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Anesth Analg 2000;90:509-516
© 2000 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

Platelet-Rich Plasma Sequestration, with Therapeutic Platelet Yields, Reduces Allogeneic Transfusion in Complex Cardiac Surgery

E. Price Stover, MD, Lawrence C. Siegel, MD, Patricia A. Hood, CCP, Geraldine E. O’Riordan, RN, and Timothy R. McKenna, BS

Department of Anesthesia, Stanford University School of Medicine, Stanford, California

Address correspondence and reprint requests to E. Price Stover, MD, Department of Anesthesia, Room H3580, Stanford University School of Medicine, Stanford, CA 94305.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Platelet dysfunction is the most common cause of nonsurgical bleeding after cardiopulmonary bypass (CPB). We hypothesized that reinfusion of a therapeutic quantity of platelets sequestered before CPB would decrease the need for allogeneic platelet transfusion, as well as decrease bleeding and total allogeneic transfusion, in cardiac surgery patients at moderately high risk for bleeding. Fifty-five patients undergoing either reoperative coronary artery bypass (CABG) or combined CABG and valve replacement were randomized to control or platelet-rich plasma sequestration (pheresis) groups. All patients received intraoperative {epsilon}-aminocaproic acid infusions. There was no significant difference between groups with respect to preoperative characteristics, duration of CPB, or target postoperative hematocrit. Mean platelet yields were 6.2 ± 2.1 units (3.1 x 1011 platelets). Mean pheresis time was 44 min. Allogeneic platelets (range = 6–12 units) were transfused to 28% of control patients, compared with 0% of pheresis patients (P < 0.01). Allogeneic packed red blood cells were transfused to 45% of control patients (1.2 units per patient) versus 31% of pheresis patients (0.7 unit per patient) (P = 0.35). Total allogeneic units transfused were significantly reduced in the pheresis group (P < 0.02). Mediastinal chest tube drainage was not significantly decreased in the pheresis group. In this prospective, randomized study, therapeutic platelet yields were obtained before CPB. In contrast with recent studies with low platelet yields, these data support the conclusion that platelet-rich plasma sequestration is effective in reducing allogeneic platelet transfusions and total allogeneic units transfused in cardiac surgery patients at moderately high risk for post-CPB coagulopathy and bleeding.

Implications: Transfusion of allogeneic blood products, including platelets, is common during complex cardiac surgical procedures. In the present prospective, randomized study, a significant reduction in allogeneic platelet transfusion and total allogeneic units transfused was observed after the reinfusion of a therapeutic quantity of autologous platelets sequestered before cardiopulmonary bypass.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Cardiac surgery accounts for nearly 20% of all allogeneic transfusions in the United States (1). Patients undergoing reoperative coronary artery bypass grafting (CABG) and combined procedures, including CABG and valve replacement, are at increased risk for exposure to allogeneic blood products (2,3). Whereas multiple etiologies may contribute to coagulopathy after cardiopulmonary bypass (CPB), platelet dysfunction is believed to be the most common cause of nonsurgical bleeding after CPB, often requiring perioperative transfusion of both allogeneic red blood cells and platelets (4). Pre-CPB sequestration of autologous platelet-rich plasma (PRP) is thus one potential solution to the problem of bleeding and transfusion in cardiac surgery. The concept of removing platelets from a patient immediately before CPB, thereby potentially sparing platelets many of the insults associated with CPB, followed by post-CPB platelet reinfusion, seems a reasonable approach to the problem of postbypass platelet dysfunction and bleeding. Earlier studies examining the efficacy of PRP sequestration in primary CABG patients described a reduction in either mediastinal chest tube drainage or in allogeneic red blood cell transfusion (5–9). In contrast, more recent, prospective, randomized, and blinded studies reported no significant transfusion-sparing or hemostatic effect of PRP sequestration in either primary CABG surgery (10) or reoperative valve surgery (11). However, these recent studies obtained an average of only 2.7 units of platelets per patient before CPB. One unit of platelets is equivalent to 5 x 1010 platelets; the American Association of Blood Banks guidelines for an effective platelet pheresis product for storage and allogeneic use require collection of a minimum of 3 x 1011 platelets (6 units) (12). These low platelet yields, rather than study methodology, could have accounted for the reported lack of efficacy regarding bleeding and transfusion requirements. We therefore hypothesized that reinfusion of a therapeutic quantity of autologous platelets harvested before CPB would reduce the need for allogeneic platelet transfusion, as well as reduce bleeding and total allogeneic transfusion requirements in cardiac surgery patients at moderately high risk for bleeding and allogeneic transfusion.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The protocol was approved by our institutional review board, and all patients signed written, informed consent forms. Sixty-two patients undergoing reoperative CABG or combined CABG and valve replacement were prospectively enrolled and, for each procedure, randomized to either a control group or a group that underwent pre-CPB platelet sequestration. All patients enrolled had a preoperative platelet count >150,000/µL, a hematocrit (Hct) >30%, an ejection fraction >30%, and an aortic valve area >=0.5 cm2. None of the patients had been on IV heparin within 12 h of operation, on ticlopidine within 2 wk of operation, or on mechanical ventricular assist devices within 72 h before or after operation. All patients received {epsilon}-aminocaproic acid (EACA) administered by initiation of a preincision loading dose of 150 mg/kg over 30 min, followed by a 20 mg · kg-1 · h-1 infusion throughout the operation; in addition, 75 mg/kg was added to the CPB circuit priming volume.

Platelet-rich plasmapheresis was performed with the AT1000 manufactured by Medtronic Electromedics, Inc. (Parker, CO). Blood removal was accomplished via the sideport of a 9F introducer sheath (Braun, Bethlehem, PA) placed in the right internal jugular vein. Blood was initially removed from the patient at a rate of 100 mL/min at a centrifuge speed of 5600 rpm. Patients were given a total of 250–500 mL of 5% albumin for volume repletion before and during the pheresis procedure. The blood removal rate could be reduced based on the hemodynamic condition of the patient. Once the centrifuge bowl was filled, the centrifuge speed was reduced to 2400 rpm and the PRP was removed at a blood draw rate of 50 mL/min. The PRP removed consisted of the buffy coat and a 1-min elution of the red cell layer. Each such removal constituted a single "pass" in the pheresis procedure. Pheresis occurred from the time of anesthetic induction and 9F internal jugular introducer placement until heparin administration. A maximum of six passes was permitted. Platelet-poor plasma and red blood cell components were returned to the patient. All patients in the study also received intraoperative red cell salvage with the AT1000. Salvaged red blood cells were returned to the patients before departing the operating room (OR).

All patients received fentanyl, midazolam, and isoflurane for anesthesia and vecuronium or pancuronium for muscle relaxation. CPB was conducted with nonocclusive roller pump, membrane oxygenator, arterial line filtration, and cold crystalloid or blood:crystalloid (4:1) hyperkalemic arrest. Hemoconcentration was used to maintain a Hct of >=18% during CPB as long as the venous reservoir volume was adequate. Activated clotting time (ACT) was measured with kaolin activator (HemoTec; Medtronic Electromedics) and maintained at greater than 400 s as a measure of adequate anticoagulation during CPB. Systemic hypothermia to a bladder temperature of 24°–34°C was maintained during aortic cross-clamping. At the termination of CPB, protamine was administered at 10–13 mg/1000 units of initial heparin bolus; additional doses of protamine (50–100 mg) were administered at the discretion of the surgeon and/or anesthesiologist, either in an attempt to return to baseline ACT or based on results obtained from the Heparin-Management System (Medtronic Electromedics) to assess adequacy of heparin reversal. Total heparin and protamine doses were recorded, as was the lowest recorded bladder temperature during bypass. Preoperative and postoperative coagulation variables (platelet count, prothrombin time [PT], international normalized ratio, activated partial thromboplastin time, and fibrinogen concentration) were measured. Post-CPB and post-PRP reinfusion platelet counts were also measured. Allogeneic transfusions and mediastinal chest tube drainage were recorded. The direct costs to the hospital (not patient charges) for additional disposables used for pheresis, for colloid (5% albumin), and for allogeneic platelets, fresh frozen plasma (FFP) and packed red blood cells (PRBCs) were determined for both control and pheresis patients.

Seven different anesthesiologists and seven different surgeons participated in the study. A study coordinator or assistant was present and supervised the transfusion protocol in the OR and postoperatively in the intensive care unit (ICU) for 8 h. Uniform transfusion criteria were enforced as follows: PRBCs were transfused for a Hct <=24% before commencement of CPB and after termination of CPB. Clinical bleeding requiring treatment was first diagnosed by the attending anesthesiologist and attending cardiac surgeon before the algorithm guiding treatment was used. Clinical bleeding was defined as copious mediastinal bleeding that would preclude safe closure of the mediastinum before the end of surgery or by a postoperative chest tube output of >200 mL/h for 2 h or longer. In the setting of post-CPB clinical bleeding, residual heparin effect was first excluded (HMS, Medtronic Electromedics), and careful inspection for surgical bleeding was performed. Subsequently, in the setting of clinical bleeding, allogeneic platelets were administered for platelet count <100,000 µL, FFP was administered for PT >150% of normal, and cryoprecipitate for fibrinogen <100 mg/dL. Finally, in the setting of clinical bleeding requiring therapy, and only subsequent to exclusion of surgical bleeding or other demonstrable etiology of coagulopathy as defined herein, allogeneic platelets were administered for presumed platelet dysfunction.

A power analysis based on the transfusion of allogeneic platelets in our study population revealed that detection of a 75% reduction in allogeneic platelet transfusions with 80% power and {alpha} = 0.05 required a total of 54 patients to be studied. Statistical analysis included Student’s t-test for parametric data, expressed as mean ± SD. Nonparametric data were expressed as median (25–75 quartiles) or median (range) and were analyzed by the Mann-Whitney ranked sum test. Binary data were analyzed with Fisher’s exact probability test. P < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Of the 62 patients enrolled, 55 completed the study. Five were excluded from analysis because they were placed on mechanical assist devices within 72 h of operation. Two patients were excluded from analysis for protocol violations: one having undergone platelet sequestration had received heparin within 12 h of operation (and subsequently received no perioperative allogeneic blood products); the other underwent pre-CPB platelet sequestration, had only 50-mL chest tube drainage in the first postoperative hour, but allogeneic platelets were administered in the ICU rather than returned to the blood bank per surgeon desire. Thus, 55 patients, including 19 patients undergoing reoperative CABG and 36 patients undergoing combined CABG plus valve replacement, remained in the study for analysis. Data were analyzed for 29 control patients (10 reoperative CABG, 19 combined CABG-valve replacement) and 26 treatment (pheresis) patients who underwent pre-CPB PRP sequestration (9 reoperative CABG, 17 combined CABG-valve replacement). When comparing the two groups, there was no significant difference detected between the pheresis and control patients with respect to preoperative characteristics, including age, weight, Hct, platelet count, or aspirin therapy (Tables 1 and 2). Approximately 50% of both treatment and control patients had received aspirin within 5 days before operation. In addition, there were no significant differences between groups for several intraoperative variables, including the duration of CPB, which on average exceeded 2 h for both groups, or the total heparin and protamine doses received (Table 1). The mean 24-h-postoperative and discharge Hcts were identical for the two groups. Perioperative coagulation variables, measured preoperatively, on arrival in the ICU and 24 h postoperatively, were not significantly different between control and pheresis groups (Table 2).


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  		Table 1. Patient Demographics and Perioperative Characteristics
 

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  		Table 2. Perioperative Coagulation Data
 
The mean pre-CPB platelet yield sequestered with this methodology was 6.2 ± 2.1 units of platelets per patient (mean ± SD). This equates to a mean of 3.1 x 1011 platelets sequestered per patient (12). The mean volume of PRP was 567 ± 169 mL; mean platelet concentration in the PRP was 560,000 ± 189,000/µL. This therapeutic quantity (12) was obtained with a mean of 4.5 ± 1 passes in a mean pheresis time of 44 ± 9 min. As shown in Table 2, the mean patient postpheresis platelet count was 143,000/µL, compared with the pheresis patients’ preoperative mean of 213,000/µL. Only 4 patients had postpheresis platelet counts <100,000/µL; these platelet counts were 95, 94, 85, and 65 x 103/µL. Platelet counts after CPB were significantly decreased from preoperative values for both control and pheresis patients (P < 0.01, Table 2). Platelet counts were not significantly different between control and pheresis patients, either before or after reinfusion of PRP (Table 2). ICU arrival and 24-h postoperative platelet counts were also not significantly different between control and pheresis groups (Table 2).

Figure 1 depicts allogeneic platelet and PRBC transfusions. The percentage of patients receiving platelet transfusions is shown for both the control group and the pheresis group. Eight of 29 patients in the control group (28%) received allogeneic platelet transfusions. Three control patients received 6 units of platelets, 4 patients received 8 units of platelets, and 1 patient received 6 units of platelets twice (with posttransfusion platelet count = 107,000/µL). None of the 26 patients who underwent prebypass PRP sequestration received allogeneic platelet transfusions. This difference between groups was significant (P < 0.01). Forty-five percent of patients (13/29) in the control group received PRBC transfusions versus 31% of patients (8/26) in the pheresis group. Median PRBC transfusion was 0 units for both groups. Total allogeneic units transfused (platelets, FFP, and PRBCs) were significantly reduced for pheresis patients (P < 0.02, Table 3). The control group was transfused with allogeneic PRBCs at a mean amount of 1.2 units per patient; the pheresis group received 0.7 unit per patient (Table 3, P = 0.35). Mediastinal chest tube drainage was not significantly different between control and pheresis groups (Table 3).



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  		Figure 1. Percentage of patients receiving allogeneic platelet transfusions and packed red blood cell transfusions. Pheresis patients underwent sequestration of platelet-rich plasma prior to cardiopulmonary bypass, followed by reinfusion of sequestered platelets after protamine administration. There was a significant reduction in the percentage of pheresis patients who received allogeneic platelets.

 

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  		Table 3. Blood Loss and Transfusion Data
 
Retrospective analysis of the appropriateness of allogeneic transfusion and adherence to the transfusion algorithm showed that eight control patients had post-CPB platelet counts <100,000 and, per protocol, in the absence of clinical bleeding, were not transfused with allogeneic platelets. Eight control patients with clinical bleeding received allogeneic platelets, after exclusion of surgical bleeding and residual heparin effect. Of these eight patients, four had platelet count <100,000/µL, and three patients had platelet counts equaling 110,000, 112,000, and 117,000/µL. Of these latter three patients, two had PT and fibrinogen valves that did not justify transfusion with FFP or cryoprecipitate per algorithm. One bleeding patient had PT 150% of normal and received plasma but also required therapy with allogeneic platelets to achieve hemostasis. One control patient that had a platelet count of 173,000/µL had clinical bleeding, no surgical source of bleeding, documented reversal of heparin (by ACT and protamine titration), a PT of 14.4 s and a fibrinogen of 365 mg/dL. The surgeons felt that treatment with platelets (the next step in the algorithm) was necessary for closure before leaving the OR. After allogeneic platelet transfusion, the bleeding stopped. None of the pheresis patients had significant bleeding, according to the attending anesthesiologist and surgeon, that justified therapy in the OR per algorithm, nor did any of the treatment patients have postoperative mediastinal chest tube drainage >200 mL/h for 2 or more h. Only 4 of 26 pheresis patients had post-CPB, postreinfusion platelet counts <100,000 per µL; these platelet counts were: 98,000, 98,000, 97,000, and 96,000/µL.

Whereas pheresis patients did experience increased colloid administration (34% of control patients, 100% of pheresis patients), the protocol specifically called for 5% albumin infusion to begin before commencement of pheresis. In addition, there was no significant difference between control and pheresis patients with respect to vasopressor administration pre-CPB (Table 1). Two patients in the control group received allogeneic FFP for bleeding and PT >150% normal, and no patients in the study received allogeneic cryoprecipitate. None of the four patients with postpheresis, pre-CPB platelet counts <100,000/µL received allogeneic PRBCs or hemostatic blood components. No patient in the study returned to the OR because of bleeding. Rates of myocardial infarction (Q wave infarction documented by serial electrocardiograms), stroke (new focal neurologic deficit), mechanical assist device placement, dialysis-dependent renal failure, or death were not increased in the patients who underwent PRP sequestration, but these were not primary end points of the study, and the study population was too small to provide meaningful conclusions regarding the lack of statistical difference between groups for these low-frequency events.

The direct cost savings with PRP sequestration were determined. When accounting for the cost of disposables needed for pheresis (beyond that required for routine intraoperative red cell salvage), colloid administration, and allogeneic platelets, PRBCs and FFP, the cost of pheresis and allogeneic transfusion was US $164 per patient. This compared with a cost of US $300 per patient for colloid administration and allogeneic transfusion in the control group. PRP sequestration thus netted a direct cost savings of US $136 per patient in this group of reoperative CABG and combined CABG-valve replacement patients.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Cardiac surgery accounts for a substantial proportion of allogeneic transfusion in the United States (1). These transfusions are accompanied by well known risks and costs (13). Multiple etiologies may contribute to post-CPB coagulopathy and bleeding, including dilutional thrombocytopenia (14), dilution of coagulation factors (15), fibrinolysis (16), inadequate reversal of heparin (17), and excess administration of protamine (18). Platelet dysfunction, however, is believed to be the most common cause of nonsurgical bleeding after CPB, often requiring perioperative transfusion of both allogeneic red blood cells and hemostatic blood components, including allogeneic platelets (4).

PRP sequestration before CPB, with reinfusion of the autologous platelets after CPB, is one potential solution to the problem of bleeding and transfusion in cardiac surgery. The present prospective, randomized study of pre-CPB platelet sequestration in cardiac surgery patients at moderately high risk for bleeding and allogeneic transfusion demonstrates significant reduction in the percentage of patients exposed to allogeneic platelet transfusions and significant reduction in total allogeneic units transfused among patients undergoing PRP sequestration. With our methodology, more than 6 units of autologous platelets were sequestered per patient, consistent with an accepted therapeutic dose (12). Moreover, the average time for obtaining this platelet yield was an acceptable 44 minutes, occurring from the time of anesthetic induction and 9F introducer placement to the time of heparin administration. Significantly fewer patients (zero) in the pheresis group were transfused with allogeneic platelets, noteworthy for a group of reoperative CABG patients and combined CABG-valve patients (2,3), particularly given that the mean CPB time exceeded two hours for both the control and treatment groups in the present study. Although the number of platelet units transfused was not significantly different between the groups (median = 0 for both groups), when a patient received a platelet transfusion, it often represented 6–8 donor exposures. Therefore, a significant reduction in the frequency of allogeneic platelet transfusion by pre-CPB pheresis, as we observed, confers a significant benefit to those patients who are able to avoid transfusion with pooled donor platelets.

Bleeding and isolated allogeneic PRBC transfusion were not significantly reduced in the pheresis group. This lack of a significant measurable reduction in bleeding and allogeneic PRBC transfusion alone is, in retrospect, not surprising given the overall low magnitude of bleeding and PRBC transfusion that ultimately occurred in the study population. To detect a difference in PRBC transfusion incidence as we observed (45% of control patients versus 31% of pheresis patients), with 80% power and {alpha} = 0.05, a total of 376 patients would have to be studied. This minimal bleeding and allogeneic PRBC transfusion requirement likely reflects the use of an enforced transfusion algorithm (19), with resultant appropriate PRBC transfusion therapy and appropriate use of hemostatic blood components when indicated, and the use of appropriately dosed EACA for all patients. Recent prospective, randomized, and placebo-controlled studies with the synthetic antifibrinolytics, EACA and tranexamic acid, have demonstrated a reduction of mediastinal drainage and allogeneic red blood cell transfusion in both primary and reoperative cardiac surgery (20,21). Sparing of allogeneic platelet transfusions has not been demonstrated for the synthetic antifibrinolytics. As previously indicated, total allogeneic units transfused was significantly reduced for pheresis patients, reflecting the combined reduction of both allogeneic platelet and PRBC transfusion.

It is worth noting that none of the patients enrolled was unable to complete the pheresis procedure because of significant hemodynamic instability. There was no difference in the documented incidence of vasopressor use before commencement of CPB, suggesting the ability to sequester platelets from these patients safely and efficiently. Whereas the protocol called for colloid administration during the pheresis procedure, crystalloid administration alone may be adequate for volume repletion; this practice is being evaluated.

Several studies of PRP sequestration suggested efficacy in reducing either mediastinal chest tube output or PRBC transfusion; these studies were performed in primary CABG patients at lower risk for bleeding complications (5–9). Not all of these studies were prospective or randomized, and none was blinded. Furthermore, the reported mean platelet yields exceeded 4.8 units per patient in three of the studies, but two studies reported mean platelet yields of only 3.0 units per patient. Although it is possible that, in a population at low risk for bleeding and platelet dysfunction, such as primary CABG, a lower quantity of platelets might be effective in enhancing post-CPB hemostasis, study bias cannot be excluded as an explanation for the reported efficacy of PRP observed in studies with low platelet yields. More recent studies, with the advantage of being prospective, randomized, and blinded, reported no significant hemostatic or transfusion-sparing efficacy of PRP sequestration in either primary CABG surgery (10) or reoperative valve surgery (11). However, these studies sequestered a mean of only 2.7 units of platelets per patient before CPB, a quantity that could be considered almost predictably subtherapeutic (12,22). Thus, despite an otherwise excellent study design, the low platelet yields obtained with the pheresis methodology in these latter studies could have accounted for the reported lack of efficacy. More recent evidence from Christenson et al. (23) suggested that pre-CPB platelet sequestration, with therapeutic platelet yields, could in fact reduce allogeneic transfusions in patients at moderately high risk for bleeding, specifically in reoperative CABG patients. Unfortunately, that prospective study excluded patients in whom a therapeutic platelet yield could not be obtained. This exclusion criteria might well have introduced bias into the study, because the same patients that do not tolerate the pheresis procedure might be at higher risk for other complications, including longer CPB times, and thus for a higher incidence of platelet dysfunction and bleeding. Moreover, the methodology used by Christenson et al. required an average of seventy-two minutes because a direct withdrawal technique was not used. Most importantly, no discussion or presentation of results regarding the effect of PRP sequestration on allogeneic platelet transfusions, with the potential for multiple donor exposures, was presented. In contrast to our study, none of the studies of PRP sequestration in the literature has incorporated concomitant therapy with known hemostatic, transfusion-sparing, and cost-effective antifibrinolytic therapy (20,21).

Limitations of our study include the lack of blinding of the OR personnel to the pheresis procedure, which could have potentially biased practitioners to avoid allogeneic transfusion in the pheresis group or overtransfuse the control group. Although study bias can never be completely excluded in an unblinded study, several observations argue against the presence of bias in the present investigation. Seven anesthesiologists and seven surgeons participated in the implementation of a uniform transfusion algorithm, enforced by a study coordinator intraoperatively and the first eight hours postoperatively. Clinical bleeding was diagnosed by the attending anesthesiologist and surgeon. Several patients in the control group had post-CPB platelet counts of less than 100,000/µL, but were not transfused with allogeneic platelets in the absence of clinical bleeding requiring treatment. In fact, only one bleeding patient had a platelet count >117,000/µL and received allogeneic platelets per protocol; exclusion of this patient from analysis would not have affected the significance of the results with respect to decreased allogeneic platelet transfusions or total allogeneic donor exposures for pheresis patients. Retrospective analysis of all allogeneic platelet transfusions demonstrated the appropriateness of the transfusions and adherence to the transfusion algorithm. In addition, there was no difference in either postoperative Hct or discharge Hct between the control and pheresis groups, also arguing against bias toward reduced transfusion of either platelets or red blood cells in the pheresis group. If platelet transfusions were inappropriately withheld from the pheresis patients, either a lower postoperative or discharge Hct caused by excessive bleeding or a higher rate of mediastinal chest tube drainage or PRBC transfusion in the face of untreated coagulopathy and bleeding would be expected; none of these phenomena was observed. It is also worth noting that blinding of the study would have involved pheresis of all patients with pre-CPB return of the autologous platelets in the control group, and this would therefore have precluded obtaining information regarding the relative safety of the procedure with respect to tracking the incidence of vasopressor use in the pheresis group or the proportion of patients that would have to be excluded from pheresis due to hemodynamic instability. An additional shortcoming of this and all studies to date regarding PRP sequestration is the lack of an accepted, rapid, and reliable measure of platelet function post-CPB (24), other than the clinical criteria we used in the present study algorithm (absence of other demonstrable coagulopathy, quantity of mediastinal chest tube drainage, and appearance of surgical field, including diffuse microvascular bleeding) (25).

Future studies of this promising technique might include a blinded-study design with the current methodology that efficiently sequestered a therapeutic quantity of platelets; a study that included a rapid, reliable evaluation of post-CPB platelet function, when available, to further guide allogeneic platelet transfusion; and also studies to further define the appropriate patient populations that would benefit from sequestration of a therapeutic quantity of platelets before CPB, both in terms of efficacy and cost-effectiveness.

In conclusion, reinfusion of a therapeutic quantity of platelets sequestered pre-CPB appeared effective in decreasing both the frequency of allogeneic platelet transfusion and the total allogeneic units transfused in complex cardiac surgery. In addition, the efficacy and cost-savings of pre-CPB platelet sequestration in patients undergoing reoperative CABG, or combined CABG and valve replacement, were demonstrated in the presence of antifibrinolytic therapy.

In the February 2000 article by Patrizia Ceccarelli et al. (2000;90:482–8), "Inhaled Nitric Oxide Delivery by Anesthesia Machines," an author was omitted from the title page. The correct list is Patrizia Ceccarelli, MD, Luca M. Bigatello, MD, Dean Hess, RRT, PhD, Jean Kwo, MD, Luis Melendez, BET, and William E. Hurford, MD.


   Acknowledgments
 
This work was funded, in part, by a grant from Medtronic Electromedics, Inc.


   Footnotes
 
This work was presented in part at the American Society of Anesthesiologists Annual Meeting, New Orleans, LA, October 1996 and has appeared as an abstract in Anesthesiology 1996;85:A67; and at the European Association of Cardiothoracic Anesthesiologists Annual Meeting, Thessaloniki, Greece, June 1997 and has appeared as an abstract in British Journal of Anesthesia 1997;78:A70.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication November 2, 1999.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press