Infusion of a stable prostacyclin analogue, iloprost, to patients with peripheral vascular disease: lack of antiplatelet effect but risk of thromboembolism.
OBJECTIVE
Prostacyclin, a potent inhibitor of platelet function and vasodilator, has been used to treat peripheral vascular disease. The aim of this study was to monitor the thrombotic status of patients treated by infusion of a stable prostacyclin analogue, iloprost.


METHODS
Thirteen patients with peripheral vascular disease underwent iloprost infusion for 3 days (8 hours each day) in a dose ranging from 0.5 to 2 ng/kg/minute. Variable parameters of thrombosis such as platelet reactivity (shear-induced hemostatic plug formation and thrombus formation on a collagen fiber), coagulation, and spontaneous thrombolysis (dislodgment of hemostatic plugs) were measured from non-anticoagulated blood samples by hemostatometry immediately before and 1 hour after the infusion and on the last day, 4 hours after initiation of the infusion.


RESULTS
Analysis of data from all patients 1 hour after the infusion showed no changes in platelet reactivity and spontaneous thrombolysis, but coagulation was significantly enhanced. In four patients, significant platelet hyperreactivity was observed after the infusion. Four of the five patients tested while undergoing iloprost infusion showed an enhanced thrombotic reaction and markedly enhanced coagulation. Iloprost employed in vitro in a concentration that corresponds to the therapeutic peak blood level caused no inhibition of platelet function but significantly enhanced coagulation. The threshold in vitro iloprost concentration at which anti-platelet effect and increased spontaneous thrombolysis were observed was twice that of the therapeutic blood level.


CONCLUSIONS
These findings challenge the view that antagonism of platelet function is an important factor of iloprost therapy. Furthermore, platelet hyperreactivity in some patients and markedly enhanced coagulation during and after infusion of iloprost in general, represent a risk of thromboembolism, especially as patients are already in a prethrombotic condition.
Thrombosis Unit, St. Bartholomew's Hospital, London, England.
I B
IB
Kovacs
S C
SC
Mayou
J D
JD
Kirby
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006801:Humans; D016285:Iloprost / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D012306:Risk; D013923:Thromboembolism / Q000139:chemically induced*; D014652:Vascular Diseases / Q000188:drug therapy*
D016285:Iloprost