JBJS | Current Concepts Review - Blood Transfusion in Orthopaedic Operations*

The Journal of Bone & Joint Surgery, Volume 78, Issue 8

Current Concepts Review | August 01, 1996

Current Concepts Review - Blood Transfusion in Orthopaedic Operations*

MARK J. LEMOS, M.D.†; WILLIAM L. HEALY, M.D.†, BURLINGTON, MASSACHUSETTS

*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.

The Journal of Bone & Joint Surgery. 1996; 78:1260-71

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Introduction

The use of blood transfusion to treat acute blood loss was first reported in the early nineteenth century when Blundell¹⁴, known by some as the father of modern autologous transfusion, described the reinfusion of blood resulting from postpartum hemorrhage. Homologous, now properly called allogenic, blood transfusion began in the twentieth century^22,25, after Landsteiner⁷² described blood groups in 1901. In 1937, Cook County Hospital in Chicago opened the first hospital blood bank in order to deal with the increasing demand for blood transfusion. The success of blood transfusion in resuscitating victims of trauma during World War II popularized transfusion for the treatment of blood loss in elective operative procedures after the war.

Blood banks and allogenic blood components have had an important impact on operative treatment and health care worldwide. Resuscitation after trauma, radical operations for the treatment of cancer, coronary artery bypass grafting, and transplantation of major organs became not only possible but routine because of the availability of allogenic blood and blood products. However, blood transfusion has been limited by the availability of donor blood.

In the 1950's and 1960's, allogenic blood was usually available to meet the demand for blood transfusion, and its use was considered safe according to medical knowledge at that time. Blood donors were usually laborers and factory workers. During the 1970's, this population decreased, as did the availability of allogenic blood, and the demand for blood increased simultaneously. The blood-donor population decreased further in the 1980's, when a general fear of acquiring transmissible diseases was prevalent and donors began to be tested for such diseases, including hepatitis and acquired immunodeficiency syndrome. From 1981 to 1990, the demand for blood transfusion increased 100 per cent, whereas the collection of blood increased only 30 per cent⁶⁶.

In the 1990's, the risks of allogenic blood transfusion have become well known to physicians and patients²⁶. These risks include the transmission of hepatitis and human immunodeficiency virus, as well as various reactions to transfusion. Cognizant of these risks, patients and surgeons have carefully scrutinized the indications for and the safety of blood transfusion. In the current review, the use of blood transfusion and its alternatives in association with orthopaedic operations will be discussed.

†Department of Orthopaedic Surgery, Lahey Hitchcock Medical Center, 41 Mall Road, Burlington, Massachusetts 01805. Please address requests for reprints to Dr. Healy.

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TABLE I ROUTINE SCREENING PRACTICES FOR ALLOGENIC BLOOD DONATION⁶⁶

Blood Test	Disease to Be Detected
Human immunodeficiency virus-1, human immunodeficiency virus-2	Acquired immunodeficiency syndrome
Human T-cell leukemia/lymphoma virus-1	Human T-cell leukemia/lymphoma virus or human T-cell leukemia/lymphoma virus-1-associated myelopathy
Hepatitis B Ag	Hepatitis B
Hepatitis B core Ab	Non-A, non-B hepatitis
Serum alanine transaminase	Hepatitis
Hepatitis C Ab	Hepatitis C
Syphilis serology	Syphilis

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TABLE I ROUTINE SCREENING PRACTICES FOR ALLOGENIC BLOOD DONATION⁶⁶

Blood Test	Disease to Be Detected
Human immunodeficiency virus-1, human immunodeficiency virus-2	Acquired immunodeficiency syndrome
Human T-cell leukemia/lymphoma virus-1	Human T-cell leukemia/lymphoma virus or human T-cell leukemia/lymphoma virus-1-associated myelopathy
Hepatitis B Ag	Hepatitis B
Hepatitis B core Ab	Non-A, non-B hepatitis
Serum alanine transaminase	Hepatitis
Hepatitis C Ab	Hepatitis C
Syphilis serology	Syphilis

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TABLE II RISKS RELATED TO TRANSFUSION OF ALLOGENIC BLOOD

*As reported in the study by AuBuchon et al.⁶.†As reported in the study by the Centers for Disease Control²⁰.‡As reported in the study by Dodd²⁶§As reported in the study by Fernandez et al.⁴³.

Risk	Prevalence
Transfusion reaction	5 per cent*
Fatal hemolytic	<1:1,000,000*
Non-fatal hemolytic	1:25,000*
Fever or urticaria	1 to 3:100*
Transmission of disease
Human immunodeficiency virus-1	1:200,000 to 1:800,000†
Hepatitis B	1:200,000‡
Hepatitis C	1:3000 to 1:5000‡
Immunomodulation
Infection	20 to 25 per cent increase postoperatively§
	postoperatively§

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TABLE II RISKS RELATED TO TRANSFUSION OF ALLOGENIC BLOOD

Risk	Prevalence
Transfusion reaction	5 per cent*
Fatal hemolytic	<1:1,000,000*
Non-fatal hemolytic	1:25,000*
Fever or urticaria	1 to 3:100*
Transmission of disease
Human immunodeficiency virus-1	1:200,000 to 1:800,000†
Hepatitis B	1:200,000‡
Hepatitis C	1:3000 to 1:5000‡
Immunomodulation
Infection	20 to 25 per cent increase postoperatively§
	postoperatively§

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TABLE III NORMAL RANGES FOR HEMATOCRIT AND HEMOGLOBIN*⁷¹

*All values were determined with use of a five-milliliter lavender-top tube containing ethylenediaminetetra-acetic acid.

Age	Hematocrit	Hemoglobin
	(Per cent)	(g/L)
Boys
17 yrs.	42—52	135—170
16 yrs.	40—51	132—170
12 yrs.	37—46	122—154
8 yrs.	35—44	116—147
4 yrs.	34—43	110—143
2 yrs.	33—43	110—142
1 yr.	33—42	—
9 mos.	35—42	—
6 mos.	34.5—42	110—140
3 mos.	31—37	110—142
1 mo.	32—43	110—143
<1 mo.	No reference range	No reference range

Girls
17 yrs.	36—50	120—160
16 yrs.	—	120—154
12 yrs.	36—46	120—152
8 yrs.	35—44	117—148
2 yrs.	33—43	110—142
1 yr.	33—42	110—140
9 mos.	—	110—139
6 mos.	35—42	110—140
3 mos.	31—37	110—142
1 mo.	33—43	110—143
<1 mo.	No reference range	No reference range

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TABLE III NORMAL RANGES FOR HEMATOCRIT AND HEMOGLOBIN*⁷¹

*All values were determined with use of a five-milliliter lavender-top tube containing ethylenediaminetetra-acetic acid.

Age	Hematocrit	Hemoglobin
	(Per cent)	(g/L)
Boys
17 yrs.	42—52	135—170
16 yrs.	40—51	132—170
12 yrs.	37—46	122—154
8 yrs.	35—44	116—147
4 yrs.	34—43	110—143
2 yrs.	33—43	110—142
1 yr.	33—42	—
9 mos.	35—42	—
6 mos.	34.5—42	110—140
3 mos.	31—37	110—142
1 mo.	32—43	110—143
<1 mo.	No reference range	No reference range

Girls
17 yrs.	36—50	120—160
16 yrs.	—	120—154
12 yrs.	36—46	120—152
8 yrs.	35—44	117—148
2 yrs.	33—43	110—142
1 yr.	33—42	110—140
9 mos.	—	110—139
6 mos.	35—42	110—140
3 mos.	31—37	110—142
1 mo.	33—43	110—143
<1 mo.	No reference range	No reference range

Allogenic Blood Transfusion

Utilization

The use of allogenic blood components in elective operative procedures varies from specialty to specialty. In orthopaedic operations, packed red blood cells are the most common unit of transfusion. These cells are available in units of 225 to 300 milliliters and are composed of concentrated erythrocytes, leukocytes, and platelets in about eighty milliliters of plasma and anticoagulant. Usually, 100 milliliters of normal saline solution with adenine is combined with the packed red blood cells and plasma to increase the shelf life to forty-two days. Allogenic blood is carefully screened according to standards established by the American Association of Blood Banks⁶⁶ (Table I).

Transfusion with packed red blood cells is used to increase the oxygen-carrying capacity of blood in patients who have anemia. Packed red blood cells should not be used as a volume expander, a hematinic, or an enhancer of wound-healing¹¹⁰. Surgeons have other options in their armamentarium when dealing with these problems. A blood hemoglobin level as low as seventy grams per liter or less may meet physiological requirements in patients who have adequate intravascular volume for adequate tissue perfusion^18,111.

Reactions to Transfusion

The most common reaction to blood transfusion is a febrile response associated with chills and generalized discomfort or even severe pain. Febrile reactions, which occur after 1 to 3 per cent of approximately four million allogenic transfusions done each year, can be caused by an antibody response against leukocytes in the donated blood⁵¹. These febrile reactions can be minimized by using an absorptive leukocyte filter when a transfusion is performed. Such filters remove 99 per cent of donor white blood cells, decreasing the potential for a febrile reaction^6,74,102. Bacterial contamination should be considered in all patients who have a severe febrile reaction associated with hypotension¹¹⁰ (Table II).

A less common reaction to transfusion is an allergic or immune response to donated blood, which produces chills, fever, and urticaria. This reaction is usually seen in patients who have an IgA deficiency; rarely, it progresses to anaphylaxis. The occurrence of allergic hypersensitivity reactions is related to cumulative exposure. Each unit of transfused blood products confers one donor exposure to the recipient^51,95. Immune reactions, which can be immediate or delayed, may cause no symptoms and thus may go undetected, compromising future transfusions. These responses occur in approximately 5 per cent of the approximately four million patients who have a blood transfusion each year⁶. It is important for surgeons who order allogenic transfusions to understand that immune reactions can occur even with sophisticated cross-matching techniques^51,95.

Immediate hemolysis is a serious and sometimes fatal reaction that occurs in association with one of every 100,000 transfusions of allogenic blood. The symptoms and physical findings include fever, chills, chest pain, circulatory collapse, hemoglobinuria, and coagulopathy^51,95. Hemolytic reactions are usually a result of incompatibility within the ABO blood group, generated by misidentification of the recipient or the donor. The management of a hemolytic crisis includes stopping the transfusion, maintaining vascular volume with administration of normal saline solution, maintaining renal output with judicious use of diuretics, and treating shock and disseminated intravascular coagulation.

Transmission of Disease

The transmission of infectious disease, including acquired immunodeficiency syndrome and hepatitis, is the most feared risk associated with the transfusion of allogenic blood⁴. The reported risk of transmission is one in 200,000 to one in 800,000 for the human immunodeficiency virus²⁰, one in 200,000 for hepatitis B²⁶, and one in 3000 to one in 5000 for hepatitis C²⁶ (Table II). Other infectious diseases associated with transfusion of allogenic blood include human T-cell lymphotrophic virus²⁶, human immunodeficiency virus-2⁶⁶ (thirty-one cases as of July 1991), malaria⁶⁶ (one in 1,000,000), cytomegalovirus, babesiosis, toxoplasmosis, and Chagas disease. These diseases, which are rare in the United States, are more common in third-world countries^29,110.

Schreiber et al.¹⁰³ recently reported on 586,507 individuals who had each donated blood more than once (a total of more than two million donations of allogenic blood), at five different blood centers, between 1991 and 1993. During the so-called infectious window, the risk associated with units that had passed all screening tests was one in 493,000 (95 per cent confidence interval) for the human immunodeficiency virus, one in 641,000 for the human T-cell lymphotrophic virus, one in 113,000 for the hepatitis-C virus, and one in 63,000 for the hepatitis-B virus. The hepatitis-B and C viruses accounted for 88 per cent of the over-all aggregate risk of one in 34,000. Schreiber et al. concluded that these risks will decrease even more with the availability of new screening tests.

The transmission of acquired immunodeficiency syndrome is the greatest fear among patients who receive allogenic blood. The retrovirus of acquired immunodeficiency syndrome, human immunodeficiency virus-1, was responsible for 140,822 reported clinical cases of acquired immunodeficiency syndrome through July 1990²⁰. Of these infections, 4609 (3 per cent) were acquired through exposure to blood products²¹. Routine screening of blood for antibody to human immunodeficiency virus-1 became standard practice at blood banks in April 1985. Currently, screening for human immunodeficiency virus includes analysis for antibodies to human immunodeficiency virus-1; more specific detection of human immunodeficiency virus-1 antigen and culture techniques¹⁰⁹ are being developed. These tests, along with more rigorous screening of personal and medical histories, have reduced the risk of transmission of acquired immunodeficiency syndrome through transfusion of blood products²⁶.

Hepatitis usually presents clinically as a mild episode of jaundice and malaise, but it can progress to liver failure and death. As perceived by most patients, the risk of contracting hepatitis is overshadowed by the risk of contracting acquired immunodeficiency syndrome. However, the risk of contracting hepatitis from blood transfusion is greater than that of contracting acquired immunodeficiency syndrome¹⁹. Carson et al.¹⁹ used a decision-analysis technique to estimate the risk of death from human immunodeficiency virus or hepatitis C after transfusion. Hepatitis C accounted for 98 per cent of deaths and human immunodeficiency virus, for less than 1 per cent. Recent screening tests for hepatitis C have decreased the risk of contracting hepatitis from transfusion (from one in 500 to one in 3000 to 5000), but the risk still exceeds the risk of contracting the human immunodeficiency virus¹⁹.

Immunomodulation

Immunomodulation, or alteration of the immune system, may prove to be the greatest potential hazard for a recipient of allogenic blood⁹⁶. Systemic immunosuppression associated with changes in cellular and humoral responses has been documented after transfusion of allogenic blood in several animal studies^17,125. Specific immunomodulatory effects include altered function of macrophages, abnormal migration of cells, suppression of the lymphocytic response to antigens, and a decreased ratio of helper to suppressor T-cells^{2,12,15,42,47,63,94,98,119,125}. The quantity and quality of physiological changes associated with immunomodulation after blood transfusion remain to be defined.

It has been suggested that transfusion of allogenic blood is an independent predictor of an increased risk for the development of postoperative infection¹¹⁸. Investigators have reported that the number of postoperative infections after transfusion of allogenic blood is fourfold to tenfold greater than that after transfusion of autologous blood^13,43,85,88. Other studies have not demonstrated an increased rate of infection¹²¹ or suppressed function of the immune system¹¹⁵ in association with transfusion of allogenic blood. The possible immunomodulatory effect of transfusion of allogenic blood and the potential for an increased rate of infection suggest that surgeons should use allogenic blood as infrequently as possible.

Alternatives to the Transfusion of Allogenic Blood

In consideration of the risks associated with the transfusion of allogenic blood, surgeons have pursued alternative methods for dealing with blood loss¹¹³. Spence et al.¹¹⁰ described four measures to improve the safety of the blood supply: screening of donors, laboratory testing, inactivation of viruses, and rational use of allogenic blood. Whereas the blood bank is in control of the first three measures, the surgeon makes the decision concerning rational use of transfusion, on the basis of hemoglobin and hematocrit values⁷¹ (Table III) as well as other factors.

Reduction of Use

The most effective way to reduce the use of blood transfusion at the time of operations is to control the amount of blood loss. Methods of accomplishing this include careful operative exposure through avascular tissue planes, meticulous hemostasis, and judicious use of intravascular volume replacement with crystalloid and colloid solutions.

Approximately twenty million blood components are transfused to approximately four million patients in the United States each year, and many of these units are given during an operation¹¹². Most surgeons and anesthesiologists request cross-matching of the number of blood units that will permit a surplus of blood for their needs. This request is usually based on previous patterns of practice rather than on the acute clinical requirement. It has been demonstrated that the Maximum Surgical Blood Ordering Schedule is a cost-effective approach to determining blood requirements for operative procedures while maintaining safety standards for patients⁷⁷. With this schedule, operative procedures are matched with the maximum number of units of blood to be cross-matched before the operation; the goal is to make preoperative orders for blood coincide with actual use. The Schedule is determined jointly by the blood bank and the surgeon, on the basis of actual practice and information from the literature. The advantage of this system is that it permits blood banks to improve efficiency by preparing blood as soon as an operation is scheduled, thus reducing unnecessary cross-matching and waste.

When blood is cross-matched for a patient it is taken out of the general blood-bank pool and reserved for that patient for forty-eight hours. To maintain the inventory of fresh blood and to avoid waste, the oldest safe blood in the blood bank is used for cross-matching. If cross-matched blood that is being reserved for a specific patient outlives its expiration date (forty-two days) before it is used, it cannot be put back into the blood bank. In this situation, the blood is discarded and therefore wasted. The Maximum Surgical Blood Ordering Schedule is an attempt to prevent this from happening.

The Maximum Surgical Blood Ordering Schedule program monitors the ratio of cross-matches to transfusions in the blood bank. An optimum cross-match-to-transfusion ratio is 2.5:1 or lower. When the ratio for a specific type of operation is consistently found to be greater than 5:1, that procedure will require only typing and screening in the future. Lowery and Clark⁷⁷ compared data for hospitals that used the Maximum Surgical Blood Ordering Schedule with those for hospitals that did not. The cross-match-to-transfusion ratio decreased from 5:1 to 2:1 with implementation of the Schedule, resulting in an annual savings of more than $110,000 for each institution⁷⁷.

Operative Planning

Operative planning for the potential use of blood transfusion begins with the preoperative visit. If appropriate, a medical evaluation should be performed. Blood dyscrasias, anemias, and coagulopathies should be identified and treated.

Careful preoperative planning can decrease blood loss. Such planning includes reviewing the procedure and having instruments available to permit the procedure to move along efficiently. During the operation, careful hemostasis and efficient use of time can reduce the loss of blood. Operative approaches that involve dissection through tissue planes conserve blood. Judicious use of collagen pads, thrombin powders, and fibrin glue can be effective. However, fibrin glue is a pooled blood product derived from multiple donors, and its use is associated with some of the risks that have been associated with the transfusion of allogenic blood⁶⁹.

The choice of anesthetic can influence blood loss during the operation. Nelson and Bowen⁹⁰ used hypotensive anesthesia in 100 Jehovah's Witnesses during primary total hip replacement and found that the intraoperative loss of blood was reduced by 40 per cent compared with that in matched controls.

During joint-replacement procedures, fixation of the implant, use of a tourniquet, and continuous passive motion have varied effects on blood loss. Fixation of the implant with cement is associated with decreased loss of blood compared with the blood loss associated with porous-ingrowth or press-fit fixation¹⁰⁵. Lotke et al.⁷⁶ showed that intraoperative release of the tourniquet coupled with immediate continuous passive motion after the operation led to increased loss of blood associated with total knee arthroplasty; however, those authors were unable to separate the factors statistically. The patients with the least blood loss had had the tourniquet released after application of a compressive dressing and a protective splint without immediate continuous passive motion⁷⁶.

Pharmacological Agents

Several pharmacological agents have been used to reduce blood loss and decrease the need for replacement. Vasopressin or its analogue, desmopressin, induces increased levels of factor VIII in the blood, which theoretically reduces blood loss during operations. In a prospective randomized double-blind study, Karnezis et al.⁶⁴ found that vasopressin had no effect on the requirements for blood transfusion in total joint arthroplasty. In contrast, Johnson and Murphy⁶² reported a decrease in blood loss in association with lumbar arthrodesis when vasopressin was used. More research is required before recommendations regarding these agents can be made. Other agents that may reduce intraoperative blood loss include ?-aminocaproic acid, aprotinin, pentoxifylline, prostacyclin, and bombesin^23,99,110.

Erythropoietin is a natural glycoprotein that is a powerful stimulator of erythropoiesis. Natural erythropoietin is secreted by the kidney in response to hypoxemia and hemorrhagic stress. It binds to erythropoietin receptors in erythroblast cell membranes in the bone marrow and stimulates the production of red blood cells⁴⁴. Recombinant human erythropoietin is identical in its amino acid sequence to human erythropoietin and has been approved by the Food and Drug Administration for use in patients who have anemia associated with renal failure, acquired immunodeficiency syndrome, and non-myeloid malignant disease¹¹⁰. Erythropoietin has been studied for its potential to decrease the need for allogenic transfusion during and after operations^38,92,111. Several authors^{48,84,101,114} demonstrated that erythropoietin can maintain the hemoglobin level and hematocrit during the preoperative period, before donation of blood for autologous transfusion during and after total joint arthroplasty. Those authors also documented that erythropoietin permits safe predonation of more blood than can be predeposited without it. The use of erythropoietin has not been approved by the Food and Drug Administration for programs for the predonation of autologous blood, and the cost of erythropoietin is high¹¹⁰. Erythropoietin has been used successfully before total joint-replacement operations to potentiate erythropoiesis in Jehovah's Witnesses^90,91. Weekly doses of erythropoietin at our hospital cost more than $200.00 each, exclusive of professional and administrative costs. Erythropoietin is not currently recommended for use in routine orthopaedic procedures.

Blood Substitutes

Blood substitutes are being developed to supplement the volume of blood and to assist in the transport and delivery of oxygen. Colloid substances, such as synthetic hydroxyethyl starch and albumin, increase the intravascular volume of blood and indirectly increase the delivery of oxygen. Perfluorocarbons are capable of directly increasing oxygen-carrying capacity. Fluosol, an emulsion of two perfluorocarbons (perfluorodecalin and perfluorotripropylamine), can deliver large amounts of oxygen to tissues. Potential adverse reactions to these blood substitutes include inactivation of complements, interference with the function of neutrophils, and anaphylactoid reactions⁵⁷.

There is currently no safe substitute for blood. Clinical trials of hemoglobin-derived substitutes are in their early phases, but reactions to suspected chemicals, including endotoxins, impurities, nitric oxide, and oxygen-free radicals, have caused concern^40,41. The potential use of these products as true substitutes for blood will require elimination of their toxic effects and a better understanding of their chemistry and action.

Autologous Transfusion

The safest and most effective way to treat blood loss is to give a patient his or her own blood^89,124,125. This can be accomplished with preoperative donation, preoperative hemodilution, intraoperative salvage, or postoperative salvage of autologous blood. Replacement of lost blood with previously donated blood or salvaged shed blood from the patient is effective and eliminates the risk of transfusion-transmitted disease^{8,9,24,28,30-34,50,52,53,65,67,70,128}. All major problems of allogenic blood are avoided except errors associated with collection, storage, identification, and administration. A disadvantage of autologous transfusion is increased cost in certain situations.

Preoperative Donation

Preoperative donation of autologous blood is useful before elective operative procedures that have a known potential for blood loss, such as spinal arthrodesis and joint replacement. The advantages include decreased use of banked blood, a decrease in erythrocyte mass and in loss of erythrocytes at the time of the operation, and stimulation of erythropoiesis. Predeposited autologous blood is collected, tested, and typed. It is transfused only to the patient from whom it was obtained. If this blood is not used, it is discarded.

The process of donating and transfusing autologous blood is not without limitations. The criteria for the predonation of autologous blood are not the same as those that apply to the donation of allogenic blood. In a review of twenty-five non-hospital blood centers, 5660 individuals who had donated autologous blood preoperatively were evaluated and 16 per cent did not meet the criteria for safe allogenic donation⁵. The American Association of Blood Banks has extensive criteria for the acceptance of both allogenic and autologous blood donation¹²⁴. The criteria for allogenic blood donation include a hemoglobin level of more than 125 grams per liter; an age of more than seventeen years; a weight of more than fifty kilograms; and negative results on testing for hepatitis, syphilis, and human immunodeficiency virus. No definitive criteria for age or weight have been established for autologous donation, and individuals are not tested for transmissible diseases. The hemoglobin level should exceed only 110 grams per liter¹²⁴. Adverse outcomes from autologous transfusion are less frequent when donors meet the criteria for allogenic donation. AuBuchon and Popovsky⁵ noted a 2.7 per cent prevalence (129 of 4774) of adverse reactions after autologous transfusion in patients who met the standard requirements for allogenic donation and a 4.3 per cent prevalence (thirty-eight of 886) in those who did not. An increased prevalence of adverse reactions after autologous transfusion was noted in patients less than seventeen years old, in women weighing less than 110 pounds (49.9 kilograms), and in patients who had a history of reactions to transfusion. Additionally, coronary artery disease, which results in a decreased ability to perfuse tissues secondary to diminished cardiac reserve, accounts for 12 to 30 per cent of adverse reactions to predeposited donations⁵.

Predeposited autologous blood is not available to all patients who have an orthopaedic operation¹⁰⁶. An emergency operation eliminates predonation as an option. Also, a level of hemoglobin of 110 grams per liter is required for most programs for the predonation of autologous blood, and 10 to 15 per cent of patients who are referred for predonation have an insufficient level of hemoglobin⁴⁹. Goodnough and Brittenham⁴⁹ reported that fifteen of forty-five female patients could not predonate blood because of decreased iron stores and erythrocyte mass.

Relative contraindications to predonation of autologous blood include cardiac dysrhythmia, congestive heart failure, myocardial infarction within the previous six months, angina, seizures, cardiovascular disease, and labile hypertension¹²³. Even in the presence of these conditions, predonation can be successful if the hemodynamic status of the patient is monitored carefully. No increased risk is associated with preoperative donation of autologous blood by patients who have cancer⁷³.

The availability of programs for the predonation of autologous blood is well known to the general public, and many patients request the opportunity to donate their own blood before an elective operation. This practice contributes to wasted autologous blood and extra cost. Renner et al.⁹⁷, in a study of 612 hospitals, found that 23.5 per cent of autologous blood was donated for procedures for which the chance of transfusion was less than 10 per cent. The Maximum Surgical Blood Ordering Schedule program⁷⁷ recommends typing and screening but not obtaining autologous blood for procedures for which the cross-match-to-transfusion ratio is greater than 5:1. Currently, 50 per cent or more of predonated autologous blood is discarded.

Toy et al.¹¹⁶ evaluated the underutilization of predonated blood in a study of 4996 patients in eighteen hospitals and found that only 5 per cent of the 1287 eligible patients had predonated blood. This represents an estimated 68 per cent increase in the use of allogenic blood¹¹⁶. Moore et al.⁸⁷ used an automated referral program for their orthopaedic patients, all of whom were screened for autologous donation at the time that the operation was scheduled. Of the 328 possible candidates, 269 (82 per cent) were assessed; 230 (86 per cent) used only autologous blood, compared with fifty-eight (26 per cent) of 220 patients in a control, non-screened group. This screening led to a 78 per cent utilization of predonated blood, with 526 of 675 units that had been collected being transfused. With use of a physician referral system rather than an automated referral system, the rate of utilization of predonated blood at our institution was 61 per cent in 1994; this rate was higher than that in the control group of Moore et al., but it did not equal that in their group that had had automated referral.

In 1995, Etchason et al.³⁵ used a decision-analysis model to evaluate the cost-effectiveness of preoperative donations of autologous blood. They found a substantial increase, ranging from $68.00 to $4783.00, in the cost of autologous blood per unit transfused. Those authors concluded that, given the improved safety of allogenic transfusion, the increased protection afforded by use of autologous blood is limited and may not justify the increased cost.

The use of predeposited autologous blood has resulted in a 30 to 50 per cent reduction in the use of allogenic blood^{55,59,110,120,126,127}. On the basis of our evaluation of the available data, our hospital has adopted a practice of using Maximum Surgical Blood Ordering Schedule guidelines to determine the amount of blood to be predonated for each orthopaedic operation. Patients are referred by surgeons, and eligible patients donate one unit a week as necessary before the operation. Supplementation with iron is recommended. We do not use other pharmacological agents in our program for the predeposition of autologous blood.

There is a cost for the collection, testing, and typing of predeposited autologous blood. It has been our experience that the cost of collecting such blood is less than that of collecting allogenic blood. However, we have also found that the use of predeposited autologous blood can be more expensive per unit than that of allogenic blood because of the considerable waste associated with predeposited autologous blood. Furthermore, when predeposited autologous blood is donated elsewhere and shipped to our hospital at the time of the operation, the cost of administration and transportation may make it more expensive than allogenic blood.

Preoperative Hemodilution

Normovolemic hemodilution is a process of diluting the concentration of erythrocytes without reducing the intravascular volume. This technique is performed in the operating room after the induction of anesthesia. As many as four units of whole blood can be removed, stored temporarily, and replaced with crystalloid or colloid solution. This process results in a 20 to 30 per cent decrease in the hematocrit. The hemodynamic effects of normovolemic hemodilution include increased cardiac output secondary to decreased viscosity and increased venous return. Cardiac disease may be affected by hemodilution because of the increased demand on myocardial tissue.

In a randomized study for the comparison of hemodilution with autologous predonation, Ness et al.⁹² demonstrated that the two techniques were equally effective in reducing the need for allogenic blood. Currently, hemodilution is used extensively in cardiothoracic and urological operations, and it has the potential for benefiting patients who have orthopaedic operations as well.

Intraoperative Salvage of Blood

The intraoperative salvage of shed blood from the drainage of wounds, with subsequent reinfusion, has been shown to be a successful method of blood replacement^36,39. Blood can be salvaged intraoperatively either with systems that collect and reinfuse whole blood or with those that collect, wash, and reinfuse packed red blood cells.

When whole blood is collected for reinfusion intraoperatively, it is suctioned from the wound and deposited in a collection and reinfusion device. The shed blood is anticoagulated with heparin or citrate-phosphate-dextrose solution, and the salvaged blood is filtered and reinfused into the patient. This shed whole blood contains erythrocytes, platelets, fibrinogen, and clotting factors^{104,107,108,117}.

Intraoperative shed blood may also be salvaged with devices such as the Cell Saver (Haemonetics, Braintree, Massachusetts). The shed blood is washed and spun to remove cellular debris, hemolytic byproducts, anticoagulants, complement, fat, bone fragments, methylmethacrylate monomer, plasma hemoglobin, fibrin degradation products, D-dimer, and byproducts of platelet and complement activation. The shed blood is filtered and reinfused as packed red blood cells. The Cell Saver can also be used in the recovery room to wash and spin shed blood from suction catheters used to drain wounds^46,54. The rate of salvage of red blood cells is 50 to 60 per cent when these techniques are applied meticulously⁷⁹.

The efficacy of use of intraoperative washed autologous shed blood for transfusion in total joint arthroplasty was demonstrated by Semkiw et al.¹⁰⁵. This type of blood replacement is recommended for orthopaedic operative procedures in which blood loss is expected to be greater than 900 milliliters⁴⁶. Systems that deliver intraoperative shed whole blood to patients are simpler and less expensive to use than those that wash blood. Systems without washing collect blood by means of a suction device that adds either heparin or citrate-phosphate-dextrose anticoagulant to a collection chamber. These systems have the advantages of technical simplicity, low cost, and availability and do not require a trained perfusionist¹²³.

Postoperative Salvage of Blood

The postoperative salvage of shed blood for blood replacement has also been shown to decrease the need for allogenic blood in total joint arthroplasty^45,60,61. However, the use of unwashed autologous shed blood from wound drainage for transfusion after orthopaedic operations is controversial⁷⁸. Drainage from orthopaedic wounds may be contaminated by fat particles, bone fragments, or methylmethacrylate monomer in addition to the vasoactive mediators, clotting factors, fibrin degradation products, and free hemoglobin that accompany a healing wound. Shed blood is deficient in coagulation factors and platelets, and it may contain increased levels of free hemoglobin and fibrin degradation products from hemolysis and lysis of clots³⁹. Byproducts of platelet and complement activation also are present in shed blood^12,79,81,83.

The clinical efficacy of postoperative autologous transfusion with unwashed shed blood has been demonstrated by Blevins et al.¹¹, Faris et al.³⁹, Groh et al.⁵⁸, Healy et al.⁶⁰, and Martin et al.⁸². Those authors evaluated collection and reinfusion devices that obtained shed blood from wound-suction catheters after total hip arthroplasty, total knee arthroplasty, and operations on the spine. In each study, unwashed shed blood effectively replaced lost blood and reduced the need for transfusion of allogenic blood.

Autologous transfusion with unwashed shed blood was evaluated by Healy et al.⁶⁰, who found it to be safe when one or two units was reinfused within four to six hours after the beginning of collection. However, questions regarding safety persist. Other authors^27,39 have reported febrile reactions in association with reinfusion of unwashed autologous shed blood. These fevers have not been associated with transfusion reactions, renal injury, or coagulopathy. Unwashed shed blood may contain soluble products such as vasoactive agents and free hemoglobin, which may cause adverse effects such as hypotension or hyperthermia. Clements et al.²¹ reported hypotension (immediate [two patients] and delayed) and hyperthermia in association with postoperative reinfusion of unwashed shed blood. To avoid these potential problems, autologous transfusion with unwashed shed blood should be limited to two units, which should be reinfused within six hours after the commencement of collection. The use of an anticoagulant is not necessary^11,21,38.

Another controversy regarding unwashed autologous shed blood has centered around the clotting factors^27,86. Liquid-preserved allogenic banked blood or autologous predeposited blood contains decreased levels of labile clotting factors, such as factor V and factor VIII. In contrast, autologous shed blood contains increased levels of thrombin, D-dimer, and fibrin degradation products. This raises the question of whether clotting abnormalities might accompany reinfusion of unwashed autologous shed blood. However, the authors of several clinical reports^{3,7,10,11,39,58,60,82} have suggested that the reinfusion of unwashed filtered autologous shed blood is not associated with coagulopathy or bleeding disorders.

Relative contraindications to the use of shed blood for autologous transfusion include infection and tumor, although salvaged blood has been safely reinfused in the presence of these conditions^93,122. Bacterial cultures of specimens of shed blood from non-infected patients have been found to be positive despite washing and filtering of the blood¹⁶. Staphylococcus aureus grew on culture of washed shed blood from 12.7 per cent of 401 non-infected patients who had had a cardiac operation and prophylactic management with antibiotics³⁷. The addition of cefoxitin, ampicillin, gentamicin, and clindamycin to shed blood has been demonstrated to decrease bacterial counts¹⁰⁰.

The largest series on the contamination of shed blood with tumor cells (from transitional-cell carcinoma of the bladder and renal-cell carcinoma) was reported by Klimberg⁶⁸. The rate of local recurrence or metastasis was the same for patients who had received salvaged shed blood and those who had not received it. The presence of bacterial contamination or tumor load in salvaged blood has not been shown to increase the risk of infection or the recurrence of tumor; thus, these conditions should be considered relative contraindications.

Indications for Transfusion

The indications for postoperative transfusion involve multiple factors. According to the traditional ten/thirty rule, transfusion is recommended when the level of hemoglobin is less than ten grams per deciliter (110 grams per liter) or the hematocrit is less than 30 per cent. This rule was questioned at the National Institutes of Health Consensus Development Conference⁸⁹ in 1988. The recommendation at the Conference was for a lower level of hemoglobin (eighty grams per liter) as the indication for transfusion, and it was suggested that decisions regarding transfusion should include an assessment of clinical needs and symptoms rather than be based on laboratory values alone⁸⁹.

Spence et al.¹¹⁰ proposed two important concepts for determining the need for transfusion: the optimum and minimum acceptable hemoglobin level and hematocrit. The traditional ten/thirty rule for transfusion originated when Adams and Lundy¹, in 1942, recommended that all patients who have a level of hemoglobin of less than ten grams per deciliter before the operation have preoperative transfusion. This suggestion was based on clinical experience and the physiology of the transport and release of oxygen but not on scientific studies¹. Since then, many physicians have shown that patients can survive with levels of hemoglobin as low as five and one-half grams per deciliter (fifty-five grams per liter)^{18,56,110,111}. Much information on this subject has come from the treatment of Jehovah's Witnesses.

Current data are inadequate for us to recommend a specific indication for transfusion in orthopaedic operations. Moreover, the human body is a dynamic system, and an appropriate indication for transfusion for one patient may be inappropriate for another. For example, patients who have chronic renal failure may be able to tolerate a hemoglobin level as low as sixty grams per liter, but they may not tolerate a decrease as large as one tolerated by patients who had a normal level of hemoglobin (150 grams per liter). A decision to transfuse must be accompanied by consideration of the initial level of hemoglobin along with any change in the level and the interval during which the change occurred.

A reliable indication for transfusion cannot be a static number. In deciding whether to transfuse, we assess the underlying health of the patient, the rate of change in the level of hemoglobin, the absolute level of hemoglobin, and the development of cardiovascular symptoms such as shortness of breath, angina, postural hypertension, and dizziness.

The treatment of blood loss in association with orthopaedic operations is based on the concept of conservation of blood in conjunction with safe, reliable replacement of blood to facilitate resuscitation and recovery. This is achieved by a combination of preoperative medical evaluation to determine the needs and risks associated with blood transfusion in the patient, minimization of the use of allogenic blood, preoperative donation of autologous blood, minimization of the intraoperative loss of blood, and salvage of intraoperative and postoperative shed blood for autologous transfusion.

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Saikawa, I.; Hotokebuchi, T.; Arita, C.; Inaba, S.; Shuto, T.; Tsutsui, H.; and |and |Sugioka, Y.: Autologous blood transfusion with recombinant erythropoietin treatment. 22 arthroplasties for rheumatoid arthritis. Acta Orthop. Scandinavica,65: 15-19, 1994.6515 1994 [CrossRef]

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Sayers, M. H.; Anderson, K. C.; Goodnough, L. T.; Kurtz, S. R.; Lane, T. A.; Pisciotto, P.; and |and |Silberstein, L. E.: Reducing the risk for transfusion-transmitted cytomegalovirus infection. Ann. Intern. Med.,116: 55-62, 1992.11655 1992 [PubMed]

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Semkiw, L. B.; Schurman, D. J.; Goodman, S. B.; and |and |Woolson, S. T.: Postoperative blood salvage using the Cell Saver after total joint arthroplasty. J. Bone and Joint Surg.,71-A: 823-827, July 1989.71-A823 1989

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Topics

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TABLE I ROUTINE SCREENING PRACTICES FOR ALLOGENIC BLOOD DONATION⁶⁶

Blood Test	Disease to Be Detected
Human immunodeficiency virus-1, human immunodeficiency virus-2	Acquired immunodeficiency syndrome
Human T-cell leukemia/lymphoma virus-1	Human T-cell leukemia/lymphoma virus or human T-cell leukemia/lymphoma virus-1-associated myelopathy
Hepatitis B Ag	Hepatitis B
Hepatitis B core Ab	Non-A, non-B hepatitis
Serum alanine transaminase	Hepatitis
Hepatitis C Ab	Hepatitis C
Syphilis serology	Syphilis

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TABLE I ROUTINE SCREENING PRACTICES FOR ALLOGENIC BLOOD DONATION⁶⁶

Blood Test	Disease to Be Detected
Human immunodeficiency virus-1, human immunodeficiency virus-2	Acquired immunodeficiency syndrome
Human T-cell leukemia/lymphoma virus-1	Human T-cell leukemia/lymphoma virus or human T-cell leukemia/lymphoma virus-1-associated myelopathy
Hepatitis B Ag	Hepatitis B
Hepatitis B core Ab	Non-A, non-B hepatitis
Serum alanine transaminase	Hepatitis
Hepatitis C Ab	Hepatitis C
Syphilis serology	Syphilis

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TABLE II RISKS RELATED TO TRANSFUSION OF ALLOGENIC BLOOD

Risk	Prevalence
Transfusion reaction	5 per cent*
Fatal hemolytic	<1:1,000,000*
Non-fatal hemolytic	1:25,000*
Fever or urticaria	1 to 3:100*
Transmission of disease
Human immunodeficiency virus-1	1:200,000 to 1:800,000†
Hepatitis B	1:200,000‡
Hepatitis C	1:3000 to 1:5000‡
Immunomodulation
Infection	20 to 25 per cent increase postoperatively§
	postoperatively§

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TABLE II RISKS RELATED TO TRANSFUSION OF ALLOGENIC BLOOD

Risk	Prevalence
Transfusion reaction	5 per cent*
Fatal hemolytic	<1:1,000,000*
Non-fatal hemolytic	1:25,000*
Fever or urticaria	1 to 3:100*
Transmission of disease
Human immunodeficiency virus-1	1:200,000 to 1:800,000†
Hepatitis B	1:200,000‡
Hepatitis C	1:3000 to 1:5000‡
Immunomodulation
Infection	20 to 25 per cent increase postoperatively§
	postoperatively§

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TABLE III NORMAL RANGES FOR HEMATOCRIT AND HEMOGLOBIN*⁷¹

*All values were determined with use of a five-milliliter lavender-top tube containing ethylenediaminetetra-acetic acid.

Age	Hematocrit	Hemoglobin
	(Per cent)	(g/L)
Boys
17 yrs.	42—52	135—170
16 yrs.	40—51	132—170
12 yrs.	37—46	122—154
8 yrs.	35—44	116—147
4 yrs.	34—43	110—143
2 yrs.	33—43	110—142
1 yr.	33—42	—
9 mos.	35—42	—
6 mos.	34.5—42	110—140
3 mos.	31—37	110—142
1 mo.	32—43	110—143
<1 mo.	No reference range	No reference range

Girls
17 yrs.	36—50	120—160
16 yrs.	—	120—154
12 yrs.	36—46	120—152
8 yrs.	35—44	117—148
2 yrs.	33—43	110—142
1 yr.	33—42	110—140
9 mos.	—	110—139
6 mos.	35—42	110—140
3 mos.	31—37	110—142
1 mo.	33—43	110—143
<1 mo.	No reference range	No reference range

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TABLE III NORMAL RANGES FOR HEMATOCRIT AND HEMOGLOBIN*⁷¹

*All values were determined with use of a five-milliliter lavender-top tube containing ethylenediaminetetra-acetic acid.

Age	Hematocrit	Hemoglobin
	(Per cent)	(g/L)
Boys
17 yrs.	42—52	135—170
16 yrs.	40—51	132—170
12 yrs.	37—46	122—154
8 yrs.	35—44	116—147
4 yrs.	34—43	110—143
2 yrs.	33—43	110—142
1 yr.	33—42	—
9 mos.	35—42	—
6 mos.	34.5—42	110—140
3 mos.	31—37	110—142
1 mo.	32—43	110—143
<1 mo.	No reference range	No reference range

Girls
17 yrs.	36—50	120—160
16 yrs.	—	120—154
12 yrs.	36—46	120—152
8 yrs.	35—44	117—148
2 yrs.	33—43	110—142
1 yr.	33—42	110—140
9 mos.	—	110—139
6 mos.	35—42	110—140
3 mos.	31—37	110—142
1 mo.	33—43	110—143
<1 mo.	No reference range	No reference range