transfusion requirements in living donor liver transplantation e role of laboratory assessment and...

Transfusion requirements in living donor liver transplantation e Role of laboratory assessment

and Model For End Stage Liver Disease (MELD) score

Original Article

Transfusion requirements in living donor livertransplantation e Role of laboratory assessmentandModel For End Stage Liver Disease (MELD) score

R.N. Makroo a,*, R. Walia b, A. Bhatia c, M. Chowdhry d

aDirector, Senior Consultant, Department of Transfusion Medicine, Indraprastha Apollo Hospitals, Sarita Vihar,

New Delhi, IndiabDNB Resident, Department of Transfusion Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi,

IndiacSr. Registrar, Department of Transfusion Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi,

IndiadAssociate Consultant, Department of Transfusion Medicine, Indraprastha Apollo Hospitals, Sarita Vihar,

New Delhi, India

a r t i c l e i n f o

Article history:

Received 17 April 2014

Accepted 3 May 2014

Available online xxx

Keywords:

MELD score

Liver transplant

Living donor

Prediction models

a b s t r a c t

Introduction and aims: Liver transplant surgery is often associated with considerable

bleeding. This study was undertaken to analyse the average blood component consump-

tion and the effectiveness of preoperative laboratory assessment and Model For End Stage

Liver Disease (MELD) score in the estimation of transfusion requirements in Living Donor

Liver Transplantation (LDLT).

Material and methods: Univariate and stepwise regression analysis were employed to

establish the significance of correlation of the preoperative laboratory variables, including

haematocrit, platelet count, INR, total bilirubin, serum creatinine, blood urea and MELD

score with the total consumption of Packed Red Cells (PRCs), cryoprecipitates, aphaeresis

platelets and Fresh Frozen Plasma (FFP). Stepwise discriminant analysis was used to

identify those preoperative factors which have a significant predictive value for the total

consumption of each blood component and these results were employed to construct

separate prediction models for the utilization of each blood component and the respective

R square values were determined.

Results: A total of 509 patients were included. On an average, 8.44 units (SD ¼ 6.11) of PRCs,

2.58 units (SD ¼ 2.95) of cryoprecipitates, 0.81 units (SD ¼ 1.16) of aphaeresis platelets and

2074.85 ml (SD ¼ 1240.20) of FFP were consumed per LDLT. The blood component prediction

models could be employed to accurately predict the total utilisation of PRCs, cry-

oprecipitates, FFP and aphaeresis platelets in 23, 22.6, 17.8 and 20.7 per cent of our patients,

respectively.

Conclusion: We have been able to identify those preoperative factors which can be

employed to predict the consumption of various blood components in living donor liver

graft recipients. These variables were further employed to construct prediction models,

* Corresponding author.E-mail address: [email protected] (R.N. Makroo).

Available online at www.sciencedirect.com

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journal homepage: www.elsevier .com/locate/apme

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Please cite this article in press as: Makroo RN, et al., Transfusion requirements in living donor liver transplantation e Role oflaboratory assessment and Model For End Stage Liver Disease (MELD) score, Apollo Medicine (2014), http://dx.doi.org/10.1016/j.apme.2014.05.010

http://dx.doi.org/10.1016/j.apme.2014.05.0100976-0016/Copyright ª 2014, Indraprastha Medical Corporation Ltd. All rights reserved.

separately for each blood component. We also identified those preoperative variables

which significantly influence the in hospital mortality and PLOS in LDLT recipients.

Copyright ª 2014, Indraprastha Medical Corporation Ltd. All rights reserved.

1. Introduction

Liver transplant surgery is often associated with considerable

bleeding, necessitating transfusion of blood and blood com-

ponents.1,2 Bleeding occurs largely because liver is an

extremely vascular organ3 and the associated bleeding is

compounded by the presence of portal hypertension4 and

abnormalities of the haemostatic system.5,6 This poses a

challenge to the blood transfusion services, particularly when

the supply of blood components is limited.7 Therefore, pre-

operative estimation of the blood component requirements in

patients undergoing liver transplantation would prove bene-

ficial for the blood transfusion services, by improving their

preparedness for such a major surgical procedure and helping

them in better resource allocation.

In order to address this issue, various factors have been

hypothesised as the potential predictors of blood component

usage in liver transplant surgeries. The proposed factors

include the recipient characteristics including recipient’s age,

gender, underlying diagnosis and the presence of any previ-

ous abdominal surgery; preoperative laboratory parameters

like haemoglobin, platelet count, international normalized

ratio (INR), renal parameters and the preoperative Model for

End Stage Liver Disease (MELD) score.8 However, there have

been conflicting reports as to whether such estimation can be

made preoperatively.9,10 In addition, only a limited number of

such reports are available for living donor liver trans-

plantations (LDLT).2

Therefore, the present study was undertaken to document

the average blood component consumption and to analyse the

effectiveness of preoperative laboratory assessment and

MELD score in the estimation of total i.e. intraoperative aswell

as the postoperative transfusion requirements in LDLT.

2. Material and Methods

After the approval of the hospital ethical committee, this

study was conducted at the Department of Transfusion

Medicine and Department of Surgical Gastroenterology &

Liver Transplant, Indraprastha Apollo Hospitals, New Delhi,

from January 2009 to May 2012. The records of all the patients

who underwent LDLT at our centre, between January 2009 and

February 2010, were analysed retrospectively and since,

March 2010 all the liver graft recipients were prospectively

followed up during their stay in the hospital.

At our centre, whenever a liver transplant surgery is

planned, a blood component request form is sent to the blood

bank for the arrangement of 10 units of cross matched and

leukoreduced Packed Red Cells (PRCs), 4 units of cry-

oprecipitates, 10 units of fresh frozen plasma (FFP), 2 units of

single donor aphaeresis fresh frozen plasma and 2 units of

single donor aphaeresis platelets, which are kept ready one

day prior to the potential liver transplant surgery. A fresh

blood component request form is sent to the blood bank in

case a further need arises. The intraoperative blood compo-

nent transfusions were based on the clinical condition of the

patient and the results of Thromboelastography (Haemoscope

Corporation, USA). Unless contraindicated, each recipient

received Tranexamic acid in an initial bolus dose of 15 mg/kg

during the induction of anaesthesia and its subsequent use

was guided by the thromboelastography results.

Relevant data, including the patient’s age, gender, history

of dialysis in the week prior to surgery and preoperative

haematocrit, platelet count, INR, total serum bilirubin, serum

creatinine and blood urea, was obtained from the patient’s

case file. The formula, MELD ¼ 9.57 � loge [creatinine mg/

dL] þ 3.78 � loge [bilirubin mg/dL] þ 11.20 � loge [INR] þ 0.643

was used to calculate the MELD score of each liver graft

recipient, based on the preoperative laboratory values of

serum bilirubin, serum creatinine, INR and history of dialysis

in the week prior to surgery.11

Data pertaining to the total number of blood components

consumed by each liver graft recipient during the intra-

operative and postoperative period was obtained from the

blood bank issue records. The number of units of plasma

(FFP and single donor plasma) was converted into plasma

volume in millilitres (ml). This calculation was based on the

results of our quality control measurements which show

that on an average, 1 unit of FFP is equivalent to 200 ml and

the volume of 1 unit of single donor aphaeresis plasma

prepared on a cell separator (Haemonetics, USA) is approx-

imately 600 ml.

Pearson’s correlation coefficients were employed in the

univariate statistical analysis to establish the significance of

correlation of the preoperative laboratory variables, including

haematocrit, platelet count, INR, total bilirubin, serum creat-

inine, blood urea and MELD score with the total consumption

of PRCs, cryoprecipitates, single donor aphaeresis platelets

and FFP. Further, stepwise regression analysis was performed

with all these variables to determine the bestmodel that could

be employed to predict the utilization of each blood compo-

nent. A stepwise regression analysis and multivariate logistic

regression was employed to analyse the effect of various pa-

rameters on mortality during the hospital stay and post-

operative length of stay (PLOS) in the hospital. The various

parameters analysed were recipient’s age; preoperative labo-

ratory parameters including haematocrit, platelet count, INR,

total bilirubin, serum creatinine and blood urea; MELD score

and PRC use (intraoperative, postoperative and total). To

determine the effect of recipient’s gender on mortality and

PLOS in the hospital, Independent t-test and ManneWhitney

test were employed. SPSS version 15.0 was used for all sta-

tistical analyses and all the correlations were defined as sig-

nificant at p-value less than 0.05.



3. Results

A total of 534 patients underwent LDLT during the period of

study. Out of these, twenty-five caseswere excluded, nineteen

of the recipients being under 16 years of age, three of the re-

cipients had a concomitant renal transplant and three had a

second liver transplant. None of the adult recipients included

in the study population received a cadaveric donor liver graft

and no intraoperative deaths were reported during the study

period. Out of the 509 patients remaining in the study popu-

lation, 416 (81.7%) were males and 93 (18.3%) were females.

The age of the patients included in the study ranged from 16 to

74 years, with a median of 50 years and mean age of 48.38

years (SD ¼ 10.27). The descriptive characteristics of various

parameters analysed are shown in Table 1.

On an average, a total of 8.44 units (SD ¼ 6.11) of PRCs were

consumed in a liver transplant (Fig. 1, Table 2). In the present

study, seventeen of the liver graft recipients, required no

intraoperative PRC transfusion while in eleven of them, no

PRC was transfused even in the postoperative period. Two of

the liver graft recipients did not require any transfusion dur-

ing the hospital stay. The average consumption of cry-

oprecipitates and aphaeresis platelets and per liver transplant

was 2.58 units (SD ¼ 2.95) and 0.81 units (SD ¼ 1.16),

respectively (Fig. 1, Table 2). The mean volume of FFP

consumed in a liver transplant was 2074.85 ml (SD ¼ 1240.20)

(Fig. 2, Table 2).

As shown in Table 3, univariate analysis demonstrated

that except for the preoperative serum creatinine (p value

>0.05), all the other variables correlated significantly (p< 0.05)

with the consumption of one or more blood components in a

liver transplant. Further evaluation with the stepwise

discriminant analysis, identified those preoperative factors

which have a significant predictive value for the total con-

sumption of each blood component in a liver graft recipient.

These results were further employed to construct separate

predictionmodels for the utilization of each blood component

and their respective R square values were determined. As

shown in Table 4, it was observed that the total PRC con-

sumption had a significant correlation with preoperative

haematocrit, blood urea and the MELD score. The total con-

sumption of cryoprecipitates was influenced by four factors

including the preoperative platelet count, haematocrit, MELD

score and INR. The total utilisation of FFP could be predicted

by employing preoperative MELD score, haematocrit and total

bilirubinwhile the preoperative platelet count andMELD score

influenced the total platelet transfusions (Table 4).

Multivariate logistic regression demonstrated that mor-

tality was significantly related to recipient’s age, preoperative

MELD score and total PRCs consumed. It was observed that

with a one year increase in age, the probability of mortality

increases by 4.3 per cent while with a one unit increase in

preoperative MELD score and that of total PRCs transfused,

there is an increase in the probability of mortality by 4.9 per

cent and 9.4 per cent respectively. We also calculated that the

total PRC consumption and preoperative blood urea had a

significant positive correlation with the PLOS in the hospital.

4. Discussion

In the present study, it was calculated that, on an average 8.44

units of PRCs were consumed per LDLT, with a median of 7

units. The average number of cryoprecipitates and single

donor aphaeresis platelets transfused was 2.58 units and 0.81

units, respectivelywhile the average utilisation of FFP per liver

transplant was 2074.85 ml (Table 2). As shown in Table 4, the

total PRC consumption had a significant correlation with

preoperative haematocrit, blood urea and the MELD score

while the total consumption of cryoprecipitates was influ-

enced by the preoperative platelet count, haematocrit, MELD

score and the INR. It was also observed that the total uti-

lisation of FFP could be predicted by employing preoperative

Table 1 e Descriptive characteristics of various parameters.

Parameter Mean S.D. Median Minimum Maximum

Age (years) 48.38 10.27 50.00 16.00 74.00

Hct 0.27 0.06 0.27 0.13 0.44

Plt (�109/L) 74.78 51.47 62.00 7.00 469.00

INR 1.94 0.84 1.80 0.90 9.40

T. bilirubin (mmol/L) 115.25 156.81 54.72 3.42 957.26

B. urea (mg/dL) 38.29 32.10 27.00 8.00 209.00

S. crt (mmol/L) 76.27 66.40 46.98 5.00 433.16

MELD score 19.14 7.39 18.00 6.00 44.00

PLOS (days) 21.04 11.52 18.00 2.00 116.00

Abbreviations: Hct, Haematocrit; Plt, Platelet count; INR, International Normalised Ratio; T. bilirubin, Total bilirubin; B. urea, Blood urea; S. crt,

Serum creatinine; MELD, Model for End Stage Liver Disease; PLOS, Postoperative Length of Stay; SD, Standard Deviation.

Fig. 1 e Mean number (units) of blood components used in

liver transplant.

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MELD score, haematocrit and total bilirubin. Similarly, total

platelet transfusions were significantly correlated to preop-

erative platelet count, haematocrit and the MELD

score (Table 4).

Our study demonstrates that the preoperative haematocrit

had a negative influence on the consumption of PRCs, cry-

oprecipitates, FFPs and platelets i.e. a lower preoperative

haematocrit was associated with a higher consumption of

these blood components (Table 4). A negative association of

preoperative haematocrit with the PRC transfusion in liver

transplantation has also been reported previously by Massi-

cotte, et al.12 Moreover, the observed association of the pre-

operative haematocrit and the consumption of

cryoprecipitates, FFPs and platelets can be attributed to a

resultant decrease in haematocrit in the wake of active

bleeding that is associated with abnormalities of the coagu-

lation system and therefore, necessitates transfusion of these

blood components. A significant correlation was also

demonstrated between the preoperative INR and platelet

count with the total consumption of cryoprecipitates and

platelets, respectively (Table 4).

We also observed that the preoperative blood urea had a

positive association with the total utilization of PRCs which

can be attributed to uraemia, which is associated with

impaired renal function and may lead to disturbed coagula-

tion status and subsequent bleeding,13 requiring transfusion

with PRCs. Deakin et al, also concluded that elevated blood

urea was one of the predictors of bleeding in liver trans-

plants.7 The association of renal function impairment and

transfusion requirements in liver transplantation has also

been described in other studies.14e16 Moreover, renal

dysfunction that may be associated with End Stage Liver

Disease can aggravate anaemia as a result of reduced levels of

erythropoietin, leading to increased requirements of PRC

transfusion.17

Our findings show that the preoperative MELD score had a

positive correlation with the total consumption of all the

blood components including PRCs, cryoprecipitates, FFPs and

platelets and the observed associations were highly signifi-

cant. It was also reported by Peter E. Frasco, et al that MELD

score has a significant association with the blood component

therapy in liver transplantation.18 The observed association

of MELD score with the blood component utilization may be

due to the fact that the MELD score is calculated by using

serum bilirubin, serum creatinine and INR11 which represent

Table 2 e Blood component use in liver transplant.

Blood component Mean S.D. Median Minimum Maximum

Intraoperative PRC (units) 6.67 4.39 6.00 0.00 41.00

Cryo (units) 2.39 2.70 2.00 0.00 17.00

FFP (ml) 1735.17 845.25 1600.00 0.00 4400.00

Platelets (units) 0.57 0.73 0.00 0.00 4.00

Postoperative PRC (units) 1.77 3.45 0.00 0.00 31.00

Cryo (units) 0.19 1.13 0.00 0.00 16.00

FFP (ml) 349.02 815.11 0.00 0.00 8000.00

Platelets (units) 0.24 0.78 0.00 0.00 9.00

Total PRC (units) 8.44 6.11 7.00 0.00 41.00

Cryo (units) 2.58 2.95 2.00 0.00 17.00

FFP (ml) 2074.85 1240.20 2000.00 0.00 10,400.00

Platelets (units) 0.81 1.16 0.00 0.00 9.00

Fig. 2 e Mean volume (ml) of FFP used in liver transplant.

Table 3 e Univariate analysis of various parameters with blood component transfusion.

Total blood components Hct Plt (�109/L) INR T. bilirubin (mmol/L) B. urea (Mg/dl) S. crt (mmol/L) MELD

PRC (units) Correlation �0.37 �0.08 0.19 0.23 0.32 0.02 0.33

p-value 0.001 0.09 0.001 0.001 0.001 0.62 0.001

Cryo (units) Correlation �0.22 �0.21 0.34 0.27 0.13 �0.03 0.40

p-value 0.001 0.001 0.001 0.001 0.003 0.45 0.001

FFP (ml) Correlation �0.26 �0.09 0.31 0.22 0.19 �0.004 0.38

p-value 0.001 0.05 0.001 0.001 0.001 0.93 0.001

Platelets (units) Correlation �0.24 �0.36 0.17 0.13 0.15 0.014 0.25

p-value 0.001 0.001 0.001 0.004 0.001 0.76 0.001

Abbreviations: Hct, Haematocrit; Plt, Platelet count; INR, International Normalised Ratio; T. bilirubin, Total bilirubin; B. urea, Blood urea; S. crt,

Serum creatinine; MELD, Model for End Stage Liver Disease.



a recipient’s hepatic, renal and haemostatic status,

respectively.

We observed that our blood component prediction models

could be employed to accurately predict the total utilisation of

PRCs, cryoprecipitates, FFP and aphaeresis platelets in 23, 22.6,

17.8 and 20.7 per cent of our patients, respectively (Table 4). This

shows that besides the preoperative laboratory parameters and

MELD score, other variables might also influence the blood

component consumption in liver transplants. These variables

could possibly include the intraoperative, technical and general

patient factors,whichwerenot considered in the present study.

It was also seen that the in hospital mortality was signifi-

cantly related to recipient’s age, preoperative MELD score and

total PRCs consumed. A one year increase in the recipient’s

age, increased the probability of mortality by 4.3 per cent.

Similarly, with one unit increase in preoperative MELD score

and that of total PRCs transfused, there was an increase in the

probability of mortality by 4.9 per cent and 9.4 per cent

respectively. PLOS in the hospital was also calculated to be

positively influenced by the total PRC consumption and pre-

operative blood urea.

To the best of our knowledge, the present study is one of

the largest single centre studies that have been undertaken to

identify the significance of preoperative laboratory assess-

ment in estimating the transfusion needs in LDLT. We have

tried to present an extensive analysis of the total i.e. intra-

operative and postoperative, consumption of various blood

components in liver transplantation and have also con-

structed separate prediction models to estimate the use of

each blood component.

However, there still are some limitations in our study. The

present study is limited to the preoperative laboratory vari-

ables and the MELD score only and does not include the effect

of intraoperative, technical and general patient factors on

blood component consumption. It is possible that the inclu-

sion of all these factors might even have resulted in the con-

struction of improved prediction models with higher R square

values and better predictive power. However, the main focus

of our study was to analyse the effect of preoperative labora-

tory parameters and MELD score only, in order to draw defi-

nite conclusions with regard to their predictability by

analysing their role in such a large number of patients.

Moreover, our findings may not be applicable to centres

following a different protocol for liver transplantation and to

centres performing cadaveric donor liver transplants.

To conclude, we have calculated our blood component

consumption in 509 LDLTs. Moreover, we have been able to

identify those preoperative factors which can be employed to

predict the consumption of various blood components in

living donor liver graft recipients. These variables were

further employed to construct prediction models, separately

for each blood component. We also identified those preoper-

ative variables which significantly influence the in hospital

mortality and PLOS in LDLT recipients.

Conflicts of interest

All authors have none to declare.

r e f e r e n c e s

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7. Deakin M, Gunson BK, Dunn JA, et al. Factors influencingblood transfusion during adult liver transplantation. AnnRoyal Coll Surg Engl. 1993;75:339e344.

Table 4 e Blood component prediction models.

Predicted bloodcomponent

Predicting factors R2 (%) Prediction model P-value

Total PRC (units) Hct

B. urea (mg/dL)

MELD score

23.0 12.454e30.7 � Hct þ 0.036 � B. urea þ 0.156 � MELD 0.001

Cryo (units) MELD score

Plt (�109/L)

Hct

INR

22.6 1.775 þ 0.113 � MELD�0.012 � Plt�4.9 � Hct þ 0.461 INR 0.001

FFP (ml) MELD score

Hct

T. bilirubin (mmol/L)

17.8 1748.996 þ 75.310 � MELD�3589.3 � Hct�19.870 � (T. bilirubin/17.1) 0.001

Platelets

(units)

Plt (�109/L)

MELD score

Hct

20.7 1.317e7.7 � 10�3 Plt þ 0.037 � MELD�2.3 � Hct 0.001

Abbreviations: Hct, Haematocrit; Plt, Platelet count; INR, International Normalised Ratio; T. bilirubin, Total bilirubin; B. urea, Blood urea; MELD,

Model for End Stage Liver Disease.

a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1e6 5


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11. Floden A, Castedal M, Friman S, Olausson M, Backman L.Calculation and comparison of the model for end-stage liverdisease (MELD) score in patients accepted for livertransplantation in 1999 and 2004. Transpl Proc.2007;39:385e386.

12. Massicotte L, Beaulieu D, Thibeault L, et al. Coagulationdefects do not predict blood product requirements duringliver transplantation. Transplantation. 2008;85:956e962.

13. Noris M, Remuzzi G. Uremic bleeding: closing the circle after30 years of controversies? Blood. 1999;94(8):2569e2574.

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15. McCluskey SA, Karkouti K, Wijeysundera DN, et al.Derivation of a risk index for the prediction of massive bloodtransfusion in liver transplantation. Liver Transpl. 2006;12(11):1584e1593.

16. Hendriks HG, van der Meer J, Klompmaker IJ, et al. Blood lossin orthotopic liver transplantation: a retrospective analysis oftransfusion requirements and the effects of autotransfusionof cell saver blood in 164 consecutive patients. Blood CoagulFibrinolysis. 2000;11(suppl 1):S87eS93.

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transfusion requirements in living donor liver transplantation e role of laboratory assessment and...

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