Coagulation Disorders and Blood Product Use in Patients Undergoing Thoracoabdominal Aortic Aneurysm Repair

Coagulation Disorders and Blood Product Use in Patients Undergoing Thoracoabdominal Aortic Aneurysm Repair Claudio S. Cina ` and Catherine M. Clase Repair of thoracoabdominal aortic aneurysms (TAAA) is associated with major blood loss, often exceeding the patient’s intravascular volume, and complex intraoperative and postoperative coagulopathies necessitating large-volume transfusion of blood products. Abnormalities sufficient to cause thrombocytopenia or clinically important prolongation of clotting parameters are rarely present before surgery in elective aneurysms but are more common with ruptured aneurysms. The finding of intraoperative and postoperative deficiencies of clotting factors, along with thrombin generation and activation of

the thrombolytic system, is reflective of massive blood losses, visceral ischemia, and massive transfusions. An aggressive strategy of transfusion of blood products is critical to the prevention of clinically significant coagulopathy during surgery. Adjuncts to reduce blood losses and blood product use include low-dose aprotinin or e -aminocaproic acid, intraoperative blood salvaging, and acute normovolemic hemodilution. In TAAA repair, an average blood loss of 5000 to 6000 mL and average transfusion of allogeneic blood products of 50 to 60 U are to be anticipated. A 2005 Elsevier Inc. All rights reserved.

HORACOABDOMINAL aortic aneurysms (TAAA) are traditionally defined as aneurysms involving either the thoracic and abdominal aorta or the suprarenal segments of the abdominal aorta. Treatment is graft replacement of the diseased segment of the aorta, requiring extensive exposure, temporary aortic, visceral and intercostal artery occlusion, and revascularization of these arteries. Thoracoabdominal aortic aneurysm affect 10% of patients with aneurysms of the aorta.1 Aortic aneurysms occur in 1% to 4% of the total population older than 50 years and cause 1% to 3% of all male deaths older than 65 years.2,3 Greater longevity, improved detection, and better community awareness of this disease are likely to lead to increasing numbers of patients undergoing major aortic surgery. According to the extent of the disease, thoracoabdominal aortic aneurysms are classified as follows4: group I, aneurysms of most of the descending thoracic and upper abdominal aorta (24%); group II, aneurysms of most of the descending thoracic aorta and most of the abdominal aorta (26%); group III, aneurysms of the distal descending thoracic aorta and most of the abdominal aorta (26%); and group IV, aneurysms of the abdominal aorta including visceral vessels segment (24%). This classification has prognostic significance in terms of results and complications. Repair of TAAA is associated with major blood loss often exceeding the patient’s intravascular volume and complex intraoperative and postoperative coagulopathies necessitating large-volume transfusion of blood products.5-7 Moreover, the

presence of coagulopathy causes excessive postoperative bleeding which may result in need for surgical reexploration and additional morbidity and mortality.8,9 All these issues combine to create a substantial burden on the limited resource of blood products.9

T

HEMOSTASIS IN THORACOABDOMINAL AORTIC ANEURYSM

Coagulation disorders represent an important aspect of the management of patients with TAAA. Coagulation abnormalities have been described before, during, and after surgery. Hemorrhage is responsible for deaths in 12% to 38% of patients in several series10-12 and frequently is the consequence of severe coagulopathy rather than technical problems. Coagulation Abnormalities Before Surgery Preoperative disturbances of coagulation were first described in a case report of clinical and laboratory evidence of disseminated intravascular coagulation (DIC) in a patient with an acute dissection of the thoracic aorta.12 Since this report, further cases of DIC coexisting with elective,13-15

From the Division of Vascular Surgery, and Division of Nephrology, McMaster University, Hamilton, Canada. Address reprint requests to Dr Claudio S. Cina`, Victoria Medical Centre, 304 Victoria Avenue North, Suite 305, Hamilton, ON, Canada L8L 5G4. 0887-7963/05/$ – see front matter n 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.tmrv.2004.11.003

Transfusion Medicine Reviews, Vol 19, No 2 (April), 2005: pp 143-154

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inflammatory,16 and ruptured abdominal aortic aneurysms17-19 and with elective thoracoabdominal aneurysms20 have appeared in the literature. Most case reports and even case series17 of DIC in this setting give no indication of the size of the pool of patients from which their cases were drawn and do not permit an estimation of the incidence of the problem. However, the prospective study of Fisher et al20 describes 76 consecutive aortic aneurysms evaluated at a single quaternary referral center in a 6-month period. Three (9%; 95% confidence interval [CI] 2%-25%) of 32 TAAA and none (95% CI 0%-8%) of 44 AAA were associated with frank DIC; however, isolated elevation of fibrin degradation products (FDP), without other evidence of consumption coagulopathy (ie, absence of clinical bruising or bleeding and normal platelet counts), was noted preoperatively in 14% of TAAA and 8% of infrarenal AAA, suggesting that a compensated process may obtain in at least a proportion of these patients preoperatively. Results were not presented separately for acute and elective problems. In a series of 84 patients with ruptured and unruptured AAA, reported by Getaz and Louw,18 no patients had preoperative clinical evidence of DIC. However, of the patients with ruptured aneurysms, 50% (95% CI 28%-68%) had platelet counts less than 150
109/L, and 56% (95% CI 35%-74%) had 1 or more abnormalities of coagulation. Thrombocytopenia was observed in 28% (95% CI 17%-42%) of patients with unruptured aneurysms. This study is subject to ascertainment bias (only 67% of ruptured and 18% of unruptured aneurysms having had the relevant laboratory determinations) that may have led to overestimation of the incidence of the problem. In a series of 32 elective patients with aortic disease,21 a 3% incidence of preoperative abnormality in prothrombin time (PT) and partial thromboplastin time (PTT) was reported, and no patient had abnormal levels of platelets or fibrinogen. The inclusion in this report of a number of patients with nonaneurysmal disease likely results in underestimation of the incidence of coagulation abnormalities. Another small series of elective AAA22 found entirely normal PT, PTT, and thrombin clotting time in these patients. In contrast to these results, in a larger series of ruptured AAA,23 16 (37%, 95% CI 23%-53%) of 43 patients had prolongation of

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international normalized ratio (INR) and the same proportion, thrombocytopenia. The preoperative prevalence of DIC and of coagulation disturbances in patients with aneurysms is further complicated by the different definitions of DIC and the variability of the tests used over time and in different studies. Other studies have reported more subtle disturbances in coagulation. A report of 20 consecutive patients with TAAA or thoracic dissection found levels of antithrombin, FDP, thrombin-antithrombin complex, and a 2-antiplasmin–plasmin complex to be elevated preoperatively, with normal levels of fibrinogen.6 Very similar results have been obtained in AAA, with the additional documentation of normal clotting parameters by routine testing.7 However, bleeding time, activated PTT, PT, thomin time (TT), serum plasminogen, a 2-antiplasmin, serum fibrinogen, and FDP were all within the laboratory reference range in the series of 33 patients undergoing TAAA repair of Godet et al.24 Baseline parameters in these patients did not predict the development of intraoperative hemorrhagic complications. Illig et al in a group of 10 patients with more extensive suprarenal AAA and 8 patients with AAA confined to the infrarenal aorta showed that hemostatic parameters before surgery were normal except for elevation in d-dimer (1466 F 377; normal, b400 ng/mL), and there were no differences according to the extent of disease.25 We reported preoperative coagulation parameters in 30 consecutive patients undergoing TAAA repair.26 No patients had a history of easy bruising or physical evidence of petechiae, and none had thrombocytopenia. No patient (95% CI 0%-12%) with elective or ruptured aneurysm had a platelet count less than 150
109/L. Two (10%, 95% CI 1%-29%) of 22 elective and 1 (13%, 95% CI 0%50%) of 8 ruptured had PT prolongation greater than an INR of 1.2 s; 3 (14%, 95% CI 3%-35%) of 22 elective and no patient (95% CI 0%-37%) with a ruptured aneurysm had PTT prolongation greater than 34 s. Descriptive statistics of coagulation parameters for patients with elective aneurysms and ruptured aneurysms and control patients without aneurysms are summarized in Table 1. Preoperative hemoglobin, INR, PTT, and platelet count differed between the 3 groups. Patients with aneurysms, whether elective or ruptured, had PTT significantly prolonged (mean difference 4.5 s, 95% CI 0.5-9.0 s, P b .05) compared with controls. Not

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Table 1. Preoperative and Postoperative Coagulation Parameters in Patients With Elective Thoracoabdominal Aortic Aneurysm Repairs Elective Total (n = 22)

Preoperative Hemoglobin (g/L) INR PTT Platelets Postoperative Hemoglobin (g/L) INR PTT (s) Platelets (
109/L)

Non-ANHPET (n = 15)

ANHPET (n = 7)

Ruptured (n = 8)

134 1.1 29 258

F F F F

12 0.2 4y 88

131 1.1 30 273

F4 F 0.1 F1 F 101

134 1.1 27 225

F F F F

12 0.2 3 40

99 1.1 30 319

F F F F

9 0.1 1y 102

117 1.2 31 185

F F F F

9 0.1 5 54

116 F 9 1.2 F 0.1 34 F 5z 169 F 14§

119 1.2 26 218

F F F F

16 0.1 2 70

108 1.24 41 135

F F F F

17 25 68 62

Controls* (n = 10)

127 1.1 25 233

F F F F

11 0.1 5 70

na na na na

NOTE. Treated with and without ANHPET, ruptured thoracoabdominal aneurysms, and in controls: sequential cohort study. Data shown are mean values F SDs. Abbreviations: ANHPET indicates acute normovolemic hemodilution and partial exchange transfusion; na, nonapplicable. *Controls were patients undergoing carotid endarterectomy who had no evidence of aneurysmal disease by ultrasound (aorta b3 cm in maximum diameter). yP b .05 elective vs controls, and ruptured vs controls. zP b .01 Non-ANHPET vs ANHPET. §P b .05 Non-ANHPET vs ANHPET.

surprisingly, hemoglobin levels were lower (mean difference 33 g/L, 95% CI 15.5-61.5 g/L, P b .001) in the ruptured aneurysm group compared with other groups. It appears that some patients with extensive aneurysmal disease may have preoperative activation of coagulation and thrombolytic pathways, which is sufficiently low grade to be compensated in terms of fibrinogen synthesis. The correlation between the internal surface area of aneurysms and the degree of activation of coagulation and thrombolysis,7 together with the scintigraphic localization of radiolabeled fibrinogen17 and platelets 27 to the wall of aneurysms, implicates the aneurysm itself in the pathogenesis of this dysregulation of hemostasis. The clinical importance of these findings, however, is not known. Coagulation Changes During and Immediately After Surgery Surgery for TAAA is associated with major blood loss necessitating large-volume transfusion.5-7,28 Plasma procoagulants are diluted by transfusion of stored blood and crystalloid causing prolongation of PT and PTT. For each 500 mL of blood loss that is replaced in an adult with red cells devoid of plasma, a 10% decrease in the concentration of clotting proteins might be anticipated. If the coagulation proteins fall to 25% of

normal, bleeding may occur based on dilutional coagulopathy.29 A similar dilutional effect on platelet concentration can be seen with massive transfusion.30 In an adult, each 10 to 12 U of transfused red cells can produce a 50% fall in the platelet count.30 The common denominator of all surgeries for TAAA is the need for supraceliac clamping and ischemia of the visceral arteries. In a dog model of visceral ischemia without bleeding, Cohen et al31 showed that platelet levels dropped to 64% of baseline level after 30 minutes of supraceliac clamping, to 43% after 60 minutes, and to 20% after 90 minutes. Seven hours after the experiment, fibrinogen levels were 60% of baseline levels after 30 to 60 minutes of clamping and 40% after 90 minutes. Because the severity of coagulation abnormalities was correlated to the duration of clamping, the authors interpreted these findings as expression of DIC caused by visceral ischemia and reperfusion injury. In a case-control study of 10 patients (8 patients undergoing infrarenal aortic surgery and 2 undergoing TAAA repair) who developed severe coagulopathy, compared with matched controls who did not, Levy et al32 described an association between liver ischemia and DIC. Nine of the case patients died, and autopsy performed in 7 patients demonstrated extensive liver necrosis.

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Godet et al24 studied 33 patients undergoing TAAA repair. In this series, blood products (red blood cells [RBCs], fresh frozen plasma [FFP], and platelets) were not given prophylactically, but only when hematocrit fell to below 30% or abnormal coagulation parameters (laboratory or clinical) developed. During surgery, before clamping of the thoracic aorta, a picture of hemodilution was observed in all patients: reduction in serum proteins, hematocrit, platelets, plasminogen, and a 2-antiplasmin. Even at this stage, however, levels of FDP and tissue plasminogen activator (t-PA) antigen increased from baseline. Eight patients developed significant intraoperative coagulopathy and 3 died. In these patients, an increased thrombolytic activity was noted after unclamping and in the immediate postoperative period. Gertler et al33 prospectively evaluated the causes of coagulopathy during TAAA repair in 19 consecutive patients. All surgeries were done without the use of heparin or extracorporeal bypass, with administration of clotting factors primarily based on clinical observation and blood turnover. In addition, based on the hypothesis that the duration of visceral ischemia is related to the severity of coagulopathy, prophylactic earlier administration of clotting factors and inhibitors of thrombolysis was used in those patients in whom prolonged clamp times were anticipated. Clotting factors (II, V, VII, VIII, IX, X, XI, and XII) and fibrinogen were reduced, and d-dimer and prothrombin fragment F1.2 increased, 30 minutes after supraceliac clamping. However, clinical coagulopathy did not occur, perhaps because of the preemptive approach to management of coagulopathy. In patients who underwent supraceliac clamping for pararenal aortic aneurysm repair, compared with patients who underwent infrarenal clamping, Illig et al34 demonstrated a significant increase in FDP ( P = .02), an increase in t-PA activity ( P = .0006), and a decline in a 2-antiplasmin levels ( P b .002). Similarly, in 59 patients with thoracic aneurysms or dissection who underwent endovascular stent grafting, a significant decrease in platelet count and antithrombin and a significant increase in a 2-antiplasmin–plasmin complex, FDP, and d-dimer were observed on the first day after surgery.35 However, routine clinical laboratory values were relatively normal after surgery in our cohort of 22 patients undergoing elective TAAA repair (Table 1).36 In this cohort, the strategy of

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blood product transfusion, in the context of hypotension or observed brisk bleeding, was to transfuse allogeneic RBCs and FFP (in a 1:1 ratio) replacing estimated losses, volume for volume. These studies suggest a uniform deficiency of clotting factors, likely dilutional, thrombin generation, and activation of thrombolysis. Mesenteric and liver ischemia appears to play a role in the latter 2 processes. The contribution of this coagulopathy to overall blood losses cannot be easily estimated. However, in the setting of prolonged mesenteric or liver ischemia, hypotension, hypothermia, or acidosis, systemic thrombolysis may develop that is clinically important and occasionally may lead to devastating hemorrhage.37 When prolonged clamping of the thoracic aorta or the intra-abdominal supraceliac aorta is required, systemic thrombolysis may result in a coagulopathy more severe than that produced by dilution or consumption of coagulation factors. In such cases, preemptive coagulation factor support and antithrombolytics may prove valuable. Coagulation Disorders After Repair of Aneurysms The activation of the coagulation and thrombolytic systems identified in patients with aortic aneurysms and dissections seems to improve on long-term follow-up after surgical repair38 but still persists in short, intermediate, and long-term follow-up.7,39 Holmberg et al40 reported 18 patients who underwent repair of infrarenal aortic aneurysms. Prothrombin fragments 1 and 2, thrombinantithrombin complex, and FDP were significantly higher before surgery than those found in agematched healthy controls; they were significantly lower in the postoperative period, but at a median follow-up of 19 (5-37) months, these markers of activation of coagulation and thrombolysis were still higher than those found in the control group. These changes, however, were clinically nonsignificant. The limitation of this study is that no information is given regarding the existence of aortic pathology in the thoracic aorta. The existence of unknown aneurysm or dissection at this level may contribute to persistence of abnormal coagulation parameters, as reported by Cummins et al.41 Other mechanisms, however, may be responsible for persistent activation of coagulation compared with normal controls: age, the presence of non-

COAGULATION AND BLOOD PRODUCT UTILIZATION IN THORACOABDOMINAL ANEURYSMS

aneurysmal atherosclerotic disease,42,43 and the chronic process of injury and repair of the pseudointima which forms on the luminal side of the aortic graft. PREEMPTIVE TRANSFUSION

Preemptive transfusion, defined as transfusion of blood products before detectable laboratory abnormalities are recognized, is central to the intraoperative transfusion strategy for TAAA. Blood losses are sufficiently rapid (sometimes exceeding a liter per minute) that even the turnaround time for tests achieved with point-of-care testing is insufficiently responsive to the evolving situation. Direct evidence on this issue is limited to 1 study: Godet et al24 reported the use of a reactive transfusion strategy—the administration of blood products only when the hematocrit fell to below 30% or laboratory or clinical evidence of coagulopathy developed—in 33 patients who underwent surgery for TAAA repair. Eight of them developed clinically significant intraoperative hemorrhagic complications not attributable to surgical techniques, and 3 of these patients died during surgery. These results are out of keeping with expectations for surgical bleeding and strongly suggest that a preemptive strategy should be used. In our center, at times of rapid bleeding, we infuse packed red cells and plasma in a 1:1 ratio, at a total infusion rate equal to the estimated blood loss. USE OF HEPARIN

In infrarenal aortic aneurysm repair, heparin may reduce distal thrombosis but at the expense of increased bleeding. In the absence of definitive randomized assessment of the risk/benefit ratio, we and others44 - 48 do not use heparin routinely for this indication, whereas other groups use heparin selectively.49 A prospective randomized study of 284 patients undergoing infrarenal aortic aneurysm repair showed no difference between groups treated with and without heparinization with respect to the primary outcomes, blood transfusion, and lower limb thrombotic complications.50 In early descriptions of TAAA repair without the use of extracorporeal bypass (the bclamp-and-goQ technique) because of the overriding concern about bleeding from coagulopathy, no heparin was used.51-53 Subsequently, Svenson et al,54 Cina` et al,55 and Safi et al,56 adopted the partial bypass

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(usually atriofemoral) to maintain distal circulation for the duration of the aortic clamping. The use of the extracorporeal circuit led to the practice of using heparin, typically 100 U/kg bolus, at the initiation of bypass. Risks associated with this include the difficulty of assessing the correct amount of protamine to use at the end of the case to reverse the heparin effect (because coagulation parameters toward the end of the case reflect the coagulopathies discussed in detail above, in addition to heparin effect), the hemodynamic consequences of protamine administration,57 and of course the probability that intraoperative coagulopathy is potentiated by heparin. With the use of circuits with heparinbonded tubing, the use of heparin may not be necessary. Hoffman et al58 reported the successful use of partial cardiopulmonary bypass with heparinbonded tubing and without systemic heparinization for all repairs of the descending thoracic aorta. Downing et al59 reported repair of traumatic injuries of the thoracic aorta in 50 patients treated with heparin-bonded partial bypass with no thrombotic complications related to the lack of systemic heparinization. Other authors recommend the use of no heparin or selective use of low-dose heparin in thoracic and thoracoabdominal aortic surgery with the use of biocompatible extracorporeal tubing.60-63 DRUGS ENHANCING COAGULATION

The use of drugs enhancing coagulation is one of the several strategies to reduce blood loss in surgery for TAAA. In these patients, one of the major aspects of the hemostatic derangement is activation of the thrombolytic system. Lysine analogs (e-aminocaproic acid [EACA] and tranexamic acid) and aprotinin, specific inhibitors of thrombolysis, are potentially ideal in this context. Three meta-analyses64-66 have shown that these agents reduce blood loss, transfusion of blood products, mortality, and surgical reexploration in patients undergoing cardiac surgery. With respect to the outcome cluster postoperative reexploration for bleeding or mortality, the thrombolytic inhibitors aprotinin and lysine analogues (EACA and tranexamic acid) reduced the incidence of events compared with placebo (odds ratio [OR] 0.55 [95% CI 0.34-0.90] and 0.37 [0.25-0.55], respectively). Deamino-d-arginine vasopressin did not have similar beneficial effects. Meta-analysis of data from patients undergoing cardiac surgery showed

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that high-dose aprotinin (2 million units [MU] in the solution used to prime the cardiopulmonary bypass pump, 2 MU intravenous bolus, and 500 000 U/h, a total of 6 MU) and deamino-d-arginine vasopressin were also associated with a 2-fold increase in myocardial infarction, whereas lowdose aprotinin (1-4 MU) was not.65 In cardiac surgery, low-dose aprotinin or EACA (5-g intravenous bolus, followed by 1 g/h for 6 hours) is routinely used. In patients who have previously received aprotinin, because of the risk of severe allergic reactions, either a test dose should be given or aprotinin should be avoided and EACA or tranexamic acid used instead. No data are available on the risk/benefit ratio of these agents in TAAA surgery. In the second half of the TAAA series of Svensson et al54 from 1975 to 1990, most patients received EACA during surgery. We currently use intraoperative aprotinin 2 MU IV bolus at induction and 500 000 U/h, a total of 4 to 6 MU during the entire procedure in all patients with groups I, II, and III TAAA. BLOOD-SALVAGING TECHNIQUES

Preoperative Autologous Blood Donation Preoperative autologous blood donation (PABD) refers to the technique of harvesting a patient’s own RBCs for later use at the time of surgery. Donations usually take place weekly over several weeks but within 45 days before a planned elective operation. The advantages and disadvantages of this intervention have been described in cohort and randomized trials and reported in a recent review of the subject.67 Preoperative autologous blood donation leads to preoperative anemia, increases the incidence of postoperative anemia, and possibly increases the likelihood of transfusion with its attendant risk.68 In the meta-analysis by Forgie et al,69 patients who received PABD were less likely to receive allogeneic transfusions (OR 0.17) but were more likely to receive transfusions of autologous or allogeneic blood (OR 3.0). The technique is generally limited to RBC, does not eliminate the possibility of clerical error and bacterial contamination, and is not cost-effective.70-74 The large volume of blood loss compared with the amounts that can be preoperatively banked is a further limitation in patients undergoing TAAA repair. For these reasons, PABD does not appear a

promising technique for conservation of autologous products in TAAA. Intraoperative Blood Salvage Intraoperative blood salvaging (IBS) involves the collection and reinfusion of red cells, usually using cell-washing devices, in which case the transfusate does not contain platelets, white cells, or coagulation factors. The results of several small cohort studies offer conflicting information with respect to the effectiveness of IBS with some suggesting reduction in blood product use, infection, and length of stay,75 and others showing no beneficial effects and no cost saving.81-85 Bell et al86 reported the results of an unblinded, randomized, controlled trial of IBS compared with standard transfusion strategy without IBS in patients undergoing cardiothoracic surgery. In the treatment group, the median red cells usage was 3 U, and in the control group, it was 4 U ( P = .0023), with no difference in the use of other blood products, early complications rates, or coagulopathy. Postoperative hemoglobin was higher in the IBS group than in controls (116 F 11 vs 112 F 98 g/L; P b .001). Clagett et al87 reported an unblinded, randomized, controlled trial of IBS in 100 patients undergoing aortic surgery. Total in-hospital blood usage was 2.1 (standard deviation [SD] 2.1) U in the treatment group and 2.3 (SD 2.1) U in the control group ( P N .05) with no difference in clinical outcomes. A meta-analysis suggested that intraoperative cell salvage in cardiac surgery reduced the use of allogeneic blood products (OR 0.85 [95% CI 0.79-0.92]).88 It is possible that the relatively modest blood loss during these procedures limits the utility of the technique. However, in procedures such as TAAA repair where blood losses are extreme, retransfusion of salvaged blood has the potential to have a greater impact on overall transfusion requirements and is used in many centers. Salvaged blood may be washed and centrifuged at times in the operation when blood loss is moderate, but when blood loss is most rapid, we and others (oral communication, July 23, 2004, H Safi, Chair, Department Cardiothoracic and Vascular Surgery, University of Texas) directly reinfuse filtered, unwashed, uncentrifuged blood (eg, using the rapid infusion system). Two caveats apply here. First, this practice is feasible in TAAA repair because we do not use irrigation

COAGULATION AND BLOOD PRODUCT UTILIZATION IN THORACOABDOMINAL ANEURYSMS

fluids in the wound. This means that during the phases of rapid blood loss, the fluid retrieved by the suction device has virtually the same hematocrit as the patient’s circulating blood. If irrigation fluids are used, cells must be washed or at least packed before reinfusion. Second, when direct reinfusion of filtered salvage blood is used, point-of-care testing for frequent assessment of ionized calcium, acid-base balance, and electrolytes is mandatory to minimize complications from the infusion of citrate from the retrieval canister. The advantages are the retention of platelet and coagulation factors, whereas the disadvantages include the retransfusion of anticoagulants and tissue thromboplastins, including (most importantly) tissue factor on activated monocytes.89 Our impression, however, is that with the patient systemically anticoagulated and using citrate as an anticoagulant for the retrieved blood, the reinfusion of unwashed blood does not carry a significant risk of coagulopathy and reduces the transfusion of allogeneic red cells. However, no quantitative data in TAAA repair are available. Acute Normovolemic Hemodilution Acute normovolemic hemodilution (ANH) is a technique used by anesthesiologists during surgery to reduce the usage of allogeneic blood. Immediately before or soon after induction of anesthesia, phlebotomy is used to collect whole blood in anticoagulant-containing bags and transfused as indicated during or soon after the surgical procedure. During the blood collection process, crystalloids or colloids (acellular fluids) are infused to maintain normovolemia, leading to hemodilution.90 The patient’s blood is preserved at room temperature in single blood packs containing citrate phosphate dextrose, which are placed on a weighing scale to estimate the volume obtained. Toward the end of the case, the fresh autologous whole blood is retransfused. This is thought to decrease the need for allogeneic blood and to reduce the risk of further bleeding or oozing by improving hemostatic parameters. Two prospective observational studies91,92 and 2 randomized controlled trials, 1 in orthopedic surgery93 and 1 in general surgery,94 reported that hemodilution to a hematocrit of 20% to 25% is responsible for detectable changes in coagulation parameters (reduced platelet count,

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increased PT, and PTT) which are not associated with increased risk of bleeding or requirement for allogeneic transfusion. Two prospective observational studies, 1 in TAAA36 and 1 in cardiac surgery,95 and 1 randomized controlled trial in cardiac surgery96 reported improvement in coagulation parameters with infusion of autologous blood retrieved with ANH. A meta-analysis of randomized and nonrandomized studies in cardiac surgery showed that ANH reduced the volume of transfused RBC (OR 2.08 [95% CI 1.89 to 2.27]).97 Bryson98 reported a meta-analysis of 24 randomized controlled trials of different types of surgery (cardiac, orthopedic, gastrointestinal, thoracic, hepatic, ear nose and throat, urologic, and vascular surgery) enrolling 1218 patients (589 controls, 629 ANH). When all eligible trials were considered (using a random-effects model), ANH significantly reduced the likelihood of exposure to at least 1 U of allogeneic blood (OR 0.3 [95% CI 0.2-0.6]) and reduced the number of units of allogeneic blood transfused (weighted mean difference 2.2 U [95% CI 3.6-0.9]). Acute normovolemic hemodilution offers, at least in theory, specific advantages in TAAA repair because the volume of blood loss is predictably large. To take advantages of this characteristic, we have described a modification of the ANH technique which we called ANH and partial exchange transfusion (ANHPET). Standard ANH technique90 is initiated before induction of anesthesia with the goal of reducing the patient’s hemoglobin concentration to approximately 90 to 100 g/L. In the PET phase, a further phlebotomy of 1 to 1.5 L is performed with each liter of autologous blood replaced with 600 mL of allogeneic RBCs and 400 mL of 5% albumin. Immediately before clamping the proximal aorta, an additional 450 to 750 mL of autologous blood is removed. Reinfusion of autologous blood is started when the surgeon is performing the distal aortic anastomosis.99 The autologous blood, withdrawn before major blood losses occur and stored at room temperature, contains functional platelets and labile clotting factors in normal concentration. The transfusion of this blood at the end of the TAAA repair appears to have a beneficial effect on the clotting mechanism and a sparing effect on use of allogeneic blood components (FFP, platelets, and cryoprecipitate).99 However, definitive evidence of

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the benefit of this technique in TAAA surgery is lacking. Unique characteristics of TAAA repair suggest that the treatment may be of more benefit here than in other surgery where blood loss is less extreme: a randomized controlled trial of this intervention is needed. BLOOD PRODUCT USE IN SURGERY FOR THORACOABDOMINAL AORTIC ANEURYSM

The successful repair of TAAA requires the administration of large volumes of fluids over a short period. Patients can lose their entire blood volume in a few minutes becoming severely hypotensive with fatal or disastrous consequences unless rapidly reinfused. Svensson et al54 reported the median number of units of blood and blood products used during surgery in Crawford’s experience from 1960 to 1991. In 1509 patients who underwent TAAA repair with the use of a cell saver, the following utilization was observed: RBC 7 (range 1-46) U, FFP 16 (range 0-132) U, platelets 20 (range 0-110) U, cryoprecipitate 0 (0-100) U, and autotransfused cells 8 (range 0-68) U. The median number of intraoperative blood products transfused was 51 U. In the latter part of this series, most patients received prophylactic EACA. In a similar cohort study at our center between 1991 and 1995, median intraoperative blood product transfusion in our patients was 40 U, although a cell-saver device was not used.

Fig 1.

Godet et al24 described the use of blood products in 33 patients undergoing TAAA repair. A strategy of avoiding transfusion of blood products (RBC, FFP, and platelets), unless indicated by hematocrit or abnormal coagulation parameters, was used. In the absence of the results of appropriate tests, transfusions were given only when intraoperative surgical bleeding was clinically evident. In this series, the use of RBC was 9 (SD 6) U, FFP 8 (SD 7) U, and autotransfused cells 12 (SD 9) U. Mean blood product transfusion intraoperatively was 29 U. Svensson et al54 and Godet et al24 reported the use of blood products during the intraoperative period only. We described the estimated blood losses and the total in-hospital blood product use in our cohort study. The estimated blood losses as expected were high, on average, 6 (SD 1.1) L. Figure 1 is a graphical summary of intraoperative and postoperative blood product transfusion. It is important to notice that over 30% of the total blood products used were transfused in intensive care after surgery. Results are reported in details in Table 2. The ANHPET group, compared with NonANHPET, received fewer transfusions of platelets (8 vs 22 U, P = .0004), and cryoprecipitate (0 vs 13 U, P = .02). Use of FFP was 11 and 17 U, respectively ( P = .08). A clinically and statistically significant reduction in the total number of units of blood products transfused was observed with ANH (30 vs 68 U, P = .003).

Use of blood products: sequential cohort study in TAAA surgery. Plt indicates platelets; Cryo, cryoprecipitate.

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Table 2. Estimated Blood Loss and Total Blood Products Transfused in Patients With Elective Thoracoabdominal Aortic Aneurysms Non-ANHPET (n = 15)

Estimated blood loss (L) RBCs (U) Platelets (U) FFP(U) Cryoprecipitate (U) Total (U) Autologous blood retransfused (U)

6.1 17.8 22 16.8 13 68

F 2.3 F8 F 8* F 8y F 13z F 29* na

ANHPET (n = 7)

5.5 12.8 8 11

F F F F 0 30 F 9F

1.5 6.9 4 4 12 1

NOTE. Treated with and without ANHPET: sequential cohort study. Data shown are mean values F SDs. ANHPET indicates acute normovolemic hemodilution and partial exchange transfusion; U, units. *P b .01. yP = .08. zP b .02.

We were also able to show that the extent of the aneurysm affected the total transfusion, with patients with groups II and III receiving on average 27 U of blood products more than those with group I, group IV, and distal arch aneurysms.36 Because significant transfusion of blood components may be necessary after surgery, total transfusions (ie, intraoperative and postoperative) are more representative of the blood products usage in these patients. Our experience and those of others, therefore, suggest that an average blood loss of 5000 to 6000 mL and average transfusion of allogeneic blood products of 50 to 60 U are to be anticipated.

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SUMMARY

Preoperative coagulopathy is generally subtle and of doubtful clinical importance. Intraoperative coagulopathy reflects extreme blood loss, massive transfusion, and visceral ischemia. We and others33,36,99-101 believe that a preemptive strategy of transfusion of blood products is critical to the minimization of the overall use of blood products and to the prevention of clinically significant coagulopathy during surgery. With such a preemptive strategy to the prevention of intraoperative coagulopathy, postoperative coagulopathy can generally be minimized. Clinically important blood loss does, however, continue in the postoperative period, and total average transfusions over the whole intraoperative and postoperative period of 50 to 60 U of blood products should be anticipated. The use of intraoperative heparin in patients whose intervention includes partial bypass is common but not well justified and requires further study. Supplementary interventions that are likely to be beneficial include the use of a conventional cell saver or rapid infusion system device, the use of potent inhibitors of thrombolysis such as aprotinin and EACA, and possibly ANH with or without PET. Several areas in the field of coagulopathy and blood transfusion strategies in TAAA repair require further study. A partial list includes studies of heparinization and antithrombolytic regimens, washed compared with unwashed red cell salvage, the use of ANH with or without PET, and the optimal use of factors enhancing coagulation.

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