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The Journal of Bone and Joint Surgery 78:574-80 (1996)
© 1996 The Journal of Bone and Joint Surgery, Inc.

Effect of Preoperative Donation of Autologous Blood on Deep-Vein Thrombosis following Total Joint Arthroplasty of the Hip or Knee*

MARK J. ANDERS, M.D.{dagger}, ROBERT M. LIFESO, M.D.{dagger}, MICHAEL LANDIS, M.D.{dagger}, JAMES MIKULSKY, B.SC.{dagger}, CRAIG MEINKING, R.P.A.{dagger} and KELLY S. McCRACKEN, {dagger}, BUFFALO, NEW YORK

Investigation performed at the Veterans Administration Medical Center, Buffalo


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
The effect of preoperative donation of autologous blood on postoperative deep-vein thrombosis was retrospectively studied in men who had been managed consecutively with elective total joint replacement of the hip or knee because of osteoarthrosis. The patients had, on the average, two of nine considered risk factors for deep-vein thrombosis. Two hundred and thirty-seven patients were evaluated postoperatively with ascending venography, and they form the basis of this study. Fifty-four patients had venographic evidence of deep-vein thrombosis of the lower extremity, with most having asymptomatic clots distal to the knee. The prevalence of deep-vein thrombosis was nineteen (16 per cent) of 116 after total hip arthroplasty, compared with thirty-five (29 per cent) of 121 after total knee arthroplasty (chi square = 4.6, p = 0.03). Deep-vein thrombosis developed in twenty-eight (17 per cent) of the 161 patients who had donated blood preoperatively, compared with twenty-six (34 per cent) of the seventy-six patients who had not donated blood preoperatively (chi square = 7.7, p = 0.006). Through logistic regression analysis, the donation of autologous blood was shown to reduce significantly the development of postoperative deep-vein thrombosis for patients managed with total knee arthroplasty (p < 0.01) but not for patients managed with total hip arthroplasty. Additional neural network analysis showed the donation of autologous blood to be the most important prognostic factor in predicting the absence of postoperative deep-vein thrombosis. In addition to diminishing the need for transfusion of homologous blood after total joint arthroplasty, preoperative donation of autologous blood appears to protect against postoperative deep-vein thrombosis after total knee arthroplasty.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
The prevalence of deep-vein thrombosis following elective total joint arthroplasty without prophylaxis may be as high as 70 to 84 per cent. Hull et al.18 noted that deep-vein thrombosis developed in seventy-seven of 158 control patients after arthroplasty, while Lotke et al.26 reported that 126 of 172 patients had thrombi in the calf after total knee replacement. Stulberg et al.40, reporting on a series of 517 patients who had had 638 knee replacements, found deep-vein thrombosis in 267 (57 per cent) of 468 patients who had had total knee arthroplasty with prophylaxis, compared with forty-one (84 per cent) of forty-nine patients who were so managed without prophylaxis. Numerous prophylactic strategies have been used, including medications for anticoagulation, mechanical pneumatic compression devices, and early mobilization, all with the goal of decreasing the prevalence of potentially fatal pulmonary embolism24,45.

Similarly, since the mid-1980's, preoperative donation of autologous blood has become routine, partially because of concerns about the risks associated with transfusion of homologous blood.

In this retrospective study, we evaluated the effect of preoperative donation of autologous blood on postoperative deep-vein thrombosis. The series included men at high risk for deep-vein thrombosis who were managed with elective total hip or knee arthroplasty for non-inflammatory degenerative joint disease.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Two hundred and sixty-five men who were at high risk for deep-vein thrombosis were managed consecutively, from 1988 through 1991, with elective primary or revision total joint arthroplasty in the lower limb because of degenerative joint disease. They were studied after approval from our institutional review board and after fully informed consent had been obtained. As the study was conducted at a Veterans Administration hospital, the few women who were managed during the study period were excluded to maintain as homogeneous a group as possible. The operative procedures were performed primarily by the orthopaedic chief resident, under the supervision of the senior one of us (R. M. L.) or two other staff orthopaedic surgeons. Patients who had a fracture or known rheumatoid, psoriatic, or infectious arthritis were excluded.

Autologous donation was controlled according to the Standards for Blood Banks and Transfusion Services1,2 through the blood bank at Veterans Administration Medical Center at Buffalo. Patients donated at seven to ten-day intervals preoperatively, although they were allowed to donate as frequently as every four days. This regimen provided a preoperative hematocrit of at least 34 per cent (0.340). We attempted to obtain two or three units of packed red blood cells from each patient. Iron-replacement therapy, consisting of 325 milligrams of ferrous sulfate administered orally three times daily, was started with the first donation of autologous blood. The shelf life of the packed red blood cells was forty-two days.

All of the patients received perioperative prophylaxis against deep-vein thrombosis with Coumadin (warfarin) or intermittent pneumatic-compression stockings (Kendall, Boston, Massachusetts), or both. The prophylaxis with Coumadin consisted of ten milligrams administered orally on the night before the operation, with the daily postoperative dosage based on a target prothrombin time of approximately fourteen and one-half to fifteen seconds. The stockings were placed bilaterally immediately postoperatively in the operating suite. Prophylaxis with both Coumadin and pneumatic compression stockings was used after revision arthroplasty for eighteen patients. Prophylaxis was continued until the patient was mobile, at which time ascending venography was performed bilaterally, routinely between the seventh and the tenth postoperative day. The venography was done by radiologists who were blinded to the study and to the treatment groups with respect to the method of prophylaxis and the use of blood products. Patients who had definitive venographic evidence of deep-vein thrombosis were maintained on anticoagulation therapy for three months. Equivocal or suspicious results were treated as positive.

Venographic studies were successfully completed for 237 of 265 patients. The remaining patients either had an unsuccessful evaluation or refused to have venography performed. Thus, 237 patients formed the basis of this study. Venous Doppler studies were performed for the patients in whom deep-vein thrombosis was suspected clinically but for whom venograms were not made.

Twenty-seven variables were analyzed for each patient, including previously reported potential risk factors20,21 for deep-vein thrombosis. These risk factors were preoperative varicose veins, cardiac disease, hypertension, obesity, previous deep-vein thrombosis or previous pulmonary embolism, a previous cerebrovascular accident, a malignant lesion, a history of smoking, and diabetes mellitus. The total of these considered risk factors was analyzed as a separate variable. Patients who had stopped smoking less than six months preoperatively were arbitrarily considered to be smokers. According to the protocol, use of medications such as aspirin and other non-steroidal anti-inflammatory medications was routinely discontinued two weeks before the operation.

Additional patient-related variables included the age; race; type of procedure; preoperative hemoglobin level, platelet count, and prothrombin time; number of units of autologous blood that had been donated; number of units of autologous blood that had been transfused; and number of units of homologous blood that had been transfused. The duration of hospitalization, the type of prophylaxis against deep-vein thrombosis, and early infection or death within two years after the operation were also recorded. The intraoperative data that were reviewed included the duration of the arthroplasty, the use of cement, and the type of anesthesia.

An epidemiologist performed the statistical analysis using IBM SPSS/PC+ software (SPSS, Chicago, Illinois) for all initial and basic exploratory analyses, as well as for analysis of variance and logistic regression analysis. Data concerning the blood products that had been used, the procedure, and the venographic results were available for all 237 patients. Patients who had incomplete data sets for any of the previously mentioned variables were excluded from the logistic regression analysis.

The data were also analyzed with a neural network system conventional back error propagation feed forward algorithm (Brain Cell [for Lotus] Promised Land Technologies, New Haven, Connecticut). This unique approach to data analysis, unrelated to standard statistical methods, permits the forecasting of outcomes on the basis of repeated integrating of collected data and is extremely powerful for recognizing patterns in multiple variable data sets.

The study sample comprised men who were at high risk for deep-vein thrombosis. The average age (and standard deviation) was 66.5 ± 8.1 years (range, thirty-five to ninety-two years). The average number of defined risk factors for deep-vein thrombosis was 2 ± 1.2. Only twenty-four patients (10 per cent) had no known defined risk factors. The most common risk factors, in order of decreasing frequency, were hypertension (113 patients; 48 per cent), heart disease (eighty-six patients; 36 per cent), and smoking (eighty patients; 34 per cent). Fifty-four patients (23 per cent) were considered obese, although this was probably underestimated. Obesity was defined as a clinical weight at the time of the operation of more than 15 per cent above estimated norms for height and age. Other risk factors included diabetes mellitus (forty-two patients; 18 per cent), a malignant lesion (thirty patients; 13 per cent), a cerebro-vascular accident (twelve patients, 5 per cent), varicose veins (eleven patients; 5 per cent), and known previous deep-vein thrombosis or pulmonary embolism (nine patients; 4 per cent).

The procedures included 121 total knee arthroplasties and 116 total hip arthroplasties. Forty-four operations (twenty-nine hip and fifteen knee arthroplasties) were reoperations, with four being second or subsequent revisions. Complete intraoperative data were available for 225 procedures. Cement was used in 108 procedures, primarily for fixation of tibial and patellar components in eighty-four knee replacements and for fixation of the femoral component in twenty-four hip replacements. Use of cement correlated with increased age (r = 0.27, p < 0.001). However, no significant increase in deep-vein thrombosis with use of cement was demonstrated by logistic regression analysis. The average duration of the operation was 143 ± 47.8 minutes (range, forty to 360 minutes). General anesthesia was used for 160 patients and spinal anesthesia, for sixty-five. Several patients who had received epidural anesthesia were included with those who had received spinal anesthesia for the purposes of analysis. Coumadin was used by 141 patients for prophylaxis against deep-vein thrombosis; intermittent compression stockings, by seventy-five; and both, by eighteen. Three patients received no prophylaxis because of administrative error. Preoperative laboratory values included an average hemoglobin level of 0.133 ± 0.016 gram per liter, a platelet count of 269.5 ± 82.6 x 109 per liter, and a prothrombin time of 10.2 ± 0.92 seconds.

One hundred and sixty-one (68 per cent) of the 237 patients donated blood preoperatively, with an average donation of 1.7 ± 1.4 units from each patient. Seventy-six patients donated no blood, nineteen patients donated one unit, eighty-three patients donated two units, and fifty-nine patients donated three units or more.

During the study period, the donation of autologous blood before total joint arthroplasty became increasingly prevalent46. Thirty-seven (63 per cent) of fifty-nine patients who were operated on in 1988 had donated blood preoperatively, whereas forty-six (78 per cent) of fifty-nine patients had done so in 1991. An average of 1.6 ± 1.2 units of autologous blood was reinfused for the patients who had donated blood. Forty-five (28 per cent) of the patients who had donated autologous blood received no transfusion. An average of 0.6 unit of homologous blood was transfused in the entire series. The subset of patients who had donated blood received an average of 0.4 unit of homologous blood, compared with an average of 1.2 units for the patients who had not donated blood. One hundred and seventy-nine patients received no homologous blood, fifteen received one unit, twenty-five received two units, and eighteen received three units or more. All of the patients who received three units or more had a revision procedure or had no autologous blood available.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Adequate ascending venograms were made for 237 patients seven to ten days after the operation. Venograms were made once the patient was able to walk and before discharge either to home or to the Rehabilitation Medicine Service. One hundred and eighty-three venograms were negative and fifty-four were considered positive for deep-vein thrombosis. Most of the positive studies showed asymptomatic thrombi distal to the knee. All patients who had a positive venogram were managed intravenously with heparin followed by oral administration of Coumadin for three months. Thirty-one of the fifty-four positive venograms showed deep-vein thrombi in the calf, distal to the trifurcation; five, in the popliteal vein; and ten, in the femoral vein. The exact location of the thrombi on eight reportedly positive venograms was inadequately documented. Seven of the fourteen venograms that were positive after total hip replacement showed deep-vein thrombi that were popliteal or more proximal in location, but only eight of the thirty-two positive venograms after total knee replacement showed thrombi that were proximal to the trifurcation. The prevalence of deep-vein thrombosis after total hip arthroplasty was nineteen (16 per cent) of 116, compared with thirty-five (29 per cent) of 121 after total knee arthroplasty. Cross tabulation indicated that this difference was significant (chi square = 4.6, p = 0.03).

Deep-vein thrombosis was found in twenty-eight (17 per cent) of the 161 patients who had donated blood preoperatively, compared with twenty-six (34 per cent) of the seventy-six patients who had not; this difference was significant (chi square = 7.7, p = 0.006). Furthermore, the number of units of donated autologous blood showed a significant negative correlation with postoperative deep-vein thrombosis on regression analysis (r = -0.23, p = 0.002). Correlational analysis showed this negative correlation to be significant for the patients who had a total knee replacement (r = -0.31, p = 0.003) but not for those who had a hip replacement (r = -0.12, p = 0.26).

The patients who donated blood had a significantly lower average value for hemoglobin preoperatively (0.132 gram per liter) than those who did not (0.140 gram per liter), as shown by analysis of variance (F = 12.96, p < 0.001). This correlation of a decreased hemoglobin level with preoperative donation of blood remained significant within both the hip and the knee arthroplasty subgroup. However, on analysis of variance, the association between the preoperative hemoglobin level and the venographic result reached only borderline significance: the value was 0.138 gram per liter for the patients in whom deep-vein thrombosis later developed, compared with 0.133 gram per liter for those in whom it did not (F = 3.88, p = 0.07). The platelet count was not related to either the preoperative donation of blood or the venographic result. Although the patients who donated blood preoperatively were significantly younger than those who did not (65.6 compared with 68.4 years; F = 4.13, p = 0.043), age did not differ significantly between those in whom deep-vein thrombosis developed and those in whom it did not (68.4 compared with 66.5 years; F = 2.25, p = 0.14).

Logistic regression analysis for venographic outcome by all measured variables (with preoperative donation of blood, in numbers of units donated, as a continuous variable) revealed the preoperative donation of blood to be related significantly (odds ratio = 0.60, 95 per cent confidence interval = 0.39 to 0.88) to a lesser number of positive venograms. In addition, operative duration was a significant risk factor for the subset managed with total knee arthroplasty (odds ratio = 1.02, 95 per cent confidence interval = 1.0006 to 1.04). With the numbers available, no significant difference in the rate of deep-vein thrombosis was seen between the patients who were managed with Coumadin and those who were managed with pneumatic compression stockings. The number of units of homologous blood that was transfused also did not have a significant effect on the development of deep-vein thrombosis. Within the subset of patients who had a total hip arthroplasty, none of the examined variables proved significant with respect to the development of postoperative deep-vein thrombosis.

Neural network analysis35 by back error propagation feed forward algorithm was used to analyze simultaneously the relative importance of each measured variable in predicting the development of deep-vein thrombosis for this population (p < 0.05). The trained neural network could identify accurately, at a chosen confidence limit, patients in whom postoperative deep-vein thrombosis was expected to develop. The number of donated autologous units was assigned the highest negative weight for the development of deep-vein thrombosis. In other words, the most important factor in allowing the trained neural network to predict the patients in whom deep-vein thrombosis would not develop was the number of autologous units of packed red blood cells that had been donated. The four most highly weighted negative predictors, in order of relative importance, were the number of donated units of autologous blood, the transfusion of homologous blood, the method of prophylaxis, and the preoperative prothrombin time. Positive predictors, in order of relative weight, were the age of the patient, varicose veins, the type of procedure, and the preoperative hemoglobin value. These positive predictors were associated with an increased tendency toward the development of deep-vein thrombosis. The clinical relevance of these results is not certain, but a positive or negative association with postoperative deep-vein thrombosis in this data set is suggested. In addition, the neural network model can suggest the number of units of blood that, if donated, would be theoretically protective for a patient who has known risk factors.

The average duration of hospitalization, including time on the Rehabilitation Medicine Service for non-acute convalescence, was 25 ± 14.6 days. The duration averaged twenty-three days for patients who had no evidence of deep-vein thrombosis and thirty days for those who did. However, exclusion of one patient with deep-vein thrombosis who was hospitalized for 390 days decreases the average stay of patients with deep-vein thrombosis to twenty-four days, which was not significantly different than the average hospital stay of those without deep-vein thrombosis. With the numbers available, we could not determine a significant relationship between medical complications and the venographic results, for the group as a whole or for the hip or knee arthroplasty subgroups. Anticoagulation with Coumadin was not associated with any documented or suspected complications related to bleeding, probably because of the low level of anticoagulation that had been sought. Similarly, there were no complications related to the use of the pneumatic compression stockings. Eight infections (six superficial and two deep) developed postoperatively, but none led to early removal of the implant. No pulmonary embolism was clinically documented. Several ventilation-perfusion scans were made because of clinical findings, but they were interpreted as demonstrating a low probability of pulmonary embolism or as being indeterminate. Pulmonary angiograms were not made. One patient was managed with heparin because of clinical suspicion of pulmonary embolism, despite an indeterminate ventilation-perfusion scan. No routine screening test for subclinical pulmonary embolism was performed.

Eighteen patients died within two years after the index operation. Eight of them died within one year after the operation and five, within three months. Of these five patients, one died of sudden cardiopulmonary arrest on the fifteenth postoperative day (no autopsy was performed) and two died of a cerebrovascular accident—one of intra-abdominal etiology and one of unknown causes. The average age (sixty-eight and one-half years) and the number of risk factors for deep-vein thrombosis (two) for the patients who died within one year after the operation did not differ markedly from those for the group as a whole. However, seven of the eight patients who died within one year after the operation had had a total hip replacement. Three patients had documented deep-vein thrombosis, one of which was proximal and two of which were distal; three patients had negative venograms; and two had inadequate venographic data.


   Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Virchow43 first proposed the etiology of deep-vein thrombosis as a triad of changes in the vessel wall, in the coagulability of the blood, and in blood flow. All three mechanisms have since been validated repeatedly4,5,11,39. Planès et al.33 demonstrated the role of local vascular injury during total hip arthroplasty. Distant intraoperative venous dilation with concomitant intimal injury recently was postulated as an etiology of deep-vein thrombosis by Stewart et al.39. Studies have suggested underlying deficiencies of plasma protein in individuals who are at risk for deep-vein thrombosis, and changes in intraoperative blood flow have also been examined during total hip arthroplasties5.

The focus of prophylaxis against thrombosis has primarily been either on maintenance of venous blood flow by sequential compression devices or on anticoagulation with Coumadin or heparin and derivatives. Perioperative intimal injury can be reduced but never completely eliminated. Thus, the optimum regimen for prophylaxis against deep-vein thrombosis after total joint arthroplasty remains controversial3,8-21,24-29,31,34-38,40-45,47. The known high prevalence of deep-vein thrombosis and the potential sequelae of pulmonary embolism and late venous insufficiency without prophylaxis make it unethical to include a true control group in a study of prophylaxis against this complication.

We analyzed many variables that potentially affect the development of deep-vein thrombosis after elective total hip and knee replacement. Essentially none of the previously proposed risk factors for deep-vein thrombosis that we examined proved to be significant in our series. The exception was prolonged operative duration, which correlated with an increased prevalence of deep-vein thrombosis in the subset managed with knee arthroplasty; Sharrock et al.36 previously noted a similar finding for patients managed with hip arthroplasty. Use of cement was associated with an increased rate of deep-vein thrombosis after total knee replacement in a study by Kim22. Use of cement correlated with increased age (r = 0.27, p < 0.001) in the present study but not with the rate of deep-vein thrombosis. The type of anesthesia had no effect on the rate of postoperative deep-vein thrombosis in this study, in contrast to the findings in many previous reports30,41,44. This may be due to the relatively small size of our series and the small number of patients (sixty-five) who received spinal or epidural anesthesia. The type of prophylaxis (compression stockings or anticoagulation with low-dose Coumadin) did not significantly affect the prevalence of deep-vein thrombosis in our group.

To our knowledge, this is the first study to address specifically the effect of preoperative donation of autologous blood on the postoperative development of deep-vein thrombosis. A significantly lower percentage of the patients who had donated blood preoperatively had deep-vein thrombosis postoperatively (17 per cent [twenty-eight], compared with 34 per cent [twenty-six] of the patients who had not donated blood; chi square = 7.7, p = 0.006). This observation was supported both by logistic regression analysis and by neural network analysis. However, this effect was seen only for the subgroup of patients who had had a total knee arthroplasty. No significant variable affecting postoperative deep-vein thrombosis in the subgroup that had been managed with hip replacement was identified with regression analysis.

The mechanism by which autologous donation appears to protect patients from postoperative deep-vein thrombosis in this population is uncertain. Blood viscosity, and therefore blood flow in large vessels, is primarily dependent on the hematocrit23. Preoperative donation of autologous blood decreases red blood-cell mass, as seen by the significantly lower level of hemoglobin in the patients who donated blood compared with the level in those who had not (0.132 compared with 0.140 gram per liter; F = 12.96, p < 0.001). While the average level of hemoglobin was also lower in the patients who did not later have deep-vein thrombosis, this difference reached only borderline significance (F = 3.88, p = 0.07). By substantially lowering the preoperative level of hemoglobin, donation of autologous blood may decrease viscosity, although viscosity was neither directly measured nor calculated in this study.

Several studies have supported the use of normovolemic hemodilution as a possible means of prophylaxis against deep-vein thrombosis8,42. Ernst et al.10 noted significant decreases in the viscosity of blood (p < 0.05) and plasma (p < 0.05) with hemodilution in a placebo-controlled double-blind study of twenty-four men who had peripheral vascular disease. Hemodilution effected significant improvement in claudication (p < 0.01) but no significant changes in measured clotting parameters. Repeat transfusion of donated autologous blood in the present study did not appear to reduce the beneficial effects of donation. However, the timing of the transfusion was not fully analyzed. It frequently followed the operation by one to several days, and the timing was based on postoperative hemoglobin and hematocrit values.

The preoperative donation of autologous blood did not affect the measured clotting parameter (prothrombin time) or the platelet count. However, a number of other factors that are presently being investigated with respect to thrombogenicity, such as fibrinogen degradation products, antithrombin III, tissue plasminogen activator, anti-factor Xa, and others13, were not assayed.

Finally, resistance of red blood cells to deformation, as seen in hemoglobinopathies such as hereditary spherocytosis, increases thrombogenicity. Aged erythrocytes also have been known to have increased density, viscosity, and osmotic and mechanical fragility as well as decreased deformability5. The possible effect of the donation of autologous blood on the average age of circulating red blood cells was not considered, as the reticulocyte index was not measured. However, such a hypothesis would be consistent with the significant effect seen in the patients who had a total knee replacement, which was performed with tourniquet hemostasis, and the lack of effect seen in the patients managed with total hip replacement.

Paiement et al.32 suggested that Coumadin prophylaxis with sonographic surveillance for detection of deep-vein thrombosis was theoretically cost-effective after total hip replacement. No cost analysis was performed in the present study. Specifically, the cost of collecting and transfusing autologous blood was not compared with the proposed savings attributable to a decrease in the prevalence of deep-vein thrombosis. Furthermore, the prolonged stays in both the acute and the convalescent ward of the Veterans Administration system during the study period do not reflect today's efforts at cost containment.

In summary, preoperative donation of autologous blood decreases the need for transfusion of homologous blood after elective total joint arthroplasty. This study shows an additional potential benefit of preoperative donation of autologous blood as adjunctive prophylaxis against deep-vein thrombosis in a high-risk population. We do not believe that autologous donation alone is sufficient for prophylaxis. Both Coumadin and pneumatic compression stockings proved effective in preventing clinically important pulmonary emboli. However, in light of the ongoing search for more effective and economical prophylaxis against deep-vein thrombosis, the role of preoperative donation of autologous blood remains a potentially simple and safe adjunct to standard prophylaxis.


   Footnotes
 
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

{dagger}Department of Orthopaedic Surgery, University at Buffalo, State University of New York, 462 Grider Street, Buffalo, New York 14215.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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