To the Editor:—
It has recently come to our attention that the etiology and suitability of fresh frozen plasma with a marked green color are not well understood by a significant number of anesthesia providers. We reviewed the issue of “green plasma” after a unit with a striking green color (fig. 1
) appeared in our operating room. Because of the contrast with the typical yellow appearance of plasma, the anesthesiologist refused to accept the unit. Although the blood bank assured him that the unit was safe, the anesthesiologist decided to take the more conservative approach and returned the unit to the blood bank for disposal.
We shared the picture below with more than 30 members of our departments and other departments, including anesthesiologists, nurse anesthetists, internists, intensivists, and surgeons. With one exception, no clinician identified the green color of the plasma as a possible normal variant for the color of fresh frozen plasma, and all suggested infection or bacterial contamination as the most likely reason for the green color. The vast majority concurred with the anesthesiologist’s decision to refuse the unit.
We could find no reports on green plasma in the past 40 yr in either the surgical or the anesthesia literature, which perhaps explains the lack of knowledge on the part of today’s clinicians. However, we found several articles dating back to the 1960s.1–3
At that time, green plasma was appearing in blood banks in fairly significant numbers (as many as 1% of all plasma units in large blood bank centers in England). Discoloration of plasma units by gram-negative cryophilic contaminants such as the Pseudomonas
species was still a concern at that time but was increasingly less likely in the antibiotic age and did not explain the relatively sudden increase in the number of green units. An additional etiology was therefore sought.
The yellow color of plasma is due to the presence of the yellow pigments bilirubin, carotenoids, hemoglobin, and iron transferrin. A previous report had noted the green appearance of sera obtained from donors with rheumatoid arthritis and had identified a corresponding decrease in the yellow pigments of these sera, especially in patients with disease duration of more than 10 yr.4
However, Tovey and Lathe1
reported hundreds of units of strikingly green plasma subsequently identified to be from a second cohort of donors (young married women) who did not have rheumatoid arthritis and whose sera had normal levels of yellow pigments. They were unsuccessful in extracting a green pigment from the green plasma; however, they found an unexpected blue precipitate. This pigment was subsequently identified as ceruloplasmin. Ceruloplasmin is a normal plasma glycoprotein, α2
globulin, that functions as a carrier for copper and also acts as an acute phase reactant.5
The level of ceruloplasmin can be elevated with elevated copper levels, in rheumatoid arthritis, and in high-estrogen states such as pregnancy and oral contraceptive use.6,7
Tovey and Lathe were able to confirm elevated ceruloplasmin levels in the green plasma units in their study.1
A subsequent study by Wolf et al.2
also found high normal or elevated ceruloplasmin levels in 15 donors, all of whom were taking oral contraceptives and all of whom had extremely green plasma. The authors suggested oral contraceptives, which were just then gaining wide clinical use, as the most likely cause of the increase in the number of green plasma units. They also noted that more modern techniques of blood collection (use of large-bore needles etc.
) had resulted in less hemolysis at the time of donation, and consequently there were no longer large amounts of yellow pigments from free hemoglobin in the sera.
The unit of green plasma that reached our operating room was cleared as a normal color variant by both regional and hospital blood bank staff using a visual inspection standard published by the American Red Cross and last updated in 2006. This can be viewed online.*
As part of our post hoc
review, we sought the ceruloplasmin level of this unit of plasma; however, the refused unit had already been discarded. Blood bank records showed that the donor was a 27-yr-old female graduate student in excellent health, absent all medical conditions and medications, except for a 5-yr history of oral contraceptive use.
Currently, approximately 0.3% of the inventory of fresh frozen plasma in our region is greenish in color. The American Association of Blood Banks is pursuing strategies to reduce the number of blood donors known to be at risk for leukocyte alloimmunization (pregnant females) as part of their plan to reduce the number of transfusion-related acute lung injury. Whether this strategy will make green plasma of only historical interest is doubtful. Blood banks will not be able to exclude pregnant women or women on birth control pills altogether as plasma donors because they simply will not be able to meet the needs of the country. Anesthesia providers should be aware of variations in physical properties of blood products and consult with their local blood banks or the online resources of the national blood bank.
Nabil M. Elkassabany, M.D.†
Geralyn M. Meny, M.D.
Rafael R. Doria, M.T., S.B.B.
Catherine Marcucci, M.D.
†Philadelphia VA Medical Center, University of Pennsylvania, Philadelphia, Pennsylvania. firstname.lastname@example.org
1. Tovey LA, Lathe GH: Caeruloplasmin and green plasma in women taking oral contraceptives, in pregnant women, and in patients with rheumatoid arthritis. Lancet 1968; 14:596–600
2. Wolf P, Enlander D, Dalziel J, Swenson J: Green plasma in blood donors. N Engl J Med 1969; 281:205
3. Clemetson CA: Caeruloplasmin and green plasma. Lancet 1968; 2:1037
4. Swinburne K, Losowsky MS, Hall DA: Pigmentation of serum in rheumatoid arthritis. Proc R Soc Med 1963; 56:818–20
5. Johnson DA, Osaki S, Friedan E: A micromethod for the determination of ferroxidase (ceruloplasmin) in human serums. Clin Chem 1967; 13:142–50
6. Scheinberg IH, Cook CD, Murphy JA: Concentration of copper and ceruloplasmin in maternal and infant plasma at delivery. J Clin Invest 1954; 33:963
7. Koskelo P, Kekki N, Virkkunen N, Lassus M, Somer T: Serum ceruloplasmin concentration in rheumatoid arthritis, ankylosing spondylitis, psoriasis, and sarcoidosis. Acta Rheum Scand 1966; 12:261–6
© 2008 American Society of Anesthesiologists, Inc.