Platelet metabolism during storage of platelet concentrates at 22 degrees C

Abstract

The development of methods for storing platelet concentrates (PCs) at 22 degrees C for transfusion has been predominantly empiric, with minimal knowledge of metabolic events occurring during storage. It is known that a decrease in pH due to accelerated production of lactic acid in hypoxic conditions is a major cause for loss of platelet viability. In the current studies, we have measured metabolic parameters such as O2 and glucose consumption rates and CO2 and lactic acid production rates. We have also determined the O2 and CO2 transport capacities of various containers and the buffering capacity of plasma. The O2 consumption rate was 1.10 +/- 0.16 (SD) nmol/min/10(9) platelets. In well-oxygenated systems, lactic acid formation was 1.74 +/- 0.12 nmol/min/mL PC for PCs with a platelet count of 1 to 2 X 10(9)/mL; and 0.52 mol of glucose was consumed per 1 mol lactic acid produced. In a completely oxygen-free system, lactic acid production increased 5–8-fold. These calculations suggest that 85% of energy generation is derived through oxidative metabolism and that glucose may not be the primary substrate for this metabolism. Bicarbonate concentration, initially 22.1 +/- 1.6 mEq/L, decreased 1.41 +/- 0.18 nEq/min/mL PC for PCs with counts 1 to 2 X 10(9) platelets/mL. The loss of bicarbonate was caused by displacement by lactic acid and as a consequence of spontaneous CO2 efflux from the container. CO2 production, 2.3 +/- 0.4 nmol/min/10(9) platelets, was derived from oxygen consumption and the CO2 liberated from bicarbonate as it was consumed. A rapid fall in pH to levels below 7.0 (22 degrees C) took place when the bicarbonate concentration fell below 5 mEq/L as lactate concentrations reached 20 to 25 mmol/L. A further increase in lactate concentration from 25 mmol/L to 40 mmol/L correlated with a further fall in pH to 5.8. Thus, the ultimate storage life of a PC is determined by continuous lactate production and the fixed buffering capacity of plasma and by the glucose concentration of the PC. With knowledge of these parameters, methods for predicting pH as a function of time, platelet count, and O2 and CO2 transport capability of the container have been developed as guidelines for future work.

Autologous transfusion recovery of WBC‐reduced high‐concentration platelet concentrates

“…Glucose consumption increased with lactate production. While the lactate rates are within the ranges previously observed, the glucose rates are higher than expected assuming a 2 to 1 molar lactate to glucose ratio as discussed by Kilkson et al 16 The lactic acid generation rates are internally consistent with pH changes over storage time with HCP Group 1 units having a larger fall in pH commensurate with more lactic acid production.…”

“…APCs and HCPs in Group 3 are within reported ranges for apheresis platelets in the ELP bag (30‐70 μmol/10 12 platelets/hr) 15 . Lactate generation rates were approximately doubled in HCP Group 1, indicating some up regulation of glycolysis, but much less than 468 μmol per 10 12 platelets per hour reported by Kilkson et al 16 for full up regulation of glycolysis at 22°C under anaerobic conditions. Glucose consumption increased with lactate production.…”

Platelet concentrate functionality assessed by thromboelastography or rotational thromboelastometry

“…In other words, the absence of agitation and air permeability resulted in acceleration of the storage lesion and eventually no PLT contribution toward clot formation. However, TEG's MA reflected that adequate gas exchange in the storage bags affected clotting functionality in the PC units more than did shaking, as previously reported …”

Storage of apheresis platelet concentrates after manual replacement of >95% of plasma with PAS 5

“…Two concurrent biochemical processes provide energy in stored platelets (PLTs): glycolysis in the cytoplasm and β‐oxidation of long‐chain fatty acids in mitochondria. Though only 15% of energy is derived from glycolysis , Holme , Gulliksson and most recently, Saunders et al . have found glucose to be critical for PLT storage.…”