944 DDAVP INHIBITS PROSTACYCLIN FORMATION: A POTENTIAL MECHANISM FOR BLEEDING TIME (BT) CORRECTION IN HEMOSTATIC DISORDERS

Abstract

A recent study has shown that DDAVP normalizes the B.T. in plt. functional defects. In vitro evidence also suggests that DDAVP enhances plt-vascular adherence. We assessed the effects of DDAVP on prostacyclin as a possible mediator of these effects. Initial studies on human vessels revealed that incubation of segments with DDAVP ↓ 6KPGF_1α formation. Values of 3.4±.0.8 and 2.5±0.7 pmol/mg were obtained in the presence of 0.1 and 1.0 μg/ml DDAVP, with paired control values of 4.1±1.0 and 4.0±1.1 (p<0.01). No differences in 6KPGF_1α were observed when segments were incubated with DDAVP vehicle alone (0.1μg/ml), although at 1μg/ml a slight ↓ in 6KPGF_1α was seen. Direct assessment of the effects of DDAVP on ionophore (10μM) stimulated release of 6KPGF_1α from bovine endothelial cell monolayers revealed that at 1μg/ml both DDAVP and its vehicle caused a ↓ in 6KPGF_1α release (33+18 and 31±16 pmol per 10⁶ cells versus control values of 121±46 pmol;p<0.01). Finally, changes in plasma 6KPGF_1α are being assessed in patients (n=5) with plt. functional defects in whom DDAVP has been used as a therapeutic modality to correct their prolonged BTs. A ↓ in plasma 6KPGF_1α has been observed with mean levels of 0.32 and 0.25 pmol per ml prior to and 90′ post DDAVP respectively. These studies, demonstrating an in vitro and in vivo effect of DDAVP on endothelial cell prostacyclin production, suggest a potential, hitherto unrecognized, mechanism for BT correction in hemostatic disorders.

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