In vitro and in vivo effects of desmopressin on platelet function.
OBJECTIVE
Desmopressin (DDAVP) may shorten bleeding time in patients with disorders of platelet function, but its mechanism of action in these conditions is still a matter of debate. In particular, contrasting results have been obtained concerning the ability of DDAVP to interact with platelets and to activate them directly. To gain further information on the DDAVP-platelet interaction, we studied the in vitro and ex vivo effects of DDAVP on platelet function.


METHODS
Platelet responses to DDAVP both as a single agent and in conjunction with agonists of platelet activation were investigated. For in vitro experiments platelets were obtained from healthy adult volunteers, while the ex vivo effects of DDAVP were studied in 12 patients with a bleeding disorder receiving a test dose of this drug.


RESULTS
DDAVP in vitro did not induce either platelet aggregation or surface expression of the activation-dependent antigens; it did, however, greatly inhibit platelet aggregation response to vasopressin (AVP) and increased the maximal extent of platelet aggregation induced by collagen and ADP. DDAVP infusion did not promote the expression of activation antigens, but significantly enhanced ex vivo platelet aggregation stimulated by ADP and collagen. This priming effect was observed in patients with von Willebrand's disease, hemophilia A, May-Hegglin anomaly, gray platelet syndrome and Ehlers-Danlos syndrome. In all these patients bleeding time was shortened by DDAVP infusion. In contrast, neither platelet aggregation nor bleeding time was modified in two subjects with Glanzmann's thrombasthenia.


CONCLUSIONS
Our in vitro experiments indicate that DDAVP interacts directly with platelets and facilitates their activation via other agonists. In vivo results suggest that this effect occurs and is clinically relevant in patients with platelet dysfunction responding to DDAVP with a shortening of bleeding time.
Balduini
C L
CL
Istituto di Medicina Interna e Oncologia Medica, IRCCS San Matteo, p. le Golgi, 27100 Pavia, Italy. c.balduini@smatteo.pv.it
Noris
P
P
Belletti
S
S
Spedini
P
P
Gamba
G
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D006470:Hemorrhage / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010974:Platelet Aggregation / Q000187:drug effects
D015703:Antigens, CD; D000244:Adenosine Diphosphate; D003094:Collagen; D003894:Deamino Arginine Vasopressin