Asian Journal of Transfusion Science
Home About Journal Editorial Board Search Current Issue Ahead of print Back Issues Instructions Subscribe Login  Users: 391 Print this page  Email this page Small font sizeDefault font sizeIncrease font size 


 
ORIGINAL ARTICLE Table of Contents   
Year : 2011  |  Volume : 5  |  Issue : 1  |  Page : 18-22
Hexamoll DINCH plasticised PVC containers for the storage of platelets


1 Consultant, R&D Center, Terumo Penpol Ltd, Trivandrum, Kerala, India
2 Deputy Manager, R&D Centre, Terumo Penpol Ltd, Trivandrum, Kerala, India
3 Senior Executive, R&D Centre, Terumo Penpol Ltd, Trivandrum, Kerala, India

Click here for correspondence address and email

Date of Web Publication21-Jan-2011
 

   Abstract 

Introduction : Containers for the storage of platelets are made using polyvinyl chloride plasticised with di, (2-ethyl hexyl) phthalate, n-butyryl, tri (n-hexyl) citrate and tri (2-ethyl hexyl) mellitate or using special poly olefins without plasticiser. Of these, the first two have disadvantages such as plasticiser leaching and impairment of platelet function. Polyolefin bags cannot be HF welded or steam sterilized. Mellitate plasticised bags can store platelets well for five days but they are not completely phthalate free. Research and Development: We have developed a new generation of containers made of PVC plasticised with the non DEHP, non aromatic plasticiser,1,2- Cyclohexanedicarboxylic acid, diisononyl ester (Hexamoll DINCH) which can store platelets without loss of function for at least six days. Observation: The present studies show that DINCH plasticised PVC bags (TPL-167) are well suited for the storage of platelet concentrates for more than five days. Conclusion: The present studies show that the PVC plasticised with the non phthalate, non aromatic, non toxic plasticiser DINCH is a viable alternative to other existing containers for the storage of platelets for more than five days.

Keywords: Hexamoll DINCH plasticiser, Non DEHP plasticizer, platelets, platelet storage bags

How to cite this article:
Bhaskaran Nair C S, Vidya R, Ashalatha P M. Hexamoll DINCH plasticised PVC containers for the storage of platelets. Asian J Transfus Sci 2011;5:18-22

How to cite this URL:
Bhaskaran Nair C S, Vidya R, Ashalatha P M. Hexamoll DINCH plasticised PVC containers for the storage of platelets. Asian J Transfus Sci [serial online] 2011 [cited 2021 Oct 21];5:18-22. Available from: https://www.ajts.org/text.asp?2011/5/1/18/75972



   Introduction Top


Platelet concentrates have a very important role in ensuring adequate hemostasis under various clinical situations and have made possible notable advances in the medical and surgical fields. In consequence, the demand for uncontaminated viable platelets, preferably with improved storage periods is rising rapidly.

Platelets get 85% of their energy requirements by aerobic metabolism in which glucose undergoes glycolysis followed by oxidative phosphorylation of the products. Substrates such as free fatty acids and amino acids are also involved in the process. The residual 15% of the energy requirements are met by anaerobic glycolysis in which glucose is converted to lactate. The conversion of glucose to ATP by the oxidative mechanism is 18 times more efficient than anaerobic glycolysis. The carbon dioxide produced during the oxidative pathway gets converted to bicarbonate which acts as the buffer system of plasma. The containers in which platelets are stored should be carefully crafted to maintain the oxidative metabolism of the platelets. This can be achieved only if the permeability to oxygen of the containers is high. At the same time, the permeability to carbon dioxide should be high enough to permit a good part of the carbon dioxide to diffuse out but it should not be very high which would cause too much of the carbon dioxide formed to leave the container, thereby compromising the production of the bicarbonate buffer.

The first generation containers for storing RBC and platelets were made of PVC plasticised with DEHP {di-(2- ethyl hexyl) phthalate}. DEHP continues to be the plasticiser of choice for blood bags for the storage of RBCs particularly because the DEHP leached into blood plasma has a distinct protective effect on the RBC membrane which enables storage of RBC concentrates for up to 42 days. Several studies have, however, shown that leached DEHP has deleterious effect particularly for newborns, very young children and patients who require frequent blood transfusions. Hence, there is a strong move to replace DEHP with other plasticisers. DEHP-plasticised PVC containers have comparatively low permeability to oxygen and carbon dioxide and this restricts the storage period for platelets. [1],[2],[3] The leached DEHP also causes reduced aggregation responses of platelets. [4] The second generation bags overcame the permeability problem by using thinner sheets of PVC plasticised with DEHP [Teroflex XT-612 (Terumo)], and by using the plasticiser TOTM (CLX, Cutter), PL-1240 (Baxter). M/s Baxter also developed special polyolefin bags without plasticiser (PL-732). Platelet concentrates could be stored in such bags for up to five days with better preservation of function and viability. [5],[6],[7],[8],[9],[10],[11]

PVC plasticised with nbutyryl tri-(n-hexyl) citrate (BTHC) was introduced in 1989. Such bags have been shown to be acceptable for the storage of platelet concentrates and RBC. [12],[13],[14],[15] M/s Terumo Corporation introduced a new PVC bag which was plasticised with di-(ndecyl) phthalate [16] which had very low leachability into blood plasma and was suitable for the five day storage of platelet concentrates.

The platelet storage bags in present day use have shortcomings such as phthalate contamination, compromised platelet aggregation, unpleasant odour and allergic reactions.

A new generation of PVC-based platelet storage bag [TPL 167] was developed in 2006 by M/s Terumo Penpol Ltd [17],[18] in which the non DEHP, non aromatic plasticiser 1,2-cyclohexane-di carboxylic acid, diisononylester subsequently referred to as DINCH, was used. These bags were comparable to TPL's standard TEHTM plasticised platelet storage bag (TPL-157) and other well-known platelet storage bags plasticised with TEHTM.

A second comparative assessment of TPL's DINCH and TEHTM plasticised platelet storage bags was done at the Apollo Hospital, Chennai.

The results of these studies are presented in this paper:


   Materials and Methods Top


The platelet storage bags used for the study were as follows.

Bags evaluated

These bags were part of top and bottom quadruple bag systems consisting of:

  • Main bag - 450 ml
  • SAGM bag - 400 ml containing 100 ml SAGM solution attached to the bottom of the main bag.
  • Platelet storage bag - 400 ml (xperimental bag)
  • Transfer bag - 400 ml.


Characteristics of test bags

The characteristics of the material of the test bags are given in [Table 1]. The bags were also tested for physical, chemical and biological requirements for conformance with the ISO 3826 standard for blood bags.
Table 1 :Characteristics of sheets used in this study

Click here to view


Blood collection and component separation

Blood of the same blood group was collected from four volunteer donors in SB 450 bags containing CPD and was kept without disturbance at room temperature for 1 h. The blood was pooled in a 2L capacity Terumo pooling bag using Terumo's sterile tube sealing device (TSCD). The blood was mixed by gentle tilting. 450 ml lots of the mixed blood were then transferred into the main bags of the two QB blood bag systems (as described earlier) using TSCD. Separation of the components was done by the Buffy coat method. After a holding time of 1 h, the bags were centrifuged at 3300 rpm for 13 min at 20°C in a Hitachi Rotosilenter 630 RS centrifuge.

Three layers separated as follows:

  • Top layer of platelet poor plasma
  • Middle layer of Buffy coat
  • RBC concentrate


PC preparation

The RBC concentrate was transferred to the bottom bag containing 100 ml of SAGM solution and the plasma was transferred to the corresponding plasma bag. These bags were separated after sealing off the connecting tube. The Buffy coat rich in platelets remained in the main bag. It was kept suspended for 24 h at 20 - 24°C. This bag was given a soft spin at 600 rpm for 5 min at 20°C and the separated platelet concentrate was transferred to the platelet bag under test. The platelet volume was adjusted to 70 ml by the addition of plasma. The platelet bags were stored in a platelet agitator with horizontal shaking at 22°C ± 2°C. PC samples were drawn on zero, one, three, five and seven days after separation to components and the holding time of 24 h.

Parameters studied

  1. RBC count, leucocyte count and platelet count

    These were measured using the automatic blood cell counter Beckman LH 750- 5 part differential cell counter.
  2. pH, pO 2 , pCO 2 , HCO 3

    These were measured using blood gas analyzer model Bayer, Rapid Lab 248.
  3. Lactate

    Measured using Hitachi - 911 UV spectrophotometer.
  4. Glucose, plasma Na + and K +

    Measured using L X 20 procedure in an automatic analyzer.
  5. Aggregation


PC in which the number of platelets was adjusted to 2.5 lakhs/μl with fresh frozen autologous plasma was measured at the maximum aggregation induced by collagen at a concentration of 16 μg/ml (8 μl per test) and ADP at a concentration of 80 μmol/ml (40μl per test). Chrono -Log platelet aggregometer was used for the measurements.


   Results Top


Results of platelet storage evaluation studies conducted at Apollo Hospital, Chennai are given below.

Hematological studies

The results of hematological studies are shown in [Table 2]. The platelet counts per experimental bag were in the range 5.1 to 9.2 × 10 10.
Table 2 :Hematological studies

Click here to view


Biochemical studies

The results of biochemical studies are shown in [Table 3].
Table 3 :Biochemical studies on stored blood

Click here to view


pH, pO 2 , pCO 2

pH was above 7.0 in all cases. The partial pressure of oxygen increased throughout preservation, while the partial pressure of carbon dioxide showed a gradual reduction. No significant differences were observed for both groups with regard to these parameters. It is clear that an oxidative atmosphere was maintained during the period of storage in both cases.

Glucose and lactic acid

The utilization of glucose during storage was similar in samples TPL - 157 and TPL -167.

The lactate level was comparable up to the fifth day above which increase was more marked for TPL - 157.

Bi carbonate

Decrease in bicarbonate is similar for the two samples studied.

Plasma K + , Na +

Plasma K + and Plasma Na + remained fairly stable throughout the preservation.

LDH

LDH showed a slightly increasing pattern for both the samples.

The results are similar up to five days. Beyond five days, the DINCH plasticised bags appeared to be marginally better.

Aggregation studies

The aggregation obtained for the various samples with ADP and collagen are given in [Table 4]. The results show that the aggregation was maintained well for more than five days.
Table 4 :Platelet aggregation studies on platelets stored in the test bags

Click here to view



   Discussions Top


The pH of plasma within both types of bags remained above 7.0 indicating good storage conditions. The pattern of pO 2 change indicates adequate oxygenation of the containers. The HCO 3 level is indicative of the presence of adequate buffer and stability consequent on the maintenance of optimum level of pO 2 within the containers. The lactate production was within limits and comparable for the DINCH and TEHTM plasticised bags up to the fifth day, beyond which it increased significantly for the TEHTM bags. Platelet aggregation, which is an indication of platelet function, was reasonably well maintained for more than five days. It may be noted that the Buffy coat was stored for 24 h before the platelets were separated indicating one more day of storage for platelets.

The overall pattern indicates that platelet concentrates are well preserved in DINCH plasticised containers for more than five days. The results of the present study clearly show the suitability of DINCH plasticised PVC containers to preserve the function and viability of platelets in the medium concentration range. Further studies are necessary to define the range of platelet concentration which could be used, the morphology changes and the in vivo evaluation of platelets stored in the new type of platelet storage bag.


   Conclusions Top


The present studies show that the PVC plasticised with the non phthalate, non aromatic, non toxic plasticiser DINCH is a viable alternative to other existing containers for the storage of platelets for more than five days. The bags have very low odour, are non allergenic, and have low leachability into blood plasma.


   Summary Top


The present studies show that DINCH plasticised PVC bags (TPL-167) are well suited for the storage of platelet concentrates for more than five days.

The well-accepted platelet storage bags at present are made from special polyolefins and PVC plasticised with TEHTM or BTHC. These bags have shortcomings as pointed out earlier. DINCH plasticised PVC containers seem to be the best alternative. More studies are needed on the morphology changes and the in vivo evaluation of platelets stored in this new type of platelet bag.


   Acknowledgement Top


The authors acknowledge the help and guidance received from Dr. Rema Menon, Chief Medical Officer, Department of Transfusion Medicine, Apollo Hospitals, Chennai in the planning of the work and for supervising the studies at Apollo Hospitals.

We are greatful to Mr. C. Balagopal, Managing Director, Terumo Penpol for his keen interest in the development of non-phthalate PVC containers for the storage of blood and blood components and for his unstinted support for this programme.

 
   References Top

1.Slichter S, Harker L. Preparation and storage of platelet concentrates. J Haematol 1976;34;403-9.  Back to cited text no. 1
    
2.Simon TL, Murphy S. Normal viability of platelet concentrates obtained from CPDA-1 blood after storage in CL-3000 blood containers. Vox Sang 1982;43:20-2.  Back to cited text no. 2
    
3.Murphy S, Sayar SN, Gardener FH. Storage of platelet concentrates at 22°c. Blood 1970;35:549-57.  Back to cited text no. 3
    
4.Labow RS, Tocchi M, Rock G. Platelet storage - Effects of leachable materials on morphology and function. Transfusion 1986;26:351-7.  Back to cited text no. 4
    
5.Snyder EL, Bookbinder M, Kakaiya R, Ferry P, Kiraly T. Role of micro aggregate blood filtration in clinical medicine. Voz Sang 1983;45:432-7.  Back to cited text no. 5
    
6.Snyder EL, Koerner TAW, Kakaiya R, Moore P, Kiraly T. Effect of mode of agitation on storage of platelet concentrates in PL 732 containers for five days. Voz Sang 1983;44:300-4.  Back to cited text no. 6
    
7.Snyder EL, Ezckowitz M, Aster R, Murphy S, Ferri P, Smith E, et al. Extended storage of platelets in a new plastic container - Invivo response to infusion of platelets stored for five days. Transfusion 1985;25:209-14.  Back to cited text no. 7
    
8.Grode G, Miripol J, Garber J, Buchhotz DH. Extended storage of platelets in a new plastic container - Biochemical and morphological changes. Transfusion 1985;25:206-8.  Back to cited text no. 8
    
9.Murphy S, Kahn R, Holme S, Phillips GL, Sherwood W, Davisson W, et al. Improved storage of platelets for transfusion in a new container. Blood 1982;60:194-200.  Back to cited text no. 9
    
10.Hogge DE, Thompson BW, Schiffer CA. Platelet storage for seven days in second generation blood bags. Transfusion 1986;26:131-5.  Back to cited text no. 10
    
11.Simon TL, Nelson EJ, Murphy S. Extension of platelet concentrate storage to seven days in second generation bags. Transfusion 1987;27:6-9.  Back to cited text no. 11
    
12.Buchholz D, Aster R, Menitov J, Kagan L, Simon T, Heaton A, et al. Red cell storage studies in Citrate poly vinyl chloride container. Transfusion 1989;29:85.  Back to cited text no. 12
    
13.Buchholz D, Aster R, Menitov J, Kagan L, Heaton A, Kagan T, et al. Evaluation of a new citrate plasticised container for five day storage. Transfusion 1989;29:51S.  Back to cited text no. 13
    
14.Gulliksson H, Shanwell A, Wikman A, Reppucci AJ, Sallander S, Uden AM. Storage of platelets in a new plastic container. Voz Sang 1991;61:165-70.  Back to cited text no. 14
    
15.Turner VS, Mitchell SG, Kanu SK, Hawker RJ. A comparitive study of platelets stored in poly vinyl chloride containers plasticised with butyryl trihexyl citrate or tri ethyl hexyl trimellitate. Vox Sang 1995;69:195-200.  Back to cited text no. 15
    
16.Shimizu T, Kouketsu K, Morishima Y, Goto S, Hasegawa I, Kamiya T, et al. A new poly vinyl chloride blood bag plasticised with less leachable phthalate ester analogue, di-n-decyl phthalate, for storage of platelets. Transfusion 1989;20:292-7.  Back to cited text no. 16
    
17.Indian patent Application 254/CHE/2006 , To Terumo Penpol Ltd.  Back to cited text no. 17
    
18.Indian patent Application 1407/CHE/2008 , To Terumo Penpol Ltd.  Back to cited text no. 18
    

Top
Correspondence Address:
C S Bhaskaran Nair
Consultant, R&D Centre, Terumo Penpol Ltd, Trivandrum, Kerala
India
Login to access the Email id

Source of Support: Terumo Penpol, Conflict of Interest: None


DOI: 10.4103/0973-6247.75972

Rights and Permissions



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

This article has been cited by
1 Toxicity of Hexamoll® DINCH® following intravenous administration
Raymond M. David,Randy D. White,Michael J. Larson,Jay K. Herman,Rainer Otter
Toxicology Letters. 2015; 238(2): 100
[Pubmed] | [DOI]
2 Stoffmonographie für 1,2-Cyclohexandicarbonsäure-di-isononylester (Hexamoll® DINCH®) – HBM-Werte für die Summe der Metabolite Cyclohexan-1,2-dicarbonsäure-mono-hydroxyisononylester (OH-MINCH) und Cyclohexan-1,2-dicarbonsäure-mono-carboxy­isooctylester (cx-MINCH) im Urin von Erwachsenen und Kindern
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. 2014; 57(12): 1451
[Pubmed] | [DOI]
3 Synthesis and application of an alternative plasticizer Di(2-Ethylhexyl)-1,2-cyclohexane dicarboxylate
Yuanhui Ou,Xuejia Ding,Long Zhang
Journal of Applied Polymer Science. 2014; 131(2): n/a
[Pubmed] | [DOI]
4 A development and biological safety evaluation of novel PVC medical devices with surface structures modified by UV irradiation to suppress plasticizer migration
Yuji Haishima,Kazuo Isama,Chie Hasegawa,Toshiyasu Yuba,Atsuko Matsuoka
Journal of Biomedical Materials Research Part A. 2013; 101A(9): 2630
[Pubmed] | [DOI]
5 Screening study on hemolysis suppression effect of an alternative plasticizer for the development of a novel blood container made of polyvinyl chloride
Yuji Haishima,Tsuyoshi Kawakami,Chie Hasegawa,Akito Tanoue,Toshiyasu Yuba,Kazuo Isama,Atsuko Matsuoka,Shingo Niimi
Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2013; : n/a
[Pubmed] | [DOI]
6 2-(Diethylhexyl)phthalate in blood bags: Is this a public health issue?
Shaz, B.H. and Grima, K. and Hillyer, C.D.
Transfusion. 2011; 51(11): 2510-2517
[Pubmed]
7 2-(Diethylhexyl)phthalate in blood bags: is this a public health issue?
Beth H. Shaz,Kathleen Grima,Christopher D. Hillyer
Transfusion. 2011; 51(11): 2510
[Pubmed] | [DOI]



 

Top
 
  Search

  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
    Introduction
    Materials and Me...
    Results
    Discussions
    Conclusions
    Summary
    Acknowledgement
    References
    Article Tables

 Article Access Statistics
    Viewed6942    
    Printed432    
    Emailed4    
    PDF Downloaded47    
    Comments [Add]    
    Cited by others 7    

Recommend this journal

Association Contact us | Sitemap | Advertise | What's New | Feedback | Copyright and Disclaimer

© 2006 - Asian Journal of Transfusion Science | Published by Wolters Kluwer - Medknow
Online since 10th November, 2006