Time-dependent histamine release from stored human blood products

Abstract

Perioperative transfusion of whole blood has been shown to amplify trauma-induced immunosuppression, which could be attenuated by perioperative administration of histamine2 receptor antagonists. Supernatants from different blood products were, therefore, analysed for histamine content during storage. Whole blood (six units), plasma-reduced whole blood (six units), and plasma- and buffy coat-reduced (saline-adenine-glucose-mannitol) (SAGM) blood (six units) from unpaid healthy donors were stored in the blood bank for 35 days at 4 degrees C. Plasma histamine and total cell-bound histamine content at donation, and histamine concentration in samples drawn from the units on days 0, 2, 5, 9, 14, 21, 28 and 35 were analysed with an enzyme-linked immunosorbent assay. Median plasma histamine concentration was 4.8 (range 1.9-14.3) nmol/l (n = 18). Median total cell-bound histamine content was 417.0 (range 176.0-910.0) nmol/l in whole blood and 475.0 (range 360.0-1560.0) nmol/l in plasma-reduced whole blood, while it was undetectable in SAGM blood. Spontaneous histamine release increased in a time-dependent manner from a median of 6.7 (range 2.2-17.4) nmol/l at the time of storage to 175.0 (range 33.0-485.0) nmol/l at day 35 in whole blood, from 18.8 (range 8.2-38.5) to 328.5 (range 224.0-1137.0) nmol/l in plasma-reduced whole blood, and from 0.5 (range 0.5-1.5) to 2.2 (range 1.4-6.9) nmol/l in SAGM blood. These results show spontaneous histamine release during storage of human blood products which contain full amount of leucocytes, and this may play a significant role in detrimental effects of blood transfusion.

Immunomodulating Effect of Blood Transfusion: Is Storage Time Important?

“…Granulocytes seem to disintegrate during storage [6] and these cells contain intracellular granules with different preformed bioactive substances. There is significant, time-dependent extracellular accumulation of eosinophil cationic protein, eosinophil protein X [10], myeloperoxidase [10] and histamine [11] in SAGM and WB storage at +4 °C. Granulocyte-derived substances responsible for inactivation of LPS [40, 41] could be involved in the time-dependent immunomodulation, but the results from PHA stimulation indicate that other substances also may be involved.…”

“…Although the leukocytes disintegrate during storage [6], about half are still viable after 3 weeks [7], and they can still produce immunologically active substances [8, 9]. We have already shown that there is time-dependent extracellular accumulation of various bioactive substances in erythrocyte suspensions [10, 11]. As some of these substances have an immunomodulatory effect, transfusion-induced immunomodulation may depend on storage time.…”

Prestorage leukofiltration of whole blood and SAGM blood prevents extracellular bioactive substance accumulation

“…We have previously shown that MPO, ECP, and histamine from granulocytes, and PAI-1 from platelets, are accumulated extracellularly in WB and, with exception of PAI-1, also in SAGM blood during storage [15,16].…”

“…Histamine may lead to immunosuppression and growth of tumor tissue [7,8], MPO may amplify toxic reactions and tissue damage by free oxygen radicals [9,10], ECP may contribute to immunosuppression [11], and lead to neurotoxic reactions [12] and PAI-1 may induce coagulation dysfunction [13], and participate in cancer cell dissemination [14]. Bioactive substances are accumulated extracellularly in both whole blood and SAGM blood during storage [15,16] and potentially, bedside filtration may not prevent transfusion of released substances. Therefore, storage time may be important when filtration is performed bedside.…”

Erythrocytes and Proinflammatory Mediators in Wound Drainage

“…In the case of histamine, these values are up to 217 times higher than the concentrations in stored blood (0.5–2.2 mmol/l in plasma – and buffy-coat-reduced SAGM blood) [27]. Histamine given intravenously causes not only increased heart rate, hypotonia, bronchospasm, and gastric hyperacidity, but even cardiac arrest with concentrations of 100 ng/ml [21].…”