but it is uncertain whether other kinds of herbal therapy would increase the VTE risk.

Laboratory Indexes



Preoperative Laboratory Index. Two papers examined four kinds of indexes as risk factors of VTE. One study found blood glucose level ≥ 200 mg/dl with an increased VTE risk for both THA and TKA. This result is not consistent with that from papers focusing specifically on diabetes mellitus.

Resting PaCO2 ≥ 45 mmHg has also proven to be a VTE risk factor. Resting PaO2 < 75 mmHg and RVSP ≥ 35 mmHg were reported by only one paper focusing on TKA patients and showed no significant association with VTE.

Postoperative Laboratory Index



Two papers examined four risk factors of VTE for TKA alone. Each of these factors was reported with an increased VTE risk. All factors were presented in Table 7.

Higher platelet counts, hemoglobin ≧ 10.5 g/dl and AaDO2 ≧ 34 Torr were investigated by one paper. All of the three laboratory indexes were collected 1 day postoperatively and were found to be VTE risk factors for TKA patients.

One articles have studied the seroconvertion of IgG-class HIT (heparin-induced thrombocytopenia) antibody, an indicator of the thromboembolic omplication that can occur with heparin using. The result of this paper shows that the seroconvertion of HIT antibody can increase VTE risk of TKA patients. To our knowledge, this factor has not been studied in THA patients.

Health Care Provider-related Factors



Surgery Type. Twelve papers examined surgery types as risk factors of VTE. All factors reported were presented in Table 8.

TKA is a VTE risk factor, reported by two from four papers, compared to THA. Bilateral arthroplasty surgery were reported with a significant increases VTE risk by one paper for THA and two for TKA.

One paper compared the VTE rates between THA and THRA (total hip resurfacing arthroplasty) and found the former with significant increased VTE risk.

Another paper for THA and two for TKA took the revision surgery as a potential VTE risk factor, compared to primary surgery. Except for the result from one paper in which the revision surgery turned out to a risk factor, other results show no significant association between the revision surgery and VTE rate.

The surgery sides of the knee, e.g. right side and left side, were also investigated by one article. The result shows no significant difference between the two sides, as expected.

Surgical Technique



Five papers examined surgical technics, e.g.fixation and ROBODOC milling system, as risk factors of VTE. One from two papers and two from three papers reported an increased VTE risk associated with cement fixation, for THA and TKA patients respectively, while another article found ROBODOC system a protective factor compared to traditional technic.

Operating Time



Four papers examined surgery time as a risk factor of VTE for THA or TKA. Only one paer found longer surgery time (surgery lasting more than 2 hours) with increased VTE risk. Other papers which used different cut-off value, e.g. 3 hours, found no significant association between surgery time and VTE risk.

Anesthesia



Five papers examined anesthesia types as risk factors of VTE. Three papers for THA and three for TKA found general anesthesia with no significant association for VTE. Spinal anesthesia was reported with no significant association of TKA by one paper either.

Bleeding



One paper examined bleeding volume as a risk factor of VTE for TKA and found it with an increased risk when more than 1280 ml. The bleeding volume was defined as the cumulative bleeding volume measured on the day after the surgery.

Hospital Volume



Two papers examined lower hospital volume as a risk factor of VTE for THA and TKA.

The former article which is focusing on TKA, took the hospitals with the lowest 40% surgical volume as the "low volume" ones, and those with the highest 20% surgical volume as the "high volume" hospitals, respectively. In this article, higher hospital volume was found to be VTE risk factor.

The latter article applied a variety of specific cut-off value of the hospital volume, e.g. 25, 100 and 200. Significant association between higher volume and increased VTE risk was verified for THA patients, but not for TKA patients.

Insurance Type



One paper examined insurance types, e.g. private insurance and Medicare/Medicaid, as risk factors of VTE for THA patients. No significant association was found in this study. Because this study was conducted in the United States, the insurance types to be investigated were based on domestic condition of US, which need to be mentioned and noticed by the readers.

Thromboprophylaxes



Chemoprophylaxis. 28 papers (see Table 4) examined several chemoprophylaxis schemes as risk factors of VTE for THA and TKA. Comparisons and results were listed in Table 9.

Initiating and Lasting of the Prophylaxis



Two papers examined preoperative low molecular weight heparin (LMWH) compared to postoperatively LMWH using. One paper for THA and two for TKA found the initiating time(preoperative vs. postoperative) with no significant association to VTE. Extended prophylaxis, which is defined in different way by two studies, was compared with short-duration and reported with a decreased VTE risk.

Mechanical and Physical Prophylaxis



Five papers examined a variety of mechanical and physical prophylaxis, e.g. stockings and early mobilization, as risk factors of VTE for THA and TKA. Earlier mobilization/ambulation was found to significantly decrease VTE risk, if achieved at either of the three time points: 24 hours after surgery, 72 hours after surgery and before discharge. No significant association with VTE was found when regarding to the following comparisons: mechanical prophylaxis (vs. chemoprophylaxis), below-knee stockings (vs. up-knee) and weight bearing within 48 h.

Confirmed Factors



Risk directions of factors examined in at least three articles were included in further analysis to be confirmed, see Table 10. We found six risk VTE factors of THA and seven risk factors of TKA. Protective factors (four of THA and four of TKA) and controversial factors (four of THA and seven of TKA) were also presented in Table 10. The definition of "confirmed" was described in the "Analysis" section in this article.
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