Thromboembolic Complications of Intravenous Immunoglobulin (IVIG) in Hypogammaglobulinemic Patients with Chronic Lymphocytic Leukemia (CLL).

Abstract 4416

Infectious complications represent a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The etiology is postulated to be secondary to aberrations in cell-mediated immunity, as well as to therapy-related immunosuppression.

Hypogammaglobulinemia, which occurs in virtually all patients with CLL, may beprofound and correlates with disease duration and stage. In 1981 during treatment of two children with hypogammaglobulinemia and coincidental idiopathic thrombocytopenic purpura (ITP), physicians in Switzerland observed a reproducible increase in the platelet count following IVIG treatment. This clinical observation and follow up systemic investigations further intensified the widespread clinical use of IVIG as a potential immune modulatory agent. Intravenous immunoglobulin (IVIG) therapy has been used successfully to prevent and treat infections in this cohort of patients.

Today, Intravenous immunoglobulin (IVIG) is used in a broad spectrum of autoimmune, inflammatory, and primary and secondary immunodeficiencies. The efficacy has been demonstrated in several control studies. IVIG is a blood product prepared from the serum of between 1,000 and 15,000 donors per batch. The mechanism of action validated by in-vitro models is exerted by a combined effect on autoantibodies, complement activation, cytokines, and saturation of Fc receptors on tissue macrophages.

However IVIG administration and treatment is not benign and should be used with caution given the potential manifestations of thromboembolic complications. High concentration and rapid infusion rate of the IVIG, as well as increased dose and osmolarity of the solution are thought to predispose to thrombotic events. Serum viscosity is the implicated mechanism for compromised blood flow and predisposition of high-risk patients to cardiovascular or cerebrovascular infarction.

In this retrospective review, we detail IVIG related thromboembolic manifestations in CLL patients, to highlight the importance of risk stratifying patients prior to treatment administration. The current consensus surrounding IVIG is that of a relatively safe treatment, with minor adverse effects such as hypertension, fever and chills, nausea, myalgias, or headache.

However our report highlights the importance of proceeding with caution in the application of this therapy, as it's proclivity for thrombotic complications has not been fully elucidated in patients with underlying malignancies. Pre-existing thrombogenic risk factors should be carefully evaluated in patients undergoing treatment with IVIG. Clinical evaluation, with careful attention to vascular history and underlying co-morbidities can potentially unmask the high-risk patient where IVIG could be lethal.