Our 22nd Year of Publication
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Cover Story

The Introduction Of Non DEHP Plasticizers And Its Impact On Blood Transfusion Technologies

Dr. C. S. B. Nair
Technical Advisor
Terumo Penpol Ltd.

DINCH and DOTP are plasticizers available in commercial quantities at high purity levels. Both have a very safe toxicological profile, low solubility in water and are fully compatible with PVC.

These plasticizers have the potential to replace DEHP, in Blood bags for the collection and storage of blood and blood components, for tubings, containers and devices for medical applications and for apheresis procedures.

The replacement of DEHP would therefore solve a major problem in blood transfusion, thereby making Blood transfusion safer and more effective. Technical developments to this effect are at an advanced stage in Europe, India and Japan.

With the rapid developments in the field of Medicine and Surgery, blood transfusions have become an integral part of hospital procedures. Modern medical practice increasingly relies on the use of components of blood such as red blood cells, platelets, granulocytes, clotting factors, plasma, albumin and so on.

Transfusion Technology has undergone tremendous changes from the latter part of the 19th Century. Notable advances have been made in the detection of bacterial and viral contamination in blood and blood products and for their inactivation, development of sophisticated filters for the removal of leucocytes and other blood components and in apheresis technologies which is a fast developing field with great possibilities.

Yet another development which will have great impact in the technology of blood bags and medical products is the likely replacement of the phthalate plasticizers such as DEHP, which have certain undesirable effects, with non-phthalate plasticizers.

Interest in the field has been rapidly growing. The countries of the European Union have been particularly active in this field and have developed DINCH plasticized blood bags for the storage of RBCs, platelets and blood plasma.

M/s.TerumoPenpol has been a pioneer in this field since 2002. They have shown the possibility of replacement of DEHP with the BASF plasticizer HexamollDINCH for the collection and storage of whole blood. RBCs, Platelets and blood plasma. Another non DEHP plasticizer which has shown promise for the storage of blood and blood components in studies conducted at Terumo Penpol is Di-Octyl Terephthalate (DOTP).

The Introduction of plastic bags for the collection of blood and blood components

The first blood bag was invented by Dr. Carl Walter in 1947 which was made using poly vinyl chloride polymer plasticized with dioctyl phthalate (actually di, 2-ethyl hexyl phthalate - DEHP). The selection of this plasticizer was an uncanny achievement bordering on the miraculous because of its excellent plasticizing characteristics for PVC which conferred most desirable physical characteristics and ability to enhance the storage quality of blood and more particularly the red blood cells. DEHP remains the plasticizer of choice even now.

The collection, separation and administration of blood and blood products were done exclusively in glass bottles till the year 1970, even though PVC plasticized bags were used experimentally during the Korean War in order to prevent wastage of blood stored in glass bottles during air dropping operations to forward areas.

Benefits of DEHP Plasticized PVC Containers for the Collection and Storage of Blood and Blood Components

Plasticized PVC containers have a number of advantages which makes it ideal for the medical and more particularly for blood contact applications. The plasticizers used in the compounding of PVC plays the main role for building in the desirable characteristics such as low toxicity, transparency, flexibility, mechanical strength, elongation, stability at low and high temperatures, permeability to water, oxygen and carbon dioxide. A wide range of plasticizers do meet these requirements, for food contact, and medical devices. For contact with blood and blood products, however, the choice of plasticizers is very much restricted. The plasticizers Di, 2-ethyl hexyl phthalate (DEHP) offers all the benefits of overall performance, ready availability at high purity levels and cost effectiveness.

DEHP has the unique ability to reinforce red blood cell membranes, thereby reducing the development of brittleness on storage and consequent lysis of red blood cells. This remarkable protective effect seems to be a characteristic of phthalates in general. Possibly, the structure of phthalate with a hydrophilic aromatic ring and two hydrophobic tails enables them to replace defects in the RBC bilayer skin consisting of phospholipid molecules which are characterized by a hydrophilic end group with two hydrophobic chains.

Recent observations, however, seem to indicate that the harmful effects of DEHP may, in fact, be due to the mono ethyl hexyl phthalate (MEHP) which is formed by the hydrolysis of DEHP during processing.

The Leaching of DEHP into Blood and Blood products

DEHP is not covalently bonded to PVC and so could migrate out of the plastic into aqueous media particularly in the presence of solubilizing lipids, lipoproteins and albumin. In 1970 Jaegar and Rubin reported that DEHP leached into blood and blood products, when these were stored within blood bags plastized with DEHP.

This observation caused an avalanche of studies on the effect of the leached plasticizer on patients and possible harmful effects therefrom. There are over 3000 research papers covering every aspect of this problem. Very comprehensive and critical assessments on the massive research data and information available for vulnerable groups of people have been made. The present position is that the DEHP leached out from medical devices is of concern particularly to prenatal male babies, male new borns, young males and patients who need frequent blood donations and/or dialysis including exchange transfusions or extra corporeal membrane oxygenations.

Storage of Platelets

The metabolism of platelets, unlike that for RBC, follows a predominantly aerobic pathway. Hence containers for their collection and storage should have higher permeability to oxygen and carbon dioxide. Platelets can be stored with reasonable post transfusion recovery and survival for upto 72 hours in DEHP plasticized PVC bags. DEHP is not considered the best plasticizer for platelet storage bags. Non DEHP containers such as TEHTM, BTHCplasticised PVC containers and modified Poly olefin containers (Baxter) are preferred for better efficiency of storage.

Storage of Blood Plasma

Blood Plasma contains over ten million immunoglobulins and thousands of plasma proteins. Plasma proteins are needed for patients suffering from antibody deficiencies and hemophiliacs.

Frozen plasma is a stable product which can be stored for ten years. It can also be stored in dry form. Blood plasma should be collected and stored in containers which donot have leachable materials such as DEHP.

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