The Vermont Transfusion Project

Red Cell Transfusions in the 1990's
Maintaining Adequate Tissue Perfusion
Non-Indications and Special Considerations
Complications of RBC Transfusion
Guidelines for RBC Use
Risks and Adverse Consequences
References 

In 1998 the hospitals in the State of Vermont joined in a statewide contract for the provision of blood products with the New England region of the American Red Cross Blood Services. Included in this contract was an agreement to launch a cooperative effort, the Vermont Transfusion Project, designed to educate physicians throughout the state about the appropriate use of blood products and their risks. As part of this project the following article was written by Dr. Robert Westphal, the former Medical Director of the Vermont-New Hampshire region of the American Red Cross, in collaboration with Drs. Mark Popovsky and Mary O'Neill from the ARC and Dr. Bruce MacPherson, Medical Director of the FAHC Blood Bank. The transfusion guidelines described in this article have been presented to medical staffs throughout the state for their consideration and appear on the Blood Component Order Sheet. 

Red Cell Transfusion in the 1990's: A Reassessment of the Transfusion Trigger  

The use of red blood cell (RBC) transfusions remains an important part of medical and surgical practice. However, the AIDS epidemic of the 1980's, greater awareness of transfusion-transmitted hepatitis and a better understanding of red cell physiology have resulted in closer attention to the indications for RBC transfusion. Evidence exists that a significant proportion of RBC transfusions are not clinically indicated, and place the patient at unnecessary risk of adverse effects. A 1988 NIH consensus conference shattered the 10 g/dL (hematocrit = 30%) transfusion "trigger" that had been used for many years (1). Since then, other studies have shown that the transfusion trigger must be reassessed.The decline of the HCT = 30% threshold: Tissue oxygenation often does not improve as the hematocrit increases beyond 30% (2) A common misconception is that the delivery of oxygen to tissues increases linearly as the hematocrit rises. Studies reveal that the resistance to flow increases as the hematocrit increases; the presence of more red cells increases the viscosity of blood, and may hamper its passage through smaller vessels (3). Thus, for some patients, particularly those with arteriosclerosis, blood flow and tissue oxygenation may not rise, and could even be reduced as hematocrits increase beyond 30%.

Patients Often Tolerate Low Hematocrits

Studies of hemodilution of healthy humans suggest that cardiac output does not begin to increase until the hematocrit falls to about 27% (4). A recent study of acute reduction in hemoglobin to 5 g/dL (with insovolemic non-RBC fluid replacement) in 32 healthy individuals demonstrated that systemic oxygen delivery was sufficient to maintain normal end-organ function (5). These studies underscore the point that as long as insovolemia is maintained, even severe anemia may be tolerated, at least acutely. It must be noted that the data for transfusion guidelines in patients with preexisting myocardial or severe pulmonary disease are less substantial than the data for other types of anemic patients. However, a recent study comparing "conservative" and "liberal" transfusion strategies in critically ill patients found that transfusions given to maintain the hemoglobin level between 8-10 g/dL were at least as safe, and possibly safer than transfusions given to maintain the hemoglobin level above 10 g/dL (6).

The experience of surgery on Jehovah Witnesses, who choose not to accept blood transfusion, indicates that complex surgery can be performed at hematocrits much lower than conventionally considered "necessary". A recent study of almost 20,000 Jehovah's Witnesses undergoing surgery for many types of procedures found that the risk of mortality increased significantly only when hemoglobin fell below 7 g/dL. In that study, underlying cardiovascular disease was an additional risk factor for increased morbidity (7).

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The maintenance of adequate tissue perfusion is more important than a high hematocrit in delivering oxygen to such critical vascular beds of the heart and kidneys. This can often be accomplished by adequate maintenance of intravascular volume with crystalloids or colloids (e.g. albumin, hetastarch).

What's in a Unit of Red Blood Cells?

A unit of RBC is anticoagulated with citrate and preserved with a saline solution containing dextrose and adenine. The hematocrit is approximately 55% and the volume is approximately 200 ml. There is less than 60 ml of plasma. Unless modified by special means, the typical unit contains approximately 2 billion white blood cells.

Why Transfuse Red Blood Cells?

Red blood cells are needed to improve O2-carrying capacity in the treatment of signs and symptoms of anemia. Those signs and symptoms may include syncope, dyspnea, cyanosis, tachycardia, angina, pallor, and decreased exercise tolerance. A drop in blood pressure and rapidly dropping hemoglobin and hematocrit associated with acute blood loss may also merit consideration for transfusion. Because all these signs and symptoms are nonspecific, they may be due to other causes.

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Age: Age alone is not an indication for transfusion.

Wound Healing: Transfusing post-operative patients to a higher hematocrit is not associated with improvement in wound healing. Healing is normal at a hemoglobin of 7 g/dL. 

Cerebrovascular Disease: It is not known whether the criteria for transfusion should be either more liberal or conservative in patients with cerebral vascular disease.

Myocardial Disease: A remote history of cardiac disease, without evidence of recent injury, is not itself an indication for transfusion. Recent myocardial injury favors more liberal use of RBC.

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Complications of Red Blood Cell Transfusion 

Hepatitis: Due to the sensitivity of current blood donor screening tests, the risks of hepatitis B and hepatitis C are very low (1 in 60,000 and 1 in 100,000 per unit transfused, respectively). However, evidence suggests that other hepatitis viruses, yet unidentified, will be found that are associated with transfusion.

HIV/AIDS: With current tests, the risk of infection with HIV from a unit of blood is about 1 in 500,000. 

Hemolytic Reaction: Immediate hemolytic transfusion reactions generally result from in-hospital identification or clerical errors involving the ABO system. The risk is approximately 1 in 30,000 and the risk of death is approximately 1 in 250,000 transfusions. Delayed hemolytic reactions are much more common, occurring in about 1 in 1000 transfusions. 

Circulatory Overload: This is congestive heart failure due to hypervolemia, usually seen in very young or elderly patients. Until recently, this risk has been much underrecognized. A recent study suggests that 1% of orthopedic surgery patients may develop circulatory overload, a potentially life-threatening complication (7). 

Acute Lung Injury: This is adult respiratory distress syndrome due to transfusion. Antileukocyte antibodies in donor plasma reactive against recipient leukocytes are frequently associated with this life-threatening complication. The risk is approximately 1 in 5,000. The mortality is approximately 10%. 

Bacterial Contamination: Despite the use of aseptic venipuncture and sterile needles and equipment, bacteria can enter the collection system for blood. This is among the most frequent causes of death from transfusion. Gram-negative or gram-positive organisms may be implicated.

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Accepted guidelines for RBC Transfusion include the following:

Re-evaluate the patient between units.
Much unnecessary RBC use results from orders of multiple units when a smaller number would have been adequate. Unless patients are profoundly anemic or bleeding actively, the hemoglobin/hematocrit should be checked between units.

Autologous Transfusions: Autologous blood has many advantages. However, with increasing safety, some studies suggest that its cost-benefit has decreased markedly (8). Nevertheless, preoperative autologous donation or intraoperative blood salvage should be considered for some surgical patients.Leukocyte-reduced RBC: For selected patients, leukocyte reduction is considered desirable. Currently, the accepted indications include: 1) prevention of recurrent febrile reactions, 2) prevention of HLA alloimmunization, 3) prevention of CMV infection.

These guidelines are not a substitute for medical judgment for individual patients.

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Risks of Adverse Consequences Resulting From Blood Transfusions

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References

1. Consensus Conference Perioperative Red Blood Cell Transfusion. JAMA 1988; 260: 2700-2703.
2. Avorn J, Soumerai SB, Salem S, Popovsky M. Current Concepts in transfusion Practice. The decision to use red cells: time to re-assess the transfusion trigger? 1998.
3. Leveen HH. In: Autotransfusion. Hauer MJ, Thurer RL, eds. New York: Elsevier North Holland Inc. 1981: 71-82.
4. Watkins GM, Rabilo A., et al. Surgery, Gynecology & Obstetrics 1974; 139: 161-175.
5.  Weiskopf, RB, Viele MK, et al. JAMA 1998; 279: 217-221.
6. Hebert PC, et al. NEJM 1999; 340: 409-418.
7. Carson JL, et al. JAMA 1998; 279: 199-205.
8. Popovsky M, Audet AM, et al. Immunohematology 1996; 12(2): 87-89.
9. Etchason J. Petz L, et al. N Eng J Med 1995; 332: 719-724.
10. Simon T, et al. Arch Pathol Lab Med 1998; 122: 130-138.
11. Goodnough LT, et al. NEJM 1999; 340: 438-447.

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