Platelet aggregation in different antithrombotic regimens. Possible proaggregant effect of low level oral anticoagulation.
Few trials have studied platelet activity during oral anticoagulation and all show a tendency for platelet aggregation to increase. This adverse effect has also been shown in some patients treated with unfractionated heparin, the so-called white clot syndrome. We studied platelet aggregation in patients with atrial fibrillation enrolled in the NASPEAF study and receiving antiaggregant, anticoagulant and both treatments.


METHODS
15 healthy control subjects (group C) and 99 patients were enrolled, the latter receiving 4 different antithrombotic regimens for platelet aggregation: group 1, 600 mg of the antiplatelet drug triflusal; group 2, anticoagulation for an INR of 2-3; and both treatments with 2 different levels of anticoagulation, mean INR of 1.85 (group 3) and of 2.15 (group 4). The same amounts of the agonists ADP, arachidonic acid and collagen were used in all tests. For statistical analysis we used the interval in min, from the addition of the agonist to the beginning of aggregation and the % of aggregation at 5 and 8 min.


RESULTS
After arachidonic acid was given, the interval to the beginning of aggregation was shorter in group 2 than in group C: 0.6 +/- 0.21 and 1.1 +/- 1.2, and in both was significantly shorter than in the other three receiving antiplatelet drugs alone: group 1 = 1.58 +/- 1.4 or combined with anticoagulants: group 3 = 1.7 +/- 1.7 and group 4 = 2.4 +/- 2.1. The % of aggregation at 5 min, in groups C, 2, 1, 3 and 4 was respectively 48 +/- 24, 43.2 +/- 19, 29.6 +/- 17, 34.8 +/- 22 and 23.2 +/- 22.5. The data showed significantly increased platelet activity in groups C and 2 compared to groups 1, 3 and 4. Group 3 with a low anticoagulation level (mean INR = 1.85) showed a tendency to greater platelet activity than group 1 and 4 with p value = 0.08.


CONCLUSIONS
The antiplatelet drug triflusal alone or combined with a therapeutic level of anticoagulation effectively reduces platelet aggregation and is not influenced by anticoagulant treatment. A low level of anticoagulation (INR < 2) shows a tendency to increase platelet activity.
Perez Gomez
F
F
Hospital Universitário San Carlos, Madrid, Spain. fperezg@hcsc.insalud.es
Lourenzo
P I
PI
Companion
J
J
Escriba
A
A
Perez Saldaña
D
D
Guillén
M
M
Vargas
E
E
S-Harguindey
L
L
D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000704:Analysis of Variance; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D016718:Arachidonic Acid / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications; D001792:Blood Platelets / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology; D004617:Embolism / Q000097:blood / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012459:Salicylates / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D013997:Time Factors
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; C016167:triflusal; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D000074:Acenocoumarol