A comparative study done at Terumo Penpol showed that TEHTM and DINCHplasticised PVC containers could be used for the storage of blood plasma for more than one year without deterioration.

Developments in apheresis

The novel approaches and techniques in apheresis, have developed into a major revolution in blood transfusion. Remarkable advances have been made in wide ranging fields such as sophisticated on line centrifugal techniques, electronic sensing and control, specially designed plastic containers, equipment, disposables and software programs. It is now possible to donate RBCs, platelets, blood plasma and granulocytes under apheresis.

A great advantage in plateletpheresis is that donors may donate up to 4 to 6 units of platelets per donation. Another plus point is that donations could be made more frequently with an interval of at least two days. This method is commonly used to supply HLA matched platelets to patients who have become HLA sensitized and require platelets from a single donor whose HLA type matches theirs.

Therapeutic apheresis is another developing field with wide ranging possibilities. The object of the system is to remove a pathologic element from blood such as myasthenia gravis, red cells in sickle cell anemia, leucocytes in hyper leukocytosis, or platelet in marked thrombocytosis.

The preferred plasticizer used in PVC for making blood bags for the collection and storage of blood and blood components tubing’s, accessories for apheresis operations and medical devices continues to be DEHP. The consequent harmful effects to patients and donors due to the DEHP leached into blood and blood products, which can go beyond acceptable tolerable daily intake, is a major problem which is calling for urgent solutions. All blood bag manufacturers, more particularly in the European Union are striving to find alternate safe plasticizers. M/s.TerumoPenpol has made significant contributions in this field.

Developments in Europe to control DEHP contamination of blood products

The harmful effects of DEHP have been well realized in European Countries and they had taken the initiative to ban its use in the foods and industry. Its use in the medical care field still continues, owing to the non-availability of a plasticizer which could match the benefits of DEHP particularly for RBC storage.

The persistence to degradation of DEHP plasticized PVC in the environment has also been causing great concern. Incineration of PVC causes the release of dioxins, greenhouse gases and hydrochloric acid. When used as landfill, PVC additives, particularly the heavy metals leach out into water bodies and contaminate drinking water sources. Because of these factors there is a strong move in Europe to replace both DEHP and PVC.

A broad consortium of healthcare suppliers and clinicians in Scandinavia consisting of the Swedish Green Chemistry Research Institute - Jegrelius, Finnish Medical Packaging film extruder - Wipak, medical tubing manufacturer - Totax (Denmark), Polyolefin compounder - Mellitek (Denmark), and the Italian Blood Bag manufacturer - Haemotronic plan to develop “PVC free Blood Bags”. The leading Swedish Hospital - the KarolinskaUniversity Hospital have offered to test the blood bags for compliance with standards.

The technical specifications needed for the first prototype is proposed to be based on the multilayer polyolefin system created in the USA but not yet commercialized. M/s. Lubrizol is reported to be developing a polyurethane based formulation to replace PVC. The prototypes are expected to be ready by March 2016.

Non Phthalate Plasticizers under development

1 Di-isononyl cyclohexane dicarboxylate (Hexamoll® DINCH®)

M/s.BASF marketed their plasticizer Hexamol® DINCH in the year 2002. M/s. TerumoPenpol was the first company to initiate studies for using this plasticizer for blood bag applications. They showed that DINCH plasticized PVC containers could store whole blood for up to 35 days, RBC concentrates with SAGM for 35

days, platelet concentrates prepared by the PRP method for six days and blood plasma for an year. This was followed by a comparative study of DINCH plasticized PVC bags and TPL’s standard TEHTM plasticized platelet storage bags. DINCH plasticized bags could maintain the platelets in viable state for six days.

In a further modification, Ultra High Molecular Weight PVCof K value over 90 plasticized with DINCH was found to have higher permeabilities to oxygen and carbon dioxide and bags made with this compound could store six units of platelets prepared by the buffy coat method for more than seven days in 1.2 litre capacity bags.

DINCH plasticized bags could be used to store blood plasma for an year without deterioration of the viability of coagulation factors. Studies on the storage of RBC concentrates for at least 42 days are in progress. Some countries in the European Union have evinsed keen interest to develop DINCH plasticized PVC bags for the storage of blood components. Blood bags meeting guidelines are - Platelet storage bags for single unit platelets (Fresenius Kabi), RBC concentrates (MacoPharma) and for the storage of blood plasma (MacoPharma).

2 Di, (2- ethyl hexyl) Terephthalate (DOTP)

This plasticizer has been developed and is marketed by M/s.Eastman Chemcials, USA under the name Eastman 168. It has been in use for making tubes and devices used for food contact and medical devices and for various other commercial purposes.Recently M/s Eastman has introduced a higher purity DOTP under the name Eastman 168 SG DOTP has been under study at TPL for making blood bags and blood contact applications since 2010.DOTP plasticized PVC bags could be used for storage of whole blood for 35 days and single unit platelets for 5 days. RBC concentrates in SAGMshowed increase in haemolysis beyond 35 days. Studies to enhance the performance of DOTP plasticized bags are in progress.

Studies in Progress

Studies are in progress at M/s Terumo Penpol, India and in other countries to improve the storage performance of RBCs by the use of more effective RBC preservative solutions, and by improvements in technology. Studies are also in progress for improvements in the storage of platelets, blood plasma, cord blood collection, other blood components and in apheresis.

References:-

• Walter C.W. The use of the plastic blood containers. Panel VIII. Proceedings of the conference on the preservation of the formed Elements and of the proteins of the blood. University Laboratory of physical chemistry, Harward Medical School, Jan. 6, 1949.

• “The selection of plastic Materials for Blood Bags”. Transfusion Reviews. Jan. 1993, Vol. VII, No.1 pages 1-8.

• Indian Patent Application. 6, Feb 2006 (To Terumo Penpol Ltd.)

• Indian Patent Application. 10, June 2006 (To Terumo Penpol Ltd.)

• BASF Customer Workshop, Mumbai 2007

• Report of the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) 6, Feb 2008.

• Indian Patent Application, 23 Dec. 2008 (To Terumo Penpol Ltd.,)

• Hexamoll DINCHplasticized PVC containers for the storage of platelets. Asian Journal of Transfusion Science 2011.Vol.5, Issue 1,pp 18-22

• Commercially available Blood Storage Containers Browse et al, Vox. Sanguinis, 2014, 106

• Studies on the Storage of Pooled Platelets in non DOP PVC containers. International Journal of Pharma and Bio Sciences, Jan.2014, p-520 – p-531.