Specific thromboxane synthetase inhibition and haemostasis in insulin-dependent diabetics

Specific thromboxane synthetase inhibition is associated with a significant fall in abnormal albumin excretion rate in insulin-dependent diabetics (IDDs). This may be due to an effect on haemostasis or changes in renal blood flow. We have studied the effect of a specific thromboxane synthetase inhibitor, UK-38,485, on coagulation parameters in 15 IDDs, at -8, 0, 8 and 16 weeks after double blind administration of drug or placebo. Serum thromboxane B2 fell in the drug group (695 +/- 205 vs 134 +/- 180 pg/ml, n = 7, p less than 0.001), but not in the placebo group (713 +/- 409 vs 614 +/- 178 pg/ml, n = 8). The drug group showed significant reduction in adrenaline primary maximum (24 +/- 7 vs 37 +/- 7%, p less than 0.05) and ADP maximum (71 +/- 14 vs 81 +/- 7%, p less than 0.05) aggregation not seen in the placebo group. Dilute whole blood clot lysis time was, however, increased in the drug group (7.1 +/- 1.6 vs 6.25 +/- 2.4 hr, p less than 0.05) and no effect was observed in either group on in vivo parameters of platelet aggregation (beta-thromboglobulin, platelet factor 4 and platelet micro-aggregates). We conclude that specific thromboxane synthetase inhibition is probably not associated with an overall improvement in haemostasis and the clinical effects observed cannot be explained on this basis.