Rapid infusions of human normal immunoglobulin 50g/l are safe and well tolerated in immunodeficiencies and immune thrombocytopenia (original) (raw)
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American Journal of Hematology, 2007
Intravenous immunoglobulin (IGIV) therapy is generally considered to be a safe and effective treatment for idiopathic thrombocytopenic purpura (ITP). The usual initial treatment dose is 1-2 g/kg body weight, which results in an extended infusion time, significantly impacting patients' day-to-day activities. Two crossover studies assessed the safety and tolerability of a novel IGIV preparation (IGIV-C; Gamunex 1 , 10%) when infused at rates ranging from 0.08 mL/kg/min (the standard maximum licensed rate) to 0.14 mL/kg/min in patients with ITP. The first study included 28 patients and 3 infusion rates; 0.08, 0.11, and 0.14 mL/kg/min. The second study included 8 patients and 2 infusion rates; 0.08 and 0.14 mL/kg/min were evaluated. The incidence of infusion-related adverse events was similar for all infusion rates. Headache was the most commonly reported infusion-related adverse event. The incidence, combined for Studies 1 and 2, was 14.7% (n 5 34), 18.2% (n 5 22), and 19.4% (n 5 31) of patients, for each infusion rate of 0.08, 0.11, and 0.14 mL/kg/min, respectively. The majority were mild in severity. None of the other drug-related, treatment-emergent events were serious; most were mild, in spite of the higher rate of fluid loading over a shorter period of time for patients infused at 0.14 mL/kg/min. There were no clinically important changes in parameters that distinguished between infusion rates; there were no signs of hemolysis. The results suggest that IGIV-C infused at rates up to 0.14 mL/kg/min in patients with ITP is well tolerated. Am. J. Hematol. 82:192-198, 2007. V V C 2006 Wiley-Liss, Inc.
Thromboembolic complications of intravenous immunoglobulin treatment
2004
Introduction: 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 be profound and correlates with disease duration and stage. Intravenous immunoglobulin (IVIG) therapy has been used successfully to prevent and treat infections in this cohort of patients. 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. We report a case of IVIG related thromboembolic manifestations in a CLL patient, to highlight the importance of risk stratifying patients prior to treatment administration. Case presentation: We present a 55-year-old Caucasian man with CLL who presented to our clinic with neutropenic fevers following a cycle of chemotherapy. Laboratory parameters revealed hypogammaglobulinemia prompting IVIG administration. Shortly thereafter, he developed a massive cascade of thromboembolic phenomena precipitating his demise. Conclusion: 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.
Thrombosis Research, 2014
To estimate the incidence and predictors of symptomatic arterial and venous thromboembolic events (TEE) from intravenous immunoglobulin (IVIg) therapy according to its indications. Methods: We performed a retrospective cohort study of patients seen at our institution and treated with IVIg over a 36-month period. Indications, comorbility and comedication associated with TEE were identified by a stepwise logistic regression analysis. Results: Of 303 patients included with at least one infusion of IVIg over three years, TEE were identified in a total of 50 patients treated with IVIg, for an incidence of 16.9% (CI 95%: 13.0-21.6); 27 (54%) arterial (9.1%;CI 95%: 6.3-13.0%) and 23 (46%) venous TEE (7.8%; CI95%: 5.2-11.4%), overall mortality was 32%. Per indication there were more patients with autoimmune conditions, secondary immunodeficiency, dysimmune neuropathies, acute rejection of solid organ transplantation and sepsis. Patients with TEE were significantly older, were more likely to be men, they had more comorbid conditions; the doses of IVIg were high (589.4 mg/kg/day vs 387.0 mg/kg/day, p b 0.001) and differences in comedication were found. The stepwise logistic regression analysis retained high doses of IVIg (OR 3.03; CI 95%: 1.49-5.67) and diuretics therapy (OR 1.69; CI 95%: 1.06-3.97) when combined with the usual comorbid confounders. Conclusions: The incidence of TEE from IVIg therapy remains high at one in six patients treated. The most remediable factor is a high daily IVIg load. Decreasing the daily IVIg dose together with carefully weighing diuretics therapy and comorbid risk factors may be the keys to saving lives.
International Immunopharmacology, 2014
Intravenous immunoglobulin (IVIG) is increasingly recommended for many diseases apart from primary immunodeficiency diseases (PID). Although effective and safe, adverse reactions may occur. We conducted a 2-year prospective observational study in 117 patients with PID who received regular IVIG replacement therapy at a median dose of 600 mg/kg every 3 to 4 weeks to examine IVIG's adverse effects; 1765 infusions were performed (mean = 15/patient) in 75 males and 42 females (aged 3 months to 77 years) in 3 groups: ≤9 years (34.2%), 10-19 years (26.5%), and ≥20 years (39.3%). Fifty patients had common variable immunodeficiency (CVID), 11 had X-linked agammaglobulinemia (XLA), and 55 had other immune system disorders. The drugs administered were Octagam® (49.1%), Tegeline® (17.3%), Imunoglobulin® (18.6%), Flebogama® (12.9%), Vigam® (1.2%), and Kiovig® (0.4%). Immediate infusion-related adverse reactions occurred in the cases of 38 out 1765 infusions (2.15%, IC95% 1.53%-2.94%), which were classified as mild (81.6%), moderate (10.5%), or severe (7.9%). Time until reaction ranged from 10 to 240 min (mean = 85.7, median = 60). Reaction rates were similar across age groups. The most common reactions were malaise, headache, and abdominal pain. Reported severe events were tightness of the throat and seizure. All symptoms improved with temporary or complete IVIG interruption and symptomatic medications. Sixteen of 38 reactions to infusions occurred in the presence of an acute infection (p = 0.09). Tegeline® represented a greater reaction risk factor than Octagam® (p b 0.001). These results indicate that IVIG infusion can be considered a safe procedure. Low reaction incidence and few severe immediate infusion-related adverse reactions were observed.
Blood, 2001
The clinical benefit of intravenous immunoglobulin (IVIG) preparations in the treatment of immune thrombocytopenic purpura (ITP) is supposed to be mediated by blockade of Fcγ receptor–bearing phagocytes. In 2 experimental models for ITP, it is shown that the therapeutic efficacy of IVIG preparations is related to the IgG dimer content present in these preparations. A rat monoclonal antibody (mAb; MWReg30) directed to the murine platelet-specific integrin αIIbβ3 (gpIIb/IIIa) was administered intraperitoneally either as bolus injection or continuous infusion. With bolus injection, the circulating platelet count dropped to almost zero within 3 hours. Pretreatment with cobra venom factor did not affect platelet depletion, whereas pretreatment with anti-FcγRII/III mAb 2.4G2 or IVIG greatly reduced platelet clearance. With continuous infusion, platelet numbers reached a steady state after 4 days, at approximately 25% of control. This reduction in platelets was, however, not observed in mi...
Intravenous immunoglobulin consensus statement☆☆☆
Journal of Allergy and Clinical Immunology, 2001
Intravenous immunoglobulin (IVIG) preparations are a mainstay for a number of disorders that include primary immunodeficiency, acute inflammatory conditions, hematological disorders, infections, and neuroimmunological disorders. The range of therapeutic activity is attributed to IVIG's myriad action mechanisms. IVIG can interact and bind onto complement factors, which can prevent complement-mediated tissue damage, modulate T-lymphocytes, alter cytokine profiles, and modulate the immune system. These interactions can act alone or in combination to maintain immune balance while preserving homeostasis. A consensus panel was convened in 2000 to evaluate and define new advances in IVIG therapies. (J Allergy Clin Immunol 2001;108:S139-46.)
Clinical Application and Functional Mechanisms of Intravenous Immunoglobulin: an Overview
2015
Submitted 5 Dec 2014; Accepted 8 Jan 2015; Published 8 Mar 2015 Previous, Intravenous Immunoglobulin (IVIG) has been used for treatment of patients with immunodeficiency. However, recent studies have shown that IVIG is a suitable approach for treatment of inflammatory and autoimmune diseases. Although the exact mechanism of IVIG action is not well known, but recent findings have demonstrated the IVIG effects on expression and function of FC receptors of immunoglobulins, modulation of complement activation and cytokines. In addition, IVIG regulates the cell proliferation, and it can affect T, B and dendritic cells differentiation. Correspondingly, its side effects are classified into three categories, including immediate side effects (which can occur during infusion, including anaphylaxis reactions, facial flushing, and dyspnea), delay effects (which occurs in a few hours or a few days after the injection as side effects on the skin, lung, kidney, aseptic meningitis, arthritis, cereb...
Intravenous immunoglobulin-induced acute thrombocytopenia
Transfusion, 2018
Intravenous immunoglobulin (IVIG) has known efficacy in various hematologic conditions, including immune thrombocytopenic purpura. We present the clinical course of a patient with splenic marginal zone lymphoma, who developed acute thrombocytopenia on three consecutive episodes, with nadir counts of 27 × 10, 50 × 10, and 9 × 10/L, upon administration of Intratect IVIG for hypogammaglobulinemia. An immunofluorescence test applying flow cytometry and monoclonal antibody immobilization of platelet antigens (MAIPA) assay were used to evaluate the reaction between IgG present in the IVIG preparations and the patient's or healthy donors' platelets (PLTs). A strong direct binding reaction was observed between the patient's PLTs and Intratect IgG using both methods. A similar reaction failed to materialize with controls. Binding was not antigen specific according to MAIPA. This is the first reported case of thrombocytopenia as a possible adverse effect of IVIG.