Patients undergoing spinal fusion and instrumentation often sustain perioperative blood loss that approaches their total estimated blood volume (1–3). Significant blood volume loss is replaced by the administration of crystalloid, colloid, and blood products, including predonated autologous blood, intraoperative autotransfusion (IAT), and allogeneic blood. Previous studies of patients undergoing massive transfusion have reported increased bleeding from a dilutional thrombocytopenia (4,5). An investigation by Murray et al. (3) suggested that the cause of surgical bleeding in patients undergoing elective spine stabilization was coagulation factor dilution rather than thrombocytopenia. An additional etiology of increased bleeding during major spinal surgery may be activation of the fibrinolytic system, because bone is a source of tissue plasminogen activator and urokinase (6). Finally, a preexisting coagulation defect may be present in patients with idiopathic scoliosis or ankylosing spondylitis (7,8). A preoperative coagulopathy resulting from hepatic dysfunction or anticoagulant therapy may also predispose the patient to blood loss. Therefore, the cause of increased bleeding in patients undergoing spinal fusion and instrumentation may be surgical, congenital, the dilution of coagulation factors and platelets, fibrinolytic, or a combination of etiologies. Ideally, coagulation tests could be used perioperatively to determine which patients are at risk for developing significant bleeding and guide transfusion therapy. However, few studies have addressed the utility of coagulation tests among this patient population, and the coagulation test values that are normal or abnormal have not been previously defined. This study was undertaken to evaluate the sensitivity and specificity and accuracy of different coagulation tests and to determine the coagulation test cut-point value that could be used to guide transfusion therapy.
The records of 244 pediatric and adult patients undergoing thoracic, lumbar, or sacral spinal fusion with or without instrumentation between January 1994 and July 1995 were retrospectively reviewed after approval of our IRB. Patient demographics, including age, sex, height, and weight, were recorded. The presence of a preexisting coagulopathy (defined as excessive bruising or bleeding) was noted. The administration of preoperative anticoagulant medication (warfarin within 7 days or heparin within 24 h of surgery) or antiplatelet medications within 7 days of surgery and chronic steroid use were recorded. Preoperative hemoglobin levels and the results of coagulation tests, including platelet count (normal values, 184–370 × 109/L for males and 196–451 × 109/L for females), prothrombin time (PT) (normal values, 8.4–12.0 s), activated partial thromboplastin time (aPTT) (normal values, 23–37 s), and thromboelastogram (TEG®; Haemoscope Corporation, Skokie, IL) (normal values: R, 13–26 mm; angle, 32–54°; maximum amplitude [MA], 43–64 mm; and lysis+30, 0%–15%), were recorded.
Surgical indication, surgical approach, and number of levels fused were recorded. All surgical procedures were performed under general anesthesia. Monitoring during the procedure included direct arterial and central venous pressures, electrocardiogram, pulse oximetry, capnography, and urinary output. The anesthesiologist in charge of the case selected the type of anesthesia on the basis of the use of intraoperative neurophysiologic monitoring. Nineteen patients were monitored during surgery with motor evoked potential and received an IV anesthetic (primarily opioids and benzodiazepines). The remaining 225 patients (92.4%) received a balanced anesthetic (primarily inhaled anesthetics and opioids). Induced hypotension, defined as sustained systolic blood pressure <100 mm Hg, was performed at the request of the surgeon in 70 patients (28.5%). Total surgical and anesthesia times were recorded.
IAT was used in all patients, except those undergoing surgery for tumor or infection. The total volume of IAT blood transfused was determined. The number of autologous and allogeneic blood products transfused perioperatively was recorded. Surgical blood loss was estimated by measuring blood collected from the surgical field and by qualitative assessments of surgical sponges. Blood volume was estimated to be 70 mL/kg for males and 60 mL/kg for females. The surgical note was reviewed for reference to excessive and unanticipated blood loss. Increased surgical bleeding, as noted by the surgeon, was defined as recurrent bleeding despite the adequate use of electrocautery and suture or decreased clot formation of blood pooled within the surgical field. Intraoperative and postoperative hemoglobin levels and coagulation tests were recorded. Not all patients underwent intraoperative coagulation monitoring of the PT, aPTT, or TEG®. If coagulation tests were repeated, the most abnormal value was used in our investigation. The surgeon was not blinded with regard to the results of intraoperative coagulation testing in all cases. Autologous, IAT, and allogeneic transfusion requirements for the first 24 h after surgery and for the entire postoperative period were determined.
The relationship between increased surgical bleeding and estimated blood loss, perioperative transfusion requirements, and changes in hemoglobin level, platelet count, aPTT, PT, and TEG® was assessed with Wilcoxon’s ranked sum test. Results are reported as median (range) and mean ± sd. Significance was defined as P < 0.05. The analysis of sensitivity, specificity, and negative and positive predictive values was accomplished with the receiver operating characteristic (ROC) curve. This statistical method to evaluate diagnostic accuracy requires a definition of disease state and abnormal test results. The definition of disease state in this study was excessive bleeding during surgery as noted by the surgeon. The laboratory cut-point is the test value such that any observed value above it is considered positive of disease (an abnormal test result) and any value below is considered negative for the disease. With the ROC analysis, the cut-point is changed throughout the potential range of the test under study to examine the sensitivity and specificity of the test. The test result that maximizes both sensitivity and specificity is the value frequently chosen to differentiate the normal from the disease state (excessively bleeding). The definition of sensitivity was the percentage of patients with excessive bleeding who had an abnormal test result. The definition of specificity was the percentage of patients without excessive bleeding who had a normal test result. The area under the curve represents the accuracy of the test. A useless test would have an area under the curve of 0.5 or less because it would be equivalent to flipping a coin. A perfect test would have an area (accuracy) of 1, 100% sensitivity, and 100% specificity.
Patient age was median (range) 52 yr (1–83 yr) (Table 1). There were 139 females (57%) and 105 males (43%). In 39 patients (16.0%), increased surgical bleeding was reported by the surgeon in the operative note. Patients with a preexisting preoperative coagulopathy were more likely to develop increased intraoperative bleeding. However, preoperative use of warfarin, heparin, and aspirin or other nonsteroidal antiinflammatory medications did not result in excessive bleeding during surgery. Surgical variables associated with excessive bleeding included tumor surgery and an increased number of posterior levels surgically fused.
Patients with increased clinical bleeding sustained larger estimated blood losses than those with normal hemostasis. In addition, these patients received significantly more IAT and allogeneic red blood cells during surgery and required more platelets and fresh frozen plasma (FFP), both during and after surgery (Table 2). The total number of units of perioperative allogeneic red blood cells, platelets, and FFP was also more in patients with increased bleeding during surgery. There was no significant difference in the number of autologous blood units transfused between groups.
Preoperative hemoglobin was significantly higher in the patients with normal hemostasis, but there was no difference in the preoperative platelet count, aPTT, or PT (Table 3). During surgery, patients with increased bleeding demonstrated decreased hemoglobin levels. Intraoperative PT was increased more than normal values in both groups but was significantly longer in patients with increased bleeding compared with patients with effective hemostasis. Although the platelet count was decreased to less than normal values in patients with increased bleeding, there were no significant differences in platelet count, aPTT, or TEG® variables among patients during surgery. After surgery, the platelet count was significantly less in patients who had demonstrated increased surgical bleeding.
The intraoperative coagulation tests with the highest sensitivity and specificity were the international normalized ratio (INR), PT, and aPTT (Table 4). The intraoperative INR and PT were able to differentiate patients with clinical evidence of excessive bleeding from those with normal hemostasis at cut-points of approximately 1.5 times the control values. There was an insufficient number of intraoperative platelet count tests to perform a ROC analysis. Overall, the TEG® values were of marginal use. The intraoperative TEG® MA had the highest accuracy of the TEG® values, with the R+K, α angle, and lysis+30 having poor sensitivity, specificity, and accuracy.
Age and sex were not predictors of excessive intraoperative bleeding. In addition, evaluation of age and sex in a multiple regression model did not change the relationships between intraoperative coagulation tests and the transfusion of blood products.
The most recent consensus conference convened to publish recommendations for the transfusion of different blood components is that produced by the American Society of Anesthesiologists (9). These guidelines strongly recommended the use of coagulation tests to guide transfusion of platelets, FFP, and cryoprecipitate. Specifically, they noted that transfusion of FFP is beneficial to patients with microvascular bleeding or hemorrhage who are massively transfused if the PT/aPTT values exceed 1.5 times the laboratory’s normal values. This value is similar to our ROC-generated cut-points for the INR and PT (1.4 and 13.5 seconds, respectively). The INR had a higher sensitivity, specificity, and accuracy than the PT. This may have been the result of the reduced variability in test values as a result of the calculation of the INR from the PT. Because the INR essentially standardizes the PT by correlating an individual laboratory’s thromboplastin sensitivity with an international standard, we report both the PT and INR to facilitate comparison of the cut-points between institutions.
In our study, multilevel spine surgery is associated with a high risk of excessive bleeding (16.0%), allogeneic red blood cells (36.1%), and coagulation product transfusion (13.9%). This incidence of transfusion is similar to other surgical procedures that are considered high risk for allogeneic blood transfusion (i.e., cardiac surgery), for which guidance of transfusion therapy with coagulation tests and transfusion algorithms has previously been advocated and defined. Ideally, by using this established model, preoperative coagulation tests and preexisting medical conditions would identify patients at risk for increased bleeding, and intraoperative coagulation tests would also correlate with bleeding risk and guide transfusion therapy. Surgical evaluation has been established as a reliable assessment of excessive bleeding and the need for transfusion of blood components (3,9,10).
A prospective study by Murray et al. (3) evaluated the coagulation changes during elective posterior spinal stabilization in patients who receive packed red blood cells for massive blood losses. The PT and aPTT increased and platelet and fibrinogen levels decreased with blood volume replacement. However, many patients were judged to have normal hemostasis despite the prolongation in PT or aPTT. Increases in the PT and aPTT were greater in patients who had abnormal hemostasis, but platelet count decreased similarly in both groups. FFP was judged effective in correcting abnormal hemostasis in 82% of patients with increased bleeding. There was no evidence of a disseminated intravascular coagulopathy among the studied patients. The authors concluded that coagulation factor dilution, not a dilutional thrombocytopenia, was the primary cause of excessive surgical bleeding and that correction of coagulation factor levels with FFP is required before platelet transfusion. These results appear to contradict those of previous studies, which recommended platelet transfusion before the administration of FFP (4,5). However, these investigations replaced blood loss with whole blood, rather than with red blood cells. Whole blood contains sufficient levels of coagulation factors, except for the labile factors V and VIII, to maintain hemostasis. Although also present in whole blood, platelets are rendered nonfunctional by processing and storage. Therefore, replacement of massive blood loss with whole blood would produce a dilutional thrombocytopenia necessitating platelet replacement. Theoretically, transfusion of whole blood would reduce the need for blood component therapy, but the need for blood components in the United States precludes the widespread use of whole blood and limits its availability.
An increase in the intraoperative PT above normal values was a common finding among our patients, with a longer prolongation noted in cases with increased bleeding compared with those with normal hemostasis. These results are similar to those of Murray et al. (3) and suggest that a dilution of coagulation factors occurs often in patients undergoing major spine surgery, but a coagulopathy requiring clotting factor replacement is much less common. The direct correlation between intraoperative PT and aPTT and volume of blood transfused may also indicate a dilutional coagulopathy. In contrast to the study by Murray et al. (3), patients with increased bleeding in our investigation required more perioperative transfusions of FFP and platelet concentrates to restore hemostasis.
Although the TEG® may be a useful test in cardiopulmonary bypass patients, its usefulness in orthopedic patients is unknown (10). Our results suggest that aside from the TEG® MA, the test may not be useful in this population. The TEG® MA cut-point value of 48.5 mm is virtually identical to the value of 48 mm found for cardiac surgery patients (10). Therefore, our results validate the scientific basis for transfusion practice and aid the development of evidence-based clinical guidelines for blood component therapy in patients undergoing major spine surgery.
Our study was retrospective. Despite the large number of patients included, only 17.2% had intraoperative coagulation monitoring of the PT, aPTT, or TEG®. Although coagulation tests were often repeated, we reported only the most abnormal values in our investigation. However, the relationship to surgical events, such as decortication or harvesting of bone graft, and the coagulation test was not discernible. Finally, many of the decisions regarding transfusion of blood products by the anesthesiologist were made before the return of the coagulation test results, on the basis of clinical judgment, because of the 30- to 45-minute delay between sample draw and test completion. It is difficult to retrospectively assess the effect point-of-care testing would have had on the amount and type of blood products transfused. Prospective studies are needed to address these issues, but this study provides direction on which coagulation tests may be most useful to guide transfusion therapy in this patient population.
In conclusion, major spinal surgery has a high risk of increased intraoperative bleeding and blood component transfusion. The intraoperative INR and PT were able to differentiate patients with clinical evidence of excessive bleeding from those with normal hemostasis at cut-points of approximately 1.5 times the control values. Therefore, this study provides information to establish a stronger scientific basis for transfusion practice and aids the development of evidence-based clinical guidelines for blood component therapy.
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