Computers and Chemical Engineering 106 (2017) 355–372

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Computers and Chemical Engineering

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

Raising quality and safety of platelet transfusion services in a

patient-based integrated supply chain under uncertainty
Hamidreza Ensafian a , Saeed Yaghoubi a,∗ , Mohammad Modarres Yazdi b
a
School of Industrial Engineering, Iran University of Science and Technology, Tehran, Iran
b
School of Industrial Engineering, Sharif University of Technology, Tehran, Iran

a r t i c l e i n f o a b s t r a c t

Article history: This paper develops a stochastic multi-period mixed-integer model for collection, production, storage,
Received 24 April 2017 and distribution of platelet in Blood Transfusion Organizations ranging from blood collection centers to
Received in revised form 6 June 2017 clinical points. In this model, the age of platelet and ABO-Rh priority matching rules are incorporated
Accepted 7 June 2017
based on the type of patient to raise the quality and safety of platelet transfusion services. At first, a dis-
Available online 23 June 2017
crete Markov Chain Process is applied to predict the number of donors. Afterwards, the uncertain demand
is captured using a two-stage stochastic programming. A challenging aspect of applying stochastic pro-
Keywords:
gramming in a dynamic setting is to construct an appropriate set of discrete scenarios. Therefore, we
Blood platelet supply chain
ABO-Rh priority matching rules
introduce an improved approach for scenario reduction which well represents multivariate stochastic
Donor prediction processes for uncertain parameters. To manage risk, a straightforward approach to reduce the expected
Tow-stage stochastic programming value and variance of cost is proposed. Finally, management strategies inspired from a real case study
Scenario reduction are presented.
© 2017 Elsevier Ltd. All rights reserved.

1. Introduction
Platelet (PLT), as a highly perishable blood product, is widely
used in hospital blood transfusion centers as a lifesaving medical
treatment. Platelet transfusion is extensively utilized in medical
practices for those patients who have a low platelet count or
impaired platelet performance. The platelet supply chain includes
the process of collecting both whole blood and platelet from
donors, testing, producing, and finally distributing platelet to clin-
ical points. The distinction of blood groups, the uncertainty in the
supply and demand, and blood platelet’s short shelf life (typically
5 days), are three major factors which complicate platelet supply
chain. The main challenge in platelet supply chain is the accessi-
bility of donors in the right time to reduce wastage and shortage
rates resulting from uncertain demand and very limited shelf life.
According to the World Health Organization (WHO), 87.5% of devel-
oping countries collect less than half of the blood needed while
the percentage of blood wasted during the years 2012, 2013, and
2014 was recorded as 30.1%, 26.4% and 23.4%, respectively (Kurup
et al., 2016; Hall, 2010). Because platelets have a very short life time
∗ Corresponding author.
E-mail address: yaghoubi@iust.ac.ir (S. Yaghoubi).
there is always a need for donors while only 5% of the population of
eligible people actually donate their blood (Schreiber et al., 2006).
Generally, there are two types of platelets: Whole Blood-
Platelets (Random Platelets) which are derived from random
donors and Apheresis platelets (also called Single Platelets) which
are drawn directly from one donor. A full dose of platelets col-
lected by using Apheresis method is 6–8 times more than those
produced from the collected whole blood. Both of these products
are in widespread clinical use (Table 1).
According to Jacobs et al. (2011) the third leading cause of
transfusion-related fatalities between 2005 and 2009 was bacte-
rial contamination. The storage time of platelet products negatively
affects their safety and allows bacterial contamination to spread
which can adversely affect transfusion outcomes. Thus, fresh
platelets are superior to old platelets for therapeutic use especially
in the case of patients whose immune system has been weakened
(Caram-Deelder et al., 2016; Jerad and Prane,1997; Muylle et al.,
1992).
ABO-identical PLTs are preferably used in clinical points because
ABO-incompatible PLTs may have a negative effect on transfusion
outcome and can sometimes cause hemolysis (Aster, 1965). The
challenge during transfusion is to match the PLTs according to ABO
and Rh types. The ABO-Rh priority matching rules for platelet are
shown in Table 1 in accordance with clinical preference (World
Health Organization, 2014). The desirable platelet type (random or

http://dx.doi.org/10.1016/j.compchemeng.2017.06.015
0098-1354/© 2017 Elsevier Ltd. All rights reserved.
356 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372

Table 1
Priority matching rules for platelet transfusion (World Health Organization, 2014).

Donor blood group priority

Recipient blood group O+ O− A+ A− B+ B− AB+ AB−

+
O 1 2 5 6 3 4 7 8
O− 5 1 7 3 6 2 8 4
A+ 7 8 1 2 5 6 3 4
A− 8 4 5 1 7 3 6 2
B+ 7 8 5 6 1 2 3 4
B− 8 4 7 3 5 1 6 2
AB+ 7 8 3 4 5 6 1 2
AB− 8 4 6 2 7 3 5 1

Table 2
The desirable platelet type for three types of patients.

Treatment ABO-Rh Patient type Desirable platelet product Desirable age Reference
compatibility of platelet

Stem cell transplantation, ABO-Rh full Type 1: Patients requiring Single-pre-qualified donor Fresh Witter et al. (2009), Murphy et al.
Transfusion to refractory compatible stem cell transplantation, (selected donor) (1986), Stroncek and Rebulla (2007),
patients, Transfusion to refractory patient, patients Heal and Blumberg (2004), World
patients using using HLA-matched PLT Health Organization 2014)
HLA-matched PLT
Frequent or higher doses of (Rh-identical) Type 2: Cancer patients, Single, random donor Young Asllani et al. (2014), Gunpinar and
platelet transfusions for Oncologic and Hematologic Centeno (2015), Haijema et al. (2007),
patient with Rh (D) patients, patients Heal and Blumberg (2004), World
undergoing cardiac surgery Health Organization (2014)
Low doses and infrequent ABO-Rh match Type 3: Patient with Single, Random donor Old Heal and Blumberg (2004), World
platelet transfusion is ideal but not bleeding and general Health Organization (2014)
vital surgery (except children
under 10 years and women
of child-bearing age)

Table 3
Any age group of platelet and related definition.
Type of Age
demand
Fresh 1 day old
Young 2 to 3 days old Gunpinar and Centeno (2015)
Old 4 to 6 days old Gunpinar and Centeno (2015)
single platelet) and the ABO-Rh priority matching rules according
to different patient types are shown in Table 2. Furthermore, for
platelet demand a classification can be made between three types
of patients. For the first type of patient who needs ABO-Rh or HLA-
matched PLTs, ‘fresh’ units derived from a single donor through
Apheresis procedure are highly preferable. To treat these patients,
transfusion service centers try to prevent transfusion of Random
PLTs derived from various donors (Champlin et al., 2000). For the
second type, mostly oncologic and hematologic patients, ‘young’
platelets following the Rh(D) matching rules are widely used while
for the third type, any age of platelets up to the maximal shelf life,
can be used. For more information about Table 2, we refer the read-
ers to Appendix A. The definitions of “fresh”, “young” and “old” PLTs
and their associated usage are presented in Table 3.
Optimization approaches can assist blood service centers to
overcome the complexity of platelet supply chain, ranging from
donor management in collection centers to the delivery of care
services in hospitals.
The specifications of platelet and complexity of its supply chain
necessitate developing a methodology and a close relationship
between all stages of platelet supply chain including collecting,
processing, and distributing. In this paper, we consider an inte-
grated platelet supply chain network addressing several collection
centers, a single regional blood center, and several hospitals con-
sidering three types of patients (Fig. 1).
The motivation for this study is to optimize all platelet supply
chain stages in order to achieve a better use of voluntary donations
and to increase the service quality and safety in medical points con-
sidering the ABO-Rh priority matching rules and age-differentiated
demand according to three types of patients. The main contri-
butions which differentiate this study from relevant studies are
presented as follows:
• Procurement of whole blood, production, and distribution of
platelets are integrated in the form of an integer programming
mathematical model in which the main operational and tactical
decisions are made.
• The ABO-Rh priority matching rules have been formulated as one
of the factors that strongly affect management decisions.
• By introducing the two measures of Substitution Index (SI) and
Complexity Index (CI) blood groups are analyzed and Manage-
ment Strategies are presented.
• A finite-state Markov chain model is applied to predict the num-
ber of donors in each period.
• Three types of patients have been categorized and incorporated
into the model according to their need to ABO-Rh compatibility
and age of platelets.
The incremental contributions are as follows:
• Apheresis and whole blood collection were considered in the
integer programming model as two common types of collection
methods.
• A novel approach to cope with inherent uncertainty in the
demand parameter is proposed as a two-stage stochastic-based
optimization programming model.
• The proposed model is implemented in a real case study to show
the practicality of the presented application.
The remainder of this paper is organized as follows: the related
literature is reviewed in Section 2. In Section 3, the Markov chain
model is presented to predict the number of donors in each period
 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372 357

Fig. 1. Platelet supply chain network.

and then the deterministic and stochastic models are formulated. A Though blood platelet management is a challenging area in the
solution including an improved approach for scenario reduction is real world health services, most of the articles have investigated
provided in Section 4. In Section 5 the proposed models are imple- whole blood or RBC inventories management and few papers such
mented based on a real world case study and managerial insights as Haijema et al. (2009), Zhou et al. (2011) and Duan and Liao (2013)
obtained from computational results are presented. Finally, the have focused on platelets inventory challenges in particular. To
contributions of this paper are concluded and some future research minimize the inventory holding cost, outdating and shortage costs,
opportunities are presented in Section 6. Civelek et al. (2015) addressed a periodic-review inventory man-
agement system for platelet where demand varies across different
ages and proposed an inventory replenishment policy and alloca-
2. Literature review
tion heuristic as a Markov Decision Process (MDP) model hoping
that newer items are preserved for subsequent use. In order to assist
Integrated planning for perishable items has been extensively
regional blood centers for daily platelet production and collection
attended to in the operations research literature throughout the
decisions, Ghandforoush and Sen (2010) provided a non-convex
recent years. Considering the item under investigation, perishable
integer programming to establish a primary decision support sys-
goods are classified into Fixed and Variable types according to their
tem (DSS). The objective was to minimize the total daily cost
lifetime. In the case of perishable blood products, a fixed lifetime is
including collection, production, and shortage costs. Although the
typically considered (Nahmias, 1978).
collection and production constraints were considered, they did not
In the present study, at first, the related literature on integrated
incorporate inventory variables into their model. They concluded
planning models for fixed-lifetime perishables has been reviewed.
that the amount of supply and production should be proportion-
Amorim et al. (2012) considering fixed and loose shelf-life, pre-
ate to the demand. To minimize shortages and spoilages, Haijema
sented an integrated planning framework as a multi-objective
et al. (2007) presented a combined Markov dynamic programming
model to investigate its advantages from both economic and fresh-
(MDP) and simulation approach in which two types of demand
ness aspects. Pires et al. (2015) considering the perishable nature of
have been addressed according to various patient types. In their
food products, addressed a single-echelon multi-period production
proposed model, ‘young’ platelets are used to meet the demand of
planning model in which freshness and age-dependent demand
oncologic and hematologic patients whereas for traumatology and
have been incorporated into mixed-integer programming. Lütke
general surgery treatments, using platelets of ‘any’ age up to the
entrup et al. (2005), without taking an integrated supply chain, pro-
maximal shelf life is allowed. Blake et al. (2003) applied a dynamic
posed three Mixed-Integer Linear Programming (MILP) models to
programming approach for determining local inventory ordering
schedule production planning in the case of yoghurt industry. In
policies for platelet suppliers. Gunpinar and Centeno (2015) consid-
their study, to improve the freshness of the product, a linear objec-
ering two types of patients and age-differentiated demand for red
tive function has been formulated. Farahani et al. (2012) studying
blood cells and platelets, proposed a dynamic multi-period integer
how the quality of perishable foods can be improved by decreas-
programming model to minimize the total cost including shortage
ing the time interval between production and delivery, applied
and wastage costs. Their supply chain under investigation included
an integrated mixed integer programming approach (in which no
a hospital and a blood center where decisions related to opera-
inventory decision is considered) for planning production, schedul-
tional and tactical levels were made within a planning horizon.
ing, and distribution.
Although ABO-Rh compatibility has a significant impact on inven-
Reviewing blood supply chain in the field of perishable products,
tory decisions, Gunpinar and Centeno (2015) have not formulated
Pierskalla (2005) provided a comprehensive overview in which
their model based on ABO-Rh compatibility.
some tactical and operational aspects related to collecting, produc-
Despite the fact that ABO-Rh compatibility plays an important
ing, controlling inventory levels, issuing policy of blood products,
role in the inventory management of blood products and the effi-
and delivery decisions are covered. In the past few years, Beliën and
ciency of treatment, few papers have been formulated based on the
Forcé (2012) and Osorio et al. (2015) provided a reviewing study
matching rules between donors and patients. To figure out optimal
to support researchers whose aim is to identify the main challeng-
blood PLT production policies Van Dijk et al. (2009), formulated
ing problem in the field of blood supply chain. According to Osorio
a general mathematical framework where ABO and Rhesus blood
et al. (2015) little attention has been paid to relationships among
groups have been addressed. They concluded from computational
different stages of blood supply chain and most published articles
results that the optimal policy for platelet production is “order-up-
deal with individual echelons.
358 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372
to” rule which prescribes a fixed order-up-to level for each day of
the week. Asllani et al. (2014) developed a simulation-based deci-
sion support system to reduce wastage and shortage of Apheresis
platelets according to the ABO priority matching rules in which
various patient types have not been considered. Abdulwahab and
Wahab (2014) considering eight blood types and ABO-Rh compat-
ibility for substitution, stochastic demand, and stochastic supply,
used a set of methodologies such as news vendor problem, linear
programming and approximation dynamic programming to model
the inventory of a blood platelet bank. Without taking priority
matching rules into account, they used a binary matrix where 1
indicates that substitution is allowed between recipient and donor
blood types and 0 means that substitution is not allowed between
them. Recently, Dillon et al. (2017), without taking the types of
patients into account, developed a multi-period two-stage stochas-
tic integer programming for red blood cells inventory management
to minimize operational costs, shortage and wastage. Eight blood
types, perishability and demand uncertainty are also considered
which significantly enhance the practical application of their pro-
posed model. Although the ABO-Rh priority matching rules have
been established by assigning a penalty cost for the substitution
in the objective function so that preferred substitute types have
been prioritized, determining penalty cost for blood group substi-
tution which is associated with operational aspects is intrinsically
complex. On the other hand, inappropriate estimation of the cost of
substitution determined by DM may lead to wrong operational and
tactical decisions. Moreover, priority rules are not practical with-
out considering a patient’s conditions. In this study, we formulate
priority matching rules without considering substitution costs. Fur-
thermore, the demand for a certain blood type is met in order of
ABO-Rh substitution priority according to patient types which is
completely consistent with the real world.
Using an optimal issuing policy in a perishable inventory sys-
tem has a significant impact on reducing total cost, shortage and
wastage levels. Determining an optimal issuing policy for distri-
bution of perishable products to the demand area is an issue that
has been addressed in many studies. Pierskalla and Roach (1972)
evaluated the FIFO and the LIFO policies in the perishable inven-
tory system considering multiple demand categories according to
the shelf life and concluded that total backlog/lost sales and out-
dates are minimized following FIFO issuance policy. Kendall and Lee
(1980) proposed a goal programming framework to address allo-
cating blood units to clinical points according to their remaining
shelf life. In their study, inventory stock levels, the amount of fresh
inventory, age of blood, outdating level and cost have been ana-
lyzed as the key factors in realizing the efficiency of the solutions
in each policy. To minimize the expected spoilage rate under a pre-
designed maximal allowable shortage level, Duan and Liao (2013)
proposed an age-based replenishment policy and concluded that a
policy which considers age distribution of inventories is preferable
to a policy which does not take into account age differences.
Despite the important role of donors on the overall blood supply
chain performance, only a few studies have focused on optimiza-
tion issues arising in the registration and donation phase and on the
estimation of the supply of blood from donations (Chen et al., 2016).
Borkent-Raven et al. (2010) developed a donation model based on
demography to estimate the supply of whole blood donations con-
sidering annual donor retention rates, donor recruitment rates, and
mean number of donations per donor and per year. Ritika and Paul
(2014) compared different classification algorithms to figure out
an efficient classification technique for prediction of blood donors.
Ferguson and Bibby (2002) used a prospective model to explore
the efficacy of several factors affecting the number of future blood
donations and to find out the relationship between past and future
donors’ behaviors. Akita et al. (2016) applied the Markov model
to estimate future blood donations until 2050 based on the data
collected from all donations from 2006 to 2009.
Reviewing the literature, many of the proposed models failed
to embrace all the complex aspects of the problem and just a
simulation-based study implemented by Asllani et al. (2014) con-
sidered ABO priority rules and the shelf life of PLTs. None of the
reviewed papers classified patients according to their needs to
ABO-Rh matching rules and age of platelets and their models were
not patient-based. Furthermore, no study formulated the ABO-
Rh matching rules in the form of a mathematical model without
assigning a penalty cost for substitution. Our study is different from
other papers in that three types of patients are classified according
to the age group of PLTs and ABO-Rh compatibility priority rules. As
a sustainable platelet supply chain requires an appropriate approx-
imation for the recurrent donor, we also proposed a methodology
to estimate the number of donors in each period. Moreover, two
common types of collection methods (Apheresis and whole blood
collection) are considered in our proposed model.
3. Problem definition and mathematical formulation
Motivated by the gap found in the literature, we formulate our
model considering various features of platelets such as perisha-
bility and ABO-Rh priority matching rules. In this study, various
patient types are classified based on their condition and their
demand is satisfied by different types of platelets. Different types of
patients are distinguished based on their need to platelets in terms
of age and ABO-Rh compatibility. Thus, in this study in addition
to age-differentiate platelet demands of patient groups, the ABO-
Rh compatibility matching rules are also considered. Furthermore,
our paper differs from previous papers in using discrete Markov
methodology for estimating the amount of blood supply in each
period. For this purpose, we propose a mixed-integer programming
model in which the demands of each age group are met accord-
ing to ABO-Rh priority rules. For example, O+ blood group is the
first priority choice for satisfying the demand of a patient with
O+ blood group and in the absence of sufficient inventory of O+,
the second priority choice is O- and so on (World Health Organi-
zation, 2014). In the real world, donation units collected at blood
stations are sent to regional blood centers for production of blood
components. Donated whole blood units must be transferred to
blood centers up to 6 h, otherwise donation units cannot be used
for platelet production (Mobasher et al., 2015). Hence, a blood cen-
ter keeps no inventory of whole blood for subsequent orders. Blood
components are processed at regional blood centers and delivered
to clinical points based on their daily demands. Upon the arrival of
PLTs transferred from blood centers, hospital blood banks catego-
rize and stock the units based on their age group and blood type
and use them for different medical treatments.
The main purposes of this study are to investigate how much
blood should be collected from donors, how much platelet should
be produced, and how much platelet should be transferred to hos-
pitals in each period in order to reduce shortage and wastage levels
and also increase service quality in medical points. Therefore, we
consider an integrated supply chain including all stages of collec-
tion, production, and distribution of platelets. In this integrated
supply chain PLT units are delivered from a regional blood cen-
ter to hospitals based on the daily demand. It is noteworthy that
two days are required to test and process the whole blood platelets
(Gunpinar and Centeno, 2015). In fact, to meet its platelet daily
demand, a blood center has to supply the right amount of whole
bloods from collection centers two days earlier. Based on the con-
sumption rate of platelets during prior periods in each hospital,
the optimal platelet consignment in each period should be identi-
fied for each hospital by a blood center. Then, the required whole
 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372 359

the amount of collected donations in each period appropriately. To

predict the number of blood donations, changes in the number of
blood donors should be estimated based on the frequency of blood
donations. Therefore, blood donation behavior transition probabil-
ity is defined as the probability that groups donating blood zero,
one, two (Experienced donor), or more (Regular donor) times in a
certain year would have a different frequency of blood donation in
the next year (Fig. 2). To predict the number of donors in each time
period, we applied finite-state Markov chain model by using cur-
rent conditions and a probability transition matrix assuming that
transition probability is not time-dependent. The applied method
is explained below.

3.2. Chapman Kolmogorov equations

Let P (n) be the matrix whose (i, j)th entry refers to the probability
that the system is in state j at the nth transition, given that it was in
state i at the start (i.e. at time zero), thenP (n) = P n , i.e., the matrix
(n)
P (n) is the nth order transition matrix of the system. In fact, let Pij
be the (i, j)th element of P (n) then we have
(2)

Pij = Piv Pvj

(3)

v∈ϕ
(2)
 (2)
Pij = Piv Pvj = Piv Pvj
v∈ϕ v∈ϕ
.. ..
.=. (1)
(n)
 (n−1)
 (n−1)
Fig. 2. The Markov state transition diagram of number of blood donations. Pij = Piv Pvj = Piv Pvj

(n)

v∈ϕ
(m) (n−m)
v∈ϕ
blood should be collected from donor groups in collection facilities. Pij = Piv Pvj
According to the abovementioned reasons, applying an integrated v∈ϕ
multi-period model can be very practical in the case of platelet sup- matrix form → P (n) = P (n−m) P (m)
ply chain. Multi-period models have been applied in several studies
in the related literature (Gunpinar and Centeno, 2015; Hemmel- Since P (2) = P 2 from the first of the above equations, by a sim-
mayr et al., 2010, 2009; Abdulwahab and Wahab, 2014; Zahiri and ple induction, we will know P (n) = P n holds for any non-negative
Pishvaee, 2017; Ensafian and Yaghoubi, 2017) integer n. This is the well-known Chapman–Kolmogorov equation.
In this study, the following assumptions have been considered: The probability of each transition state refers to the probability
that the donor is in state j at period t, given that it was in state
• In hospitals, platelets are mostly collected from a family mem- i at period t-1. A numerical example is presented in Appendix B.
ber or members of charity committees who are called selected Hereafter, the parameters and decision variables are introduced
donors. Since the related tests to detect possible contaminations and the mathematical model is presented.
are performed on the blood sample of selected donors before
Apheresis donation, fresh platelets are ready for transfusion as 3.3. Mathematical programming
soon as they are produced.
• The capacity for the production of PLTs from whole blood at blood The following notations are used in the proposed deterministic
centers and apheresis procedure in both blood centers and hos- mathematical programming.
pitals is limited. Indices:
• Because two days are required for processing and testing PLTs in f, g Blood groups f, g = 1,...,8
i Collection facilities, i = 1,. . .,I
blood centers, PLTs younger than 3 days old cannot be delivered
j Hospitals, j = 1,. . .,J
to hospitals. l Priority choice l = 1,...,8
• The age of platelet units arrived from blood centers varies over- r Age of platelets, r = 1,. . .,U
time in the blood bank of hospitals. t Periods, t = 1,. . .,T
• The delivery time of PLTs from blood centers to hospitals is neg- Parameters:
Capj Capacity of platelet bank at hospital j
ligible and has no effect on the age of the products. CPU Maximum capability of PLT production at the blood center
• A shortage cost is incurred when a demand is not satisfied in f
Dj,t Total demand of hospital j for platelet units of blood group f in
hospitals. period t
• A wastage cost is considered when platelets are expired without r,f r,f,s
dj,t /dj,t Patient consumption amount (patient demand) of platelet at
being used both in the blood center and the hospital. age r and blood group f at hospital j in period t/under scenario s
Gg,f,l Auxiliary binary matrix which indicates ABO-Rh for lth priority
• Hospital platelet banks have a limited capacity.
choice
M Big M (a large number)
3.1. Blood supply estimation sh Shortage cost of one platelet unit
T Planning horizon length
trj Transportation cost of one platelet unit from the blood center
A major challenge facing blood centers is to supply the sufficient
to hospital j
amount of donations at the right time whenever it is required. The U Platelet lifetime
first step for having an efficient platelet supply chain is to estimate
360 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372

h,f
UPHj,t The number of Apheresis donors with blood group f in Subject to:
period t at hospital j  f
QPt ≤ CPU ∀t
b,f
UPHt The number of Apheresis donors with blood group f in (3)
period t at the blood center
i,f f
UWBt The number of whole blood donors with blood group f at
collection facility i in period t  r,f
ϑh Holding cost of one platelet unit at the blood center j,t
≤ 1 ∀f, j, t (4)
wPLT Wastage cost of one platelet unit at hospitals r
ϕi Transferring cost of one whole blood unit from collection  i,f f
facility i to blood center × WBt−2 ≥ QPt ×  × (1 + ε) ∀f, t = 3, . . ., T (5)
v Production cost of one unit whole blood platelet at the
center i
aph Production cost of one Apheresis platelet unit in hospitals i,f i,f
 Quantity of whole blood units used for producing one WBt ≤ UWBt ∀i, t, f (6)
platelet unit  r,f
ε Percentage of whole blood units which are not appropriate IPHj,t ≤ Capj ∀j, t = 3, . . ., T (7)
for platelet production
f r
 Quantity of extracted platelet units from a donor by using
Apheresis procedure
Proportion of whole blood collected used to produce

U
r,f

U
r−1,f

U
 r,f f
platelets
IPBt = IPBt−1 − j,t
× Dj,t ∀f, t = 3, . . ., T (8)
Variables: r=4 r=4 r=4 j
h,f
APHj,t Quantity of Apheresis platelet with blood group f prepared
at hospital j in period t
3,f b,f f 2,f
 3,f f
APHt
b,f
Quantity of Apheresis platelet with blood group f prepared IPBt =  × APHt + QPt + IPBt−1 − j,t
× Dj,t ∀f, j, t = 3, . . ., T
at the blood center in period t j
r,f,g,l r,f,g,l,s
dxj,t /dxj,t The quantity of patient demand for age r and blood group g (9)
which is satisfied by blood group f using lth priority choice
at hospital j in period t/under scenario s
r,f
IPBt Inventory level of platelet at blood center with age r and
1,f 1,g,f,1 Fr,f
blood group f in the end of period t dj,t = dxj,t × Gg,f,1 + SLHj,t ∀f, j, t (10)
r,f r,f,s
IPHj,t /IPHj,t Inventory level of platelet at hospital j with age r and blood

r,f,l r,f,l,s
group f in the end of period t/under scenario s 
3
r,f

3 
4
 r,g,f,l Y,f
Ej,t /Ej,t 1 if platelet inventory with age r in hospital j is used to dj,t = dxj,t × Gg,f,l + SLHj,t ∀f, j, t (11)
meet the demand of blood group f with lth priority choice
r=2 r=2 l=1 g
in period t, 0 otherwise/under scenario s
f
QPt Quantity of platelet which is produced from whole blood
donations with blood group f at the blood center in period t

U
r,f

U 
8
 r,g,f,l O,f
Fr,f Fr,f,s
SLHj,t /SLHj,t Unmet demand for “Fresh” platelet at hospital j in period t
dj,t = dxj,t × Gg,f,l + SLHj,t ∀f, j, t (12)
for blood group f/under scenario s r=4 r=4 l=1 g
Y,f Y,f,s
SLHj,t /SLHj,t Unmet demand for “Young” age platelets at hospital j in
1,f h,f 1,g,f,1
period t for blood group f/under scenario s IPHj,t =  × APHt − dxj,t × Gg,f,1 ∀j, f, t = 3, . . ., T (13)
O,f O,f,s
SLHj,t /SLHj,t Unmet demand for “Old” age platelets at hospital j in
period t for blood group f/under scenario s
WBt
i,f
Quantity of whole blood collected with blood group f from 
3
r,f

3
r−1,f
 3,f f
collection facility i in period t IPHj,t = IPHj,t−1 + j,t
× Dj,t
WLBt Number of outdated platelets at the blood center in period r=2 r=2 j
t
s
WLHj,t /WLHj,t Number of outdated platelets at hospital j in period
t/under scenario s

3 
6
 r,f,g,l
− dxj,t × Gf,g,l ∀t = 3, . . ., T, f, j (14)
Ytr 1 if platelet inventory with age r at the blood center is used
to meet the demand of hospitals in period t, 0 otherwise r=2 l=1 g
r,f r,f,s
j,t
/ j,t Fraction of maximum demand for platelet with age r
delivered to hospital j in period t for blood group f/under
scenario s 
U
r,f

U
r−1,f

U 
r,f f
IPHj,t = IPHj,t−1 + j,t
× Dj,t
Consequently, the deterministic mathematical model as a
r=4 r=4 r=4 j
mixed-integer programming is formulated as follows:

U 
8

Minzdeterministic − dxj,t
r,f,g,l
× Gf,g,l ∀t = 3, . . ., T, f, j (15)
 i,f
 U
r,f
r=4 l=1 g
= WBt−2 × ϕi + IPBt × ϑh
i
t
f
 r,f f

f

t r=1
r,f
r,f
j,t
≤ M × Ytr ∀t, j, r, f (16)
+ j,t
× Dj,t + IPHj,t × ϑh  
r,f

r

f j t

j f t r IPBt−1 ≤ M × 1 − Yt r
∀f, r, t (17)
f aph h,f
+ QPt × v+ Ø × APHj,t
(2) Ytr ≤ Ytr+1 ∀r, t ∀t, r (18)

t

f
b,f
j

t f
r,g,f,l r,f,l
+ Ø aph
× APHt + w PLT
× WLBt dxj,t ×G g,f,l
≤M × Ej,t ∀t, j, r, l, f, g (19)
 t f t
r,f,l r,f,l−1
+ wPLT × WLHjt Ej,t ≤ Ej,t ∀t, j, r, f, l (20)


j

t
 Fr,f Y,f O,f
APHt
b,f
× (1 + ε) ≤ UPHt−1 ∀f, t
b,f
(21)
+ sh × (SLHj,t + SLHj,t + SLHj,t )
h,f h,f
j t f APHt ≤ UPHt ∀f, t (22)
 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372 361


WLBt =
r,f
IPBt ∀t, r = U (23) 3.4. Two-stage stochastic programming model
f
In this section a scenario-based two-stage stochastic optimiza-
 r,f
tion approach is proposed to deal with uncertain demands. In the
WLHj,t = IPHj,t ∀t, j, r = U (24) two-stage framework, the first-stage variables are independent
f of scenarios and decisions for the current time period are made
‘here-and-now’ prior to the realization of uncertainty (Gupta and
r,f
IPHj,t = 0 ∀r, j, f, t ≤ 2 (25) Maranas 2003). In our study, the supply of whole blood and Aphere-
sis platelet (in the blood center and hospital), production and
r,f inventory (in the blood center) are the first-stage variables. Second-
IPBt = 0 ∀r, f, t ≤ 2 (26) stage variables which are scenario-dependent are postponed in a
‘wait-and-see’ mode and are determined after the uncertainty of
the first-stage random parameters has been revealed. Decisions
r,f f r,f r,f b,f h,f
j,t
, QPt , WBti , IPHj,t , IPBt , APHt , APHj,t , about distribution of PLT units, shortage, wastage, and inventory
(in hospitals) are considered as the second-stage variables. Con-
Fr,f Y,f O,f
WLBt , WLHj,t , SLHj,t SLHj,t , SLHj,t ≥ 0 sequently, the two-stage stochastic programming model can be
formulated as follows:
Minzstochastic
Total cost is minimized by Eq. (2). This cost includes: pro-
curement cost (including the supplying and transportation cost of  i,f

U
r,f
whole blood donated from collection facilities to the blood center), = WBt−2 × ϕi + IPBt × ϑh
production cost, inventory holding cost at the blood center and hos-
i
t
f
 f t r=1
pitals, delivery cost which occurs when platelets are delivered from + Ps ×
r,f,s
× Dj,t
f
j,t
blood centers to hospitals, outdate cost in the blood center and hos-
pitals and finally shortage cost in the hospitals. Constraint (3) puts 
r

f

j

t

s
r,f,s
 f
an upper bound on the production capacity of the blood center in + Ps × IPHj,t × ϑh + QPt × v
period t. Constraint (4) guarantees that the sum of the delivered 
j f t s r
h,f
t f
(28)
units with different ages in each period from the blood center is + Øaph × APHj,t
less than the total demand of the hospitals. Constraint (5) repre-
sents the balance equations of donated whole bloods and produced

j

t f
b,f

+ Øaph × APHt + wPLT × WLBt
platelets by considering 2 days needed for producing and testing. It
is notable that all of the collected whole bloods are not rich enough 
t

f
 t

for platelet production. Thus, to formulate our model, we incorpo- + Ps × wPLT × WLHj,t
s

rate the percentage of whole blood donations (ε) which are not used 
j

t

s
 Fr,f,s Y,f,s O,f,s
for platelets production. Constraint (6) indicates the number of esti- + Ps × sh × (SLHj,t + SLHj,t + SLHj,t )
mated donors of whole blood in the collection facilities. Constraint j t f s
(7) ensures that the inventory of the platelet units in the hospital
does not exceed the capacity of the platelet bank. Constraints (8) Subject to:
and (9) are the balance equations of platelet inventory at the blood  r,f,s
center at the end of each period for each age group and each blood j,t
≤ 1 ∀f, j, t, s (29)
group. Constraint (8) shows that the inventory of platelets more r

than three days old is equal to the remaining inventory from the  r,f,s
IPHj,t ≤ Capj ∀j, s, t = 3, . . ., T (30)
previous period minus the quantity of the units shipped to the hos-
pitals. Constraint (9) links the produced units at the blood center f r

to three-day old inventories. Constraints (10)–(12) represent the

number of platelet units of blood group f used to meet the demand 
U
r,f

U
r−1,f
U 
 r,f,s f
of blood group g in period t with lth substitution priority. Constraint IPBt = IPBt−1 − j,t
× Dj,t ∀f, s, t = 3, . . ., T
(10) ensures that type 1 patients receive fresh units and full ABO-Rh r=4 r=4 r=4 j
compatible platelets. Constraint (11) guarantees that for patients (31)
classified as type 2 ‘young’ platelets and Rh compatible platelets are
assigned. Constraints (13)–(15) are inventory balance constraints
which update end-period platelet inventory levels in the hospi- IPBt
3,f
=  × APHt
b,f f
+ QPt + IPBt−1
2,f
tal for each period based on age groups. Constraint (13) links the

Apheresis platelets derived from selected donors in the hospitals −
3,f,s f
× Dj,t ∀f, s, j, t = 3, . . ., T (32)
j,t
to one-day old inventory level. Constraints (16)–(18) represent the
j
FIFO issuing policy. Indeed, an inventory with a certain age group
cannot be allocated to a patient when older units are available in the
1,f,s 1,g,f,1,s Fr,f,s
same age group. Constraints (19) and (20) ensure that the demand dj,t = dxj,t × Gg,f,1 + SLHj,t ∀f, j, t, s (33)
is satisfied in order of substitution priority. Constraints (21) and
(22) put an upper limit on the number of Apheresis donors in the 
3
r,f,s

3 
4
 r,g,f,l,s Y,f,s
hospital and at the blood center, respectively. Constraints (23) and dj,t = dxj,t × Gg,f,l + SLHj,t ∀f, j, t, s (34)
(24) identify the number of outdated units at the blood center and in r=2 r=2 l=1 g
the hospitals. Constraints (25) and (26) show that in the beginning
of the planning no inventory is available at the blood center and in 
U
r,f,s

U

8
 r,g,f,l,s O,f,s
the hospitals. Constraint (27) specifies the range of the decisions dj,t = dxj,t × Gg,f,l + SLHj,t ∀f, j, t, s (35)
variables. r=4 r=4 l=1 g
362 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372

1,f,s h,f 1,g,f,1,s

IPHj,t =  × APHt − dxj,t × Gg,f,1 ∀j, f, s, t = 3, . . ., T (36) of a phenomenon (Naderi and Pishvaee, 2017); additionally, solv-
ing numerous scenarios requires too much time and may even lead
to an unsolvable problem. Therefore, an appropriate and limited

3
r,f,s

3
r−1,f,s
 3,f,s f number of sample scenarios should be selected. There are some
IPHj,t = IPHj,t−1 + j,t
× Dj,t
applications which allow us to solve large-scale stochastic prob-
r=2 r=2 j
lems, namely “decomposition techniques”, “lagrangian relaxation”,
and lately “optimal condition decomposition” (Conejo et al., 2006)

3 
6
 r,f,g,l,s
− dxj,t × Gf,g,l ∀t = 3, . . ., T, s, f, j (37) which are the most known ones (Sahinidis, 2004). To deal with
large-scale problems resulting from the large number of scenarios,
r=2 l=1 g
the common approach is to make the continuous distribution of
stochastic process discrete. In this regard, Monte Carlo simulation

U
r,f,s

U
r−1,f,s

U 
r,f,s is usually used to generate scenarios based on a given distribution
IPHj,t = IPHj,t−1 + j,t or stochastic process (Liu and Sahinidis, 1996). Therefore, we use
r=4 r=4 r=4 j a Monte Carlo approach to generate a finite large number of sce-
narios N  n based on the specified distribution function, and then

U 
8

×Dj,t −
f
dxj,t
r,f,g,l,s
× Gf,g,l ∀t = 3, . . ., T, s, f, j (38) using a scenario reduction approach, we select a finite number of
n scenarios. In this paper, we propose an improved approach for
r=4 l=1 g
scenario generation and reduction based on a “pre-specified con-
fidence level” that well represents the behavior of a phenomenon
r,f,s
j,t
≤ M × Ytr ∀t, j, r, f, s (39) while the stochastic model will be solvable in a reasonable time.
Indeed, a straightforward approach is applied which allows deci-
r,g,f,l,s r,f,l,s
dxj,t × Gg,f,l ≤ M × Ej,t ∀t, j, r, l, f, g, s (40) sion makers to cope with uncertainty based on their desirable
r,f,l,s r,f,l−1,s
confidence level. Additionally, using an effective method (Simul-
Ej,t ≤ Ej,t ∀t, j, r, f, l, s (41) taneous Backward Reduction) to reduce the generated scenarios,
 r,f,s
a prescribed number of scenarios is selected from all of the gen-
s
WLHj,t = IPHj,t ∀t, s, j, r = U (42) erated scenarios. The solution procedure including three phases is
f illustrated in Fig. 3.
r,f,s
IPHj,t = 0 ∀r, j, s, f, t ≤ 2 (43) 4.1. Determining the sample size

r,f,s f r,f,s r,f b,f h,f

, QPt , WBti , IPHj,t , IPBt , APHt , APHj,t , WLBt , WLHj,t
s
, Given the desired level of solution accuracy, the number of sce-
j,t
narios is determined by calculating the confidence interval of the
Fr,f,s Y,f,s O,f,s r,f,l,s
 
SLHj,t SLHj,t , SLHj,t ≥ 0 and Ej,t , Ytr ∈ 0, 1 (44) expected total cost. The Monte Carlo sampling variance estimator
which is independent of the probability distribution of the uncer-
and constriaints (3), (5), (6), (17), (18), (21)–(23), (26) tain parameters is specified by:
The total cost of the proposed scenario-based two-stage 
n’
stochastic model is minimized by Eq. (28). Constraint (29) ensures s=1 (E (Z)
− Zs )2
S (n’) = (45)
that the sum of units delivered from the blood center with different n’ − 1
ages in each period and under each scenario is less than the total where Zs is the total cost of scenario s and n is the number of sample
demand of the hospitals. Constraint (30) ensures that the inventory scenarios. Then the confidence interval of 1-˛% is given as
of the platelets under each scenario in the hospital is less than the
capacity of the platelet bank. Constraints (31) and (32) are balance S (n’) S (n’)
E (Z) − ˛/2 √ , E (Z) + ˛/2 √ (46)
equations for platelet inventories at the blood center at the end of n’ n’
each period and under each scenario for each age group. Constraints where ␣/2 is the standard normal deviation which is obtained
(33) through (35) represent the number of platelet units of blood from the following equation considering ϕ ≈ N ( = 0,  = 1).
group f consumed to satisfy the demand of blood group g in period t  
with lth substitution priority under each scenario. Constraints (36) Pr ϕ ≤ ˛/2 = 1 − ˛/2 (47)
through (38) are inventory balance equations in the hospital which Considering the sampling estimator S (n’) calculated by Eq. (45)

update end-period platelet inventory levels for each period based and the maximum possible error (er) for confidence level 1 − ␣ 2
,
on age groups and under each scenario. Constraint (39) along with the minimum number of required scenarios (n) can be obtained by
Constraints (18) and (19) guarantees the FIFO issuing policy under (Shapiro and Homem-de-Mello, 1998; You et al., 2009; Mirzapour
each scenario. An inventory of a specific age at the blood center Al-e-Hashem et al., 2013):
cannot be allocated to hospitals when older units are available. 2
Constraints (40) and (41) ensure that the demand is met in order ˛/2 S (n’)
n≥ (48)
of substitution priority under each scenario. Constraint (42) rep- er
resents the number of outdated units in the hospitals under each
scenario. Constraint (43) indicates that no inventory is available in 4.2. Scenario reduction
the beginning of the planning in the hospitals under each scenario.
Constraint (44) defines the domains of the decisions variables. Now we need to use an effective method to reduce N gener-
ated scenarios to n scenarios. For this purpose we use Simultaneous
4. Solution approach Backward Reduction (SBR) method. Indeed, SBR approach recom-
mends a conceptual algorithm which was introduced by Heitsch
The multi-period nature of the model and the large size of the and Römisch (2003). This algorithm continues until a prescribed
supply chain network make the two-stage stochastic model diffi- number of scenarios are selected from all of the generated sce-
cult to solve particularly if there are a large number of scenarios. narios. Here a scenario is denoted by ωi ∈ ˝, i = 1,. . ., N and its
The generated scenarios need to be able to simulate the behavior corresponding probability is specified by
 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372 363

Fig. 3. Solution procedure.

Table 4 Table 5
Parameter data setting. Cost parameter.

(T) () (ε) (U) (␶) (CPU) ( ) Parameter Value Unit Reference

7 (Day) 1 0.02 5 (Day) 6 ‘200 0.35 Production cost 150 ($/Unit) Haijema et al. (2007)
WB procurement cost 100 ($/Unit) Real data
Shortage cost 1500 ($/Unit) Zhou et al. (2011)
Wastage cost 150 ($/Unit) Haijema et al. (2007)
In what follows, J [i] represents the scenario subset from which Holding cost 1 ($/day*Unit) Haijema et al. (2007)
the next scenario will be selected after the sth selection and  is a Apheresis cost 500 ($/Unit) Fontaine et al. (2009)
nonnegative, continuous, and symmetric function, usually defined Setup cost 1 ($/Unit) Real data
as some norm on Rn . The intuitive idea of the SBR method is to select
a subset – from the original finite scenario set  so that  is
the subset of the prescribed size (n) that has the longest distance
from the remaining scenarios. Given the total number of gener-
ated scenarios by Mont Carlo simulation (e.g. N = 1000), we use the
be seen in Tables 5 and 6. In this study, the lifetime of platelets
Simultaneous Backward Reduction (SBR) approach to select the
(U) is assumed five days. Therefore, considering the fact that two
required number of scenarios (n) which have been estimated in
days are required for testing and processing, seven days were
Section 4.1 as follows:
considered to be the planning horizon time (T). According to the
Simultaneous Backward Reduction Algorithm:
Iranian Blood Transfusion Organization (IBTO), there are 23 blood
Step 1. 
Let s = 1, calculatethe distances of all scenario pairs donors per 1000 population (Gharehbaghian et al., 2008). At the
ck,j [1] =  ωk , ωj , i, k = 1,. . .,N, and compute the weighted
distance of each scenario to the other scenarios present time (2016), 60% of blood donors in Iran are regular,
[1] [1] [1]
zl = pl ıll l = 1,. . .,N. Select l1 ∈ argminl ∈ {1,...,N } zl , and set 28% have previous experience with blood donation and 12% are
  first-time donors. The number of potential donors in each period
J [1] := l1 ;
 which has been estimated in Section 2 is presented in Table 7.
[i] [i]
Step 2. Let i = i +1, compute zl = pk ckl l ∈
/ J [i−1] for every
(i=1,· · ·N-n)
It is noteworthy that the amount of PLT consumption is differ-
k ∈ J [i−1] ∪ {l}
ent for patients based on the type of health services provided
candidate scenario in the ith reduction,
[i]
  and choose in hospitals. Two measures for the estimation of the PLT con-
li ∈ argmini/∈J [i−1] zl , J [i] := J [i−1] ∪ li , the one that
sumption rate in hospitals are considered as follows: The type of
minimizes the weighted distance to the remaining
scenarios; services that hospitals provide for patients and the frequency of
Step 3. If the number of the preserved scenarios is less than n, blood groups among people. Roughly 10% of the demand is for
return to Step 2; ‘fresh’ platelets, and 60% is for ‘young’ and 30% is for ‘old’ platelets.
Step 4. Add to the probability of each remaining scenario the sum
Hospitals usually request platelets from blood centers more than

of the probabilities of all reduced scenarios that are close
their expected consumption amount so that approximately 50%
to it; i.e., qj = pj + pi , where
of platelet units requested by physicians are returned to the hos-
 
i ∈ Jj pital platelet bank inventory without being transfused (Jennings,
Jj := i ∈ J : j = j (i) , j (i) = argminj/∈J  (ωi , ωk ), for each i 1973).
∈ J Tehran, as the most populous city in Iran, has 18 collection cen-
ters, one regional blood center, and 5 major public therapeutic
5. Case study centers which mainly provide health services for patients receiving
hematology, oncology (chemotherapy), organ transplantation and
In this section, we present the data inspired from a real case cardiac surgery services. For this survey, we gathered the required
and applied in our numerical analysis and also demonstrate the data from a main blood center located in Tehran. The geographical
possible applications of the proposed model for integrated platelet location of the hospitals, collection centers, and the blood center
supply chain. We first solve the deterministic model and present are marked out in Fig. 4. The daily demand means of hospitals and
the managerial insight derived from our numerical experiment. patients in each period are randomly generated according to Table 8
Afterwards, the demand is assumed to follow Poisson distribu- following the Poisson distribution.
tion with varying daily means (␮) and the two-stage stochastic
model is presented. The codings of the present study were per-
formed by MATLAB programming language and GAMS 22.9 using
CPLEX solver on a laptop with Core i7 2.5 GHz CPU and 8.0 GB of 5.1. Results
RAM.
Most of the cost parameters have been taken from the litera- In this section, the numerical results obtained based on the real
ture as mentioned in (Haijema et al., 2007; Zhou et al., 2011). The case described in the previous section are presented and the appli-
parameters used in the proposed Mixed-integer programming are cability of the proposed models is investigated. The used acronyms
summarized in Table 4 while the values of cost parameters can in this section are indicated as follows:
364 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372

Fig. 4. The geographical location of the hospitals, collection centers, and the blood center in Tehran.

Table 6
Cost of shipping PLTs from the blood center to the hospitals and the cost of transferring whole blood to the blood center (based on distance).

BC to hospital Collection centers to BC

Hospital No. Value ($*10,000/Unit) Collection facility No. Value ($*10,000/Unit) Collection facility No. Value ($*10,000/Unit)

1 0.0001 1 0.00015 11 0.00011

2 0.0001 2 0.00014 12 0.0001
3 0.00012 3 0.00016 13 0.00012
4 0.00013 4 0.0001 14 0.0001
5 0.00014 5 0.00017 15 0.00015
6 0.0001 16 0.0001
7 0.0002 17 0.000166
8 0.00015 18 0.00019
9 0.0001
10 0.00012

Table 7
Number of donors in each period.

Blood group Total expected whole blood donors at Total preregister apheresis donors at Total pre-qualified selected donors at
collection facilities the blood center the hospitals

Period Period Period

1 2 3 4 5 1 2 3 4 5 3 4 5 6 7
+
O 462 503 542 577 611 32 35 37 40 42 23 25 27 29 31
O− 85 92 99 106 112 5 6 6 7 8 4 5 5 5 6
A+ 414 450 485 517 546 29 31 33 36 38 21 23 24 26 27
A− 73 79 85 91 96 5 5 5 6 6 4 4 4 5 5
B+ 109 119 128 136 144 7 8 8 9 10 5 6 6 7 7
B− 24 26 28 30 32 1 1 2 2 2 1 1 1 2 2
AB+ 36 39 42 45 48 2 2 3 3 3 2 2 2 2 2
AB− 12 13 14 15 16 0 1 1 1 1 1 1 1 1 1
Total 1215 1321 1423 1517 1605 81 89 95 104 110 61 68 72 80 85

Acronym: The proposed model is firstly solved deterministically and the

APB Apheresis Platelet collected in the Blood center numerical results are discussed. Upon delivery, platelet units are
APH Apheresis Platelet collected in the Hospital categorized and stored in hospital blood banks according to their
WPB Whole blood Platelet produced in the Blood center
age and blood group and are assigned to various patient types.
Symbol:
CIf Complexity index for blood group f Table 9 shows a summary of the obtained results for the main vari-
QPt Total whole blood platelets produced at the blood center in period t ables. The total number of PLTs delivered to hospitals with age r in
SIf Substitution index for blood group f each period (TPDtr ) and based on each blood group (TDL) are pre-
TAPtb Total apheresis platelets collected at blood center in period t sented in Table 9. As seen, 100% of the total demands of the hospitals
TAPHt Total apheresis platelets collected at hospitals in period t
have been delivered with three-day-old PLTs. Considering the fact
TPDtr Total platelets delivered to hospitals with age r in period t
that there was no available inventory in the beginning of the plan-
 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372 365

Table 8
The mean values of the hospitals and patients daily demands in each period.

No. Hospital Num. of bed Health service type period

3 4 5 6 7

1 Imam Khomeini 1200 Chemical therapy PLT consumption for patient treatment
Cardiac surgery 250 250 200 20 165
Organ transplantation Hospital demand
375 375 300 300 247

2 Taleghani 620 Haematology PLT consumption for patient treatment

Oncology 225 225 190 175 150
Organ transplantation Hospital demand
Stem cell transplantation 337 337 285 262 225

3 Rajaee 571 Cardiac surgery PLT consumption for patient treatment

150 150 120 120 100
Hospital demand
225 225 180 180 150

4 Imam Husain 427 Oncology PLT consumption for patient treatment

Cardiac surgery 180 175 145 145 120
Chemical therapy Hospital demand
145 262 217 217 180

5 Shariati 300 Stem cell transplantation PLT consumption for patient treatment
Haematology 240 235 200 190 160
Cardiac surgery Hospital demand
360 352 300 285 240

Table 9
Obtained results.

Blood group TAPH TAPB TQP TDL Period

1 2 3 4 5

O+ 94 99 591 1183 QPt 388 317 308 221 52

O- 17 16 67 165 TAPtb 50 50 50 50 50
A+ 81 69 496 910 Period
A- 15 13 29 112 3 4 5 6 7
B+ 22 36 61 278 TAPHt 50 52 55 62 24
B- 5 8 21 65 ValueofTPDtr
AB+ 7 6 15 47 Age 3 4 6 7 8
AB- 2 3 6 25 r=3 688 617 608 521 351
Total 243 250 1286 2785 r=4 0 0 0 0 0
r=5 0 0 0 0 0
Total demand Total substitution Total cost Total shortage Total wastage
4451 1348 1,321,470 434 (9.7%) 0

ning horizon, the total unmet demand (shortage) was obtained 9.7%
of which 80% was related to the old age group (this is due to the
unavailable inventory at age 4 and 5 in the beginning of the third
period). To meet approximately 90% of the total 4451 PLTs needed
in all hospitals, 1286 whole blood PLTs, 250 Apheresis platelets in
the blood center, and 243 units of Apheresis platelets in the hospi-
tals should be prepared. Approximately 34% of the total produced
PLTs are processed in hospitals.
The quantities of the produced PLTs at each blood group are also
shown in Table 9 in which as expected the most and the lowest
proportion is related to O+ and AB-, respectively. The production
quantity in each period is also depicted in Table 9. Note that since
platelets derived from random donors require two days for testing
and processing, the blood service center should collect the required Fig. 5. Consumption amount for each blood group.
amount of whole bloods or Apheresis platelets two periods earlier.
Donors who have not donated their blood for a special person and
for whom cross-match tests are not performed before donation are mately 74% of the total demand for a certain blood group is met by
called Random donors. In hospitals, the Apheresis platelets are col- the same blood group and 5%, 7%, 3%, 4%, 1%, 5% and 1% of the total
lected from “pre-qualified selected donors” on whose blood sample demand is satisfied in order of priority 2–8, respectively, follow-
related tests are performed to detect possible contamination before ing compatibility matching rules. According to Fig. 5, as expected,
the Apheresis procedure. Therefore, Apheresis platelets gathered in the blood platelet consumption for each blood group in descending
a hospital can be transfused as soon as they are produced and there order is listed as O+, A+, B+, O-, A-, B-, AB+ and AB- following their
is no need for two days of testing and processing. As was mentioned frequency percentage.
above, our model tries to follow the policy by which hospitals meet As mentioned before, in this study, we define substitution as a
the demand for PLTs based on priority substitution rules. Approxi- procedure in which due to the inadequate inventories for a cer-
366 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372

Fig. 6. The consumption amount of any blood type to meet platelet demands in hospitals.

tain blood group, an alternative blood group is assigned to satisfy
the demand. One of the most interesting results is that to sat-
isfy the demand for a certain blood group, which blood group has
the highest amount of substitution. Fig. 6 shows the amount of
substitutions among different blood groups considering priority
matching rules. For example, the blood group O− has the highest
substitution amount for satisfying the demand for the blood group
A−. On the other hand, O+ has the most significant role in meet-
ing the demand for O−. Another result implied by Fig. 6 is that the
blood groups with negative Rh (D−) have more capability for sub-
stitution than those with Rh+ (D+). For example, a large number of
the produced platelets with blood group O+ are used to satisfy the
demand of patients with blood group O+ (approximately 84%) and
only about 16% of O+ platelets are consumed to meet the demand
of patients with another blood group. On the other hand, signifi-
cant amounts of the produced platelets with O− are used to satisfy
the demand of the remaining blood groups, roughly 55%. Another
example indicates that 80% of the platelets with blood group A+ are
used to meet the demand of patients with blood group A+ while 80%
of A− platelets is used to satisfy other blood groups and only 20%
of A− platelets is consumed to satisfy the demand of patients with
A− blood group. Since most transfusion services avoid the trans-
 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372
Fig. 7. Substitution amount of each blood group.
Fig. 8. Substitution index of each blood group.
fusion of D+ PLTs to D− especially for females of childbearing age
and children under 10, it can be observed that the results shown in
Fig. 6 are quite close to reality.
Fig. 7 shows the substitution amount of each blood group.
Approximately 70% of total population have the blood group of O+
or A+ and have the most frequent donor. Thus, the high substitution
amount of these blood groups is completely reasonable. A+, O+ and
B+ have the highest substitution amounts, respectively, while the
lowest substitution amount belongs to AB-. The question that arises
is which blood group has more capability for substitution. In order
to answer this question, we define an index named Substitution
Index (SI). The SI for each blood group is equal to the substitution
amount divided by total consumption amount.
Substitution amount of blood group f
SIf =
Total consumption amount of blood group f
The amount of SI for each blood group is demonstrated in Fig. 8.
As seen, AB- has the lowest substitution amount while it also has
the highest substitution index. This shows that AB- has the high-
est substitution capability. According to Fig. 8, 15%, 57%, 22%, 41%,
34%, 58%, 65% and 73% of the blood groups O+, O-, A+, A-, B+, B-
, AB+, and AB- are respectively consumed to satisfy the demands
of other blood groups. Another question that arises is that which
blood group is exposed to greatest risk of shortage in the platelet
supply chain. The shortage amount of each blood group is depicted
by Fig. 9. To investigate which blood group has the greatest risk
of shortage we define an index named Complexity Index (CI) as
follows:
Unmet demand for blood group f
CIf =
Total demand for blood group f
1 procure them. Also, because of their fairly low substitution rates,
× these blood groups do not have a significant role in reducing the
Frequency percentage for blood group f
367
Fig. 9. Shortage amount of each blood group.
Fig. 10. Complexity index of each blood group.
As seen in Fig. 10, the blood groups AB- and O+ have the highest
and the lowest CI, respectively. Although O+ has the highest amount
of shortage, its Complexity index (CI) is placed at the lowest level.
On the other hand, AB- has the lowest shortage amount and is more
at the risk of shortage than the rest of the blood groups.
To have an efficient supply chain, challenges should be iden-
tified and managerial solutions for these challenges should be
taken. Hereafter, we suggest some managerial insights derived
from numerical results which can have a significant impact on the
performance of blood services ranging from collection, production,
and inventory, to distribution.
5.2. Managerial insights
After introducing the two indexes of CI and SI and using the
results obtained in the previous section, the blood groups are
evaluated and managerial insights are presented based on their
substitution ability and procurement complexity. After determin-
ing the two indexes of CI and SI for each blood group, the next
step is to segment the blood groups by dividing the chart into four
categories, as depicted in Fig. 11 in which the horizontal axis and
vertical axis correspond to SI and CI, respectively. Each category
has been assigned a name which describes the supply imperative
of the blood groups classified within it.
• The blood groups represented in quadrant I, which have a low risk
of supply and a low substitution rate, are referred to as tactical
blood groups. The blood groups A+ and O+ and B+ are typical
items and blood service centers do not face a serious problem to
368 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372

total cost and also the objective function components for these
ten scenarios including procurement cost, whole blood platelet
(WPLT) production cost, Apheresis production (APLT) cost, inven-
tory cost, shortage and wastage cost are shown in Table 11. Using
Eqs. (44)–(47) and taking into account the desired confidence inter-
val as 0.05 × E(z), the required number of scenarios for confidence
level 95%, is roughly set to 81.

5.3. Value-at-risk vs. conditional value-at-risk

In order to manage risk, two of the popular functions are value

at-risk (VaR) and conditional value-at-risk (CVaR) which are two
straightforward approaches to reduce the expected value and vari-
Fig. 11. Substitution Index vs. Complexity Index for each blood group. ance of cost considering a specified confidence level which is fixed
by the decision maker (Sawik, 2013). VaR (value-at-risk) repre-
Table 10 sents the maximum cost associated with a specified confidence
Insights for blood group management. level (˛) such that for 100 ˛% of the scenarios, the cost will not
exceed VaR. CVaR (conditional value-at-risk) represents the mean
Blood group Segment Management strategy
value for 100(1-˛)% of scenarios which exceed the VaR. In the model
O+,A+, B+ Tactical • Avoid collecting more than what is needed
presented below, a risk aversive decision maker wants to minimize
• Both collection methods can be used (whole
blood and Apheresis) the expected worst-case costs exceeding VaR:
• Maintaining the inventory and production 
levels to the extent that shortage does not Min C (x) = VaR + (1 − ˛)−1 Ps Ts (49)
occur s∈S

O-, A-, B-, AB+ Leverage • Investment in attracting more donors  i,f

U
r,f
• Considering health care insurance benefits Ts ≥ WBt−2 × ϕi + IPBt × ϑh
for this group of donors
• Focusing on Apheresis method to collect 
i

t

f
r,f,s f

f
 
t r=1
r,f,s
more PLT units + j,t
× Dj,t + IPHj,t × ϑh

AB- Strategic • Giving special importance to this type of 

r

f j
f
t
j f t r
h,f
donor + Qpt × v+ Øaph × APHj,t
• Considering remuneration for this type of
donor

t

f
b,f
j

t f
(50)
• Considering health insurance discounts
+ Øaph × APHt + wPLT × WLBt
• Collecting only with Apheresis method to
obtain more PLT units

t

f t
PLT s
+ w × WLHj,t

j

t
 Fr,f,s Y,f,s O,f,s
+ sh × (SLHj,t + SLHj,t + SLHj,t )
shortage rate of other blood groups and thereby increasing their j t f
supply may increase their wastage level. −VaRs ∈ S
• The blood groups categorized in quadrant II, with a relatively low
risk of supply and a relatively high substitution rate, are referred Ts ≥ 0 s ∈ S (51)
to as leverage blood groups. The blood groups A-, B-, O- and AB+ and constraints (2), (4), (5), (16), (17), (20)–(22), (25), (27)–(43)
play a crucial role in reducing the shortage level and blood service A risk aversive decision maker is willing to make decisions so
centers are able to meet the demand for these blood groups at an that the total probabilities of scenarios with costs greater than VaR
acceptable level. It is clear that investment in attracting this group do not become greater than (1-˛). To provide a managerial insight, a
of blood donors will lead to a significant decrease in shortage sensitivity analysis on the confidence level is performed which has
level. been shown in Table 12. As can be seen, increasing the confidence
• No blood groups are categorized in quadrant III. level leads to higher values of the expected cost, VaR and CVaR
• The blood groups placed in quadrant IV, with a high risk of sup- and the decision maker can select the desirable confidence level
ply and a high substitution rate, are referred to as strategic blood according to his/her preferences. For a higher value of confidence
groups. As a general blood group, AB- can be used to satisfy the level more donors are needed so that by increasing the confidence
demand of all blood groups. Because of the supply complexity of level from 0.5 to 0.99, 134 more donors are required. The expected
this blood group, more investment is needed to attract AB- blood shortage, expected wastage, total Apheresis platelet in the hospi-
donors. It is clear that by increasing the collection of this blood tal (APH) and in the blood center (APB), and the total whole blood
group, the shortage level will dramatically be reduced. platelet (WBP) are also presented at each confidence level. The rea-
son for the invariability of APB and APH is the limited number of
Some management strategies for efficient management of blood Apheresis donors.
groups based on the obtained results of the proposed model are The abovementioned model tries to minimize the worst case
presented in Table 10. as much as possible and focuses on 100(1-˛)% of scenarios which
Using Eqs. (44)–(47) to calculate the value of sampling estima- exceed the VaR. Although, by applying Eq. (48), the expected
tor and then to determine the required number of scenarios (n) for worst case is minimized and as a result variability is reduced,
a desired confidence interval, the stochastic programming model it does not guarantee that the total expected cost is also mini-
is solved with a small number of scenarios (n) (e.g. n = 10). Each mized. In the objective function (52), the expected cost and the
scenario is then assigned the same probability and the sum of the expected worst-case cost are considered simultaneously and pro-
probabilities for all the scenarios is equal to 1. The values of the vide a non-dominated solution set by the parameterization on ␭
 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372 369

Table 11
The value of objective function components under different scenarios. (10,000$).

Scenario Total cost Procurement cost WPLT production cost APLT production cost Inventory cost Transhipment cost Shortage cost Wastage cost

1 136.430 16.794 20.992 27.179 0.183 0.332 70.950 0

2 142.701 16.794 20.992 27.179 0.181 0.333 77.222 0
3 131.476 16.794 20.992 27.179 0.215 0.332 65.964 0
4 133.776 16.794 20.992 27.179 0.193 0.332 68.286 0
5 127.313 16.794 20.992 27.179 0.218 0.332 61.798 0
6 137.753 16.794 20.992 27.179 0.210 0.332 72.246 0
7 145.619 16.794 20.992 27.179 0.176 0.332 80.146 0
8 141.585 16.794 20.992 27.179 0.191 0.332 76.097 0
9 139.341 16.794 20.992 27.179 0.184 0.332 73.859 0
10 127.514 16.794 20.992 27.179 0.229 0.332 61.988 0
Expected value 136.3508 16.794 20.992 27.179 0.198 0.332 70.8556 0
Standard deviation = 6.277821.

Table 12
Sensitively analysis for the value of ␣ (␭ = 0.9)

␣ Expected cost CVaR VaR Expected shortage Expected wastage Total APB Total APH Total WBP

0.25 133.139 134.573 128.837 460 2 250 245 1345

0.5 134.038 136.815 131.261 465 5 250 245 1352
0.7 135.811 139.064 134.417 473 9 250 245 1373
0.8 137.52 140.996 136.651 476 11 250 246 1414
0.9 139.242 144.199 138.691 487 16 250 245 1414
0.95 142.825 147.803 142.563 506 31 250 245 1435
0.99 149.590 154.145 149.544 536 78 250 246 1486

Table 13
Sensitively analysis for the value of ␭ (␣ = 0.9).

␭ Total cost Expected cost CVaR VaR Expected shortage Expected wastage Total APB Total APH Total WBP

0.05 143.678 133.782 144.199 138.691 452 0 250 245 1414

0.1 143.157 133.781 144.199 138.691 452 0 250 245 1414
0.3 141.073 133.755 144.209 138.701 452 0 250 245 1414
0.5 138.981 133.744 144.219 138.711 452 0 250 245 1414
0.7 136.707 132.985 145.394 137.726 453 0 250 245 1380
0.9 134.027 132.537 147.432 138.573 455 0 250 245 1352
0.95 133.245 132.435 148.813 139.042 457 0 250 245 1339

where 0 ≤ ␭ ≤ 1. expected shortage, expected wastage, total Apheresis platelet in the

hospital (APH) and the blood center (APB) remain roughly invariant.
 i,f

U
r,f
Min H(x) =  ( WBt−2 × ϕi + IPBt × ϑh
6. Conclusion

i t f
r,f,s f
f t r=1

+ Ps × × Dj,t In this paper focusing on tactical and operational decisions, we

j,t
developed an integrated multi-period mixed-integer programming

r

f

j

t

s
r,f,s
 f model in which the uncertain demand is captured by applying
+ Ps × IPHj,t × ϑh + Qpt × v
a two-stage stochastic framework. We first applied a finite-state

j f t s r
h,f
t f
Markov chain model to predict the number of donors in each
+ Øaph × APHj,t period time by using current conditions and a probability transition
j
t f
 matrix and then mathematical programming was solved determin-
b,f istically. To cope with uncertainty, a two-stage stochastic model
+ Øaph × APHt + wPLT × WLBt
was also developed. We introduced an improved approach for sce-

t

f
 t
nario generation and reduction that well represents the behavior
+ Ps × wPLT × WLHj,t
s
of a phenomenon while the stochastic model will be solvable in a

j

t

s
  reasonable time.
Fr,f,s Y,f,s O,f,s
+ Ps × sh × SLHj,t + SLHj,t + SLHj,t We formulated the ABO-Rh matching rules in the form of a
j t f s mathematical model without assigning a penalty cost for substitu-
+(1 − )C(x) tion which significantly enhanced the practical application of the
(52) proposed model. The main contribution of our paper is considering
three types of patients according to their need to PLT age groups and
and constraints (2), (4), (5), (16), (17), (20)–(22), (25), (27)–(43), ABO-Rh compatibility priority. In our study, we proposed a patient-
(48)–(50) based application which can assist managers to decide how much
The trade-off between the expected cost and the expected blood should be collected from whole blood and Apheresis donors,
worst-case cost with ␣ = 0.9 is shown in Table 13. The results how much platelet should be produced, and how much platelet
emphasize the effect of the decision maker’s varying cost/risk should be transferred to hospitals in each period in order to reduce
preference. By increasing the value of ␭, the expected cost and shortage and wastage levels.
total produced whole blood platelet (WBP) are decreased and Since the major challenges in blood centers and hospitals are to
the expected worst case (CVaR) is conversely increased while the keep an adequate inventory of each blood group without risking
370 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372

a major shortage, and to minimize the number of outdated units,
the two measures of CI and SI were firstly introduced and then
blood groups were evaluated based on their substitution ability and
supply complexity. In the next step, the blood groups were placed
into three categories and then managerial insights were presented
based on each category.
In order to manage risk, a variance management model was
applied and also to help DM, the model was performed under dif-
ferent confidence levels.
Future researches can be implemented considering several
blood components in order to model blood supply chain. Another
case for further research is to determine optimal safety stock for
each blood group and each age group in blood centers and hospitals.
Appendix A.
PLT units are labelled as D+/−, and most transfusion services
avoid transfusing D+ PLTs to D− females of childbearing age (Cid
et al., 2013). The most adverse side effect of transfusing ABO non-
identical platelets is hemolysis. Large volumes of ABO non-identical
platelet transfusions over a relatively short time period increase
the risk of an ABO hemolytic reaction. However, ABO hemolytic
reaction is rare after a single transfusion of ABO non-identical
platelets (McManigal and Sims, 1999). Transfusion of non-identical
ABO platelets to chronically transfused patients with hemato-
logic disease makes them have lower post-transfusion platelet
counts and need almost twice as many platelet transfusions. As
a result, platelet refractoriness happens earlier for patients receiv-
ing non-identical ABO platelets than those receiving ABO identical
platelet transfusions (Heal and Blumberg, 2004; Muylle et al., 1992).
‘Refractory’ is defined as a condition in which patients fail to achieve
a significant and sustained rise in the platelet count after transfu-
sion of an appropriate dose of platelet (Rebulla, 2002). In these
conditions, refractory patients are cross-matched against single
donors (Apheresis). Patients receiving allogeneic marrow or stem
cell transplants and patients receiving chemotherapy for acute
leukaemia are exposed to more detrimental risks due to transfu-
sion with ABO non-identical platelets (Bensinger et al., 1982; Heal
and Blumberg, 2004). Patients receiving stem cell transplant who
are multiply transfused, or who have had prior pregnancy may
become refractory to platelet transfusion due to the development
of multi-specific HLA or platelet-specific antibodies. These patients
may need to receive HLA- (Human Leucocyte Antigen) or HPA-
(Human Platelet Antigen) matched donors (Murphy et al., 1986).
Since it is very time-consuming to find even a single compatible
donor for HLA-matched transfusions, Human leukocyte Antigen
(HLA) matching is possible only through Apheresis collection and
transfusion of the platelets drawn from a single donor improves the
chance of a successful treatment (Murphy et al., 1986).
Appendix B.
Here an example for the application of the method explained in
Section 3.2. is presented. The probability of transition state from
Repeated donor in period t-1 to Repeated donor in period t (PR → R )
is equal to the number of Repeat donors who have donated blood at

Table A1
State transition probabilities.
NR→R NR→E NR→Z NE→R NE→E NE→Z NZ→Z NZ→E NZ→R
Period PR→R = NR
PR→E = NR
PR→Z = NR
PE→R = NE
PE→E = NE
PE→Z = NE
PZ→Z = NZ
PZ→E = NZ
PZ→R = NZ

t0 − 6, t0 − 5 0.7 0.23 0.07 0.4 0.5 0.1 0.996 0.012 0.008

t0 − 5, t0 − 4 0.75 0.25 0.05 0.5 0.4 0.1 0.985 0.008 0.007
t0 − 4, t0 − 3 0.7 0.27 0.03 0.48 0.47 0.05 0.983 0.015 0.002
t0 − 3, t0 − 2 0.95 0.04 0.01 0.37 0.55 0.08 0.97 0.02 0.01
t0 − 2, t0 − 1 0.8 0.15 0.05 0.53 0.45 0.02 0.98 0.013 0.007
t0 − 1, t0 0.9 0.07 0.03 0.5 0.45 0.05 0.977 0.015 0.008
Average 0.8 0.16 0.04 0.46 0.47 0.07 0.979 0.013 0.008

Table A2
The number of each donor group in period t = 1,. . .,6.

Total number of donors Average in a day (beginning Expected donor

in the last year of the planning t0 )
Period NT R NT E NT F NT R + NT E

T=1 798 420 8087 1218

NR = 241800 NR = 241800/365 = 662 T=2 896 430 7962 1326
NE = 161200 NE = 161200/365 = 441
NF = 3000,000 = eligible NF = 3000000/365 = 8219
persons for donation who have
not donated in the last year
T=3 978 449 7845 1427
T=4 1052 469 7735 1521
T=5 1119 489 7632 1608
T=6 1182 508 7538 1690

Table A3
Number of repeat donors with different blood groups at each period.

Blood group Period

T=1 T=2 T=3 T=4 T=5 T=6

+
O 462.84 503.88 542.26 577.98 611.04 642.2
O− 85.26 92.82 99.89 106.47 112.56 118.3
A+ 414.12 450.84 485.18 517.14 546.72 574.6
A− 73.08 79.56 85.62 91.26 96.48 101.4
B+ 109.62 119.34 128.43 136.89 144.72 152.1
B− 24.36 26.52 28.54 30.42 32.16 33.8
AB+ 36.54 39.78 42.81 45.63 48.24 50.7
AB− 12.18 13.26 14.27 15.21 16.08 16.9
 H. Ensafian et al. / Computers and Chemical Engineering 106 (2017) 355–372 371

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