Abstract
Background
Perioperative bleeding is a predictor of morbidity following liver resection. The transfusion-related score (TRS), which is derived from five variables (cirrhosis, preoperative haemoglobin level, tumour size, vena cava exposure and associated extraliver surgical procedure), has been proposed to predict the likelihood of transfusion in liver resection.
Objective
The purpose of this observational study was to evaluate the external validity of the TRS.
Methods
In a retrospective, monocentre, observational cohort study of patients undergoing elective liver resection surgery, data for transfused and non-transfused patients were compared by univariate analysis. The TRS was calculated for each patient. The frequency of transfusion was calculated for each score level. The accuracy of the TRS was evaluated using the area under the receiver operator characteristic curve (AUC).
Results
A total of 205 patients submitted to liver resection were included. Of these, 48 (23.4%) patients received a blood transfusion. There was no significant difference between transfused and non-transfused patients in age, American Society of Anesthesiologists (ASA) score or cirrhosis. The AUC for the TRS was 0.68 (95% confidence interval 0.59–0.77). Among TRS items, only vena cava exposure and associated surgical procedures were significantly associated with risk for transfusion.
Conclusions
In the present population, the TRS appeared to serve as a weak predictor of perioperative transfusion. This study confirms that the external validity of the transfusion predictive score should be subject to further investigation before it can be implemented in clinical use.
Introduction
Despite improvements in surgical and anaesthetic techniques, postoperative morbidity following liver resection remains high.1–5 Perioperative bleeding is one of the major predictors of morbidity4–6 and blood transfusion is required in 10–38% of patients undergoing liver resection.7,8 Preoperative assessment of the risk for transfusion is useful for enhancing the information given to patients and in the development of a perioperative strategy to minimize the risk.8–11
The transfusion-related score (TRS) was proposed by Pulitanò et al. to predict the likelihood of transfusion in liver resection.8 The score was found to have good overall accuracy, but was developed in a retrospective and monocentre study. The present authors hypothesized that the TRS might be used to accurately predict units of red blood cell (RBC) transfusion at the study liver surgery centre. The purpose of this study was to evaluate the external validity of the TRS in a different population of patients undergoing liver resection.
Materials and methods
According to French legislation for the regulation of clinical research, requirements for the provision of informed consent were waived because the present study was retrospective and observational.
Patients
A retrospective, monocentre, observational cohort study in consecutive patients submitted to elective liver resection during 2008 and 2009 was performed. Standard anaesthesia monitoring was applied perioperatively. A radial arterial catheter and venous central catheter were placed for major hepatectomy.12 Anaesthesia was induced and maintained at the discretion of the attending anaesthesiologist. Haemoglobin blood levels were repeatedly estimated using a HemoCue Hb 201+ (HemoCue France, Meaux, France). Transfusion criteria followed the American Society of Anesthesiologists (ASA) Task Force and Agence Française de Sécurité Sanitaire recommendations13,14 for 7–10 g/dl according to cardiovascular status. A haemodynamic strategy with fluid restriction during hepatic resection was applied.
All elective liver surgeries were performed by any of five senior hepatobiliary surgeons. Major liver resection was defined as the resection of three or more hepatic segments. Liver parenchymal transection was conducted using an ultrasonic dissector (Dissectron®; Laboratoire Integra Neurosciences, Saint Priest, France), the Kelliclasie technique or bipolar coagulation. Intermittent pedicular clamping was performed using a protocol of 15 min of clamping followed by 5 min of non-clamping.15 Inferior vena cava clamping was performed when necessary. The hanging manoeuvre was used to facilitate the anterior approach in major liver resections.16–18
Transfusion-related score
The TRS is derived from five variables: cirrhosis; preoperative haemoglobin level of ≤12.5 g/dl; tumour size of >4 cm; need for inferior vena cava exposure, and associated extraliver surgical procedure. Each variable can be assigned 1 point and the sum of these points establishes the TRS.8
Data collection
The following data were collected from medical records: demographic data, including patient age, sex, body mass index, ASA score, malignant or benign nature of the tumour, and presence of cirrhosis, cardiopulmonary disease and diabetes; surgical data, including the number of resected segments, tumour size, perioperative vena cava exposure, any associated surgical procedure (bilioenteral anastomosis, associated colorectal, pancreatic or renal resections) and duration of surgery; preoperative haemoglobin blood levels, and the number of units of RBC transfused intraoperatively and until postoperative day 5.
Statistical analysis
Data for transfused and non-transfused patients were compared by univariate analysis using Fisher's exact test or the Mann–Whitney test as appropriate. The plasma haemoglobin level associated with risk for transfusion was investigated using the Mann–Whitney test with different cut-off values. The frequency of transfusion at each score level was calculated. The accuracy of the TRS was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC).
Data are presented as the median [interquartile range (IQR)] or number (percentage). All analyses were two-tailed; a P-value of <0.05 was accepted as indicating statistical significance. Statistical analysis was performed using stata Version 9.2 (StataCorp LP, College Station, TX, USA).
Results
A total of 205 consecutive patients submitted to scheduled liver surgery during the study period were included. Forty-eight (23.4%) patients were transfused; they received a median of 2 units (IQR: 2–4 units) of RBC. Demographic and surgical data for transfused and non-transfused patients are displayed in Table 1. There were no significant differences between transfused and non-transfused patients in age, ASA score or presence of cirrhosis. The distribution of RBC units among the 48 transfused patients is detailed in Fig. 1.
Table 1.
Demographic and surgical data for patients undergoing liver resection
| All patients | Transfused patients | Non-transfused patients | P-value | |
|---|---|---|---|---|
| (n = 205) | (n = 48) | (n = 157) | ||
| Age, years, median (IQR) | 58 (17–80) | 59 (23–80) | 58 (17–80) | 0.267 |
| ASA class of ≥3, n (%) | 13 (6.3%) | 5 (10.4%) | 8 (5.1%) | 0.189 |
| Aetiology, n (%) | ||||
| Metastasis | 92 (44.9%) | 23 (47.9%) | 69 (43.9%) | 0.740 |
| Hepatocellular carcinoma | 42 (20.5%) | 6 (12.5%) | 36 (22.9%) | 0.153 |
| Cholangiocarcinoma | 19 (9.3%) | 5 (10.4%) | 14 (8.9%) | 0.778 |
| Other reasonsa | 52 (25.4%) | 14 (29.2%) | 38 (24.2%) | 0.570 |
| Major liver resection, n (%) | 102 (49.8%) | 32 (66.7%) | 70 (44.6%) | 0.008 |
| Preoperative Hb <12.5 g/dl, n (%) | 101 (57.4%) | 30 (68.2%) | 71 (53.8%) | 0.114 |
| Cirrhosis, n (%) | 15 (7.4%) | 5 (10.4%) | 10 (6.4%) | 0.354 |
| Tumour size of >4 cm, n (%) | 100 (52%) | 22 (53.7%) | 78 (51.7%) | 0.861 |
| IVC exposure, n (%) | 83 (40.5%) | 27 (56.2%) | 56 (35.7%) | 0.012 |
| Associated surgical proceduresb, n (%) | 113 (55.7%) | 33 (70.2%) | 80 (51.3%) | 0.029 |
| Death at day 30, n (%) | 6 (2.9%) | 6 (12.5%) | 0 | <0.0001 |
Other reasons: adenoma, hepatic polycystosis.
Colorectal resections, bilioenteral anastomosis, pancreatic, spleen or renal resection.
ASA, American Society of Anesthesiologists; Hb, haemoglobin; IQR, interquartile range; IVC, inferior vena cava.
Figure 1.

Frequencies of transfusion of red blood cell units in patients undergoing liver resection (n = 205)
Among the items contributing to the TRS, a preoperative haemoglobin level cut-off of 12.5 g/dl, tumour size and cirrhosis were not significantly associated with transfusion in univariate analysis, whereas inferior vena cava exposure and associated surgical procedures were significantly associated with risk for transfusion (P = 0.012 and P = 0.029, respectively). Univariate analysis showed a preoperative haemoglobin level of <12.3 g/dl to be associated with transfusion (P = 0.008).
Transfusion rates for each TRS level are reported in Table 2 and Fig. 2. For the 163 patients (of the total population of 205 patients) for which the TRS was available. The ROC AUC for the original TRS was 0.68 [95% confidence interval (CI) 0.59–0.77] (Fig. 3).
Table 2.
Transfusion data according to the transfusion-related score (TRS) in patients undergoing liver resection
| TRS | Patients, n = 163 | Patients transfused, n = 38 | RBC, units, median (IQR) |
|---|---|---|---|
| 0 | 15 (9.2%) | 1 (6.7%) | 2 (2–2) |
| 1 | 35 (21.5%) | 3 (8.6%) | 2 (2–7) |
| 2 | 44 (27.0%) | 11 (25.0%) | 2 (1–5) |
| 3 | 47 (28.8%) | 13 (27.7%) | 2 (1–2) |
| 4 | 21 (12.9%) | 9 (42.9%) | 2 (2–5) |
| 5 | 1 (0.6%) | 1 (100%) | 1 (1–1) |
IQR, interquartile range; RBC, red blood cells n (%).
Figure 2.

Transfusion rates according to transfusion-related scores in the Pulitanò et al.8 population (n = 320) and the present population (n = 163) of patients undergoing liver resection
Figure 3.

Receiver operating curve (ROC) for the performance of the original transfusion-related score in predicting transfusion in the present population (n = 205) of patients undergoing liver resection
Using a preoperative haemoglobin cut-off value of 12.3 g/dl as one item in the score led to an AUC of 0.69 (95% CI 0.58–0.76).
Discussion
The current study was designed to evaluate the external validity of the TRS in predicting perioperative transfusion during liver resection. Of the original TRS items, only intraoperative inferior vena cava exposure and associated surgical procedure were significantly associated with perioperative RBC transfusion in the present study population. The discriminating power of the TRS in this population was moderate and does not allow for the reliable prediction of RBC transfusion.
Preoperative haemoglobin level is a consistent predictor of transfusion, regardless of the type of surgery, but the thresholds cited vary among studies.8,10,11,19–22 For example, in liver surgery, Itamoto et al. found preoperative haemoglobin level at a threshold value of 11 g/dl to be the only predictor of intraoperative transfusion,20 whereas Cockbain et al. identified a threshold value of 12.5 g/dl.10 In the present population, risk for transfusion was not significantly associated with a preoperative haemoglobin level of <12.5 g/dl, but was significantly associated with a preoperative haemoglobin level of <12.3 g/dl. This may reflect variability in transfusion practices. However, even with a threshold of 12.3 g/dl, the ROC AUC for the TRS remained moderate.
Cirrhosis is a well-known risk factor for transfusion during liver surgery.9,23,24 However, patients with cirrhosis in the present study displayed only a non-significant trend towards increased need for transfusion. This result may be related to the fact that the number of patients with cirrhosis in the present study was relatively low, which may imply insufficient power to detect this small difference. An additional explanation may refer to the severity of cirrhosis in resected patients. In accordance with current practices, elective liver surgery was performed in highly selected patients with cirrhosis (i.e. those with Child–Pugh class A status or very selected patients of Child–Pugh class B status) to limit the risk for haemorrhage related to portal hypertension or coagulation disorders.19,20
Tumour size has been proposed as an item contributing to the TRS because of tumour rich vascularization and parenchymal congestion.8,10 However, this item was not significantly associated with transfusion in the present study. This discrepancy may refer to the fact that the difficulty of the surgery seems to relate to tumour localization more than it does to tumour size.9 Moreover, improvements in surgical and perioperative management may also explain this result. In the current study, among the original TRS items, inferior vena cava exposure and concomitant extrahepatic procedures were the only surgical factors to be consistently confirmed, as significantly associated with need for RBC transfusion in liver surgery.
Finally, the varied case mix, different surgical techniques and skills used and varied transfusion practices, in combination, are likely to have impacted on the present results. All of these factors are subject to significant variability among surgical teams and thus it can be hypothesized that a universally reliable predictive score is likely to be very difficult to establish.
The present study is subject to some limitations that must be acknowledged. This was a retrospective study and lacks data justifying the delivery of transfusion for each patient (perioperative blood loss and haemoglobin value at the time of transfusion). Moreover, the present study population (n = 205) was smaller than that in the study by Pulitanò et al.8 (n = 320), and the frequency of cirrhosis was lower [15 patients (7.3%) versus 82 (25.6%) patients]. Nevertheless, before any prognostic model can be extended to other populations, external validation is necessary25 and should ideally be performed in a population other than that of the initial research.
In conclusion, in the present population of patients undergoing liver resection, the TRS appeared to be a weak predictor of perioperative transfusion, although each of the contributing items seemed clinically relevant. This study confirms that the external validity of a score for predicting need for transfusion should be subjected to further investigation before it can be implemented in a clinical setting.
Conflicts of interest
None declared.
References
- De Haas RJ, Wicherts DA, Andreani P, Pascal G, Saliba F, Ichai P, et al. Impact of expanding criteria for resectability of colorectal metastases on short- and long-term outcomes after hepatic resection. Ann Surg. 2011;253:1069–1079. doi: 10.1097/SLA.0b013e318217e898. [DOI] [PubMed] [Google Scholar]
- Cannon RM, Martin RCG, Callender GG, McMasters KM, Scoggins CR. Safety and efficacy of hepatectomy for colorectal metastases in the elderly. J Surg Oncol. 2011;104:804–808. doi: 10.1002/jso.22042. [DOI] [PubMed] [Google Scholar]
- Fan ST, Mau Lo C, Poon RTP, Yeung C, Leung Liu C, Yuen WK, et al. Continuous improvement of survival outcomes of resection of hepatocellular carcinoma: a 20-year experience. Ann Surg. 2011;253:745–758. doi: 10.1097/SLA.0b013e3182111195. [DOI] [PubMed] [Google Scholar]
- Yang T, Zhang J, Lu J-H, Yang G-S, Wu M-C, Yu W-F. Risk factors influencing postoperative outcomes of major hepatic resection of hepatocellular carcinoma for patients with underlying liver diseases. World J Surg. 2011;35:2073–2082. doi: 10.1007/s00268-011-1161-0. [DOI] [PubMed] [Google Scholar]
- Nuzzo G, Giuliante F, Ardito F, Giovannini I, Aldrighetti L, Belli G, et al. Improvement in perioperative and long-term outcome after surgical treatment of hilar cholangiocarcinoma: results of an Italian multicentre analysis of 440 patients. Arch Surg. 2012;147:26–34. doi: 10.1001/archsurg.2011.771. [DOI] [PubMed] [Google Scholar]
- Abdel-Wahab M, El-Husseiny TS, El Hanafy E, El Shobary M, Hamdy E. Prognostic factors affecting survival and recurrence after hepatic resection for hepatocellular carcinoma in cirrhotic liver. Langenbecks Arch Surg. 2010;395:625–632. doi: 10.1007/s00423-010-0643-0. [DOI] [PubMed] [Google Scholar]
- Nagino M, Kamiya J, Arai T, Nishio H, Ebata T, Nimura Y. One hundred consecutive hepatobiliary resections for biliary hilar malignancy: preoperative blood donation, blood loss, transfusion, and outcome. Surgery. 2005;137:148–155. doi: 10.1016/j.surg.2004.06.006. [DOI] [PubMed] [Google Scholar]
- Pulitanò C, Arru M, Bellio L, Rossini S, Ferla G, Aldrighetti L. A risk score for predicting perioperative blood transfusion in liver surgery. Br J Surg. 2007;94:860–865. doi: 10.1002/bjs.5731. [DOI] [PubMed] [Google Scholar]
- Yamamoto Y, Shimada K, Sakamoto Y, Esaki M, Nara S, Kosuge T. Preoperative identification of intraoperative blood loss of more than 1,500 mL during elective hepatectomy. J Hepatobiliary Pancreat Sci. 2011 doi: 10.1007/s00534-011-0399-0. [Epub ahead of print; PMID 21594557] [DOI] [PubMed] [Google Scholar]
- Cockbain AJ, Masudi T, Lodge JPA, Toogood GJ, Prasad KR. Predictors of blood transfusion requirement in elective liver resection. HPB. 2010;12:50–55. doi: 10.1111/j.1477-2574.2009.00126.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lenoir B, Merckx P, Paugam-Burtz C, Dauzac C, Agostini M-M, Guigui P, et al. Individual probability of allogeneic erythrocyte transfusion in elective spine surgery: the predictive model of transfusion in spine surgery. Anesthesiology. 2009;110:1050–1060. doi: 10.1097/ALN.0b013e31819df9e0. [DOI] [PubMed] [Google Scholar]
- Strasberg SM. Nomenclature of hepatic anatomy and resections: a review of the Brisbane 2000 system. J Hepatobiliary Pancreat Surg. 2005;12:351–355. doi: 10.1007/s00534-005-0999-7. [DOI] [PubMed] [Google Scholar]
- Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006;105:198–208. doi: 10.1097/00000542-200607000-00030. [DOI] [PubMed] [Google Scholar]
- Transfusion of erythrocyte homologues: products, indications, alternatives. Ann Fr Anesth Reanim. 2003;22:67–81. doi: 10.1016/s0750-7658(02)00852-3. [DOI] [PubMed] [Google Scholar]
- Belghiti J, Noun R, Malafosse R, Jagot P, Sauvanet A, Pierangeli F, et al. Continuous versus intermittent portal triad clamping for liver resection: a controlled study. Ann Surg. 1999;229:369–375. doi: 10.1097/00000658-199903000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Belghiti J, Guevara OA, Noun R, Saldinger PF, Kianmanesh R. Liver hanging manoeuvre: a safe approach to right hepatectomy without liver mobilization. J Am Coll Surg. 2001;193:109–111. doi: 10.1016/s1072-7515(01)00909-7. [DOI] [PubMed] [Google Scholar]
- Ogata S, Belghiti J, Varma D, Sommacale D, Maeda A, Dondero F, et al. Two hundred liver hanging manoeuvres for major hepatectomy: a single-centre experience. Ann Surg. 2007;245:31–35. doi: 10.1097/01.sla.0000224725.40979.0a. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang C-C, Jawade K, Yap AQ, Concejero AM, Lin C-Y, Chen C-L. Resection of large hepatocellular carcinoma using the combination of liver hanging manoeuvre and anterior approach. World J Surg. 2010;34:1874–1878. doi: 10.1007/s00268-010-0546-9. [DOI] [PubMed] [Google Scholar]
- Farges O, Malassagne B, Flejou JF, Balzan S, Sauvanet A, Belghiti J. Risk of major liver resection in patients with underlying chronic liver disease: a reappraisal. Ann Surg. 1999;229:210–215. doi: 10.1097/00000658-199902000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Itamoto T, Katayama K, Nakahara H, Tashiro H, Asahara T. Autologous blood storage before hepatectomy for hepatocellular carcinoma with underlying liver disease. Br J Surg. 2003;90:23–28. doi: 10.1002/bjs.4012. [DOI] [PubMed] [Google Scholar]
- Ayantunde AA, Ng MY, Pal S, Welch NT, Parsons SL. Analysis of blood transfusion predictors in patients undergoing elective oesophagectomy for cancer. BMC Surg. 2008;8:3. doi: 10.1186/1471-2482-8-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Browning RM, Trentino K, Nathan EA, Hashemi N. Preoperative anaemia is common in patients undergoing major gynaecological surgery and is associated with a fivefold increased risk of transfusion. Aust N Z J Obstet Gynaecol. 2012;52:455–459. doi: 10.1111/j.1479-828X.2012.01478.x. [DOI] [PubMed] [Google Scholar]
- Mariette D, Smadja C, Naveau S, Borgonovo G, Vons C, Franco D. Preoperative predictors of blood transfusion in liver resection for tumour. Am J Surg. 1997;173:275–279. doi: 10.1016/S0002-9610(96)00400-X. [DOI] [PubMed] [Google Scholar]
- Oberti F, Valsesia E, Pilette C, Rousselet MC, Bedossa P, Aubé C, et al. Noninvasive diagnosis of hepatic fibrosis or cirrhosis. Gastroenterology. 1997;113:1609–1616. doi: 10.1053/gast.1997.v113.pm9352863. [DOI] [PubMed] [Google Scholar]
- Steyerberg EW, Moons KGM, van der Windt DA, Hayden JA, Perel P, Schroter S, et al. Prognosis Research Strategy (PROGRESS) 3: prognostic model research. PLoS Med. 2013;10:e1001381. doi: 10.1371/journal.pmed.1001381. [DOI] [PMC free article] [PubMed] [Google Scholar]
