Platelet Inhibition as a Strategy to Permit Heparinization for CPB

Another approach for managing CPB in a patient with acute or previous HIT is to combine full heparinization with one or more antiplatelet agents. Following surgery, an alternative non-heparin anticoagulant (e.g., a DTI or danaparoid) is initiated as soon as deemed safe.

Several groups of investigators have used iloprost for this situation (Kappa et al., 1985; Long, 1985; Palmer Smith et al., 1985; Addonizio et al., 1987; Kraenzler and Starr, 1988), following the original observation by Olinger et al. (1984) that iloprost inhibited heparin-dependent platelet activation in the presence of HIT serum. Iloprost is a stable analogue of prostacyclin; thus, it stimulates adenylate cyclase, resulting in increased platelet cAMP levels, which prevents platelet activation by various platelet agonists, including HIT antibodies. In one larger case series Antoniou et al. (2002) preoperatively determined the individual concentrations of iloprost in vitro to inhibit the HIT induced platelet activation and thereafter used these individual concentrations to attenuate the HIT reaction during CPB.

Recently, this approach has experienced a resurgence with epoprostenol sodium (Flolan), a freeze-dried preparation of prostacyclin itself (Mertzlufft et al., 2000; Aouifi et al., 2001). Epoprostenol is approved for use in patients with primary pulmonary hypertension. Its very short half-life (6 min) means that continuous iv infusion is necessary. Complete inhibition of heparin-dependent platelet aggregation by HIT antibodies is generally achieved by doses ranging from 15 to 30 ng/kg/min. One protocol that does not require intraoperative monitoring of platelet aggregation gradually increases epoprostenol infusion (in 5 ng/kg/min increments made at 5-min intervals) until the target rate (30 ng/kg/ min) is reached, whereupon standard-dose UFH anticoagulation is commenced (Aouifi et al., 2001). The epoprostenol infusion is continued until 15 min following reversal of UFH with protamine. The major adverse effect is vasodilatation, leading to severe hypotension that requires intraoperative vasopressors.

Another strategy is the combination of the short-acting GPIlb/IIIa inhibitor, tirofiban, with UFH for anticoagulation during CPB (Koster et al., 2000e, 2001a,b). Tirofiban is predominantly eliminated by the kidneys, and has a plasma half-life of about 2 h. However, in contrast to prostaglandins, tirofiban exhibits no effect on vascular tone. Tirofiban is given 10 min before standard-dose UFH as a 10 mg/kg bolus followed by 0.15 mg/kg/min continuous infusion. The tirofiban infusion is stopped 1 h before end of surgery. UFH is neutralized with protamine as per usual. Using this treatment protocol, no thromboses occurred. However, in patients with severe renal impairment, tirofiban persists in the circulation and can cause major bleeding refractory to platelet transfusions: three such cases led the manufacturer to discourage use of this off-label protocol (Warkentin and Greinacher, 2003). In such patients, extracorporeal elimination of tirofiban (e.g., ultrafiltration at the end of CPB or modified zero-balanced ultrafiltration after CPB) appears to be an appropriate strategy to augment tirofiban elimination and prevent excessive hemorrhage (Koster et al., 2004b).

However, although there are no reports about thromboembolic complications following these strategies, theoretically there is a danger that HIT-associated platelet activation or thromboembolism might occur when platelet function recovers and platelet factor 4 (PF4)-heparin-antibody complexes still circulate. Therefore, immediately postoperatively iv thrombosis prophylaxis should be started with argatroban, lepirudin or danaparoid.

With regard to OPCAB surgery and vascular surgery no data are available. In theory, UFH plus antiplatelet therapy could be used during these procedures.

Blood Pressure Health

Blood Pressure Health

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