Leukocyte Reduction of Allogeneic Transfusion Products in Cardiovascular Surgery

The development of autologous blood programs has significantly decreased use of allogeneic transfusion for cardiac and other surgeries, however, allogeneic blood transfusions are still commonly received by these patients. These allogeneic blood transfusions are a matter of concern because in every type of surgery studied allogeneic blood transfusion is associated with increased risk of postoperative infection.¹

Donor leukocytes present in all allogeneic blood components are unintentionally transfused along with the intended product. The distribution of leukocytes that contaminate various blood components is shown below.

Blood Products are Not Pure

Distribution of leukocytes in whole blood and component blood products.10

Transfused leukocytes cause immunosuppression. This ‘transfusion effect’ has been used to ensure successful renal transplant. In fact, patients receiving leukoreduced blood components have experienced a lower rate of successful kidney transplantation suggesting a loss of the immunosuppressive effect related to low foreign leukocyte exposure.¹¹

Gianotti et al¹² in their animal model study showed the leukocyte to be the most profoundly influential component of blood capable of eliciting an immunosuppressive effect. The results demonstrate that leukocytes cause the greatest mortality in mice that are burned and given E. coli by gavage. A dose-response relationship between the number of leukocytes transfused and survival was demonstrated.

Leukocyte Dose-Response for the Immunosuppression Effect

Adapted from Gianotti et al12 showing leukocytes effect on immunosuppression-induced mortality following swabbing of a burn injury with a suspension of E. coli.

While it was initially thought that patient exposure to many transfusions was required to increase risk of postoperative infection, Edna and Bjerkeset showed that infection rates are significantly increased even for patients transfused with 1 to 4 units.¹³

Dose-Response for Transfusion and Infection

Patients transfused with 1 to 4 units have infectious complications rates approaching 20%.13

A similar dose-response was shown in patients undergoing coronary artery bypass graft surgeries by Murphy et al.⁷ Transfusion dose was found by Murphy et al to be the most significant predictor in cardiac surgery patients of postoperative infection.⁷

Number of Transfusions

Autologous blood exposure in surgical patients has not been associated with risk of infection compared to allogeneic blood transfusion.^4,6

Infection Rates Rise with Homologous Transfusions

Autologous blood is not associated with infectious complications.4,6

The high rate of infection seen among those patients transfused with allogeneic blood was corroborated by Jensen et al⁴ in a study of colorectal surgery patients. Their data emphasize that the immunosuppressive effect of transfusion is mediated by the white cells. When leukoreduced blood products were transfused, infection rates fell from 23% to 3%, the identical rate seen in non-transfused patients.

High Infection Rates are Lower when Leukoreduced Blood is Used

Evidence suggesting leukocytes can mediate the immunosuppressive effect of transfusion.4

Jensen et al further corroborates the protection leukocyte reduced blood components provide in her most recent study in 589 colorectal surgery patients.

Patients receiving leukocyte reduced blood had a low frequency of infection similar to patients who were not transfused.⁵

Reduces Wound Infection, Pneumonia and Reoperation

Adapted from Jensen et al5

Postoperative complications in cardiac surgery patients can more than double the length of hospital stay.¹⁴

Infection Prolongs Hospital Stay

Patients who acquire infections show a two and one-half fold increase in hospital length of stay.14

Murphy et al identified allogeneic blood transfusion dose in cardiac surgery patients as the most significant predictor of infection, days of fever, days of antibiotic therapy, and length of stay.⁷

Infected Patients Require More Resources

Adapted from Murphy et al7

Transfused cardiac surgery patients have an increased length of stay compared to nontransfused patients.⁷

Adapted from Murphy et al7

While it occurs rarely (0.4 to 5%), sternal wound infection has been identified as the most costly complication of open heart surgery.¹⁵

Costly Complications of Open Heart Surgery

Adapted from Taylor et al15

Ottino et al found blood volume transfused, longer procedures, protracted bypass times and increased stay in the ICU as factors related to sternal wound infections.⁸

Factors Related to Major Sternal Wound Infections

Adapted from Ottino et al8

Cost-effectiveness of Leukoreduction

Adapted from Jensen et al16

In cardiac surgery patients van de Watering et al found that leukocyte reduction resulted in a significant reduction in postoperative mortality in patients after surgery by lowering the non-cardiac causes of death.¹⁷

Adapted from van de Watering et al17

The mortality incidence in 867 cardiac surgery patients was significantly reduced with either prestorage leukocyte reduced blood (filtered 24 hours after collection) or stored blood filtered (6-20 days after donation) compared to the standard allogeneic blood product buffy coat depleted packed red blood cells.¹⁷

Allogeneic blood transfusion in surgical patients is linked with an average 15% increased incidence of postoperative infection¹⁸ as well as an increased incidence of postoperative mortality in cardiac surgery patients.¹⁷ This increased incidence of infection is directly linked to increased length of stay and consumption of hospital resources driving up the cost to treat patients.

Based on the above clinical studies, leukocyte reduced blood components can significantly reduce these costly complications, and are available at the time of transfusion at the bedside, the hospital blood bank, or the regional blood center.

In today's healthcare environment, leukocyte reduction is an important tool for the management of surgical transfusion. When blood transfusion will be required for surgical patients to assure safety, minimize costs, minimize infectious complications and retain ease of use, the following options are recommended:

• No transfusion
• Autologous transfusion and blood sources
• Leukocyte reduced blood components ^1,2,5,6,19

High efficiency leukocyte reducing filters can provide leukocyte reduced blood components with residual leukocyte counts significantly below the most stringent standards. These leukocyte reduced blood components serve as an integral tool in the management of surgical transfusion by providing a product with a higher safety profile, as well as one that minimizes post-operative complications to assure timely patient recovery and discharge.

• Allogeneic blood components contain leukocytes.
  
• These leukocytes are immunosuppressive and have been linked with increased incidence of postoperative infections in surgical patients and increased mortality in cardiac surgery patients.
  
• Infections in surgical patients are associated with increased length of stay and consumption of hospital resources.
  
• Leukocyte reduced blook components may prevent costly infectious complications.

1. Tartter P: Blood transfusions and bacterial infections: Clinical Studies in: immunological effects of blood transfusion ed: D.P. Singal CRC Press, Boca Raton, Florida. 1994:111-120.
2. Agarwal N, Murphy JG, Cayten CG, and Stahl Wm: Blood transfusion increases risk of infection in trauma, Arch Surg 1993; 128:171-177
3. Tartter P: Determinants of postoperative stay in patients with colorectal cancer implications for diagnostic-related groups. Dis Colon Rectum 1988; 31:694-698.
4. Jensen LS, Andersen AJ, Christiansen PA, et al: Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. Brit J Surg 1992; 79:513-516.
5. Jensen LS, Kissmeyer-Nielsen P, Wolff B, Qvist N: comparison of leukocyte-depleted versus buffy-coat poor blood transfusion and complications after colorectal surgery. Lancet 1996; 348:841-845.
6. Triulzi DJH, Vancek K, Ryan DH, and Blumberg N: A clinical and immunologic study of blood transfusion and postoperative infection in spinal surgery. Transfusion 1992; 32:517-524.
7. Murphy PJ, Connery C, Hicks GL, Blumberg N: Homologous blood transfusion as a risk factor for postoperative infection after coronary artery bypass graft operations. J Thorac Cardiovasc Surg 1992; 104:1092-1099.
8. Ottino G, De Paulis R, Pansini S, et al: Major sternal wound infection after open heart surgery: a multivariate analysis of risk factors in 2,579 consecutive operative procedures. Ann Thorac Surg 1994; 44:173-179.
9. Fernandez MC, Gottlieb M and Menitove JE: Blood transfusion and postoperative infection in orthopedic patients, Transfusion 1992; 318.
10. Data on file at Pall Corporation, East Hills, NY.
11. Persijn GG, Cohen B, Lansbergen Q, et al: Retrospective and prospective studies on the effect of blood transfusions in renal transplantation in the Netherlands. Transplantation 1979; 28:396-401.
12. Gianotti L et al: Identification of the blood component responsible for increased susceptibility to gut-derived infection. Transfusion 1993; 33:458-465.
13. Edna TH, Bjerkeset T: Association between blood transfusion and infection. J Trauma 1992; 33:659-661.
14. Kluytmans JAJW, Mouton JW, Maat APWM, et al: Surveillance of postoperative infections in thoracic surgery. J Hosp Infection 1994; 27:139-147.
15. Taylor GJ, Mikell FL, Moses HW, et al: Determinants of hospital charges for coronary artery bypass surgery: the economic consequences of postoperative complications. Am J Cardiol 1990; 65:309-313.
16. Jensen LS, Grunnet N, Hanberg-Sorensen F, Jorgensen J: Cost-effectiveness of blood transfusion and white cell reduction in elective colorectal surgery. Transfusion 1995; 35:719-722.
17. Van de Watering LMG, Hermans J, Houbiers JGA, van den Broek PJ, Bouter H, Boer F, Harvey M, Huysman HA, Brand A: Beneficial effects of leukocyte depletion of transfused blood on postoperative complications in patients undergoing cardiac surgery. Circulation 1998; 97:562-568.
18. Dzik S, Blajchman MA, Blumberg N, Kirley SA, Heal JM, Wood K: Current Research on the Immunomodulation Effect of Allogeneic Blood Transfusion. Vox Sang 1996; 70:187-194.
19. Jensen LS, Kissmeyer-Nielsen P, Wolff B, Qvist N: Postoperative infection after colorectal surgery. Lancet 1996; 348:1665-1666.