Acid-citrate-dextrose

Acid-citrate-dextrose or acid-citrate-dextrose solution, also known as anticoagulant-citrate-dextrose or anticoagulant-citrate-dextrose solution (and often styled without the hyphens between the coordinate terms, thus acid citrate dextrose or ACD) is any solution of citric acid, sodium citrate, and dextrose in water. It is mainly used as an anticoagulant (in yellow top tubes)[1] to preserve blood specimens required for tissue typing. It is also used during procedures such as plasmapheresis instead of heparin.

Formulation

Two solutions (A and B) are defined by the United States Pharmacopeia. They have the following properties:[2]

Content of USP ACD solutions, per 1000 mL
SubstanceACD-A amount (g)ACD-B amount (g)
Total Citrate (as citric acid, anhydrous (C6H8O7))20.59 to 22.75g12.37 to 13.67g
Dextrose (C6H12O6*H2O)23.28g to 25.73g13.96 to 15.44g
Sodium (Na)4.90g to 5.42g2.94 to 3.25g

To make use:

SubstanceAmount for ACD-AAmount for ACD-B
Citric acid, anhydrous (C6H8O7)7.3 g4.4 g
Sodium citrate, dihydrate22.0 g13.2 g
Dextrose, monohydrate (C6H12O6*H2O)24.5 g14.7 g
Water for injection to make1000 mL1000 mL

Dissolve the ingredients and mix. Filter until clear.

History

Blood storage

ACD was invented by Loutit et al. in 1943 for preserving whole blood. They found that the mixture offers better red blood cell survival than the then state-of-the-art, MRC 1940 (trisodium citrate plus glucose). The old solution also caramelize when autoclaved, while the new one does not due to higher acidity.[3] As a result, blood can now be stored for much longer, up to 21 days.[4]

ACD was developed into CPD (citrate-phosphate-dextrose) in 1957,[5] a version with phosphate added intended to reduce phosphate leakage from red blood cells. It does not improve shelf life appreciably, but patient recovery is improved. A later improvement was CPD with adenine (CPDA-1), which boosted RBC survival to five weeks when combined with plastic bags. CPD, in combination with adenine-mannitol additives such as SAGM, is the current blood bank preservative as of 2012.[4]

Although human blood is generally stored using newer formulations, the uptake of such technology is slower in veterinary medicine. From experimentation on horse and donkey blood, it does seem that the newer human-blood storage technogies also translate to improvements in animal blood storage.[6][7]

Apheresis

ACD is first described for use in apheresis in 1977.[8] Citrate, typically in the form of ACD solutions, is now preferred over heparin because it is cheap, safe, and cleared out of the system faster. Use of ACD is universal for centrifuge-based systems, while membrane systems may use either. Heparin is still used for high-volume procedures, as infusing too much citrate with the returned blood can cause toxicity from the chelating action, mainly hypocalcemia.[9]

References
  1. "ORDER OF DRAW FOR MULTIPLE TUBE COLLECTIONS" (PDF). Michigan Medicine Laboratories. 2019-09-15. Retrieved 2020-03-27.
  2. United States Pharmacopeia 26, 2002, pp 158.
  3. Loutit, J. F.; Mollison, P. L.; Young, I. Maureen; Lucas, E. J. (16 December 1943). "Citric Acid-Sodium Citrate-Glucose Mixtures for Blood Storage". Quarterly Journal of Experimental Physiology and Cognate Medical Sciences. 32 (3): 183–202. doi:10.1113/expphysiol.1943.sp000882.
  4. D'Amici, Gian Maria; Mirasole, Cristiana (2012). "Red blood cell storage in SAGM and AS3: a comparison through the membrane two-dimensional electrophoresis proteome". Blood Transfusion. 10 Suppl 2: s46-54. doi:10.2450/2012.008S. PMC 3418620. PMID 22890268.
  5. Gibson, J. G.; Kevy, S.; Pennell, R. (28 November 1968). "Citrate-Phosphate-Dextrose: An Improved Anticoagulant Preservative Solution for Human Blood". International Society of Blood Transfusion. 29: 758–763. doi:10.1159/000384704. ISBN 978-3-8055-0131-6. PMID 5728120.
  6. Mudge, MC; Macdonald, MH; Owens, SD; Tablin, F (September 2004). "Comparison of 4 blood storage methods in a protocol for equine pre-operative autologous donation". Veterinary Surgery. 33 (5): 475–86. doi:10.1111/j.1532-950X.2004.04070.x. PMID 15362986.
  7. Barros, IO; Sousa, RS; Tavares, MD; Rêgo, RO; Firmino, PR; Souza, FJA; Abrantes, MR; Minervino, AHH; Araújo, CASC; Ortolani, EL; Barrêto Júnior, RA (8 February 2021). "Assessment of Donkey (Equus asinus africanus) Whole Blood Stored in CPDA-1 and CPD/SAG-M Blood Bags". Biology. 10 (2): 133. doi:10.3390/biology10020133. PMC 7915378. PMID 33567685.
  8. Olson, PR; Cox, C; McCullough, J (August 1977). "Laboratory and clinical effects of the infusion of ACD solution during plateletpheresis". Vox Sanguinis. 33 (2): 79–87. doi:10.1111/j.1423-0410.1977.tb02237.x. PMID 883248. S2CID 24966385.
  9. Lee, G; Arepally, GM (2012). "Anticoagulation techniques in apheresis: from heparin to citrate and beyond". Journal of Clinical Apheresis. 27 (3): 117–25. doi:10.1002/jca.21222. PMC 3366026. PMID 22532037.
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