A study of the use of the thromboxane A2 antagonist, sulotroban, in combination with streptokinase for local thrombolysis in patients with recent peripheral arterial occlusions: clinical effects, platelet function and fibrinolytic parameters.
In peripheral thrombolysis adjuvant anti-platelet therapy may help to lyse otherwise resistant thrombus, thereby increasing the number of patients successfully treated and reducing the "time to lysis". If continued after lysis it may help to prevent early rethrombosis. In this pilot study 21 patients undergoing peripheral thrombolysis with streptokinase were randomised to receive the thromboxane receptor antagonist sulotroban or placebo. The dose of sulotroban given was 2 mg/min (four patients), 4 mg/min (five patients) or 8 mg/min (four patients), eight patients received placebo. The clinical and laboratory effects of the treatment were monitored. Thrombolysis was achieved more quickly in patients receiving sulotroban, however, there was no difference between groups in the number of patients in whom recanalisation was achieved (six of eight receiving placebo and eight of 13 receiving sulotroban) or in the number of cases of early rethrombosis. During lysis there was an increase in plasma beta-thromboglobulin with similar levels being found in patients receiving sulotroban and streptokinase and those receiving streptokinase alone. No other major changes in platelet function during lysis were seen in patients receiving streptokinase alone. Sulotroban significantly reduced platelet aggregation and 14C-5HT release in response to several platelet agonists. With the thromboxane mimetic U46619 the degree of inhibition of aggregation and 14C-5HT release depended on the dose of sulotroban used. High levels of inhibition were associated with an excess of haemorrhagic complications especially in combination with a low plasma fibrinogen level. We conclude that the use of low dose sulotroban in combination with streptokinase merits further study and may hve a role in accelerating lysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Lonsdale
R J
RJ
Department of Vascular Surgery, University Hospital, Nottingham, United Kingdom.
Heptinstall
S
S
Westby
J C
JC
Berridge
D C
DC
Wenham
P W
PW
Hopkinson
B R
BR
Makin
G S
GS
D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000188:drug therapy*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000188:drug therapy; D007866:Leg; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013300:Streptokinase / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy
D005343:Fibrinolytic Agents; D013449:Sulfonamides; D012701:Serotonin; C040624:sulotroban; D013300:Streptokinase