M. Aulmann et K. Ruf, SIGNIFICANCE OF PLATELET SERINE THREONINE PHOSPHATASES 1/2A FOR STORAGE OF PLATELET CONCENTRATES/, Infusionstherapie und Transfusionsmedizin, 22, 1995, pp. 23-26
Inhibition of phosphatases 1/2A (pp1/2A) by okadaic acid (OA) prevents
thrombin or collagen-stimulated platelet aggregation, serotonin and A
TP release, as well as intracellular Ca2+ increase. OA is added to 12
platelet concentrates (PCs) prepared from 500 ml whole blood. Microcys
tin LR (MC), a further pp1/2A inhibitor that does not penetrate the ce
ll membrane, is added to 9 PCs. 9 PCs remain untreated. Storage of PCs
is carried out on a horizontal agitator for 7 days. Samples are taken
daily to estimate WBC, RBC, PLT, cAMP, cGMP and serotonin. 12h after
OA addition, a dose-dependent drop in platelet counts is seen, accompa
nied by a corresponding increase of particles with sizes of WBC and RB
C. Increased WBC and RBC counts are artefacts brought about by platele
t aggregation. From day 4 of storage, serotonin is released massively
cAMP consumption is reduced or stopped, and cGMP concentration increas
es slightly. In untreated and MC-treated PCs no similar reactions are
observed. It seems that the inhibition of extracellular pp1/2A (ectoph
osphatases) prevents platelet activation. The inhibition of intracellu
lar pp1/2A (endophosphatases) presumably enhances platelet activation.
The different results between OA- and MC-treated PCs lead to these co
nclusions because, depending on dose and time, OA penetrates platelet
membranes, MC does not. Therefore the results of the study give rise t
o the suspicion that pp1/2A control two sites of signal transduction i
n platelets of stored PCs: extracellular pp1/2A are included in platel
et activation, while intracellular pp1/2A mediate inhibition of activa
ted platelets. Inhibition of ectophosphatases and activation of endoph
osphatases probably facilitate PC storage.