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1. BLOOD BAGS
Dr. K. C. Usha
Professor & Head
Dept. of Transfusion Medicine
Medical College
Trivandrum

2. BLOOD BAG
• Flexible
• Closed system
Device development - Physical, Biological and design requirements
Development and Selection of Material
Development work Process Development
Evaluation of Blood Bag

3. DEVELOPMENT & SELECTION OF MATERIAL
Components & Materials used
Bag - PVC unsupported sheeting
Donor tube - PVC tubing
Transfusion tubing - PVC Tubing
Transfusion Port - Injection moulded PVC
Needle Holder - PS/PP/PE
(PS – Poly styrene, PP – Poly propylene, PE - Poly ethylene)
Needle cover - PS/PP/PE
Needle - Stainless Steel
Clamps - PS/PP/ABS
(ABS- Acrylonitrite – Butadiene- Styrene Polymer)
Anti – coagulant - CPDA1/ACD
Packing Material - PE/PP/PVC film/Cardboard etc.
PVC sheeting - Critical requirements
Blood contacting Components- Non toxic, transparent, flexible

4. PROPERTIES OF BLOOD BAGS
• Should be FDA approved
• Sufficiently flexible
• Minimum resistance to filling & emptying
• Sufficient space to collect the volume of blood noted on the label
• Ideally vacuum
• Permissible air is 7 – 10 ml
• Transparent-Visual inspection of contents before and during blood collection,
during storage, during processing etc.
• Withstand centrifugal force up to 5000 g for at least 10 minutes.
• No distortion/ leaks after centrifugation
• Withstand strain (blood filled bag- fall from 5 feet height)
• Sufficient tensile strength
• Material for fabrication - weldable by conventional techniques
• Should be suitable to keep blood/ products at desirable low temperatures.
• Material should be biocompatible (Non toxic)
• Haemolytic potential within acceptable limits
• Sterile – even external sterility of bag to be assured

5. properties of blood bags contd…
• Bags once sterilised, not touched by human hand til the time of ue.
• Pyrogen free
• Anticoagulant clear, colourless
• Constituents of anticoagulant - within limits prescribed by ISO – 3826
• Container label must state volume and nature of anticoagulant and the
approximate quantity of blood to be collected
• 70% of RBC should be recovered 24 hours after transfusion
• Bag should be permeable to CO2 and O2
• Twist open and tamper evident transfusion port
• Shelf life of bag – minimum three years
• Pre donation sampling pouch – risk of bacterial contamination minimized.

6. TUBINGS
•Transparent
•Flexible
•No kink /leak
•Allow good flow of blood
Easily breakable
Valves if present
Should not break automatically during centrifugation
NEEDLE
Sharp, painless venepuncture
Stainless steel material
Size – 16 g
Needle penetration force - <20 gm force
Needle penetration force if > 20 gm force – venepuncture painful
Needle bevel smooth, should enable precise cutting
Prompt covering for needle
Needle firmly attached to tubing

7. PALSTICIZERS
• Plasticizer → PVC flexible
• DEHP - Commonly used
• Plasticizers migrate into biologic medium (leachability)
• With present technology, not possible to fully restrict leachability
• But leaching can be maintained at lower levels.
• Permissible leachable amount of DEHP is 0.25 mg / 100 ml / day
Temperature
Amount of DEHP leached Lipid content
Duration of contact
• Beneficial effect of leached DEHP on RBC membrane - maintains pliability –
increased viability and longer period of storage
• DEHP is carcinogenic
• Implicated in male sterility in animal studies
• DEHP produced a range of adverse effects on development of male reproductive
system ( animal studies)
• Precaution may be taken to limit exposure of developing male to DEHP

8. FACTORS INFLUENCING DEGREE OF RISK
1. Patient’s sensitivity to DEHP (Male foetus, male neonate, peripubertal
male)
2. Dose of DEHP received (Type of procedure, frequency and duration
of procedure)

9. DEVICES THAT CONTAIN DEHP PLASTICIZED
PVC
• Intravenous tubing
• Umbilical artery catheters
• Blood bags and infusion tubing
• Enteral Nutrition feeding bags
• Nasogastric tubes
• Peritoneal dialysis bags and tubing
• Tubing used in cardio pulmonary bypass procedures
• Tubing used in extra corporeal membrane oxygenation
• Tubing used during haemodialysis

10. PROCEDURES POSING HIGH RISK
• Exchange transfusion in neonates
•Total parenteral nutrition (TPN) in neonates (with lipids in PVC bags)
•Multiple procedures in sick neonates (High cumulative procedures)
•Haemodialysis in peripubertal males
•Hemodialysis in pregnant / lactating women
•Enteral nutrition in neonates / adults
•Massive infusion of blood in to trauma patient
•Coronary artery bypass graft surgery (CABG)
DEHP (LITTLE / NO RISK)
•Crystalloid fluids stored in PVC bags (Normal saline , Ringer lactate)
• Drugs that require a pharmaceutical vehicle for solubilisation stored in PV
bags

11. RECOMMENDATIONS
• Do not avoid life saving procedures because of possibility of health risk
associated with exposure to DEHP
• Substitute PVC devices that do not contain DEHP
• Devices made of other materials such as Ethylene Vinyl Acetate (EVA),
Silicon, Poly ethylene, Polyurethane.
• Minimise DEHP exposure by using freshest possible blood
• Report adverse events to FDA
• SMDA – Safe Medical Devices ACT of 1990
• Report deaths/injuries associated with these devices to manufactures /
Medwatch, the FDA’s voluntary reporting authority

12. Physical
STORAGE LESIONS
Chemical
Physical changes
•Morphologic changes in cytoskeleton, surface membrane and integrity of antigens
•RBC shape – biconcave disc becomes spherical due to loss of membrane lipid
•Increased viscosity
•Microaggregates
•Decreased deformability
•Increased osmotic fragility

13. Chemical changes
•Storage temperature of RBC/whole blood is 1-60 C
•Normal pH of CPDA1 is 5.6
•When mixed with blood pH becomes 7.1
•On storage pH decreases, acidity increases
•Normal Concentration of K 3.5 – 5 meq /L in plasma and 100 meq/L in RBC.
•On storage plasma K increases, RBC K decreases
•Plasma Na decreases and RBC Na increases
•Stored bank blood totally free of ionic calcium
•Increased plasma Hb levels
•Decreased viability of RBC
•Decreased 2-3 DPG content
•Decreased ATP levels
•Volume of plasma influences metabolism, pH and lactate generation
•Composition, size and surface area of containers influence Oxygenation and
metabolism
•Platelets with increased metabolic activity produces increased lactic acid
•Hence on platelet storage pH decreases, acidity increases
•Platelets release granules – function less

14. Storage lesion in a typical unit of CPDA – 1 Red Blood Cells
DDaayyss ssttoorreedd aatt 4400CC
00 77 1144 2211 2288 3355
HHeemmaattooccrriitt ((%%)) 7755 7755 7755 7755 7755 7755
ppHH 77..0044 66..9922 66..8800 66..6655 66..88 66..5555
PPllaassmmaa gglluuccoossee
228844 221111 116655 113311 9999 7788
((TToottaall mmgg))
PPllaassmmaa HHbb((TToottaall
mmgg))
2266 3388 7733 114433 224477 333344
PPllaassmmaa KK ((TToottaall
mmeeqq
00..33 44..11 55..44 66..22 66..77 77..22
PPllaassmmaa NNaa
((TToottaall mmeeqq))
1122..11 88..88 77..88 77..11 66..66
PPllaassmmaa
AAmmmmoonniiaa ((TToottaall
μμggmm))
9900 444422 668833 888822 11112233 11339999
TToottaall cciittrraattee
((ggmm))
00..4433 00..4433 00..4433 00..4433 00..4433 00..4433

15. DEVELOPMENT OF BLOOD BAGS IN INDIA
• Growth of fungus (problem)
• Solved by inhouse research and development efforts
• Novel technologies used for sterilisation and post sterilisation practics
• Quality Control at each and every stage of manufacture
• Bags should confirm to International standards such as ISO- 3826
• Requires high levels of technological excellence
•Permeability of bag to O2 and CO2 very essential to maintain viability and shelf
life blood/product
• Platelets with high metabolic rate require special containers

16. NEWER TRENDS
1. Improved phthalate plasticizers
- Solubility lesser than DEHP
- Used to make medical grade PVC compounds
- Eg:
a. Di (n – decyl) phthalate – DNDP
b. Di (Iso – decyl) Phthalate – DIDP
c. Di (IsoNonyl) phthalate – DINP
2. Non – DEHP plasticizers
More soluble
Citrates
Protective influence on RBC like DEHP
N – Butyryl Tri (n – Hexyl) Citrate – BTHC
BTHC very similar to DEHP
Low toxicity
BTHC
Metabolic products physiologically harmless
- Metabolic product of BTHC – Citric acid, Butyric acid and Hexanol
- PVC plasticized with BTHC- protective influence on RBC membrane
- High cost of citrate - problem

17. 3. Tri mellitates
•Tri (2-Ethyl Hexyl ) Trimellitate – TEHTM
•Preferred plasticizer
•No protective effect on RBC membrane
•Bags plasticized with trimelliate have sufficient O2 – CO2 permeability
•Suitable for extended storage of platelets for at least 5 days
•Advantage – Low migration, low volatility, non toxicity
4. Adipates
•Di (2-Ethyl Hexyl) adipate - DEHA and other polymeric adipates
•Used as plasticizer for PVC for medical application
•Alternative softeners can be used but need detailed testing and statutory
approvals

18. 5. Non PVC containers for Medical Application
•Blood bags made of modified poly olefines (eg PL – 732 plastic)
•Allow storage of platelets for 7 days
•Higher permeability characteristics
•Even polyolefines give off leachable materials
•Poly ethylene releases high molecular weight oligomers
•Poly propylene releases low molecular weight oligomers
•PL – 732 is not found suitable for storage of whole blood/ RBC concentrate
•M/s. Baxter Health care Corporation (USA) inroduced Blood bags made of modified
poly olefins (PL-732 )
•Compared to PVC bags polyolefine bags are less brittle at -800C and during
shipping
•Modification of ethylene propylene blends with linear rubbery polymers (EPDM)
give tough polymers (autoclavable) with good permeability characteristics

19. Contd….
Use of constrained geometry catalysts (Metallocenes) for making polyethylene
results in material with following characters
•Good heat stability
•Toughness
•Tear and punture resistance
•Softness
•Flexibility
•Printability
•Embossability
•Sterilizable by steam
M/s. Ferro Corporation (USA) developed a specially formulated poly olefine
alloy – RXLOY
•Weldable
•Sterilizable with steam
•Having high clarity
•Low extractability
•Excellent barrier properties
M/s. Cryovac introduced a polyester modified Polypropylene as a multi layer
film (M – 312 film)

20. FUTURE OF BLOOD BAGS BASED ON
PLASTICIZED PVC
• Will take some time before commercial availability of new materials
• Even when available, may need substantial modifications in technology of
fabrication of blood bags and component storage containers.
• Meanwhile PVC will continue to rule the market
• It is because of PVC’s clarity, flexibility, toughness, permeability and
adaptability to be formed into diverse shapes by high frequency
• PVC has proven track record of safety in actual use for more than 44 years

21. Thank you