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MAXIMUM SURGICAL BLOOD ORDER SCHEDULE (MSBOS) IN LIVER TRANSPLANT

RN Makroo*, V Raina**, S Gupta***, M Chowdhry ****, RS Bhanot *****, B Arora *****,and L Baburajan******

*Director, **Senior Consultant, ****Registrar, *****DNB Student, Department of Transfusion Medicine, *** Senior Consultant, ******Registrar, Department of Surgical Gastroenterology & Liver Transplant,

Indraprastha Apollo Hospitals, Sarita Vihar,New Delhi 110 076, India.

Correspondence to: Dr RN Makroo, Director, Department of Transfusion Medicine,Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India.

email: makroo@apollohospitals.com

Background: Orthotopic liver transplantation (OLT) is the replacement of a diseased liver with a healthy liverin the normal anatomic position.In this study we sought to determine the factors influencing red blood cell(RBC) transfusions during liver transplants. Liver being a highly vascular organ, surgeries like liver transplantmay involve massive blood loss making the blood banks a vital factor in the clinical transplantation program.Aims & objectives: The present study was undertaken in the Indraprastha Apollo Hospital to assess thetransfusion requirement in cadaveric and living liver transplant patients so as to assess the maximum surgicalblood ordering schedule (MSBOS) for each category. Materials & methods: 104 liver transplants performedfrom October 2006 to September 2008 were included in the study. The cases were divided into 2 subgroups:Cadaveric liver transplant (CLT, n=3) and living donor liver transplants (LDLT, n=101) They were furtherdivided into those who received >7 units of packed red blood cells (PRC) (n=62) and those who received lessthan 7 units PRC (n=42). The patients were given balanced general anesthesia. The transfusion trigger wereset to hemoglobin <8 gm/dL, Platelet count <50,000/cu mm and PT >20 seconds. The mean PRC, Freshfrozen Plasma (FFP), random donor Platelet concentrate (RDP), Single donor Platelets (SDP) on cellseparator and cryoprecipitate were assessed for both CLT and LDLT. Results: Out of the 101 LDLT, 83(82.1%) patients were males and 18 (17.9%) were females whereas all the CLT were males. The mean PRC,FFP, RDP, SDP and cryoprecipitate utilization for LDLT were 8.84 units, 7.1 units, 1.83 units, 2.36 units and2.03 units respectively whereas for CLT it was 15.3 units, 9 units, 0 units, 2.3 units & 3.3 units. The mortality ratein LDLT was 20 patients (19.8%) out of which 17 (85%) were males and 3 (15%) were females whereas in CLTthe mortality rate was 1 patient (33.3%) who was a male (100%).

Keywords: Orthotopic liver transplant (OLT), Red blood cell (RBC), Cadaveric liver transplant (CLT).

INTRODUCTION

THE number of liver transplant centers has been increasingtremendously over the past few years [1]. However; bloodloss represents a serious problem during orthotopic livertransplantation. Improvements in operative management,surgical techniques and graft preservation have widelycontributed to a significant reduction in transfusionrequirements during the last decade but blood losses remainhighly variable. The RBC transfusion in liver transplantvaries among different transplant institutions from as few as4.3 units per patient [2] to an extreme of 43 units per patient[3]. Therefore a blood bank is a vital factor in supportingclinical transplantation programs. Data suggest thattransfusion of blood or blood components prior totransplantation can affect allograft survival [4]. The purposeof this study was to assess the transfusion requirement incadaveric and living liver transplant patients so as to assess

the maximum surgical blood ordering schedule (MSBOS)for each category.

Materials and methods

A retrospective study was conducted at Department ofTransfusion Medicine, Indraprastha Apollo Hospital NewDelhi on all the liver transplant patients from October 2006to September 2008. For the multivariate analysis thepatients were divided into 2 subgroups: Cadaveric (CLT,n=3) and Living (LDLT, n=101) liver transplants. Pediatricliver lransplants were excluded from study. The samepreparation for anesthesia was used for every patient. Thevariables considered were age, sex, preoperative Hb,preoperative Prothrombin time (PT)/InternationalNormalized Ratio (INR), preoperative platelet count,average length of stay (ALOS) and diagnosis. The patientswere also divided into those who received more than seven

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units of PRC (n=62) and those who received less than 7units (n=42). The transfusion trigger for transfusion ofblood components was set to hemoglobin <8-10 gm/dL,Platelet count <50,000/ cu mm and PT > 20 seconds. Themean PRC, FFP, RDP, SDP and cryoprecipitate utilizationwere assessed for both CLT and LDLT. The mean PRCrequirement in patients with pre-transplant PT of >20 secs(n=39) and pre-transplant PT of </=20 secs (n=65), pre-transplant platelet count of </=50,000/cumm (n=27) and>50,000/cumm (n=77) and pre-transplant Hb </= 8(n=21)and those with Hb>8(n=83) was also analyzed. The ChildPugh’s score and blood/blood component requirement wasalso assessed.

RESULTS

A total of 104 transplants (both cadaveric and living)were performed from October 2006 to September 2008. Theage distribution ranged from 12 years to 63 years. Out of the101 LDLT, 83 (82.1%) patients were males and 18 (17.9%)were females whereas all the CLT patients were males(Fig.1).

The mortality rate in LDLT was 20 patients (19.8%) outof which 17 (85%) were males and 3 (15%) were femaleswhereas in CLT the mortality rate was 1 patient (33.3%)who was male. The ALOS in the hospital was 31.5 days. Itwas observed that the mean PRC requirement in CLT (15.3units) was significantly higher than LDLT (8.84 units). InCLT 2 patients out of 3 (66.7%) patients required more than7 units of blood whereas in LDLT it was 60 patients out of101(59.4%).The mean FFP requirements of CLT were 12units as compared to a mean of 7.1 units for LDLT. MeanCryoprecipitate requirement showed a variation of 3.3 unitsfor CLT and 2.03 units for LDLT. The mean SDP on cellseparators requirement for CLT was 2.3 units as comparedto LDLT which had a mean requirement of 2.36 units. TheRDP required by LDLT was 1.83 units and CLT on thecontrary did not require any RDP (Table 1).

It was observed that those with pre-transplant PT of >20seconds utilized a mean of 12.5 units of PRC whereas whenthe PT was </=20 secs a mean of 6.9 units of PRC weretransfused. When the pre-transplant platelet count was </=50,000/cumm (n=27) the mean amount of PRC requiredwere 10.6 units whereas when the pre-transplant plateletcount were >50,000/cumm (n=77) the mean PRCtransfused were 8.4 units. When the pre-transplant Hb was</= 8(n=21) a mean of 11.7 units of PRC were required ascompared to those with Hb>8 (n=83) who required a meanof 8.3 units of PRC.

The maximum patients presented with the diagnosis ofcryptogenic chronic liver disease (CLD n=38). Thediagnosis in other patients were alcoholic CLD (N=13),HCV related CLD (n=12), cirrhosis (n=11), HBV relatedCLD (n=7), CLD with portal hypertension (n=6), fulminanthepatic failure (n=4), primary sclerosing cholangitis (n=2),Hepatocellular carcinoma (n=1), autoimmune hepatitis(n=1), Criggler Najjar syndrome (n=1), biliary atresia(n=1),acute on chronic liver disease (n=2), Wilsons disease(n=1), Alcoholic CLD with HBV (n=1), Alcoholic CLDwith HCV (n=1) and extra hepatic portal vein obstructionwith secondary biliary cirrhosis (n=2) (Fig 2). Themaximum patients had a Child Pugh score in the C category.

DISCUSSION

Orthotopic liver transplant (OLT) requires complexsurgical dissections and suturing of major vascularstructures which is responsible for surgical blood loss [5].

Liver transplantation may be divided into 3 stages. StageI (preanhepatic period) begins with dissection of the inflowand outflow vascular structures of the liver is performed andends with removal of the diseased organ. Stage II (anhepaticphase) begins with implantation of the donor liver and endswith reperfusion of the new organ. Stage III (reperfusionFig 1. Number of LDLT & CLT patients with mortality rate

Table 1 Comparison between LDLT & CLT

LDLT CLT

No of patients 101 3

Mortality Rate 19.8% 33.3%

% of Males 82.1 100

Mean PRC requirement 8.84 15.3

No of patients requiring > 7 units of PRC 59.4% 66.7%

Mean FFP requirement 7.1 12

Mean Cryoprecipitate requirement 2.03 3.3

Mean platelet on cell separator (SDP) 2.36 2.3

Mean Platelet concentrate requirement 1.83 0(RDP)

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385 Apollo Medicine, Vol. 5, No. 4, December 2008

and post reperfusion period) begins with reperfusion of thegrafted liver and ends with completion of the surgery [6].

Besides the standard coagulation tests (i.e., PT, aPTT,and fibrinogen level), the thromboelastogram andcoagulation and platelet function analyzer are used in theevaluation of coagulation during liver transplantation. Thethromboelastogram is used to monitor coagulation,fibrinolysis, and bleeding time. It assesses clot formationand monitors clotting until an endpoint of clot lysis orretraction are determined. The thromboelastogram isperformed using whole blood, and it analyzes theinteractions of plasma coagulation proteins with plateletsand fibrinogen [6].

PREDICTORS OF TRANSFUSIONREQUIREMENTS

In addition to procedure related to surgery, abnormalbleeding typically occurs during liver transplantation as aconsequence of severe haemostatic dysfunction [7].Etiology of hemostasis abnormalities is multifactorial,including deficit in platelets and coagulation factors relatedto existing liver disease and increased fibrinolysis, whichcan contribute significantly to non surgical blood loss [7]. Inthe early 90’s, Mor, et al, from Dallas, were among the firstto report on the negative association between intraoperativeblood transfusion requirement and post operative outcomevariables, such as graft and patient survival, length of thestay in intensive care unit, and infectious complications [8].

Important variables affecting transfusion requirementsinclude the severity of disease or Child classification,preoperative PT, history of abdominal operations, andfactor V levels. Other factors identified as independentpredictors of transfusion include the preoperativehematocrit value, use of the piggyback transplantationmethod, and operative time.

The Child classification is a measure of disease severitythat includes assessments of ascites, encephalopathy, andmuscle wasting and measurements of serum bilirubin andalbumin. It is classified into class A to C with a scoringsystem of 5 to 15 [6].

Class A- 5-6 (less severe)

Class B- 7-9

Class C- 10-15 (more severe)

Maximum patients in our study were in Class C.

Another classification that is used is the Model for End-stage Liver Disease which has a numerical scale rangingfrom 6 (less ill) to 40 (gravely ill) which is used to assess theliver transplant urgency.

Both these classifications are used to assess the severityof the disease and with longer waiting time the diseaseprogresses as is evident by the higher score in theseclassification.

In our study we observed that the mean transfusionrequirement was 9.02 units for all transplants (cadaveric andliving donor) with the demand being considerably higherfor Cadaveric donor transplant for both blood and itscomponents. This was quite high as compared to MassicotteL, et al. [9] who had a mean transfusion requirement of just2.8 units of PRC per liver transplant. The small transfusionrate seems to be attributable to using a lower Hb value (6.8gm/dL) as the threshold for transfusing PRC. There are evena few reports in the literature of successful livertransplantation without transfusion of red cells in Jehovah’switnesses [10]. Our mean transfusion requirement washowever much better than The Mayo Clinic team that used amean of 12.6 units of blood for their first 100 transplants[11]. The Pittsburgh team which saw a fall in the number ofunits transfused with increasing experience, had a mean of37 units per patient in 1981 which fell to 17 in 1985 [12].

Fig 2. Indications of liver transplant

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Our mean PRC requirement for LDLT was 8.84 unitsand that for CLT was 15.3 units. It has been observed thatexcessive transfusion is associated with an increased 30-daymortality rate and, conversely, patients who are minimallytransfused have fewer infective complications and thehighest chance of survival [11]. This was in accordance withthe present study in which the mortality rate increased withexcessive transfusion.

According to Massicotte, et al. [9] two factors influenceblood loss: a mechanical or vascular component and abiochemical one. The latter is multifactorial and includes anumber of variables which have been evaluated in differentstudies. A multivariate analysis showed that there was arelationship between the starting platelet count, duration ofsurgery, the starting INR value, and the number of RBCunits that were transfused. The smaller the starting plateletcount, the more the patients received RBC [9]. This wassimilar to the observations made in our study where in thepre transplant PT of >20, platelet count </=50,000/cummand pre-transplant Hb was </= 8 meant more units of PRCwere transfused. Another study undertaken at QueenElizabeth Hospital, Birmingham, UK from 1982 to 1990revealed that levels of serum sodium, urea, creatinine,hemoglobin, platelet count, patient weight and the presenceof ascites were significantly related to the quantity of bloodtransfused during the transplant operation. In this group of150 patients, the 30-day mortality rate was higher in patientswho received more than 7 units of blood, 11/72 (15.3%) vs.5/78 (6.4%), but this did not reach statistical significance (P=0.079). Non-significant factors were the degree ofabnormality of liver function tests including serum albumin,aspartate transaminase, alkaline phosphatase, bilirubin,prothrombin time and diagnosis. Although a history ofprevious upper abdominal surgery frequently made thetransplant operations more tedious as adhesions wereencountered this was not reflected in an increasedtransfusion requirement [13].

Of the two factors mentioned, the mechanical factor,controlled by the surgeon, seems to be the more important ofthe factors influencing the transfusion rate [9]. This seemsto corroborate with our study in which we realize that inspite of having low hemoglobin or platelet count there havebeen patients who have required less units of bloodtransfusion, therefore the biochemical profile does not onlydecide the number of blood transfusion but a lot of otherfactors are important, the surgeons expertise being one ofthe important one.

CONCLUSION

Liver transplantation poses a challenge to the bloodbank and places additional demand on the blood transfusionservices. We observed in our study that substantial amount

of blood and its products are required for both living donoras well as cadaveric liver transplant. The transfusionpredictors include the mechanical and the biochemicalcomponent. Both the components are important so as tominimize the blood loss in liver transplant. In thebiochemical component the Pre transplant Hemoglobin,PT/INR value and platelet count are good indicators oftransfusion requirement and all liver transplant requestshould indicate these parameters. Based on this and otherdata, we recommend that MSBOS for liver transplantshould comprise 15 units of PRC, 15 units of FFP, 5 units ofSDP and 4 units of cryoprecipitate before thecommencement of the procedure.

REFERENCES

1. Fran ST. Liver transplantation in Queen Mary Hospital.Hong Kong Practitioner 1994; 16(5): 248-251.

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3. Carton EG, Rettke SR. Perioperative care of the livertransplant patient: part 1. Anesth Analg 1994; 78:120-133.

4. Brown NE. Transfusion support of the transplant patient.Can Fam Physician 1988; 34: 2503-2508.

5. Detry O, Roover AD, Delwaide J, et al. Liver transplantationin Jehovah’s witnesses. Transplant Int 2005; 18: 929-936.

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10. Liu CL, Fan ST, Lo CM, et al. Living donor livertransplantation without the use of blood products. HongKong Medical Journal 2002; 8:192-195.

11. Motschman TL, Taswell HF, Brecher ME, et al. Blood banksupport of a liver transplant program. Mayo Clinic Proc1989; 64: 103-111.

12. Lewis JH, Bontempo FA, Cornell F, et al. Blood use in livertransplantation. Transfusion 1987; 27: 222-225.

13. Deakin M, Gunson BK, Dunn JA, et al. Factors influencingblood transfusion during adult liver transplantation. Annalsof The Royal College of Surgeons of England 1993; 75:339-334.