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Infusion of clots:
Arterial and venous thrombosis after IV immunoglobulin therapy
E. Obeid, G. Emerson, T.Sreih
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Intravenous immunoglobulin (IvIg) is generally considered a safe treatment for various autoimmune and inflammatory disorders. It is used to modulate the immune response in a variety of diseases, including idiopathic thrombocytopenic purpura (ITP), hemolytic anemia, Evans syndrome, chronic lymphocytic leukemia, Guillain-Barre syndrome, and graft-versus-host disease. Although high dose IvIg is considered safe, there are rare reports that IvIg may promote life threatening thrombosis in pulmonary, coronary, cerebral, and peripheral vessels. Here we present 2 patients who encountered thrombotic complications after IvIg therapy.
A 54-year-old woman with refractory idiopathic thrombocytopenic purpura who had failed two courses of steroid therapy, and a splenectomy, was given IvIg (Gammagard 5%; Baxter Healthcare Corp.; 1g/Kg) as a 5-hour infusion daily for 2 days. During the second infusion, she developed an ischemic stroke with hemiparesis and 3 days later developed deep vein thrombosis. The second patient, a 33-year-old woman with Evans syndrome, received 400 mg/kg IvIg daily for 5 days. She developed a deep vein thrombosis 1 week after therapy that required warfarin therapy. Six months later, she received an additional course of IvIg for recurrent hemolytic anemia and died of pulmonary thromboembolism 1 day later. The mechanism of thrombosis secondary to IvIg is unknown but may be related to increased blood viscosity. The viscous effect is dose-dependent and can last weeks. In addition, IvIg has been reported to induce arterial vasospasm and platelet activation, which may further predispose to thrombosis and ischemia. It does not appear that a particular preparation of IvIg is more dangerous than others, as thrombotic complications have previously been reported with other preparations. Furthermore, the time period over which IvIg is infused is not a clear risk factor either. It appears that a characteristic of the patient, rather than the infusion, contributed to thrombosis after IvIg.
Intravenous immunoglobulin therapy may be complicated by thrombosis in both the arterial and venous circulation. We recommend caution when treating patients with Ivlg particularly if they have risk factors for thrombosis.
IvIg has an expanding role in the treatment of autoimmune and inflammatory disorders. It has many mechanisms in modulating the immune response. Although a pooled plasma product IvIg is heat-treated and therefore largely safe from the point of view of infectious disease.
The induction of hypercoagulability and the development of both arterial and venous thrombosis is a known but rare complication of IvIg.
Patients receiving IvIg often have other factors which may predispose to a thrombotic tendency. The patient reported here was suffering from autoimmune hemolytic anemia and had previously undergone splenectomy, both of which are associated themselves with a thrombotic tendency. Nonetheless, the timing of the IvIg suggested an association both with the patient's antecedent DVT and subsequent fatal PE.
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This page was last updated on 07/25/2003
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