Carotid endarterectomy in patients with heparin-induced platelet activation: Comparative efficacy of aspirin and iloprost (ZK36374)

Abstract

Patients with heparin-induced platelet activation who are reexposed to heparin may have recurrent thrombocytopenia, intravascular thrombosis, arterial emboli, or sudden death. To permit carotid endarterectomy in two patients with confirmed heparin-induced platelet activation, we compared the efficacies of aspirin and iloprost, a stable analogue of prostacyclin, in preventing heparin-induced platelet activation. In the first patient, although aspirin prevented both in vitro heparin-induced platelet aggregation (70% without and 7.5% with aspirin) and 14C serotonin release (48% without and 0% with aspirin), intraoperative administration of heparin resulted in an increase in plasma levels of platelet factor 4 from 8 to 260 ng/ml and beta-thromboglobulin levels from 29 to 39 ng/ml. In addition, the circulating platelet count decreased from 221,000 to 174,000 microliters, and 15% spontaneous platelet aggregation was observed. Fortunately, fibrinopeptide A levels remained less than 10 ng/ml intraoperatively, and no thrombotic complications occurred. In the second patient, aspirin did not prevent heparin-induced platelet aggregation in vitro (65% without and 41% with aspirin); however, iloprost (0.01 mumol/L) prevented both in vitro heparin-induced platelet aggregation (59.5% without and 0.0% with iloprost) and 14C serotonin release (56.7% without and 0.0% with iloprost). Therefore, a continuous infusion of iloprost was begun before administration of heparin and was continued until 20 minutes after reversal of heparin with protamine. After intraoperative administration of heparin, plasma levels of platelet factor 4 increased from 19 to 200 ng/ml, and beta-thromboglobulin levels increased from 56 to 76 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin-induced platelet activation: The role of thromboxane A2 synthesis and the extent of platelet granule release in two patients

“…In contrast, by elevating intracellular cyclic adenosine monophosphate, iloprost (0.01 ~mol/L), a stable prostacyclin analogue, prevented heparin-induced aggregation, granule release, and TxB~ generation in both patients. Thus we show (1) HIPA can proceed independently of TxA, synthesis; (2) heparin in certain patients can release lysosomal hydrolases, thus mimicking strong platelet agonists such as thrombin; and (3) iloprost but not aspirin prevents HIPA regardless of the biochemical pathways involved. (J VASC SURG 1989;9:574-9.…”

“…Heparin-induced thrombosis is due to an immune-mediated activation of circulating platelets and has significant clinical implications for patients with vascular disease. The purpose of this article was (1) to define the biochemical mechanisms of heparin-induced platelet activation (HIPA) and (2) to determine the relationship between thromboxane A2 (TxA2) synthesis and platelet granule release. In two patients with confirmed HIPA, heparin (3 U/ml) induced extensive platelet aggregation (61.5 % ), release of ~*C-serotonin (81.5% of releasable ~4C-serotonin, a dense granule marker) and platelet factor 4 (63.7% of releasable platelet factor 4, an alpha granule marker) and generation of TxB2, a stable metabolite of TxA2 (100% relative to serum control).…”

Use of recombinant hirudin as antithrombotic treatment in patients with heparin‐induced thrombocytopenia

“…Aspirin and dipyridamole have been used, but the in vitro inhibition of platelet activation by these two agents in heparin-induced thrombocytopenia is inconstant in vivo [ 151. Stable analog of prostacyclin (lloprost) has been used also with more potent antiplatelet activity in case of heparin-induced thrombocytopenia, but with serious hemodynamic side effects [ 16,171. Plasmapheresis, a rather heavy therapeutic approach, has been used in heparin-induced thrombocytopenia in association with aspirin [18-201. Defibrination with ancrod has been used with a target fibrinogen concentration of 0.5-1 g/L.…”

Iloprost in Peripheral Vascular Disease

“…The latter included clinical trials with iloprost in cardiopulmonary bypass procedures for cardiac surgery (7,14,5 1) and hemodialysis (18,77) but the immediate clinical benefit was clearly demonstrable only in heparin-induced thrombocytopenia (42,43,80).…”

“…Iloprost has been studied in the treatment of PAOD and conditions in which inhibition of platelet activation was assumed to be of clinical benefit. The latter included clinical trials with iloprost in cardiopulmonary bypass procedures for cardiac surgery (7,14,5 1) and hemodialysis (18,77) but the immediate clinical benefit was clearly demonstrable only in heparin-induced thrombocytopenia (42,43,80).…”