Platelet-erythrocyte interactions enhance platelet reactivity (

Santos et al.
J Clin Invest
1991
;
87
:
571
;
Valles et al.
Blood
2002
;
99
:
3978
) and reduce the effect of aspirin (ASA) as antithrombotic modality (
Santos et al.
Circulation
1997
;
95
:
63
;
Valles et al.
Circulation
1998
;
97
:
350
). These effects were studied using an experimental approach which independently evaluates platelet activation (TXA2, 5HT release) and recruitment (proaggregatory activity of cell-free releasates) during cell-cell interactions between erythrocytes (RBCs) and collagen-stimulated platelets (PTLs) or in whole blood (WB). In patients with chronic vascular disease treated with ASA, with blunted TXA2, three response groups were found: in Group A (39% of patients), recruitment was blocked in PTLs alone, PTL+RBCs and in WB; in Group B (45%), recruitment was abolished in PTLs alone but continued in the presence of RBCs and in WB; in Group C (16%), recruitment was detected in PTLs alone and was markedly enhanced by RBCs (
Valles et al.
Circulation
1998
;
97
:
350
). Using the same experimental approach, 80 patients with acute coronary syndrome (ACS) treated with aspirin (100–300 mg/d) as the only antiplatelet therapy were studied. Other medications were administered according to guidelines. ASA-free (n=80) normal subjects were also evaluated as controls. Results: In ACS patients blockade of TXA2 was observed in only 76% of patients, while partial inhibition (44.7%) was achieved in 24%. In the latter patients platelet recruitment in WB was high, equal to that in ASA-free controls (ACS X=94.58 vs. controls 87.59). When the three response groups described above were studied in the 61 ACS patients with blocked TXA2 synthesis, the proportions differed markedly from chronic patients: Group A (3% vs. 30%), Group B (18% vs. 45%) and Group C (79% vs. 16%). Since TXA2 was blunted in these patients, the results indicate that ACS patients are highly susceptible to stimulation by COX-1 independent mechanisms. In 18% (Group B) this could be attributable to the ASA-insensitive prothrombotic effect of RBCs, while in 79% (Group C) platelet hyperactivity was intrinsic to PTLs and markedly enhanced by RBCs. Conclusions: Evaluation of TXA2 synthesis in ASA-treated ACS patients is advisable, since partial TXA2 inhibition results in full platelet recruitment. COX-1-independent mechanisms of platelet reactivity are prominent in ACS patients and increased by RBCs. Since platelet recruitment is essential in thrombus growth its inhibition by ASA alone or in combination with other antiplatelet drugs could reduce occlusive thrombus formation. (Grant FIS 03/0270).

Topics:
acute coronary syndromes, aspirin, blood platelets, erythrocytes, down-regulation, antiplatelet agents, thrombus, fibrinolytic agents, hyperkinesis, vascular diseases

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2005, The American Society of Hematology
2004
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