Stabilization of standard platelet concentrates and minimization of the platelet storage lesion by a prostacyclin analogue.
Platelet concentrates were pretreated with a stable synthetic prostacyclin analogue (Iloprost) at two different concentrations before the second centrifugation step (pelleting step) of preparation. This resulted in loss of platelet sensitivity to aggregating agents. To mimic the situation after transfusion and to assess the reversibility of platelet inhibition, platelets were washed during and after storage and resuspended in fresh-frozen autologous plasma. The Iloprost-treated and washed platelets exhibited an increased sensitivity to the aggregating agents, compared with the control platelets (p less than 0.01). Post-storage recovery of the synergistic aggregation was more than 80% of prestorage aggregation. Beta-thromboglobulin (beta TG) release and thromboxane B2 (TXB2) formation were significantly inhibited in Iloprost-treated platelets (p less than 0.01). After the second centrifugation step, beta TG release was 0.7% +/- 0.3%, compared with 2.7% +/- 0.9% for the controls. TXB2 was 99 +/- 91 pg/ml, compared with 495 +/- 356 pg/ml for the controls. Platelet morphology and ultrastructure were well preserved during 5-day storage. In addition, Iloprost exerted a cytoprotective effect, as evidenced by the significant reduction in lactate dehydrogenase leakage. Post-storage LDH was 378 +/- 159 and 415 +/- 239 U/l respectively by the two Iloprost concentrations, compared with 1180 +/- 937 U/l for the control platelets. The inhibitory and cytoprotective effects of Iloprost were sustained throughout storage, in contrast to the effect of PGE1 (Prostin) which was limited to the early phase of storage.
Elias
M
M
Red Cross Blood Bank Groningen-Drenthe, The Netherlands.
Heethuis
A
A
Weggemans
M
M
Bom
V
V
Blom
N
N
McShine
R L
RL
Halie
M R
MR
Smit Sibinga
C T
CT
D000527:Alprostadil / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D001793:Blood Preservation / Q000009:adverse effects; D011464:Epoprostenol / Q000494:pharmacology*; D006402:Hematologic Diseases / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D013929:Thromboxane B2 / Q000378:metabolism; D001620:beta-Thromboglobulin / Q000378:metabolism
D001620:beta-Thromboglobulin; D013929:Thromboxane B2; D011464:Epoprostenol; D000527:Alprostadil; D016285:Iloprost