Interact CardioVasc Thorac Surg 2007;6:618-622. doi:10.1510/icvts.2007.155523
© 2007 European Association of Cardio-Thoracic Surgery
Institutional report - Cardiopulmonary bypass |
Acute plateletpheresis and aprotinin reduces the need for blood transfusion following Ross operation
Faleh Al-Rashidi,
Misha Bhat,
Leif Pierre and
Bansi Koul*
Cardiothoracic Surgery, University Hospital Lund, 221 85 Lund, Sweden
Received 7 March 2007;
received in revised form 8 July 2007;
accepted 9 July 2007
 This paper was presented as a poster at the IX Swedish Cardiovascular Spring Meeting, April 25–27, 2007, Gothenburg, Sweden.
*Corresponding author. Tel.: +46 703491649; fax: +46 46158635.
E-mail address: bansi.koul{at}skane.se (B. Koul).
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Abstract
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The effect of acute intraoperative plateletpheresis (25% platelet yield) in combination with intraoperative low-dose aprotinin (2 million units) on blood conservation was investigated in 18 young adult patients undergoing elective Ross operation. The results were compared with a group of 19 similar patients without plateletpheresis (control group). The hematological and coagulation parameters at admission and discharge were statistically similar in both groups. The total blood product transfusion requirements were significantly reduced in the plateletpheresis group compared with the control group (3.2 units and 5.1 units, respectively, P=0.036). The total blood donor exposure was also reduced significantly in the plateletpheresis group compared with the control group (3.2 and 6.9 donors/patient, respectively, P<0.001). The direct costs for the hospital for the plateletpheresis procedure, including costs for all blood products, were similar to those for blood products alone in the control group. In summary, acute plateletpheresis in combination with low-dose aprotinin significantly reduces the blood product transfusions and blood donor exposures following the Ross operation; the treatment is cost-effective.
Key Words: Blood conservation; Platelets; Cardiopulmonary bypass; Ross operation
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1. Introduction
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The Ross operation is generally indicated in young adults and children with aortic valve disease to avoid long-term oral anticoagulation. The long-term risks with the Ross operation, on the other hand, are pulmonary autograft or pulmonary homograft dysfunction requiring one or several reoperations. It is, therefore, desirable to keep the frequency of blood transfusions as low as possible in these young patients to avoid development of cross-reactive antibodies and to minimize the risks of blood-borne infections.
Several prospective randomized studies with acute plateletpheresis (APP) have shown conflicting results, varying from positive effect on blood conservation [1–7] to no effect [8–12]. However, only one study has been published so far investigating the effect of APP in combination with intraoperative aprotinin on a perioperative need for blood transfusions [7]. In the present study we describe our results with APP combined with low-dose aprotinin in patients undergoing the Ross operation.
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2. Patients and methods
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Eighteen patients undergoing an elective Ross operation and intraoperative APP were compared to 19 similar patients but with no APP (control group). All patients in the plateletpheresis group completed the plateletpheresis program aimed at providing an estimated platelet yield of 25% of the circulating platelet pool. This platelet yield corresponds to four European or six American units of platelets and conforms to the guidelines for an effective plateletpheresis in an adult [13, 14]. Preoperative patient characteristics of the patient population are summarized in Table 1. In the plateletpheresis group, platelet-rich plasmapheresis was performed immediately after anesthesia induction and completed before pre-CPB heparinization. The Sequestra 1000 Auto Transfusion System (Medtronic Inc., MN, USA) was used for APP. Blood was withdrawn from the patient into a 225 ml bowl at an initial rate of 100 ml/min and centrifuged at 5600 rpm to separate the platelet-poor plasma. Once the centrifuge bowl was filled, the rate was reduced to 50 ml/min with 2400 rpm to separate the platelet-rich plasma. The remaining red blood cells, after the platelet separation, were returned to the patient immediately. The cycle was repeated until platelet-rich plasma equivalent to 25% of the estimated circulating platelet count. This platelet-rich plasma was anticoagulated with 4% sodium citrate while stored at room temperature in plastic bags on a rocker until the completion of CPB and protamine neutralization of heparin. It was then transfused to the patient within 30 min.
During APP, the intravascular volume was maintained with administration of crystalloids to offset the temporary loss of blood volume due to the platelet-rich plasma collection process. The control group was managed in the normal fashion without acute intraoperative pre-CPB plateletpheresis.
2.1. Ross operation
The Ross operation performed by our group is described elsewhere [15].
All patients, except those subjected to hypothermic circulatory arrest, received 2 million units of aprotinin (Trasylol, Bayer AG, Germany) directly into the CPB circuit. At the termination of CPB, protamine was administered at 1 mg/100 U of total administered heparin; additional doses of protamine (50 mg) were administered either in an attempt to return to baseline ACT or based on incomplete heparin reversal as assessed by intraoperative thromboelastography or both.
In all patients undergoing APP, the residual blood in the extracorporeal circuit, together with the blood in the cell-saver (Standby kit 1/Tvättkit ATL2001, Medtronic Inc., MN, USA), was washed and red cells transfused to the patients. In the control group, the blood in the cell-saver was washed only when the total amount of blood collected in the cell-saver together with the residual blood in the extracorporeal circuit exceeded 1000 ml. Otherwise, this procedure is cost-ineffective in our set-up.
Postoperatively in the intensive care unit, the allogenic red cells were transfused if the hemoglobin was  80 g/l and the patient was hemodynamically unstable. Fresh frozen plasma and platelet concentrate were transfused if chest tube drainage exceeded 100–150 ml/h for three consecutive hours or exceeded 200–300 ml during one single hour in association with a pathological thromboelastogram. Patients were reoperated and bleeding controlled surgically if they bled postoperatively as above, despite complete heparin reversal and normal thromboelastogram. In the post-intensive care period, the allogenic red blood cells were transfused for hemoglobin levels of 90 g/l or lower only if deemed necessary for the patient's well-being as determined by the attending physician.
2.2. Cost analysis
The cost of disposable equipment for single APP at our center is 1500 SEK. This does not include the cost of the cell-saver (400 SEK) which was used in both groups. The cost of one unit of red cells and plasma at our hospital is 835 SEK and 444 SEK, respectively. Four units of non-apheresis platelets constituting one therapeutic unit cost 2051 SEK in our hospital compared with 7262 SEK for one therapeutic unit of apheresis platelets.
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3. Statistics
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The statistical analyses were performed using the non-parametric Mann–Whitney test. P<0.05 was considered significant. The blood transfusion, and/or the blood donor exposure data, was analyzed using zero-inflated Poisson regression. In this analysis the number of units of blood products and donors that each patient was exposed to can be regarded as count data, exhibiting a Poisson distribution with excess zeros (Lambert D. Zero-inflated Poisson regression, with an application to defects in manufacturing. Technometrics 1992;34:1–14). Using the rule of parsimony, a common probability of excess zeros for both groups was estimated.
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4. Results
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The plateletpheresis and control groups compare well in terms of preoperative demographics (Table 1). The median volume of blood processed for plateletpheresis before CPB was 2170 ml (range=1695–2810 ml) from which 710 ml (range=380–1120 ml) platelet-poor plasma and 310 ml (range=220–450 ml) platelet-rich plasma were sequestrated (Table 2). The platelet harvesting took a mean of 25 min.
The cell saver was used significantly more often (94%) in the plateletpheresis group since the system happened to be already in use for APP. That is why the patients in the control group had significantly lower red cell salvage and received significantly greater amounts of protamine for reversal of heparin in the unwashed transfused whole blood (Table 2).
The perioperative clinical course in both groups was statistically similar (Table 3). No major postoperative 30-day morbidity was observed in both groups and all the patients are alive and doing well.
Forty-seven per cent of the patients in the control group and 56% in the plateletpheresis group received no transfusion at all. Hence, the blood transfusion data (in units) and the corresponding donor exposure data were analyzed by zero-inflated Poisson regression. The estimate of excess zeros was 59% (42–75, 95% CL) for the red cells, 67% (49–82, 95% CL) for the plasma and 50% (34–67, 95% CL) for the red cells, plasma and platelets combined. The results were significantly in favor of the plateletpheresis group for both blood product transfusions and blood donor exposures (P=0.036 and P<0.001, respectively) (Table 4).
The direct costs for the hospital for APP were 27000 SEK whereas the costs for all blood products used in the plateletpheresis group were 26174 SEK (total=53174 SEK). In contrast, the cost of transfusion of all blood products in the control group was 50857 SEK. Had apheresis platelets been used instead in the control group, the costs for transfusion alone would have increased by 53% to 81208 SEK.
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5. Discussion
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Our primary intention in the present study was to subject all patients undergoing an elective Ross operation to APP. It was, however, the non-availability of trained staff on several occasions that determined approximately a 50:50 distribution of patients between the plateletpheresis and control groups. The unique characteristics of the study are: mean CPB time of 212 min and mean aortic occlusion time of 152 min (the longest reported in APP context studies so far), systemic hypothermia of minimum 25 °C and elective standardized Ross operation performed by the same surgeon in a consecutive manner (first study to be published in APP context). A low-dose aprotinin, 2 million units/patient was administered in a consecutive manner and the cell-saver was used in a defined manner.
This study shows that APP with a platelet yield equal to 25% of the circulating platelet pool in combination with a low-dose aprotinin significantly reduces the need for blood transfusion compared with a treatment with low-dose aprotinin alone (P=0.036). The combined need of all blood product transfusions was reduced by 47% in the plateletpheresis group, which is statistically and clinically significant. Moreover, there was a clear trend towards a lower need for isolated red cells, plasma and platelet transfusions also in the plateletpheresis group. The results of our study are comparable to the prospective randomized study published by Stover et al. [6] in which APP was combined with intraoperative infusions of e-aminocaproic acid in patients undergoing complex cardiac surgery and the results were compared with a control group receiving e-aminocaproic acid alone. As in our study, there was no statistically significant difference between the two groups in perioperative transfusion of red cells, fresh frozen plasma and platelets in isolation, but the total amount of all allogenic blood products transfused was significantly less in the plateletpheresis group. The study by Li et al. [7] which included patients undergoing first time elective coronary artery bypass grafting, showed that the use of high-dose aprotinin alone was as effective as APP in terms of blood conservation postoperatively. However, the combination of APP and high-dose aprotinin showed even better results.
The direct cost involved in plateletpheresis together with the cost for a reduced need for transfusions of blood products in the plateletpheresis group equalled the cost of transfusion of blood products alone in the control group. Moreover, the patients in the plateletpheresis group were exposed to significantly fewer blood donors (P<0.001, Table 4). Therefore, APP together with low-dose aprotinin was cost-effective since the risk of blood donor exposures for the individual patient at the same cost was significantly lower than in the control group.
Being a retrospective study, one can speculate on its limitations. The fact that all patients included in this study were operated on by the same surgical team minimizes the confounding factor related to hemostasis which may be surgeon-dependant. The overall frequency of transfusion of the allogenic blood products in the present study was fairly low which can be ascribed to the relatively low magnitude of postoperative bleeding, a uniform and strict transfusion policy in the intensive care unit and in the general ward, and the use of appropriate blood products based on early clinical and laboratory evaluation of the cause of bleeding. The patients in both groups had identical values of hemoglobin, hematocrit and platelets at admission and these values were again identical at the time of discharge, ruling out bias of over-transfusion in the control group and/or sub-optimal transfusion in the plateletpheresis group.
In conclusion, the use of APP in combination with low-dose aprotinin significantly reduces the perioperative need for overall blood product transfusion in young adult patients undergoing an elective Ross operation. Moreover, this combined treatment is cost-effective.
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Acknowledgements
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The authors are indebted to Dr. Peter Höglund, Competence Centre for Clinical Research, University Hospital Lund, Sweden for statistical analysis and to Sasha Koul and Farnaz Malekzadeh, for data collection.
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References
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- DelRossi AJ, Cernaianu AC, Vertrees RA, Wacker CJ, Fuller SJ, Cilley JH Jr, Baldino WA. Platelet-rich plasma reduces postoperative blood loss after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990; 100:281–286.[Abstract]
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- Li S, Ji H, Lin J, Lenehan E, Ji B, Liu J, Liu J, Long C, Crane TA. Combination of acute preoperative plateletpheresis, cell salvage, and aprotinin minimizes blood loss and requirement during cardiac surgery. J Extra Corpor Technol 2005; 37:9–14.[Medline]
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- Ereth MH, Oliver WC Jr, Beynen FM, Mullany CJ, Orszulak TA, Santrach PJ, Ilstrup DM, Weaver AL, Williamson KR. Autologous platelet-rich plasma does not reduce transfusion of homologous blood products in patients undergoing repeat valvular surgery. Anesthesiology 1993; 79:540–547. discussion 527A.[CrossRef][Medline]
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Abstract
1. Introduction
