Vesna Libek MD, PhDBlood transfusion specialist

Head of Blood Transfusion ServiceDeputy manager CHC Zemun Belgrade

Lecturer in Blood transfusion education department at Belgrade Medical University

SERBIA

BLOOD COMPONENTS – PROCESSING, QUALITY

ASSURANCE, STANDARDISATION 

Shenzhen, 2015

There is totally 81 million blood units transfused all over the world / per year

P.J.L Carson., Carless: The evidence base for red blood cell transfusions. ISBT Science Series (2013) 8,89-92

Veldhuizen I., Follea G., de Kort W.: Donor cycle and donor segmentation: new tools for improving blood donor management Vox Sanguinis(2013) 105, 28-37

Over 20 million blood units are collected in Europe from 13 million blood donors per year

Project DOMAINE ( Donor Managment in Europe)

Segmentation of blood donor population in blood donor types

Voluntary non-remunerated blood

donor

Allogenic and autologous whole blood donations

Collection of components by apheresis

Fixed-site blood-collections

Mobile blood collection

Production- blood

processing

Whole blood donation

High-quality blood components meeting European guidelines can be prepared by using automated devices. Think of Critical control points for the donation

process: Selection of blood donor Collection of the donation Handling and storage of the donation Transport of the donation to the processing center Distribution of blood component Avoid them with new technologies that automate the

critical control points as far as possible

During this process, following Guide to the preparation, use and quality assurance of blood

components, 17th Edition is unavoidable

PRINCIPLES: up-to-date useful information

STANDARDS: mainly adherent to European Pharmacopeia and European Directives -must be applied

Relevant legislative & regulatory references 2001/83/EC “ community code relating to medicinal products for human use”

2002/98/EC “standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components

2004/33/EC “Eligibility of donors ...Quality and safety requirements for blood

2005/61/EC “…traceability requirements and notification of serious adverse reactions and events”

2005/62/EC “… Community standards and specifications relating to a quality system for blood establishments”

PE 005-3 PIC/S GMP GUIDE FOR BLOOD ESTABLISHMENTS - 2007

GOOD PRACTICE GUIDELINES FOR BLOOD ESTABLISHMENTS AND HOSPITALS BLOOD BANKS required to comply with EU DE 2005/62 /CE - 15.11.2013

EDQM Guide to the preparation, use and quality assurance of blood components. Recommendation n. R(95)15. 17th Edition - 2013

WHO guidelines on good manufacturing practices for blood establishments -Technical Report Series, No. 961, 2011 Annex 4

Feuropean Pharmacopeia 8th Ed.

Each blood establishment must develop and maintain QS based on EU Directive 2003/94/EC Good Manufacturing Practices (GMP) and complies with the requirements identified in Directive 2005/62/EC and its Annex.

QUALITY MEANS:Quality system - organizational structure, responsibilities, processes, procedures and resources required to maintain high quality products and ⁄ or services.In blood transfusion chain setting- quality system provides a framework in a supply chain setting from a donor’s vein to a patient’s vein through the collection, processing, testing, distribution and administration of high quality, safe and effective blood and blood products.\

Quality system considers:

quality management,

quality assurance, continuous quality

improvement, personnel, premises

Control of equipment and documentation, electronic data are important part of QS.

collection, processing, testing, release, storage, distribution,

blood component recall, external and internal auditing

and issuance of blood components

Non conformities and corrective and preventive measures are included.

Quality control testing of components are done following the recommended percent of all produced components.

Strengers P.:ISBT Working Party on Quality Management. Transfusion Today, 96:4-5, 2013.

A quality assurance programs - ensure that there are processes in place, to control and monitor all critical steps

the application of quality assurance to every part of the manufacturing process from donor selection through to dispatch of the components to the hospitals.

quality assurance can ensure consistency of product, reliable results, effective risk-based decision making and reduction in wastage through minimization of errors.

Quality assurance therefore provides a strong basis for donor, product and staff safety.

QM considers:

Self inspection

to improve

some field of work as

well as

Regulatory

inspection by

Competitive

authorities or state accreditation body

Seidl C.:Standards, criteria and trainig requirements for improving quality managment. Transfusion Today, 96:6-7, 2013.

For all working procedures - SOPs (Standard Operative Procedures), which represent the exact steps in working process- need to be written.Effective, streamlined SOPs based on principles of good practice that comply with relevant regulation.

Quality policies

Quality procedures

SOPs

Records

Structure of controlleddocument system

EU-Optimal Use of Blood Projectcofounded by the European Commission

The EU-Q-Blood-SOP Projectcofounded by the European Commission

The European Commission, Public Health Program

European Project addressing the safety of blood transfusion 

Blood Quality Project - EQUAL

The main goal of the Project - “Good Quality Management” (QM) in Blood Transfusion Services

On the Basis of the Directive 2002/98/EC of Europian Comission (Blood Directive)

Through the Project the Manual for EU Standard Operating Procedures was writen

www.equal-blood.eu

Continuously improving the quality of processing procedures and the quality of final components

EDQM, WHO Harmonization of definitions connected to

QM QM include human resources too

Strengers P.:ISBT Working Party on Quality Managment. Transfusion Today, 96:4-5, 2013.

C. Seidl. European perspective of quality management in blood establishments - The EuBIS manual and training guide. XXXIth (ISBT) in joint cooperation with the 43rd Congress of the DGTI, Berlin, 2010.

C. Seidl. The EUBIS standards and criteria for the inspection of blood establishments -Introduction and overview of the EuBIS manual and training guide. XXXIth (ISBT) in joint cooperation with the 43rd Congress of the DGTI, Berlin, 2010.

Equivalent recognition of inspections of blood establishments among all Member States through the development and implementation of commonly accepted criteria and standards leading to comparable quality systems and inspection procedures.

Seidl C, Brixner V, Müller-Kuller T, Sireis W, Costello P, Cermakova Z, Delaney F, McMillan Douglas A, Nightingale M, van Galen JP , O’Connell M, Siegel W, Sobaga L, de Wit J, Seifried E. Levels of quality management of blood transfusion services in Europe. Vox Sang 2008.; 3 (1) : 54-62 Project co-funded by the European Commission, DG Sanco

 Enable that blood components are collected and prepared to

a consistently high standard of safety across Europe. Define requirements for the quality management system

for blood establishments based on the Directive 2005/62/EC

Develop pan European standards and criteria for the inspection of blood establishments (GMP guidelines, implementing the Directive 2002/98/EC and its technical annexes).

Establish a common benchmark system for deviations and improvements.

Develop a training program for inspectors                                       

EUBIS:

EUBIS - Standards and Criteria developed based on the European Blood legislation with cross-reference to common used European and International standards defined by its survey in Annex I of the Grant Agreement (Vox Sanguinis, Science Series Vol (3), Seidl et al. 2008).

Project “Optimal USE of Blood”- Improve safety for the donor - reducing the unnecessary bleeding of donors- Improve safety for the patient - improving the transfusion process, reducing the unnecessary transfusion of blood.- Improve effectiveness of health services -blood components to be used in the most therapeutically beneficial way for patients.- Improve efficiency of health services - reducing inefficient use of resources.

To summarize the current status in routine preparation process of blood components Critical parameters during the

donation process and the period before separation

Temperature control

Storage time and temperature before separation

Phagocytosis and self-sterilization

Leucodepletion

Henschler R, Müller M.M, Pfeiffer H.U, Seifried E, Sireis W.: Production of standard blood components. ISBT Science Series (2010) 5,190-195

Red cell concentrates

Platelet concentrates

Additive solutions

Agitation

Storage lesion

Cold storage of platelets

Storage period of PCs

Therapeutic plasma

Pathogen inactivation

Production of cellular blood components from undifferentiated cells in vitro

Following standards for collection of blood and blood components:

premises for donor sessions, procedures and equipment used at blood donation

sessions, pre-donation checks, labelling, venipuncture, bleeding and mixing, handling of filled blood bags following special requirements for Apheresis Not less important is having the repository of archive

samples.

Collection of blood,Initial step in preparing standardized blood components, proper mixing with the anti-coagulant continuously at all phases of the bleeding is important. From blood donation through dividing tubes and small pre donation bag, from initial blood bag and then towards producing different blood components in everyday work, depends on well-chosen equipment.

Prowse C.V., de Korte D., Hess J.R., van der Meer P.F.: Commercially available blood storage containers. Vox Sang 2014, 106:1-13.

The plastic - need to be tolerant to temperatures required for blood steam sterilization and plasma freezingClear - to allow visual assessment and processingStrong enough - to tolerate centrifugal processing and pressure infusionPolyvinyl chloride (PVC) , plasticized with di-2-ethylhexyl phthalate (DEHP) –safety?The size, and thickness of platelet bags and the fracture resistance of plasma bagPlastic bags (DEHP free, PVC free) for platelet storage with better gas diffusion capabilities are widely available.Modern bags are also sized to prevent overdrawingWith the adoption of the ambient overnight hold of whole blood before processing the importance of the plasticizer in the primary collection bag may increase.

Thibault L., Beausejour A., Jacques A., Ducas E., Tremblay M.: Overnight storage of whole blood: cooling and transporting blood at room temperature under extreme temperature conditions. Vox Sang 2014; 106: 127-136

Either to store whole blood (WB) units up to 24 h before processing, the WB is actively chilled to 22±2ºC

Usually by placing the WB bags under cooling plates filled with butane-1,4-diol

The WB is rapidly cooled from a post collection temperature of about 34ºC to 22±2ºC within 2-3h

Processing of blood Blood components may be prepared either during collection

of whole blood with further processing through centrifugation or during collection using apheresis technology.

Component separation after the initial centrifugation of whole

blood Separation after initial filtration

T/BQuadruple bag

Tests for platelet qualityMeasuring platelet activation state • CD62P expression• Annexin V binding• Extent of shape change• Morphology score• SwirlMeasuring platelet metabolic activity • Glucose• Lactate• pH

Tests of red cell concentrate qualityMeasuring red cell metabolism • 2,3- DPG• ATP and other nucleotides• GlucoseMeasuring red cell integrity • Osmotic fragility• Potassium• Morphology• CD47 level• Annexin V binding• Per cent haemolysis at outdate

Commonly used quality measures for fresh cellular components

• The condition of centrifugation determines the composition of the desired component.

• The choice of initial separation step as well as using initial filtration strongly influences the choice of methods for further processing.

• Together with methods of freezing plasma, irradiation of blood components, pathogen reduction and different additive solution we can also produce modified components using appropriate equipment.

Williamson L., Devine D.: Challenges in the management of the blood supply Lancet 2013 (381):1866-1875.

Different factors influence the possible stock period of components:

Composition of conservers, additive solutions, post production manipulation for instance- irradiation

The separation of blood components from whole blood collections can be automated by a different

devices producing standardized blood

components, good quality control and increased work

efficiency.

Processing of blood components carried out using appropriate and validated procedures including measures to avoid risk of bacterial contamination.

The labelling system for the collected blood, blood components and samples must unmistakably identify the type of the content and must be the link to obtain traceability of the donation.

There must be the safe system for realizing components after all mandatory requirements priory being fulfilled.

Procedures for storage and distribution need to keep blood component quality during whole storage period.

All processes for irradiation and leucodepletion must also be standardized.

Red cell components can be processed like:

Red cells RC buffy coat removed, RC in additive solution, RC buffy coat removed in additive solution, RC leucocyte depleted, RC leucocyte depleted in additive solution, RC apheresis, RC washed and RC cryopreserved.

Automatic separators allows even simultaneously separation of two blood units and whit the T/B quadruple blood bags we came closer to full automation with shortening separation period.

Immediately transferred data to the PC and stored in electronic form and as printed copy, enables haemovigilance.

Segments from red blood cell units should not be used for quality testingJayme D.R. Kurach1,2,3, Adele L. Hansen1,2,3, Tracey R. Turner1,2,3,Craig Jenkins1,2,3, Jason P. Acker1,2,3,*

Transfusion Volume 54, Issue 2, pages 451–455, February 2014

The quality of samples from tubing segments is not representative of the quality of the corresponding RBC unit.

Segments are not suitable surrogates with which to assess RBC quality.

QC of RBC components

Red blood cells

RBCs without BCRBCs in additive solution

RBCs without BC

In additive solution

RBCs leucocyte-depleted

RBCs leucocyte-

depleted in AS

Volume(mL)

280±50 250±50 Depends on AS Depends on AS To be defined for the system used

To be defined for the system used

Hematocrit 0,65-0,75 0,65-0,75 0,50-0,70 0,50-0,70 0,50-0,70 0,50-0,70

Hemoglobin(g/unit)

≥ 45 ≥ 43 ≥ 45 ≥ 43 ≥ 40 ≥ 40

Special demands

-Residual leucocyte

content / unit<1,2x109 per unit

-Residual leucocyte

content / unit<1,2x109 per unit

Residual leucocyte content / unit

<1 x106 per unit

Residual leucocyte content / unit

<1 x106 per unit

Haemolysis at the end of

storage(% of RC mass

<0,8 <0,8 <0,8 <0,8 <0,8 <0,8

Washed RBCs RBCs cryopreserved Apheresis RBCs

Volume(mL)

To be defined for the system used

> 185 ml To be defined by the system used

Hematocrit 0,65-0,75 0,65-0,750,65-0,75

(0,50-0,70 with AS)

Hemoglobin(g/unit)

≥ 40 ≥ 36 ≥ 40

Special demandsProtein content final

supernatant< 0,5 g / unit

Residual leucocyte content / unit

<1 x109 per unitOsmolarity < 340

mOsm/LSterile

Haemoglobin supernatant < 0,2 g /per unit

Residual leucocyte content / unit

<1 x106 per unit

Haemolysis at the end of storage(% of RC

mass<0,8 <0,8

Improve product quality through improved technology

Devine D.V., Howe D. : Processing of whole blood into cellular blood components and plasma. ISBT Science Series 2010 (5):78-82.

Gravitational separation of cells based on their density

Two methods for the ultimate preparation of platelet concentrates

PRP production ( soft spin hard spin)

“Buffy coat” production (hard spin several BC

pooled together soft spin) Development of additive solutions

Pooling BC by the system

Transfusion medicine in Germany: Current Status and Perspectives. Frankfurt 2010 (ISBT)

Pooling BC by the chain method

Platelet component can be prepared

as single unit from PRP (platelet rich plasma) or from buffy coat.

Platelets can be pooled, produced directly from whole blood derived buffy coats or after pooling 4 to 6 single units of platelets.

Platelets can be also produced as: pooled leucocyte depleted, pooled in additive solution, pooled leucocyte depleted in additive solution, or platelets pooled pathogen reduced and platelets donated by apheresis either leucocyte depleted, in

additive solution, or pathogen reduced. There are also platelets cryopreserved.

Pooled platelet concentrate

(from 4-6 blood units) –

240-360 X109 Plt in 250-300 ml of

plasma or additive solution Apheresis platelets

200-400 X109 Plt in 200-300 ml of

plasma from one donorDevine D.v.; Howe D.: Processing of whole blood into cellular components and plasma. ISBT Science Series (2010)5,78-82

Van der Meer P.F.& al. Aggregates in platelet concentrates. Vox Sanguinis (2015)108,96-100.

Collection and

storage of

platelets

Many of activation processes are

calcium dependent

Preserving Plt

functional capacity to

respond when

transfused

Preventive measures for aggregates formation:

lowering pHResting period before further

processing

Avoid Plt activation

Reduction of the ionized Ca++ level with citrate based anticoagulants inhibited Plt activation

with introduction of leucoreduction

filtersPlt activationaggregates

Janetzko K, Hinz K, Marschner S, Goodrich R, Klüter H: Evaluation of different preparations procedures of pathogenreduction technology (Mirasol®) treated platelets collected by plateletpheresis. Transfus Med Hemother2009;36:309-317.Janetzko K, Hinz K, Marschner S, Goodrich R, Klüter H: Pathogen reduction technology (Mirasol®) treated singledonor platelets resuspended in a mixture of autologous plasma and PAS. Vox Sang 2009;97:234-239.

Pathogen reduction treatment (PRT) leads to an increase of platelet metabolism and activation independent of the length of the initial rest times.

PCs resuspended in autologous plasma - stored at maximum up to day 5.

mixture of plasma and PAS improves pH and platelet metabolism but not platelet activation. Prolonged shelf-life for up to 7 days may be possible.

Recent advances in blood component processing technologyRebecca Cardigan  (Jun 1, 2014; 53446)

Increase the standard of care Pooled product based on solvent detergent

treatment Single donor based on: methylene blue amotosalen riboflavin

Pathogen inactivation

Williamson L., Devine D.: Challenges in the management of the blood supply Lancet 2013 (381):1866-1875.

Prolonged life time of Platelet concentrates to 7 days in some countries if they are tested for bacterial contamination or if they are pathogen reduced

Heaton W.A. Costs and benefits of PAS platelets: A mix of science,quality, and value . TRANSFUSION 2013;53:2597-2602.

Platelet concentrates in electrolytic medium instead of plasma supernatant

Less post transfusion reactions Better cell quality Prolonged life time to 10 days on agitators in

incubators Additional additives for better PC quality: better

energetic metabolism, reduction of metabolic stress, increase the stability of cells - post transfusion improve recovery

Hornsez et al. Freezing of buffy coat-derived, leucoreduced platelet concentrates in 6% dimethyl sulfoxide. Transfusion (2008) 48:2508-2514.

Leuco reduced Plt concentrates in small volumes with 6% DMSO frozen and kept on

-80ºC For alloimunised patients and for

military purposes During frost–defrost procedures there

is lost of 23% Plt count

QC of Plt components

Plt recovered single unit

Plt recovered pooled

Plt recovered pooled leucocyte

depleted

Plt recovered pooled

In additive solution

Plt recovered pooled LDIn additive

solution

Plt pooled pathogen reduced

Volume(mL)

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

Platelet content per final unit

> 60 x109 Minimum 2 x1011Minimum 2 x1011

Per unit

Minimum 2 x1011

Per unitMinimum 2 x1011

Per unitMinimum 2 x1011

Residual leucocytes per

final unita. Prepared

from BCb. Prepared

from PRP

a. < 0,05 x109

b. < 0,2x109

< 1 x109

per final unit(either BC pooled

or pooling of single Plt units)

< 1 x106

per final unit< 0,3 x109

per final unit< 1 x106

per final unit< 1 x106

per final unit

pH measured (+22ºC) at the

end of the recommended

shelf-life

> 6,4 > 6,4 > 6,4 > 6,4 > 6,4> 6,4

Plt apheresisPlt apheresis

leucocyte depleted Plt apheresis In additive solution

Plt apheresis LD in AS

Plt apheresis pathogen reduced

Plt cryopreserved

Volume(mL)

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

> 40 mL per 60 x109 of Plt

50 – 200 mL

Platelet content per final unit

Standard unit: Minimum 2 x1011

Per unit

For use in neonates and infants: Minimum 0,5 x1011

Per unit

Standard unit: Minimum 2 x1011

Per unit

For use in neonates and infants: Minimum 0,5 x1011

Per unit

Standard unit: Minimum 2 x1011

Per unit

For use in neonates and infants: Minimum 0,5 x1011

Per unit

Standard unit: Minimum 2 x1011

Per unit

For use in neonates and infants: Minimum 0,5 x1011

Per unit

Minimum 2 x1011

More than 40% of the prefreeze

platelet content

Residual leucocytes per

final unit< 0,3 x109

< 1 x106

per final unit< 0,3 x109

per final unit< 1 x106

per final unit< 1 x106

per final unit

pH measured (+22ºC) at the

end of the recommended

shelf-life

> 6,4 > 6,4 > 6,4 > 6,4 > 6,4

Plasma, Fresh Frozen (FFP)

Plasma, Fresh Frozen is a component for transfusion or for fractionation prepared either from Whole Blood or by apheresis, frozen within a period of time and to a temperature that will adequately maintain the labile coagulation factors in a functional state.

• Plasma, Fresh Frozen used as Human plasma for fractionation must comply with the specifications of the European Pharmacopoeia monograph Human plasma for fractionation (Ph. Eur. monograph 0853).

• Plasma, Fresh Frozen (FFP) used for clinical transfusion must comply with the specifications given in the monograph of the R 95(15) Guide (Part D, Paragraph 1).

Preparationa. From whole blood •hard spin centrifugation, •preferably within 6 hours (no > 18 hours if the unit is refrigerated). •Whithin 24 h if whole blood has been rapidly cooled between + 20 ºC and + 24 ºC •Freezing must be completed within one hour to a temperature below – 30 ºC.

The plasma core temperature reaches

-30°C within less than 1 hour.

b. By apheresis•The freezing process must commence within six hours of completion of the procedure and completed within one hour to a temperature below – 30 ºC. •If plasma is maintained between + 20 °C and + 24 °C immediately after collection can be held at that temperature for up to 24 hours prior to freezing.

c. Quarantine FFP • This FFP is released once the

donor has been retested, at least for HBsAg, anti-HIV and anti-HCV, with negative results after a defined period of time, designed to exclude the risk associated with the window period.

• A period of six months is generally applied. This may be reduced if NAT testing is performed.

QC of FFP

FFP pathogen reduced. Requirements Frequency of control

Volume(mL)

Stated volume ± 10% All units

F VIIIAverage not less than 50 IU F VIII per 100 mL

Every 3 months 10 units in the first month of storage

Fibrinogen Average (after freezing and

thawing): 60% of the potency of the freshly collected plasma unit

Every 3 months 10 units in the first month of storage

Residual cells

Red cells:< 6,0 x109 /LLeucocytes: < 0.1 x109 /L

Platelets: < 50 x109 /L

1% of, all units with a minimum of 4 units per month

If leucocyte depleted: < 1 x106 /L

1% of, all units with a minimum of 10 units per month

Leakage No in any part of container All units

Visual changes No abnormal color or visible clots.

All units

•When there is cryoprecipitate prepared, then there is also FFP cryoprecipitate depleted produced.

Cryoprecipitat Requirements Frequency of control

Volume(mL)

30 – 40 mL All units

F VIII 70 IU per unit

Every 2 months :a. A pool of 6 units of mixed blood groups

during their first month of storageb. A pool of 6 units of mixed blood groups

during their last month of storage

Fibrinogen 140 mg per unit1% of, all units with a minimum of 4 units per

month

Von Willebrand factor 100 IU per unit

Every 2 months :a. A pool of 6 units of mixed blood groups

during their first month of storageb. A pool of 6 units of mixed blood groups

during their last month of storage

LABELLING

ISBT 128 LABEL STANDARDISBT 128 LABEL STANDARD

UNIT(CDM: UNIQUE

WORLD NUMBER)

TYPE OF PRODUCT

EXP.DATE

BLOOD GROUP

The computer system of blood establishment or hospital blood bank includes:

hardware, software, peripheral devices and documentation (e.g. SOPs, manuals).

Such blood bank information system could consist of different parts, modules, connected to donation process, filing process, production management and laboratory part.

These systems are the core of the supply chain management, which records and monitors all processes from blood donation to post-transfusion follow-up in adherence to international standards.

It also consists of warning, guidance and decision support tools, which enables the adoption of processes that meet international standards.

Production of blood components in EU Production by BC method

High % of leucofiltration Some countries doesn’t produce cell components of first time

blood donation Quarantine FFP Some countries use only man FFP or nulliparous FFP in therapy High percentage of apheresis PC NAT testing for HBV, HCV, HIV Testing for bacterial contamination of PC Some of member states use only virus inactivated FFP for all

patients or some group of patients Blood components are typed in Rh system and Kell sistem

Production - statistic All WB (whole blood ) donations are separated in blood components: RBC

concentrates, plasma concentrates and BCs (buffy coats) 20% of plasma used as therapeutic – FFP (after 4 months of quarantine

storage) 80% of plasma for further fractionation Most apheresis procedures – double apheresis 40% of collected BCs for manufacturing pooled random Plt concentrates

(comprised of 4 BCs) Since 2001, RC concentrates and Plt concentrates are 100% leukodepleted Irradiation for medical purpose individually for red cells and Plt

concentrates Pathogen reduction (Plt concentrates, FFP) Washed erythrocyte concentrates in rare cases

Transfusion medicine in Germany: Current Status and Perspectives. Frankfurt 2010 (ISBT)

The administration of blood and blood components involves more than 70 steps and each of these may be subject to error.

Standard protocols for the administration of blood are essential to minimize the potential for error.

These protocols should be in place in each institution and should conform to standard practice.

A quality management system should exist in each institution.

This should include an active transfusion committee, a process to correct protocols and practice when deficiencies are identified, participation in local and regional audit and in the national haemovigilance program.

Williamson L., Devine D.: Challenges in the management of the blood supply Lancet 2013 (381):1866-1875.

Biological variations between blood donors influence the component production itself

Component processing can not completely optimize the quality of products

Blood components are highly concentrated but they are not completely free of other blood elements

1. Mountford J, Olivier E, Turner M. Prospect for the manufacture of red cells for transfusion. Br J Haematolog 2010; 149:22-34.2. Reems JA, Pineault N, Sun S. In vitro megakaryocyte production and platelet biogenesis: state of the art. Transf Med Rev 2010; 24:33-43.3. Giarratana MC, Rouard H, Dumont A, et al. Proof of principle for transfusion of in vitro-generated red blood cells. Blood 2011;118: 5071-79.

To follow the influence of specific blood donor characteristics on processed blood components

The production of blood components from hematopoietic steam cells in laboratory

Future steps

vesna.libek@gmail.com

• Blood and blood components are biological products

• Automatisation = standardisation

谢谢 !