Con: Whole Blood Transfusions are Not Useful in Patients Undergoing Cardiac Surgery

Mark D. Hershey, MD, and D. David Glass, MD

I N considering the controversy regarding the usefulness of whole blood therapy with cardiopulmonary bypass

(CPB), the hemostatic defect created during bypass must first be understood. This was described first in the mid 1960s and continues to be defined today. To the extent that the disorder is understood, the hemostatic defect can be defined as a partially reversible platelet disorder involving both activation and aggregation, and a dilution of coagula- tion factors and red blood cells.1-3 Because of this hemo- static defect, multiple investigators have attempted to show that blood spared from the rigors of CPB provides a rejuvenated hemostatic mechanism resulting in a correction of the coagulation indices. Theoretically then, there will be less bleeding and a decrease in the transfusion require- ment. However, despite numerous attempts at proving this theory, there are no confirmatory data that this is so. There is only some preliminary evidence of its effectiveness in neonates.4

The coagulation factors, although routinely decreased by 20% to 30% during CPB, do not fall below levels usually considered adequate for normal hemostasis.5 Therefore, correcting the platelet disorder should result in a normal hemostatic mechanism. However, as will be discussed, laboratory correction of the hemostatic defect has not been proven to result in less bleeding or fewer homologous blood product transfusions.

BANKED WHOLE BLOOD

Whole blood contains approximately 250 to 300 mL of plasma per unit. There is no evidence that there is any advantage to the plasma of whole blood as compared to component fresh frozen plasma (FFP). Roy et al6 demon- strated that, in 100 patients, routine prophylactic adminis- tration of FFP did not change the postoperative blood loss or routine coagulation values. There was a significant increase in the partial thromboplastin time (PIT) in the FFP group thought to be secondary to potentiation of heparin rebound. This lack of effectiveness has been reiterated in numerous studies as well as in the Consensus Conference on FFP Transfusion.’ Therefore, plasma in general is not necessary after CPB, and if there is evidence of factor deficiency as determined by factor assay, whole blood has no advantages over FFP.

Additionally, it is clear that the red blood cell (RBC) deficit associated with CPB is dilutional. There is no evidence to support any advantage to the RBCs of whole blood (banked or fresh) over packed, banked RBCs.

Platelet dysfunction, not anticoagulation protein defi- ciency or any primary RBC abnormality, is the hemostatic abnormality most frequently associated with a post-CPB coagulopathy.l Any benefit of whole blood therapy is, therefore, associated with the platelet component. Banked whole blood is essentially devoid of functional platelets. Therefore, it is of no theoretic benefit in the correction of the hemostatic defect.

FRESH WHOLE BLOOD

Theoretically, fresh platelets should result in improved hemostasis after CPB. Much of the debate surrounding the studies regarding the utility of fresh whole blood is difficult to dissect in that none of the studies was blinded and isovolemic hemodilution and blood conservation methods were not practiced. Fifteen to 20 years ago, when many of these studies were undertaken, it was common to transfuse more than 10 units of blood products. The “transfusion trigger” for many of the studies was poorly defined. Hallo- well et al* provided some of the earliest evidence in favor of fresh whole blood. They compared transfusion require- ments in patients with and without two units of fresh whole autologous blood removed immediately before bypass. They found that in the fresh whole blood group, there were seven units of blood products transfused (combination of whole blood, packed red blood cells, and FFP) versus 10 units in the nonautologous group. In looking at the amount of platelets, plasma, packed red blood cells and whole blood, the only statistically significant difference was for one unit of FFP. There was no significant difference in chest tube drainage or coagulation parameters (prothrom- bin time, PTT, and platelet count). It is difficult to con- clude, as did the authors, that in this unblinded study, with no objective criteria for transfusion, and in which both groups had large transfusion requirements, that fresh whole blood was useful.

A similar study by Ochsner et al” was plagued by similar pitfalls. In this study, the authors found that by transfusion of 20% of the blood volume of fresh whole blood, there was a saving of 1,622 mL of banked blood. Again, coagulation parameters were similar, as was chest tube drainage, but patients given the nonfresh whole blood received signifi- cantly more homologous blood components. Again, without blinding, or a known transfusion trigger, conclusions are difficult to draw.

For every study in favor of fresh whole blood, there are studies refuting its usefulness. Sherman et al’” found no difference in transfusion requirements. Again, the study was not blinded, but as stated in the article itself, the bias was toward proving that fresh whole blood decreased transfusion requirements. There was no difference in the blood loss or transfusion requirements of the patients studied. Pliam et al” studied 122 patients and found no difference in postoperative blood loss, or in whole blood, platelets, or FFP transfusion requirements.

Most recently, Hudson et alI2 restudied the same issue of

From the Departmertt OfAnesthesia, Dartmouth-Hitchcock Medical Center, Hanover, NH.

Address reprint requests to Mark Hershey, MD, Department of Anesthesia, Dartmouth-Hitchcock Medical Center, Hanover, NH 03 755.

Copyright o 1992 by WB. Saunders Company IOS3-0770/92/0606-0022$03.OOlO Key words: cardiopulmonary bypass, coagulation, blood transfusion

Journalof Cardiothoracic and Vascular Anesthesia, Vol6, No 6 (December), 1992: pp 761-763 761

762

isovolemic hemodilution and its potential for homologous transfusion reduction. The study consisted of 65 random- ized patients in whom 10% of their fresh whole blood was removed and reinfused after bypass. The study found no difference in PT, PTT, platelet count, fibrinogen, throm- boelastography, or chest tube drainage between those patients who had the infusion of whole blood versus those who did not. Therefore, the authors concluded that iso- volemic hemodilution did not improve coagulation post- bypass. Interestingly, although it did not achieve statistical significance, transfusion of banked RBCs occurred in 22% of study patients as compared to 36% of control patients. The authors hypothesized that “isovolemic hemodilution may decrease banked blood usage by preserving red blood cells.” However, as stated, this did not achieve statistical significance and will require a larger study group for clarification.

FRESH COMPONENT THERAPY

As previously discussed, the debate is not whether whole blood is beneficial, but whether the platelets of the fresh whole blood are capable of improving the known platelet defect post-CPB. Even more important is whether or not this correction will decrease the homologous blood transfu- sion requirements. Some authors have investigated whether or not prophylactic transfusion of platelets, banked as well as fresh, will reduce homologous blood transfusions. How- ever, studies evaluating blood transfusion requirements are difficult to conduct and compare in that there exists significant variability of transfusion practice. Goodnough et al,*” in a multicenter study, reviewed 540 patients undergo- ing first-time CABG. Thirty-two percent received plasma (institutional range, 0 to 97%) and 22% received platelets (institutional range, 0 to 80%). Obviously, the transfusion trigger was extremely variable. Because this variability exists, prospective randomized blinded trials are the only gold standard.

HERSHEY AND GLASS

Simon et alI4 prophylactically administered banked plate- let concentrates. In spite of the correction of the bleeding time and the platelet count, there was no difference in chest tube blood loss, transfusion requirement, or clinical out- come. Additionally, there was no correlation of bleeding time and platelet count to blood loss and transfusion requirements. Therefore, prophylactic platelets arc not recommended.r5 In studies by Giordano et alih and Jones et aI,” fresh platelet-rich plasma (PRP) was administered. Both studies found that there was a significant reduction in the transfusion of blood components. However, neither study was blinded, and, therefore, the question of bias is raised. Recently, de Castro et al’s studied, in a prospective double-blinded fashion, the effect of fresh autologous PRP administered to 3 1 patients undergoing cardiac procedures with increased risk of bleeding (ie, repeat sternotomy). They found that there were no significant differences in homologous RBC, FFP, platelet, or pooled cryoprecipitatc transfusions between the groups. Conclusions from this study obviously can be extended to fresh whole blood. If fresh platelets and plasma did not change transfusion requirements, then there will be no advantage to the use of fresh whole blood.

SUMMARY

Data supporting fresh whole blood transfusion or fresh component therapy are nonblinded, and although both are conceptually attractive, neither can be considered proven. Recent blinded studies reflect fresh blood ineffectiveness. Larger, blinded, randomized trials will need to be per- formed. Proven methods of blood conservationr”,2” as well as standardized criteria for transfusion of blood compo- nents2r will more effectively decrease homologous blood transfusion. Transfusion of fresh or banked whole blood. or its components, has yet to be shown to decrease the usage of homologous blood products.

REFERENCES

1. Mammen EF, Koets MH, Washington BC, et al: Hemostasis changes during cardiopulmonary bypass surgery. Semin Thromb Hemost 11:281-292,1985

2. Bachmann F, McKenna R, Cole ER, Najati H: The hemo- static mechanism after open-heart surgery. J Thorac Cardiovasc Surg 70:76-85,1975

3. Rinder CS, Mathew JP, Rinder HM, et al: Modulation of platelet surface adhesion receptors during cardiopulmonary by- pass. Anesthesiology 75:563-570, 1991

4. Manno CS, Hedberg KW, Bunin CR, et al: Comparison of the hemostatic effects of fresh whole blood, stored whole blood and components after open heart surgery in children. Blood 77:930- 936,199l

5. Braunstein AH, Oberman HA: Transfusion of plasma compo- nents. Transfusion 24:281-286,1984

6. Roy RC, Stafford MA, Hudspeth AS, Meredith JW: Failure of prophylaxis with fresh frozen plasma after cardiopulmonary bypass. Anesthesiology 69:254-257, 1988

7. National Institute of Health Consensus Conference. Fresh frozen plasma: Indications and risks. JAMA 253:551-553, 1985

8. Hallowell P, Bland J, Buckley MJ, et al: Transfusion of fresh

autologous blood in open heart surgery. J Thorac Cardiovasc Surg 64:941-948, 1972

9. Ochsner JL, Mills NL, Leonard CL, et al: Fresh autologous blood transfusion with extracorporeal circulation. Ann Surg 177:81 l- 816,1973

10. Sherman M, Dobnik D, Dennis R, Berger R: Autologous blood transfusion during cardiopulmonary bypass. Chest 70:592- 595,1976

11. Pham MB, McGoon DC, Tarhan S: Failure of transfusion of autologous whole blood to reduce banked-blood requirements in open-heart surgical patients. J Thorac Cardiovasc Surg 70:338-343, 1975

12. Hudson R, Zoellner PA. Williams CM, et al: Isovolumic hemodilution in cardiac bypass surgery. Society of Cardiovascular Anesthesiologists, 14th Annual Meeting, May 3-6,1992: 148 (abstr)

13. Goodnough LT, Johnston M, Toy P, the Transfusion Aca- demic Award Group: The variability of transfusion practice in coronary artery bypass surgery. JAMA 265:86-90,199l

14. Simon TL, Akl BF, Murphy W: Controlled trial of routine administration of platelet concentrates in cardiopulmonary bypass surgery. Ann Thorac Surg 37:359-364,1984

CON: WHOLE BLOOD TRANSFUSIONS 763

15. National Institute of Health Consensus Conference: Platelet transfusion therapy. JAMA 257:1777-1780,1987

16. Giordano GF, Rivers SL, Chung GKT, et al: Autologous platelet-rich plasma in cardiac surgery: Effect on intraoperative and postoperative transfusion requirements. Ann Thorac Surg 46:416-419, 1988

17. Jones JW, McCoy TA, Rawitscher RE, Lindsley DA: Effects of intraoperative plasmapheresis on blood loss in cardiac surgery. Ann Thorac Surg 49:585-590,199O

18. de Castro M, Oliver Jr WC, Ereth MH, Beynen FM: Transfusion of autologous platelet rich plasma does not reduce homologous blood usage in patients having repeat valvular surgery.

Society of Cardiovascular Anesthesiologists, 14th Annual Meeting, May 3-6 1992: 148 (abstr)

19. Chvings DV, Kruskall MS, Thurer RL, Donovan LM: Autol- ogous blood donations prior to elective cardiac surgery. JAMA 262:1963-1968, 1989

20. Dietrich W, Barankay A, Dilthey G, et al: Reduction of blood utilization during myocardial revascularization. .I Thorac Cardiovasc Surg 97:213-219, 1989

21. Goodnough LT, Johnston M, Ramsey G, et al: Guidelines for transfusion support in patients undergoing coronary artery bypass grafting. Ann Thorac Surg 50:675-683, 1990