Dr' K' C' Usha

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

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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 - Stai
nless 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
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• 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

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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.

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• 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 - lt20 gm force
• Needle penetration force if gt 20 gm force
  venepuncture painful
• Needle bevel smooth, should enable precise
  cutting
• Prompt covering for needle

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• 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

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• FACTORS INFLUENCING DEGREE OF RISK
• Patients sensitivity to DEHP (Male foetus, male
  neonate, peripubertal male)
• Dose of DEHP received (Type of procedure,
  frequency and duration of procedure)

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• 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

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• 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

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• 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 FDAs voluntary reporting
  authority

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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

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• 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

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Storage lesion in a typical unit of CPDA 1 Red
Blood Cells
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• 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

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• NEWER TRENDS
• Improved phthalate plasticizers
• Solubility lesser than DEHP
• Used to make medical grade PVC compounds
• Eg
• Di (n decyl) phthalate DNDP
• Di (Iso decyl) Phthalate DIDP
• 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

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• 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

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• 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

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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)

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• 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 PVCs 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

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Thank you