Marked blood loss during lower extremity total joint arthroplasties may lead to higher rates of transfusion, which may negatively affect surgical outcomes and yield greater complication rates. It is therefore ideal to identify factors that may increase the likelihood of blood loss, so they can be modified. From this review, it can be concluded that preoperative anemia, older age, multiple comorbidities, increased operative time, and use of postoperative anticoagulation may lead to higher blood loss and transfusion rates, although the influence of other factors remains controversial.
Key points
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Preoperative anemia is one of the strongest predictors of postoperative transfusion.
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Older age, an American Society of Anesthesiologists III score or higher, and a Charlson Index greater than 3 have been associated with an increase in intraoperative blood loss as well as increased transfusion rates.
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Men have been shown to have a higher risk for blood loss with no increased risk for receiving a transfusion, likely because of a higher baseline hemoglobin level and greater reserve.
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The risk for bleeding and allogeneic transfusions appears to be complex and multifactorial in nature, and adequate preoperative preparation is necessary.
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The use of blood loss strategies, such as tranexamic acid, may reduce the role these factors play in bleeding and transfusion risk.
Introduction
Lower extremity total joint arthroplasties (TJA) have gained popularity because of their success in treating knee and hip osteoarthritis (OA); however, they can be extensive procedures that may be associated with substantial blood loss. Moreover, this blood loss can result in complications and cost increases, which may impede the success of the surgery. In particular, patients may be subject to longer hospital admissions and worse postoperative rehabilitation. As demand for these surgeries increases secondary to the increasing prevalence of the elderly and obese populations, surgeons are seeking ways to minimize these risks and ensure ongoing success.
With substantial blood loss, these patients are also at an increased risk of requiring allogeneic blood transfusions, which are associated with a new plethora of risks and costs, which include longer hospital stays, infectious disease transmission, immunologic reactions, acute lung injury, cardiopulmonary overload, hemolytic and anaphylactic reactions, and increased mortality ( Table 1 ). In addition, allogeneic blood transfusions have been shown to modify the role of host macrophages, dampen the normal lymphocytic response to antigens, and produce a decreased ratio of helper to suppressor T cells. As a result of this immunosuppressive effect, patients are placed at a higher risk of periprosthetic joint infection.
| Adverse Event | Odds (per Event) |
|---|---|
| Fever/allergic reaction | 1:200 |
| Hemolytic transfusion reactions | 1:6000 |
| Fatal hemolytic reactions | 1:1,000,000 |
| HIV infection | 1:1,900,000 |
| HBV infection | 1:180,000 |
| HCV infection | 1:1,600,000 |
| Bacterial contamination | 1:3000 |
| TRALI | 1:50,000 |
| TACO | 1:5000 |
| Anaphylaxis | 1:50,000 |
To minimize these potential dangers, it is important to understand factors that influence blood loss and subsequent transfusions. Predicting blood loss encompasses not only preoperative factors, but intraoperative and postoperative factors as well. By being able to risk-stratify patients, clinicians can limit intraoperative loss and use postoperative protocols to improve patient outcomes.
With the advent of blood management strategies, surgeons may have an opportunity to reduce blood loss and transfusion risk. In particular, tranexamic acid (TXA) has gained popularity in recent literature for significantly reducing bleeding without an increased thromboembolic risk. Consequently, the factors that influence perioperative bleeding may eventually come to play a minimal role and TXA may considerably alter transfusion evaluation and practices. However, TXA is yet to be widely adopted in orthopedic practice, and it is thought that it is still important to outline potential predictors of blood loss in lower extremity TJA.
Therefore, in this review, the purpose is to identify preoperative, intraoperative, and postoperative factors that may influence the risk of blood loss and receiving transfusions as well as to delineate the effect of TXA on bleeding and postoperative transfusion rates.
Introduction
Lower extremity total joint arthroplasties (TJA) have gained popularity because of their success in treating knee and hip osteoarthritis (OA); however, they can be extensive procedures that may be associated with substantial blood loss. Moreover, this blood loss can result in complications and cost increases, which may impede the success of the surgery. In particular, patients may be subject to longer hospital admissions and worse postoperative rehabilitation. As demand for these surgeries increases secondary to the increasing prevalence of the elderly and obese populations, surgeons are seeking ways to minimize these risks and ensure ongoing success.
With substantial blood loss, these patients are also at an increased risk of requiring allogeneic blood transfusions, which are associated with a new plethora of risks and costs, which include longer hospital stays, infectious disease transmission, immunologic reactions, acute lung injury, cardiopulmonary overload, hemolytic and anaphylactic reactions, and increased mortality ( Table 1 ). In addition, allogeneic blood transfusions have been shown to modify the role of host macrophages, dampen the normal lymphocytic response to antigens, and produce a decreased ratio of helper to suppressor T cells. As a result of this immunosuppressive effect, patients are placed at a higher risk of periprosthetic joint infection.
| Adverse Event | Odds (per Event) |
|---|---|
| Fever/allergic reaction | 1:200 |
| Hemolytic transfusion reactions | 1:6000 |
| Fatal hemolytic reactions | 1:1,000,000 |
| HIV infection | 1:1,900,000 |
| HBV infection | 1:180,000 |
| HCV infection | 1:1,600,000 |
| Bacterial contamination | 1:3000 |
| TRALI | 1:50,000 |
| TACO | 1:5000 |
| Anaphylaxis | 1:50,000 |
To minimize these potential dangers, it is important to understand factors that influence blood loss and subsequent transfusions. Predicting blood loss encompasses not only preoperative factors, but intraoperative and postoperative factors as well. By being able to risk-stratify patients, clinicians can limit intraoperative loss and use postoperative protocols to improve patient outcomes.
With the advent of blood management strategies, surgeons may have an opportunity to reduce blood loss and transfusion risk. In particular, tranexamic acid (TXA) has gained popularity in recent literature for significantly reducing bleeding without an increased thromboembolic risk. Consequently, the factors that influence perioperative bleeding may eventually come to play a minimal role and TXA may considerably alter transfusion evaluation and practices. However, TXA is yet to be widely adopted in orthopedic practice, and it is thought that it is still important to outline potential predictors of blood loss in lower extremity TJA.
Therefore, in this review, the purpose is to identify preoperative, intraoperative, and postoperative factors that may influence the risk of blood loss and receiving transfusions as well as to delineate the effect of TXA on bleeding and postoperative transfusion rates.
Preoperative factors
As with any surgery, the most important first step is a thorough history and physical examination. Understanding the physiologic demands that the surgery will place on the patient, and its relation to their preoperative hemoglobin, age, gender, weight, and underlying medical comorbidities, is essential ( Table 2 ).
| Author, Year | Number of Arthroplasties | Risk Factor | Blood Loss (Case vs Control) | P Value | LOE |
|---|---|---|---|---|---|
| Guerin et al, 2007 | 162 | Age >70 y | 850 vs 659 mL | .035 | III |
| Mesa-Ramos et al, 2008 | 121 | Increase age by 1 y | Increase by 0.314 g/dL | <.001 | II |
| Pola et al, 2004 | 85 | Age >75 y | 1741 vs 1524 mL | .07 | III |
| Mesa-Ramos et al, 2008 | 121 | Female gender | 5.46 vs 4.78 g/dL decrease in Hb | .02 | II |
| Guerin et al, 2007 | 162 | Female gender | 988 vs 780 mL (THA) and 780 vs 689 mL (TKA) | <.05 | III |
| Pola et al, 2004 | 85 | Male gender | 1797 vs 1528 mL | .04 | III |
| BMI <27 kg/m 2 | 1639 vs 1531 mL | >.05 | III | ||
| 5.2 vs 4.3 g/dL decrease in Hb | .005 | III | |||
| Prasad et al, 2007 | 66 | RA | 235 vs 216 mL | >.05 | III |
| Pola et al, 2004 | 85 | Hypertension | 1707 vs 1474 mL | .02 | III |
| Grosflam et al, 1995 | 295 | ASA >III | NR | <.05 | III |
Preoperative Hemoglobin/Anemia
Preoperative anemia has been cited in multiple articles as the strongest and most predictive factor in determining risk for postoperative transfusion ( Table 3 ).
| Author, Year | Number of Arthroplasties | Risk Factor | Relative Risk for Transfusion | P Value | LOE |
|---|---|---|---|---|---|
| Hatzidakis et al, 2000 | 489 | Hb <13 g/dL | 5.6 | <.0001 | IV |
| Guerin et al, 2007 | 162 | Hb <13 g/dL | 1.5 | .001 | III |
| Aderinto and Brenkel, 2004 | 1016 | Hb <12 g/dL | 3 | <.001 | III |
| Rosencher et al, 2003 | 3996 | Hb <8 mg/dL | NR | NR | III |
| Frisch et al, 2014 | 1573 | Increase Hb by 1 mg/dL | 0.62 | NR | III |
Hatzidakis and colleagues analyzed the incidence of transfusion in relation to preoperative hemoglobin level in 489 consecutive patients who underwent primary lower extremity TJA. They noted that patients who had a hemoglobin level of less than 13 g/dL were 5.6 times more likely to receive a transfusion than those with a hemoglobin level greater than this ( P <.0001). The investigators noted that patients who had a hemoglobin level between 13 and 15 g/dL were also at an increased risk of transfusion, with the exception of those younger than 65 years of age. However, no patient who had a hemoglobin level greater than 15 g/dL preoperatively required a transfusion. Similarly, Guerin and colleagues prospectively reported on the impact of preoperative hemoglobin on transfusion risk in 162 patients following total hip arthroplasty (THA) or total knee arthroplasty (TKA). The investigators reported that preoperative anemia (hemoglobin <13 g/dL) had a 1.5 times greater risk of receiving an allogeneic blood transfusion compared with those with levels between 13 and 15 g/dL, and a 4 times greater risk than patients with a hemoglobin level greater than 15 g/dL ( P = .001). More recently, Aderinto and Brenkle evaluated 1016 patients who underwent unilateral THA and found that a hemoglobin level less than 12 g/dL was associated with a 3-fold increase in risk of receiving allogeneic blood postoperatively ( P <.001).
In the Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study, Rosencher and colleagues collected data on 3996 patients undergoing total hip and knee arthroplasty. They reported that patients who had a preoperative hemoglobin level of 8 mg/dL had a 75% and 69% probability of receiving a transfusion for women and men, respectively ( P <.001). The same study demonstrated that in patients who had similar risk factors, but a preoperative hemoglobin level of 16 g/dL, that the probability of transfusion in men and women reduced to 13% and 7%, respectively ( P <.001). Extrapolating on their results, Mesa-Ramos and colleagues and Frisch and colleagues found that a mean increase in 1 g/dL in preoperative hemoglobin resulted in a reduced risk for transfusion (odds ratio 0.62), which highlights the importance of preoperative patient optimization.
Preoperative anemia plays an influential role on blood loss and risk of transfusion. Having knowledge of preoperative laboratory studies at least 3 weeks before can allow for adequate preparation and action, if needed.
Age
As the proportion of elderly patients undergoing lower extremity joint arthroplasty grows, one must understand how this may affect blood loss and transfusion risk. Advanced age has been associated with decreased hematopoietic activity, reduced functioning of platelets, and a diminished response from the marrow following acute blood loss. The decreased hematopoietic activity predisposes the elderly to preoperative anemia, which decreases the margin between their baseline hemoglobin and the threshold to transfuse.
Multiple studies have demonstrated a correlation between age and blood loss or risk of transfusion ( Table 4 ). In a retrospective analysis of 489 TJA patients, Hatzidakis and colleagues found that patients greater than the age of 65 years had an increased risk of transfusion (relative risk of 2.8). In addition, Browne and colleagues analyzed data collected from the US Nationwide Inpatient Sample (NIS) to assess risk factors associated with increased transfusion rates in patients who underwent THA (n = 129,901). They observed that the strongest risk factor for postoperative transfusion was increasing age, with patients greater than 85 years old at the highest risk (odds ratio 2.9).
| Author, Year | Number of Arthroplasties | Risk Factor | Relative Risk for Transfusion | P Value | LOE |
|---|---|---|---|---|---|
| Hatzidakis et al, 2000 | 489 | Age >65 y | 2.8 | NR | IV |
| Browne et al, 2013 | 129,901 | Age >85 y | 2.9 | NR | III |
| Guerin et al, 2007 | 162 | Age >70 y | NR | >.05 | III |
| Mesa-Ramos et al, 2008 | 121 | Increase age by 1 y | NR | >.05 | II |
| Pola et al, 2004 | 85 | Age >75 y | NR | >.05 | III |
Other studies have demonstrated that increasing age may be associated with higher rates of blood loss. Guerin and colleagues found that patients greater than 70 years of age who underwent TKA had significantly higher total blood loss (TBL) than those less than 70 years of age (850 vs 659 mL; P = .035). For the patients undergoing THA, there was no significant difference in blood loss between those younger or older than 70 years ( P >.05). In addition, the risk of transfusion in either cohort was not found to be associated with age.
A prospective, randomized trial of 121 TKA patients by Mesa-Ramos and colleagues concluded that for every 1-year increase in age, there was an associated increase of 0.314 g/dL in blood loss ( P <.001). However, they also noted that there was no association with age and risk of transfusion. In a study by Pola and colleagues evaluating patients who underwent THA (n = 85), they noted that patients older than 75 years of age had more blood loss compared with those who were younger, which trended toward significance (1741 mL vs 1524 mL, respectively; P = .07). In addition, they observed that there was a significant decrease in the postoperative hemoglobin in patients greater than 75 years of age (5.3 mg/dL vs 4.53 mg/dL, respectively; P = .03). However, in regards to postoperative transfusion, they found that older age independently was not a significant risk factor, yet when analyzed concomitantly with gender, hypertension, body mass index (BMI), or preoperative anemia, the risk of transfusion became significantly higher ( P = .02).
Elderly patients are at risk of greater blood loss following lower extremity TJA due to malnutrition, poor preoperative hemoglobin, and decreased intrinsic coagulation capabilities. Thus, it is essential to appropriately discuss these risks with the patient and take the appropriate steps to mitigate this factor.
Gender
Several studies have reported that women are at a higher risk for transfusion following lower extremity arthroplasty, which has been hypothesized to be due to a lower preoperative hematocrit and smaller body habitus ( Table 5 ). Frisch and colleagues, in a retrospective review of 1573 patients undergoing primary total hip and knee arthroplasty, found an overall transfusion rate of 9.27% for TKA and 26.6% for THA. From their analysis, female patients were found to have a 2.6 times higher risk of receiving a transfusion than men ( P = .001). This conclusion was supported by Browne and colleagues, who in 129,901 patients, found that women had a higher likelihood of receiving a transfusion than men after THA (odds ratio 2.1; P <.001). Furthermore, Walsh and colleagues, in evaluating 1035 patients after THA, noted that women were also almost 2 times more likely to receive a blood transfusion (relative risk 1.9; P <.01).
| Author, Year | Number of Arthroplasties | Risk Factor | Relative Risk for Transfusion | P Value | LOE |
|---|---|---|---|---|---|
| Frisch et al, 2014 | 1573 | Female gender | 2.6 | .001 | III |
| Browne et al, 2013 | 129,901 | Female gender | 2.1 | <.001 | III |
| Walsh et al, 2007 | 1035 | Female gender | 1.9 | <.01 | III |
| Mesa-Ramos et al, 2008 | 121 | Female gender | NR | >.05 | II |
| Guerin et al, 2007 | 162 | Female gender | NR | .47 | III |
| Pola et al, 2004 | 85 | Female gender | NR | .4 | III |
There are studies that reveal no gender-specific differences in transfusion rates, despite differences in blood loss. Mesa-Ramos and colleagues analyzed 121 patients undergoing unilateral TKA and found no significant difference in transfusion rates between men and women ( P >.05), although there was a significant difference in blood loss, whereby men were found to lose a mean of 5.46 g/dL and women a mean of 4.78 g/dL ( P = .02). Guerin and colleagues prospectively evaluated 162 consecutive patients, and they demonstrated that men had greater blood loss than women in both THA and TKA cohorts (988 vs 780 mL and 780 vs 689 mL, respectively; P <.05). The investigators also noted that male patients had larger decreases in postoperative hemoglobin levels ( P <.05). However, differences in postoperative transfusion rates were not significant ( P = .47).
Pola and colleagues found that men had significantly more blood loss after THA than women (1797 vs 1528 mL, respectively; P = .04). They also noted no significant differences in transfusion rates between the 2 cohorts (20 vs 30%, respectively; P = .4). The investigators concluded that there was difficulty in predicting transfusion rates in patients postoperatively, particularly in nonanemic individuals.
Men may be at risk of greater blood loss, but this does not necessarily translate into a higher risk for transfusion. This disparity may be explained by the fact that men have been shown to have higher circulating hemoglobin levels, and thus a greater reserve before reaching the transfusion threshold. Conclusively, there is still no clear evidence regarding whether there are gender-specific differences in risk for transfusion, and further evaluation is needed.
Weight/Body Mass Index
Recent data have found that approximately one-third of the population in the United States over the age of 20 is obese. Obesity has been linked to a multitude of complications associated with TJA, including infection, early failure, and wound dehiscence. Nevertheless, the effects of obesity on blood loss and transfusion rates remain debatable ( Table 6 ). Physiologically, increases in weight are known to produce a nonlinear increase in circulating blood volume. However, this should be tempered against the possibility that obesity may make surgery more difficult with associated longer operative times and greater blood loss.
| Author, Year | Number of Arthroplasties | Risk Factor | Relative Risk for Transfusion | P Value | LOE |
|---|---|---|---|---|---|
| Ahmed et al, 2012 | 227 | Weight <70 kg | 2.1 | <.001 | III |
| Aderinto and Brenkel, 2004 | 1016 | Weight <70 kg | 2.3 | <.001 | III |
| Salido et al, 2002 | 370 | Weight ≤72 kg | NR | .002 | III |
| Walsh et al, 2007 | 1035 | BMI ≥30 kg/m 2 | 0.5 | NR | III |
| Frisch et al, 2014 | 1573 | Increase BMI by 5 kg/m 2 | 0.84 | NR | III |
| Pola et al, 2004 | 85 | BMI >27 kg/m 2 | NR | .1 | III |
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