Iloprost
Iloprost, a stable prostacyclin analogue with a circulating half-life of 15 to 30 min, consistently blocks heparin-dependent platelet activation and aggregation in vitro. Intraoperative infusion of Iloprost has permitted the uneventful administration of heparin to patients with a history of HIT undergoing both vascular and cardiac surgery. At higher doses the drug may cause hypotension requiring coadministration of vasopressor support. Although, from the reports cited earlier, this agent showed considerable promise in this setting, it is unfortunately not currently available in the United States. The monoclonal antibody to the platelet glycoprotein IIb/IIIa 7E3 (Reopro) has been shown to prevent heparin-mediated platelet aggregation induced by HIT plasma in vitro. Furthermore, recent in vitro studies have demonstrated that Reopro can significantly reduce thrombin generation initiated by tissue factor. Although preliminary studies from our laboratory and others suggest Reopro is able to block the heparin-dependent antibodyinduced platelet release reactions, platelets from patients with Glanzmann’s thrombasthenia lacking the glycoprotein IIb/IIIa receptor can be activated by HIT IgG, suggesting that inhibition of this receptor will not give complete protection against the prothrombotic manifestations of the syndrome.
Other therapies. Surgical intervention such as thrombectomy or embolectomy may be indicated for limb salvage. Insertion of an inferior vena cava filter in patients with proximal deep venous thrombosis or embolism may reduce the risk of further emboli, but has been associated with thrombosis of the inferior vena cava up to the level of the filter. There have been isolated case reports of the administration of fibrinolytic agents (streptokinase, urokinase) without bleeding complications to patients with HIT with deep venous thrombosis, pulmonary emboli and arterial thrombosis. Small numbers of patients have received plasma exchange therapy in an attempt to remove the heparin-associated IgG. After relatively few treatments (ranging from one to six, generally in association with antiplatelet agents, plasmapheresis has been followed by reversal of the heparin-associated platelet aggregation abnormality, resolution of thrombocytopenia and stabilization of thrombotic phenomena. Some preparations of high dose Ig can prevent heparinassociated platelet activation by HIT sera, presumably by competitively inhibiting binding of the HIT-IgG to the platelet Fc receptor. Correction of thrombocytopenia after administration of intravenous Ig has been reported in several patients with HIT. Mexican hgh – cheap medications online.
Readministration of heparin. In patients with heparindependent antibodies, as detected by in vitro aggregation studies, reexposure to heparin is associated with a high risk of thrombocytopenia and thrombosis. In the majority of patients, the heparin-induced aggregation will disappear within several weeks, although persistence for over 2 years has been documented. In some clinical situations, such as cardiopulmonary bypass surgery, where anticoagulation is deemed essential and the safety and efficacy of heparin are well established, some investigators have advocated awaiting disappearance of the heparin-dependent antibody, as monitored by in vitro aggregation studies, and then performing the operation or procedure with full heparinization but without postoperative heparin administration. Although anecdotal, this approach has been successful. However, it may prove dangerous in those patients for whom the available in vitro assay is not sufficiently sensitive to detect a pathophysiologically potent antibody or for the occasional patient in whom severe HIT can be provoked by reexposure to heparin. HIT with thrombosis can recur years after a previous episode, even when a negative platelet aggregation test has been confirmed after the initial event. In general, patients with a history of HIT should therefore be advised to avoid further heparin exposure for life.
Conclusions
HIT is encountered more frequently in the practice of cardiology as the application of anticoagulant therapy becomes more generalized. The thrombotic complications of HIT are associated with significant morbidity and mortality and can only be prevented by early recognition of the condition. It is therefore imperative that cardiologists maintain a high index of suspicion and perform frequent platelet counts in all patients receiving heparin therapy. Once HIT is diagnosed, heparin must be stopped immediately and eliminated from all infusion lines and flushes. In most cases, alternative anticoagulant therapy should be initiated—a task made difficult at present by the absence of a readily available alternative anticoagulant agent with proven efficacy in patients with acute coronary disease. Several direct thrombin inhibitors are being evaluated in patients with HIT, and it is hoped that the margin of benefit will be sufficient to encourage the manufacturers to make this drug available for the management of this potentially lifethreatening complication of heparin therapy.