The use of thrombin inhibitors and aprotinin in the preservation of platelets stored for transfusion.

We have evaluated the use of several thrombin inhibitors (heparin, Fragmin, hirudin, and Thromstop) in combination with cyclic adenosine 3',5'-monophosphate-active agents (prostaglandin E-1 [PGE-1] plus theophylline) and aprotinin for preparation and extended storage of platelet concentrates. Replacement of citrate with heparin resulted in accelerated clumping of platelets during storage. Fragmin, a low molecular weight heparin fraction, induced a high degree of platelet clumping, even in the presence of a standard amount of citrate (citrate-phosphate-dextrose-adenine formula 1 [CPDA-1]) plus PGE-1 and theophylline. The best anticoagulant formulation appeared to be CPDA-1 containing PGE-1 plus theophylline plus aprotinin, plus either hirudin or Thromstop for preservation of platelet responsiveness and structural integrity by in vitro markers. In eight platelet concentrates prepared with these inhibitors and stored for 15 days, the plasma pH was 6.50 +/- 0.15, the PO2 was 94 +/- 29 mm Hg, the PCO2 was 27 +/- 4 mm Hg, and the hypotonic shock response was 76% +/- 25% of the initial value recorded at Day 1 (all values expressed as mean +/- SD). Only 11% +/- 3% of the cellular lactate dehydrogenase was released, 69% +/- 8% of the platelets appeared to be in a discoid shape, and the response to 20 mumol/L adenosine 5'-diphosphate remained at 50% +/- 17% of the initial value. These results were all significantly different (p less than 0.01) from data obtained for concentrates prepared without aprotinin. The use of a factor Xa inhibitor (diamidino-benzofuranyl ethane) in place of Thromstop or hirudin did not provide substantial improvement over controls without inhibitors.