The Development of Blood Bags
Blood transfusion became safe,
dependable and convenient and a result of three important developments – the
landmark discovery of blood groups by Prof. Carl Landsteiner (1900), the safety
and effectiveness of citrate for intra venous administration by Hustin (1914)
and the development of the anticoagulant solution ACD. Modern blood banking,
however, was initiated with the pioneering work of development of PVC bags for
blood collection and storage started by Prof. Carl W Walter of Harvard Medical
School in 1947. He had to face several problems in developing his design to a
commercial product. After extensive clinical trials conducted in the USA, he
finally got permission to manufacture this item in 1962.
Plasticised PVC containers
possess a number of advantages which makes it the material of choice for medical
and more particularly for blood contact applications. Its more important
features are: ability to be welded together by high frequency – which enables
the production of leak-free products and offers infinite design possibilities,
steam sterilisability even at 121oC, its favourable cost/performance ratio and
its low bulk density offering low storage and distribution costs. The
plasticisers used in the compounding of PVC is mainly responsible for building
in the desirable characteristics for medical applications such as low toxicity,
transparency, flexibility, strengths, elongation, stability at low and high
temperatures, permeability to water, oxygen and carbon dioxide in the desired
range. While a wide range of plasticisers are available, for food contact and
medical applications, the choice for blood contact applications is very limited.
The principal plasticiser used is di, (2-ethyl hexyl) phthalate (DEHP) which
offers the benefits of overall performance, ready availability at high purity
and cost effectiveness.
The Migration of the Plasticiser DEHP into Blood and
Blood Products and its Effects
DEHP is not covalently bonded
to PVC and so could migrate out of the plastic. This is particularly so in the
presence of solubilising lipids, lipoproteins and albumin. Jaegar and Rubin
(1970) reported the leaching of DEHP into stored human blood. Several studies
conducted subsequently demonstrated the extractability of DEHP from PVC blood
bag into whole blood, platelet concentrates and plasma during storage. Concern
have been expressed about the adverse effects of DEHP leached into blood and
blood products and extensive studies have been made to assess every facet of the
problems reported including excellent reviews. PVC materials plasticised with
DEHP have been used in patient health care for over 50 years and there are over
3000 published papers discussing its potential toxicological hazards. A recent
report by Dr Everett Koop (June 1999) former Surgeon General and Chairman of an
expert panel convened by the American Council on Science and Health, sums up the
present position succinctly "DEHP in medical devices is not harmful to even
highly exposed people, those who undergo certain medical procedures such as
regular haemodialysis, or extra corporeal membrane oxygenation. The panel
concluded that "DEHP imparts a variety of important physical
characteristics that are critical to the function of medical devices and
eliminating DEHP in these products could cause harm.
The Collection and Storage of Platelet Concentrates
DEHP Plasticised PVC
It is now well established that
platelets could be stored with reasonable post transfusion recovery and survival
for up to 72 hours in DEHP plasticised blood bags. In an earlier study, it was
demonstrated that thin walled DEHP plasticised PVC containers behaved better
indicating thereby that higher oxygen and carbon dioxide permeabilities were
desirable.
The effect of DEHP plasticiser
on stored platelets was studied by Zoltan Racz and Clara Baroti (1995). They
found that :
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Platelet aggregation was the only parameter that was
slightly inhibited in DEHP plasticised bags indicating that the presence
of DEHP had no harmful effect during storage.
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Platelets from 400 ml donor blood could be stored in
DEHP plasticised bags meant for storage of platlets from 450 ml of blood
without deterioration. Such platelets were not inferior to platelet
concentrates stored for 5 days in PL 732 (Polyolefin) or PL 1240 (BTHC)
containers.
These studies indicate that
DEHP plasticised bags could be used for platelet storage if higher
permeabilities are ensured.
In vitro studies showed that
DEHP reduced platelet functions such as aggregation responses and the percentage
of hypotonic shock responses. It also prevented morphological changes in
platelets which are frequently seen in TOTM and BTHC plasticised PVC bags. These
changes have been explained on the basis of the DEHP leached into the plasma
stabilising platelet membrane and thereby preventing changes as in the case or
RBC.
Trimellitate Plasticised PVC
Grode et al studied the storage
of platelet concentrates in PVC bags plasticised with tri octyl tri mellitate
plasticiser and showed that such bags possessed sufficient gas permeability to
be suitable for extended storage of platelets for at least 5 days. They also
found a 30 fold reduction in plasticiser accumulation in platelet concentrates
as compared to DEHP plasticised bags. Studies made subsequently confirm that
such bags may be used for storing platelet concentrates for at least 5 days at
22oC. While TOTM plasticised containers were found satisfactory for storage of
most platelet concentrates, it may be desirable to use more permeable containers
if platelet yields are routinely very high.
A distinct advantage ofTOTM is its low
migration and volatility characteristics. Baxgter Health Care Corporation,
USA (PL-1240), M/s Cutter Laboratories, USA (CLX), M/s Tuta Laboratoties,
Australia and others have been using TOTM as plasticiser for platelet storage
bags.
BTHC plasticised PVC
Blood bags made with n-butyrul, tri n-hyxyl
Citrate plasticisers have been shown to be effective for storing platelets and
their behaviour is similar to TOTM plasticised bags. Measurements of pH, pO2,
pCO2, glucose, lactate, ATP, total adenine nuecleotide, lactate dehydrogenase
and platelet factor-4 )pF4) showed similar results for BTHC and TOTM plasticised
bags during five day storage of platelets. Results of in vivo studies were
similar.
An interesting observation, however, has been
made that while statistically significant higher values have been obtained for
BTHC plasticised containers than for TOTM, for pH, pO2, amd g;icpse/ The jogjer
pH levels obtained for BTHC is similar to the high pH levels observed during the
storage of platelets in blow moulded polylefin bags which have high
permeability. This observation indicates that while BTHC and polyolefin
containers ensures sufficient oxygenation to maintain an aerobic metabolism, the
carbon dioxide permeability is too high and allows too much escape of the gas as
indicated by the low pCO2.
Modified Polyolefins
This material introduced by M/s
Baxter health Care Corporation, USA (PL-732 Plastic) is suitable for the storage
of platelets for up to 7 days because of its higher gas permeability. However,
aberrant morphology has been observed after 2-3 days. The actual composition of
the plastic is not disclosed. It is reported to be free of plasticisers but
possibly it contains an antioxidant to prevent oxidative deterioration. Even
polyolefin materials have been shown to give rise to leaching. Thus
polypropylene releases many low molecular weight oligomers while polyethylene
releases higher molecular weight oligomers.
Di, n-decyl phthalate plasticised PVC (DnDP)
M/s Trumo Corporation, Japan
has developed a new PVC blood bag (X-331S) incorporating a less leachable
phthalate ester – di, n-decyl phthalate (DnDP) which has better has
permeabilities. The leachability of this plasticiser into plasma is 1/80th that
of DEHP. The LD50 values of DnDP is around ten times that of DEHP. This makes
DnDP more than 800 times safer than DEHP. The new bag has been shown to be
suitable for the five day storage of platelet concentrates....[More]
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