High-dose Intravenous Immunoglobulin Administration Research Articles

Hemolytic anemia associated with intravenous immunoglobulin in Kawasaki disease

BackgroundThe administration of high-dose intravenous immunoglobulin (IVIG) is a standard treatment for the management of Kawasaki disease (KD). IVIG is known to be a highly effective and safe treatment.Case presentationWe report the development of hemolytic anemia in seven children receiving repeated doses of IVIG. The children were aged 3–44 months and included 4 girls and 3 boys. All children received 10% IVIG and a second course of immunoglobulin because they did not respond to the first course of immunoglobulin. Two received high-dose aspirin (50 mg/kg), and five received low-dose aspirin (5 mg/kg). Two patients required additional methylprednisolone pulse therapy (30 mg/kg) after the second dose of immunoglobulin, and three patients received oral prednisolone therapy for defervescence. Three patients showed coronary artery dilation during hospitalization and normalized within two months. Pretreatment hemoglobin averaged 11.3–14.2 g/dL, and post-hemolytic anemia hemoglobin ranged from 7.4 to 9.6 g/dL, with a difference of 1.7–6.8 g/dL. Reticulocytes were increased to 3.3–13.2%. Peripheral blood smears showed normochromic normocytic anemia, and anisopoikilocytosis. All children were positive for warm-type antibodies with IgG+, C3d- in direct antiglobulin test, and the blood group was A + in five and B + in two. None of the patients received immunomodulatory therapy or red blood cell transfusions. They were followed for a year and all recovered.ConclusionEspecially, in non-O blood group KD patients who are refractory to initial IVIG and require a second dose of IVIG or 10% formulation the possibility of immune hemolytic anemia should be carefully considered, and close follow-up should be maintained after therapy.

Toxic Epidermal Necrolysis Syndrome Following Single-Dose Diclofenac Suppository, A Case Report

Introduction: Toxic Epidermal Necrolysis (TEN) is a severe disease with high mortality, which can occur following the administration of some drugs such as antibiotics, anticonvulsants and non-steroidal anti-inflammatory drugs (NSAIDs). The condition is rare in children; therefore, providing a therapeutic experience and methods of care can be very helpful in similar cases. Case Presentation: A 32-month-old girl (2.8 years) was admitted at Mousavi Hospital of Zanjan (Iran) presenting weakness, illness, scattered macular lesions on the trunk and extremities, and several blisters on the trunk. He had a history of upper respiratory tract infection and had been administered a diclofenac suppository for fever. All the clinical manifestations appeared after diclofenac administration. The lesions rapidly progressed to extensive cutaneous necrosis with the involvement of more than 70% of the body surface. He was treated with high-dose intravenous immunoglobulin (IVIG), corticosteroid, and conservative management. Fortunately, the child was discharged in good general condition approximately one month after the onset of the illness. Conclusions: Diclofenac can cause TEN in children, even in single doses and in suppositories. The most important prognostic factors include supportive therapy, contact isolation, hand hygiene, and administration of high dose IVIG for at least three days.

Acute Immune Hemolytic Anemia after administration of high dose IVIG in a child with Kawasaki disease

Background: Kawasaki disease is an acute febrile illness of unknown etiology, characterized by vasculitis of medium -sized arteries with a predilection for the coronary arteries. It is the leading cause of acquired heart disease in childhood with 20-25% of untreated children developing coronary artery abnormalities. The mainstays of therapy are intravenous Immunoglobulin (IVIG) and high dose aspirin to prevent or modify the most serious cardiac sequelae. Though rare, immune-mediated hemolysis is a recognized and potentially catastrophic side effect of administration. …

Effect of High-Dose Intravenous Immunoglobulin Administration on the Levels of Interleukin-6 in Patients with Sepsis

Background: Intravenous immunoglobulin (IVIG) is administered to patients with sepsis to improve clinical outcomes. Here, we report the effectiveness of highdose IVIG therapy in patients with sepsis admitted to a teaching hospital. Methods: We analyzed 55 patients admitted to intensive care unit (ICU) due to sepsis. The patients were categorized into 2 groups depending on their IVIG dose: Patients administered high-dose (15 g/day for 3 days; total of 45 g) sulfonated human IVIG were designated the HD group, and those administered a standard divided dose (5 g/day for 3 days; total of 15 g) were designated the S group. The courses of interleukin (IL)-6 values were examined. Results: The HD and S groups comprised 13 and 42 patients, respectively. The Log10 IL-6 values on Day 1 for HD and S groups were 3.3 ± 1.0 pg/mL and 3.4 ± 0.9 pg/mL (p=0.79). The repeated two-way ANOVA revealed no statistical inter-group difference for time course between 2 groups (p=0.42). The median Sequential Organ Failure Assessment (SOFA) scores on the day of ICU admission of the HD and S groups were 13.0 and 11.0, respectively (p=0.03). The most frequency of infection sources was abdomen in two groups, and there was no statistical difference for infection sources (p=0.18). The 28 day mortality rates for the HD and S groups were 30.8% and 14.3% (p=0.17), respectively. Conclusion: This study showed that IVIG dose had no significant effect on IL-6 values despite of slightly lower course in high-dose IVIG group.

The efficacy of different dose intravenous immunoglobulin in treating acute idiopathic thrombocytopenic purpura: a meta-analysis of 13 randomized controlled trials

The purpose of this study was to compare the effects of different dose intravenous immunoglobulin for treatment of acute idiopathic thrombocytopenic purpura. Randomized controlled trials (RCTs) comparing high-dose intravenous immunoglobulin (HD-IVIG) with low-dose intravenous immunoglobulin (low-IVIG) for acute idiopathic thrombocytopenic purpura (ITP) were identified using a predefined search strategy. Effective rate, time of cessation of bleeding, time of platelet count beginning to rise, platelet count by the first week of treatment, the number of platelets after 2 weeks of treatment, time of platelet count to reach peak, peak value of platelet count after treatment, side-effects and rate of developing into chronic ITP were extracted and compared by RevMan 4.2.8 (The Cochrane Collaboration, Oxford, UK). Thirteen RCTs (646 patients) were identified. Meta-analysis showed that effective rate, time of cessation of bleeding, time of platelet count beginning to rise, platelet count by the first week of treatment, the number of platelets after 2 weeks of treatment, time of platelet count to reach peak, peak value of platelet count after treatment and rate of developing into chronic ITP were not statistically different between the two different treatment administrations. However, low-IVIG was associated with a significantly reduced risk of side-effects {odds ratio (OR) 0.39 [95% confidence interval (CI) 0.18-0.83]; P = 0.01]. In conclusion, low-IVIG can be performed as effectively as HD-IVIG without increasing the rate of developing into chronic ITP. Furthermore, the low-IVIG regimen can have fewer side-effects than HD-IVIG administration in patients with acute ITP.

Hemolytic Reaction Following Intravenous Immunoglobulin (IVIg) for Platelet Alloimmunization During Pregnancy

AbstractAbstract 4409IVIg has become standard therapy for the prevention of severe neonatal thrombocytopenia in women with platelet alloimmunization (Bussel et al. Blood Reviews 2008). A regimen of IVIg 1g/kg twice weekly is increasingly being given for this indication. Although the benefits of this regimen outweigh its risks, clinically significant hemolysis can occur. We report here the case of a 36 year old woman who experienced hemolysis requiring red blood cell transfusions after administration of high dose IVIg for platelet alloimmunization during her second pregnancy. Her first pregnancy was terminated at 24 weeks gestation for a progressive asymmetrical ventriculomegaly first identified at 17 weeks and attributed to in utero intracerebral hemorrhage. The fetal platelet count was 5 ×109/L. Platelet antibody testing in the patient demonstrated the presence of anti-HPA-1a antibodies. The patient's genotype was HPA-1b1b and her partner's, HPA-1a1b. During the subsequent pregnancy, IVIg (Gammagard Liquid®) was started at 9 weeks gestation at a dose of 1g/kg twice weekly. Fetal genotyping was done at 15 weeks and found to be HPA-1a1b. The patient's blood group was AB+. Blood tests prior to each infusion included hemoglobin level, reticulocyte count, bilirubin, LDH, creatinine, urea, glucose and IgG as per our institutional protocol. IVIg was initially well tolerated. Between the fourth and fifth treatments, the patient complained of headache and fatigue. Her physical exam was normal. The laboratory investigation demonstrated hemolytic anemia with a hemoglobin of 74 g/L (Table). Anti-A et anti-B were present in her serum. In retrospect, her reticulocyte count and LDH had started to increase before the previous IVIg infusion (Table).IVIg infusion dateHemoglobin g/L(120-160)Bilirubin μ mol/L(5-21)LDH U/L(89-177)Haptoglobin g/L(0.16-2.0)Reticulocyte count × 109/L (18-158)Sept 141021818979Sept 1710224264121Sept 24 9hAM7418298<0.06178Sept 24 8hPM73310158Sept 25 2hAM6718260Sept 25 8hAM7721279191Sept 25 2hPM9423266191Sept 2699266238Sept 2911020290188Oct 511012205121She received 2 packed red cell transfusions as well as prednisone 1mg/kg/d for one week, followed by 0.5 mg/kg/d as planned in the context of her platelet alloimmunization. She improved and her hemoglobin stabilized. Therapy was resumed with a different preparation of IVIg (Gammagard S/D®) 1g/kg twice weekly for the remainder of pregnancy, without untoward effects. Acute hemolysis has been reported with IVIg. Hemolysis in these cases is generally due to passive sensitization with antibodies to the patient's red blood cells found in commercial IVIg. Risk factors are non O blood type, female sex and high dose IVIg (Daw Z et al. Transfusion 2008). Our patient had all three risk factors. Although anti-A and anti-B antibodies are found in all commercial preparations of IVIg, no recurrence was noted in our patient. In patients with alloimmune thrombocytopenia and hemolysis secondary to IVIg, treatment options include changing the commercial preparation of IVIg and giving a lower dose of IVIg with or without prednisone. In conclusion, this case demonstrates an infrequent reaction due to IVIg administration, to which clinicians and patients need to be aware. We now routinely monitor hemoglobin level, reticulocyte count, bilirubin and LDH prior to each IVIg infusion in all patients receiving high dose therapy and if signs of hemolysis appear consider treatment adjustments. Disclosures:No relevant conflicts of interest to declare.

Intravenous immunoglobulin therapy for severe arthritis associated with human parvovirus B19 infection

Symptoms caused by acute human parvovirus B19 (HPV-B19) infection can vary considerably, from asymptomatic to severely symptomatic. A 39-year-old Japanese woman complained of sudden, severe arthralgia with edematous limbs coincident with an outbreak of HPV-B19 infection at the elementary school attended by her daughter. A diagnosis of acute HPV-B19 infection was made by the detection of serum antibody to HPV-B19 IgM and HPV-B19 DNA. Magnetic resonance imaging revealed bilateral synovitis of the cubital joints. The patient was immunocompetent and suffered from severe arthralgia associated with persistent HPV-B19 viremia for more than 4 months after the diagnosis of acute HPV-B19 infection. The administration of high-dose intravenous immunoglobulin resulted in remission, with little change in the serum HPV-B19 DNA level. Even in our immunocompetent patient, severe and prolonged arthritis was found to be associated with persistent viremia.

High-Dose Intravenous Immunoglobulin in Recurrent Postpericardiotomy Syndrome

Postpericardiotomy syndrome is a frequent complication following cardiac surgery. It is characterized by fever, chest pain, pericardial friction rub or pericardial effusion, and laboratory signs of inflammation. Treatment includes the use of nonsteroidal antiinflammatory agents, corticosteroids, and pericardial drainage. We describe a patient with chronic postpericardiotomy syndrome and steroid dependency who was successfully treated by single administration of high-dose intravenous immunoglobulin.

Alteration of biochemical profiles after high‐dose intravenous immunoglobulin administration in Kawasaki disease

Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory treatment for several immune‐mediated diseases. Early effects of high‐dose IVIG treatment on biochemical profiles including lipids and proteins were evaluated in patients with Kawasaki disease (KD). Twelve children with KD (9 boys) were treated with IVIG at 2 g/kg over a period of 12 h. Serial sera samples were collected from the patients four times: before IVIG treatment and 2 h, 24 h and 7 d after IVIG treatment. The samples were frozen at –20°C before biochemical analysis. A significant decrease in albumin concentration was found 2 h and 24 h after IVIG treatment, but this recovered to the pretreatment level after 7 d. Total cholesterol and triglyceride increased slightly after 7 d. A significant decrease in HDL‐cholesterol and C‐reactive protein was seen 2 h and 24 h after IVIG treatment. Conclusion: High‐dose IVIG affects immediate changes in protein profiles and HDL‐cholesterol in KD. Changes in HDL‐cholesterol induced by IVIG may be the result of changes in systemic protein metabolism.

Alteration of biochemical profiles after high-dose intravenous immunoglobulin administration in Kawasaki disease

Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory treatment for several immune-mediated diseases. Early effects of high-dose IVIG treatment on biochemical profiles including lipids and proteins were evaluated in patients with Kawasaki disease (KD). Twelve children with KD (9 boys) were treated with IVIG at 2 g/kg over a period of 12 h. Serial sera samples were collected from the patients four times: before IVIG treatment and 2 h, 24 h and 7 d after IVIG treatment. The samples were frozen at -20 degrees C before biochemical analysis. A significant decrease in albumin concentration was found 2 h and 24 h after IVIG treatment, but this recovered to the pretreatment level after 7 d. Total cholesterol and triglyceride increased slightly after 7 d. A significant decrease in HDL-cholesterol and C-reactive protein was seen 2 h and 24 h after IVIG treatment. High-dose IVIG affects immediate changes in protein profiles and HDL-cholesterol in KD. Changes in HDL-cholesterol induced by IVIG may be the result of changes in systemic protein metabolism.

Variable inhibition of placental IgG transfer in vitro with commercial IVgG preparations.

Maternal administration of high-dose intravenous immunoglobulin (IVIgG) for treating fetal RhD haemolytic disease and alloimmune thrombocytopenias may be beneficial. Treatment failures, even when IVIgG is used optimally, may result from product differences. Using an in vitro placental perfusion model there was significant inhibition of placental anti-D IgG transfer with three commercial IVIgG preparations where circulating maternal IgG concentrations were > 20 g/l. One IVIgG product, which was not inhibitory, had lower circulating IgG levels (16.5 +/- 0.9 g/l) and significantly reduced placental transfer of total IgG, suggesting that the reduced functional activity of IgG from IVIgG preparations may correlate with poor clinical efficacy.

Iatrogenic Central Retinal Vein Occlusion and Hyperviscosity Associated with High-dose Intravenous Immunoglobulin Administration

To describe a patient with iatrogenically induced central retinal vein occlusions secondary to serum hyperviscosity from intravenous immunoglobulin administration. Case report. The patient developed bilateral central retinal vein occlusions in association with high-dose intravenous immunoglobulins. The central retinal vein occlusions resolved when the immunoglobulins were withheld and serum hyperviscosity decreased. Administration of high-dose intravenous immunoglobulins can be associated with hyperviscosity syndrome manifested by central retinal vein occlusion.

Repeated direct fetal intravascular high-dose immunoglobulin therapy for the treatment of Rh hemolytic disease

Recently, administration of high-dose intravenous immunoglobulin (HDivIG) either to the mother or the neonate has been proposed in an effort to prevent progressive hemolysis in Rh(D) perinatal disease, but no cases have been published with direct fetal HDivIG administration. We report a case in which HDivIG was repeatedly administered by cordocentesis to a fetus affected by Rh(D) disease from 28 to 36 weeks gestation, at doses of approximately 450 mg/kg. The fetus required no transfusions, and the neonatal evolution was satisfactory. The treatment, performed at three weeks intervals, seemed to be useful in preventing fetal hemolysis. No fetal complications were present. Recurrent administration of HDivIG therapy to the fetus in cases of severe Rh(D) disease, appears to be feasible and free of serious complications to the fetus or the mother.