Dose Of Intravenous Immune Globulin Research Articles

Thrombocytopenia Associated with Elemental Mercury Poisoning in Two Siblings - Connecticut, July 2022.

Two siblings aged 5 and 15 years from Connecticut were hospitalized with petechial rash, oral mucositis, and severe thrombocytopenia approximately 10 days after they played with a jar of elemental mercury they found in their home. Before the mercury exposure was disclosed, the siblings were treated with platelet transfusions, intravenous immune globulin (IVIG) for possible immune thrombocytopenic purpura, and antibiotics for possible infectious causes. When their conditions did not improve after 6 days, poison control facilitated further questioning about toxic exposures including mercury, testing for mercury, and chelation with dimercaptosuccinic acid. The older sibling soon recovered, but the younger child required a prolonged hospitalization for severe thrombocytopenia, ultimately receiving repeated doses of IVIG, steroids, and romiplostim, a thrombopoietin receptor agonist. Close collaboration among multiple agencies was required to identify the extent of mercury contamination, evaluate and treat the other family members, and decontaminate the home. These cases demonstrate the importance of ongoing public health outreach to promote early detection of elemental mercury toxicity, and the need to evaluate for environmental exposures when multiple close contacts experience similar signs and symptoms.

Iatrogenic ANA: An emerging source of expensive diagnostic confusion.

Intravenous immune globulin (IVIg) therapy has been shown to be useful in a multitude of disorders. IVIg is produced from pooled human plasma; therefore, autoantibodies found in the general population are also present in IVIg and transferred to those being transfused. This can prove a particular hazard for screening and diagnostic tests based on autoantibodies. We present a patient who was found to have a positive antinuclear antibody (ANA) titer after multiple IVIg transfusions, resulting in diagnostic confusion and unnecessary workup. A 45-year-old gentleman was diagnosed with atypical CIDP, initiated on a course of IVIg, and sent for inpatient rehabilitation. However, recovery was complicated by multiple readmissions for recurrent weakness, and as part of the workup for other etiologies, an ANA was found to be positive. Sub-serologies and paraneoplastic autoantibody panel were negative. In the absence of clinical symptoms, we recommended continued monitoring and repeat ANA testing 6months after the last dose of IVIg; as any drug needs 5 half-lives to be eliminated from the body. Clinicians should consider any recent IVIg treatments when evaluating the pre-test probability of detecting an underlying connective tissue disease with ANA screening. Indiscriminate ANA levels in patients recently given IVIg lead to unnecessary and expensive further testing and consultation.

Acute lower limb ischemia caused by vaccine-induced immune thrombotic thrombocytopenia: focus on perioperative considerations for 2 cases

BackgroundChAdOx1 nCoV-19 (AstraZeneca) and Ad26COV2.S (Johnson & Johnson/Janssen) adenoviral vector vaccines have been associated with vaccine-induced immune thrombotic thrombocytopenia (VITT). Arterial thrombosis and acute limb ischemia have been described in a minority of patients with VITT. These patients usually need a revascularization, but they potentially are at a higher risk of complications. Optimal perioperative care of patients undergoing vascular surgery in acute VITT is unknown and important considerations in such context need to be described.Cases presentationsWe report 2 cases of VITT presenting with acute limb ischemia who needed vascular surgery and we describe the multidisciplinary team decisions for specific treatment surrounding the interventions. Both patients’ platelet counts initially increased after either intravenous immune globulin (IVIG) or therapeutic plasma exchange (TPE). None received platelet transfusion. They both received argatroban as an alternative to heparin for their surgery. Despite persistent positivity of anti-platelet factor 4 (PF4) antibodies and serotonin-release assay with added PF4 (PF4-SRA) in both patients, only one received a repeated dose of IVIG before the intervention. Per- and post-operative courses were both unremarkable.ConclusionIn spite of persistent anti-PF4 and PF4-SRA positivity in the setting of VITT, after platelet count improvement using either IVIG or TPE, vascular interventions using argatroban can show favorable courses. Use of repeated IVIG or TPE before such interventions still needs to be defined.

Rate of Rise of Platelet Count After IVIG for Pediatric Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease causing platelet destruction, and is a common cause of symptomatic thrombocytopenia in children. Intravenous immune globulin (IVIG) is a treatment for ITP that increases the platelet counts of most patients within 24 to 48 hours. This study aimed to calculate the rate of rise in pediatric ITP after a dose of IVIG and to analyze if patient characteristics affected the rate. For 116 children treated for ITP with IVIG at Hershey Medical Center, the rate of rise of the platelet count for all patients was calculated. The rate of rise ranged from -0.1 to +4.2 K/µL/hour (average 1.3, median 1.2). 78% of patients had a rate of rise of over 0.5 K/µL/hour. There was a statistically significant correlation between the rate rise of the platelet count and the initial platelet count (P=0.0197), but rate was not affected by age or sex. This study was able to demonstrate that IVIG is effective in most patients and that demographic features do not affect the rate of rise. By providing a nomogram showing when to expect a meaningful rise in the platelet count after IVIG, we give guidance for timing of the postinfusion platelet count to avoid administering a second dose. Future studies are needed to test this nomogram prospectively.

Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes

BackgroundThe assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy.MethodsWe analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2.ResultsA total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score–matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score–matched analysis.ConclusionsAmong children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.)

Use of premedication with intravenous immune globulin in Kawasaki disease: A retrospective review.

Kawasaki disease (KD) is a significant febrile illness in children and is the leading cause of acquired pediatric heart disease in developed countries. Its recommended treatment is high-dose intravenous immune globulin (IVIG) plus aspirin. However, IVIG-related adverse events are seen frequently in this population. Premedication is commonly used to reduce this risk, but evidence supporting this practice is conflicting. Ultimately, practices vary among institutions and no standard guidelines regarding IVIG premedication currently exist. Electronic medical records for pediatric patients presenting to an academic, tertiary care medical center diagnosed with KD and who received at least one dose of IVIG were reviewed for: patient demographics, treatment characteristics, premedication use, adverse events, and coronary abnormalities at discharge. Descriptive statistics were used to evaluate study findings. Sixty-six patients receiving a total of 81 distinct IVIG administrations were evaluated. Most patients (64/66, 97%) were premedicated prior to infusion with 26% of patients (17/66) experiencing an IVIG-related adverse event, totaling 25 documented adverse events. The most common events included chills and vomiting. Overall, the average duration of hospitalization was 4.37days. Despite appropriate medication management, five patients (7.6%) developed coronary abnormalities. Practitioners demonstrated a widespread use of premedication for IVIG. However, 26% of patients still experienced an adverse event. While premedication was not shown to have an adverse impact on patient outcomes, it also did not demonstrate a notable reduction from a historic adverse event incidence.

What Is in the Literature.

What is in the Literature focuses on peripheral neuropathies with new and practical information related to the diagnosis, treatment, and management. Diagnostic and treatment guidelines are available for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but not all clinicians follow them resulting in erroneous diagnoses and prolonged treatment. Secondary axonal loss in CIDP causes increased connective tissue in muscle. Antibodies to proteins at the node of Ranvier are found in a small percentage of patients with CIDP. The differential diagnosis for CIDP-like neuropathies includes amyloid neuropathy and POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) and amyloidosis. Upper limits for cerebral spinal fluid protein are 0.45 g/L and cell count <10/µL, but both may be too low. Hyperactive reflexes may occur in Guillain-Barré syndrome and should not exclude the diagnosis. In severely affected Guillain-Barré syndrome patients, a second dose of intravenous immune globulin within 4 weeks of onset is not likely to be effective.

Striational Muscle Antibody Positivity Heralding a Diagnosis of Autoimmune Encephalitis associated with Epiglottic Squamous Cell Carcinoma: A Case Report

A 59 yo woman presented to our emergency room with confusion, spells of loss of awareness over four weeks with malaise, weakness, gait difficulties, and 30 lb weight loss over one year. Brain imaging was unremarkable. EEGs revealed diffuse slowing, triphasic GPDs, and left temporal epilepti form discharges. Spinal fluid showed an elevated protein count. She received a working diagnosis of autoimmune encephalitis and received steroids and antiepileptic medications. She experienced an improvement in symptoms and went home. Follow up revealed elevated striational muscle antibodies and enhancement of spinal nerve roots suggesting an autoimmune neurological syndrome. She received intravenous immune globulin (IVIg) therapy and had periods of improvement followed by worsening a few months later with each dose of IVIg. She presented to the hospital a year with worsening dysphagia and an endoscopy showing an epiglottic mass. Pathology confirmed squamous cell carcinoma, and she received chemotherapy and radiation. We wish to share this rare case of autoimmune encephalitis presenting with only striational antibodies as a heralding sign of a tumor. We postulate that, in the correct context, the presence of striational antibodies alone, despite low titers, may support a diagnosis of autoimmune encephalitis from underlying malignancy.

Intravenous Immune Globulin (IVIG) for Treatment of Autoimmune Heparin-Induced Thrombocytopenia: A Systematic Review.

To evaluate intravenous immune globulin (IVIG) for autoimmune heparin-induced thrombocytopenia (aHIT), including platelet recovery, IVIG dose, dosing weight, IVIG product used, and complications reported. PubMed and EMBASE were searched from inception through June 21, 2020. Search terms included heparin-induced thrombocytopenia, HIT, intravenous immune globulin, IVIG, autoimmune HIT, aHIT, and immune globulin. Patients administered IVIG for HIT and diagnosed by immunoassay (optical density ≥2) or positive activation assay were included. Twenty-four cases were reviewed; 92% had persistent aHIT. Time to IVIG administration post-nonheparin anticoagulant initiation was 9 days (median). Most common IVIG cumulative dose was 2 g/kg (dosed as 1 g/kg/d for 2 consecutive days); 75% had a favorable platelet increase (≥50 × 109/L) within 5 days of initial IVIG dosing. aHIT is characterized by critically low platelets, thrombosis, and a persistent delay in platelet recovery despite treatment with a nonheparin anticoagulant. An immunoassay and subsequent confirmatory activation assay (at low, high, and 0 IU/mL unfractionated heparin levels) is recommended to confirm diagnosis. Patients nonresponsive to nonheparin anticoagulants within 5 days of initiation should be evaluated for IVIG treatment (2 g/kg cumulative dose). More data are needed to clarify appropriate IVIG dosing weight, although based on current published literature, it is recommended to use actual body weight. Data reported support use of IVIG as adjunctive therapy for patients with aHIT. Judicious IVIG use based on key clinical and laboratory findings is critical.

Cytomegalovirus Induced Thrombocytopenia with No Platelets in an Immunocompetent Young Male

Introduction Immune thrombocytopenic purpura (ITP) is a common cause of acquired thrombocytopenia in an otherwise asymptomatic adult. It is generally believed to be caused by auto- antibodies against platelet antigens that destroy platelets peripherally and autoreactive cytotoxic T cells, as well as humoral and cellular autoimmunity directed at megakaryocytes, causing impaired platelet production. Cytomegalovirus (CMV) is a known cause of cause of morbidity and mortality in patients with immunosuppressed states, whereas in immunocompetent patients, it commonly manifest as asymptomatic or mononucleosis like syndrome. We are presenting a case of CMV induced thrombocytopenia with severe epistaxis and platelet count of 0 x10 9 in an otherwise healthy immunocompetent male who failed to improve after standard treatments with high dose steroids and intra venous immune globulin (IVIG). Case Description A 36-year-old Caucasian male without any past medical history presented to emergency room (ER) with flu like symptoms for five days associated with subjective fevers, anorexia, nausea, cough and weight loss of 15 lb. in two weeks. He also reported possible tick bite while working in the yard two days prior to admission. No dizziness, vomiting, diarrhea or any bleeding were reported. Denied any smoking, alcohol use or any illicit drug use. No significant family history was reported. On evaluation he was afebrile, normotensive with normal heart rate and respiratory rate. Physical examination was unremarkable. Initial laboratory data revealed hemoglobin of 11.2, platelet count 4 x109, white cell count of 13,100 with 4.5% atypical lymphocytes, aspartate aminotransferase of 41, alanine aminotransferase of 49, and creatinine of 1.4. He tested positive for Influenza A, CMV Immune globulin (Ig)M and IgG antibody. Serological tests for tick panel including anaplasma, babesia, Lyme disease and ehrlichia were negative. Epstein-Barr virus (EBV) antibody, parvo virus antibody, hepatitis screen, HIV screen, auto antibodies including anti-nuclear antibody and anti-double stranded DNA were negative. Coombs test was negative. Further work up includes ADAMTS13 activity was normal. No laboratory evidence of ADAMTS13 deficiency. After excluding all other causes, diagnosis of ITP was made. He was started on Tamiflu for Influenza A and high dose intra venous (IV) methyl prednisone for ITP. After platelet transfusion and two days of IV steroids platelet count improved 43 x 109 and he was discharged home with prolonged prednisone taper. Five days later, he presented to ER with severe epistaxis. Laboratory data revealed platelet count of 0 x109. Serum CMV-DNA was determined by PCR showed viral load of 8,790 copies/ml. Ultrasound abdomen showed mild splenomegaly. He received three doses of IVIG (1g/kg). Platelet count failed to improve after administration of IVIG. Bone marrow biopsy revealed hyper cellular marrow with trilineage hematopoiesis with no increase in CD 34 blasts. Per infectious disease and hematology recommendations, he was started on valganciclovir (900 mg PO BID). One month later, platelet count improved to 150 x 109 and CMV viral load dropped to 413 with subsequent resolution of patient's symptoms. Discussion Secondary ITP is an acquired thrombocytopenia caused by autoantibodies against platelets. Many patients with ITP are asymptomatic. For those who do have symptoms, initial presentations of ITP are petechiae, purpura and epistaxis, with a more severe progression to intracranial hemorrhage or gastrointestinal bleeding leading to a fatal outcome, if treatment is not started on a promptly manner. CMV induced thrombocytopenia in immunocompetent adults seems to be rare. we are presenting a case of CMV induced ITP which failed to improve after standard treatment with high dose steroids and IVIG but responded to anti-viral therapy with valganciclovir. In conclusion, it may be worthwhile to test for CMV infection in patients presenting with ITP. Further research is needed in order to establish treatment guidelines for CMV induced ITP in immunocompetent adults. Disclosures No relevant conflicts of interest to declare.

Perioperative Eltrombopag or Intravenous Immune Globulin for Patients with Immune Thrombocytopenia: A Multicenter Randomized Trial

Background: Patients with immune thrombocytopenia (ITP) may require treatment to raise the platelet count before surgery. Intravenous immune globulin (IVIG) is commonly used for this purpose, but eltrombopag, an oral thrombopoietin receptor agonist, may be a good alternative. We compared perioperative eltrombopag or IVIG for the achievement of platelet count targets for major or minor surgery. Methods: We conducted a randomized, non-inferiority trial at 8 centers in Canada.ITP patients with a platelet count &amp;lt;100 x109/L or &amp;lt;50 x109/L before elective major or minor surgery, respectively, were assigned to receive daily oral eltrombopag starting 3 weeks preoperatively or IVIG 1 week preoperatively. Eltrombopag was discontinued 1 week after surgical hemostasis, and a repeat dose of IVIG was permitted up to 1 week after surgical hemostasis. The primary endpoint was the achievement of platelet count targets (90 x109/L for major surgery, or 45 x109/L for minor surgery) immediately before surgery and for 7 days after surgical hemostasis without rescue treatment. Intention-to-treat and per-protocol analyses were done using a one-sided test for the difference in rates of achieving perioperative platelet count targets with a non-inferiority margin of 10% at a significance level of 0.05. Patients were followed for 4 weeks postoperatively. Secondary outcomes were thrombosis, adverse events and treatment satisfaction as measured using a validated patient questionnaire. Results: From 2013 to 2019, 38 patients were assigned to received eltrombopag and 36 patients were assigned to receive IVIG before major (n= 31) or minor (n= 43) surgery. Five patients did not complete the study. By intention to treat, 30/38 (78.9%) patients on eltrombopag achieved perioperative platelet count targets compared with 22/36 (61.1%) on IVIG (absolute risk difference, 17.8%; one-sided lower limit of the 95% confidence interval, 0.4%; p=0.005 for non-inferiority). Results were similar in the per protocol analysis (absolute risk difference: 15.8%; one-sided lower limit of the 95% CI, -2.1%; p=0.009). Eltrombopag was superior to IVIG in the intention-to-treat analysis (p=0.047) but not in the per-protocol analysis (p =0.074). One patient developed pulmonary embolism 14 days after minor surgery (skin biopsy) and 7 days after stopping eltrombopag when the platelet count was 135 x109/L. Of 18 patients who underwent splenectomy on study, marked post-splenectomy thrombocytosis (platelets &amp;gt;1,000 x109/L) occurred in 2 (11.1%) patients, both of whom were on eltrombopag. Global treatment satisfaction scores were higher for eltrombopag. Conclusion: Eltrombopag is non-inferior and may be superior to IVIG for achieving target platelet counts perioperatively for patients with ITP. Post-operative thromboprophylaxis should be considered with eltrombopag. Funding Source:This was an investigator-initiated trial funded by Novartis. Disclosures Arnold: Novartis: Honoraria, Research Funding; Rigel: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Principia: Consultancy. Heddle:Novartis: Research Funding. Hsia:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sholzberg:Novartis: Honoraria; Amgen: Honoraria, Research Funding. Lin:Pfizer: Consultancy; Novartis: Research Funding; Octapharma: Research Funding; Amgen: Consultancy. Larratt:Novartis: Honoraria. Amini:Amgen NL: Research Funding; Novartis NL: Research Funding. Schipperus:Novartis: Research Funding. Lim:Pfizer Canada: Consultancy, Honoraria; Portola Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Honoraria. OffLabel Disclosure: Eltrombopag is not licenced for perioperative treatment in patients with ITP.

Safety of intravenous immune globulin in an outpatient setting for patients with neuromuscular disease

Although intravenous immune globulin (IVIg) is used to treat patients in the outpatient setting, there is limited documentation addressing the safety of this practice. Retrospective analysis of 438 patients with neuromuscular diseases receiving IVIg in an outpatient setting. Adverse events (AE) overall occurred in 16.9% of patients. Headache was the most common AE, noted in 11.6% of patients. Serious AEs occurred in 0.91% of patients; aseptic meningitis was the only one noted. Multivariate analyses identified the following risk factors for AEs: first-lifetime course of IVIg, higher dose per course of IVIg, diagnosis of myasthenia gravis, women, and younger age. Intravenous immune globulin is generally safe to administer in an outpatient setting. Women, myasthenia gravis patients, and those receiving their first course or a higher total dose of IVIg are at an increased risk of experiencing an AE.

Medication stewardship using computerized clinical decision support: A case study on intravenous immunoglobulins.

BackgroundHealthcare delivery organizations face increasing pressure to manage the use of medications in terms of safety, waste reduction, and cost containment.ObjectiveTo describe a computerized provider order entry (CPOE) system intervention to optimize use of a commonly ordered, high‐cost therapeutic: intravenous immune globulin (IVIG).DesignDescription of IVIG order configuration, medication use patterns, and subsequent order set configuration development in a CPOE system.MeasurementsIVIG orders were extracted from the CPOE system before and after the implementation of a specialty orderset to determine the indications for use, dosing, and duration of therapy. Orders were compared to a theoretical dosing schedule created from published evidence and data from a prior medication use evaluation.ResultsDuring 36 months before the implementation of the IVIG order set, 1965 IVIG orders were reviewed. The prescribed IVIG dose varied considerably from the expected dose (mean = −1.8, range = −4.9‐1.5). In the 27 months after order set implementation, 848 IVIG orders were reviewed. The prescribed IVIG dose was closer to the expected dose (mean = −1.2, range = −3.9‐2.6, P < .0001).ConclusionsOrder configuration processes are cumbersome and time‐consuming, but can be streamlined to enhance a medication’s usage in the healthcare system. A better understanding of institution‐specific ordering patterns may facilitate more efficient and effective order configuration and optimize drug use.

Cervical and Lumbosacral Radiculoplexus Neuropathy Following Influenza Vaccination

Acute cervical radiculoplexus neuropathy contralateral to influenza vaccination preceded proximal and distal leg weakness, sensory loss and corresponding deficits of lumbosacral radiculoplexus neuropathy. Treatment with pulse corticosteroids followed by tapering oral corticosteroids and monthly low dose intravenous immune globulin was associated with eventual improvement.

Treatment strategy of childhood immune thrombocytopenia

Immune thrombocytopenia (ITP) of childhood is the most common hemorrhagic disease which is characterized by isolated thrombocytopenia.Depending on individual patient characteristics, appropriate initial management for newly diagnosed ITP may be either watchful waiting or pharmacologic intervention.The main options for initial pharmacologic intervention include a single dose of intravenous immune globulin(IVIG)and/or a short course of glucocorticoids.For ITP children with severe or life-threatening bleeding, it is recommended that both platelet transfusions and the combination of pharmacotherapy.Approximately 20 percent of children who present with ITP will progress to chronic ITP(CITP). Children who develop CITP should have an additional evaluation to exclude other disorders.The pharmacologic options for CITP include Rituximab, and thrombopoietin (TPO)/TPO receptor agonist (Romiplostim or Eltrombopag). Combination therapy and novel immunological targeting drugs become more effective treatment options.Splenectomy is only suit for a small number of children with chronic refractory ITP patients who present significant and persistent hemorrhagic symptoms requiring repeated pharmacologic interventions. Key words: Immune thrombocytopenia; Treatment; Child

Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy

AbstractIn patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk of thromboembolic events (TEEs), with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this retrospective cohort study of older patients with CLL or MM identified from the Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed rates of clinically serious TEEs in 2724 new users of IVIg and a propensity-matched comparison group of 8035 nonusers. For the primary end point, arterial TEE, we observed a transient increased risk of TEE during the day of an IVIg infusion and the day afterward (hazard ration = 3.40; 95% confidence interval [CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment cycle. When considered in terms of absolute risk averaged over a 1-year treatment period, the increase in risk attributable to IVIg was estimated to be 0.7% (95% CI: −0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end point. A statistically nonsignificant risk increase of 0.3% (95% CI: −0.4%, 1.5%) compared with a baseline risk of 1.1% was observed for the venous TEE end point. Further research is needed to establish the generalizability of these results to patients receiving higher doses of IVIg for other indications.

Hemolytic events associated with intravenous immune globulin therapy: a qualitative analysis of 263 cases reported to four manufacturers between 2003 and 2012.

Objectives of this study were to identify possible patient and product risk factors for intravenous immune globulin (IVIG)-associated hemolysis, a recognized side effect of IG therapy; analyze IVIG indications; and examine dose levels (g/kg body weight) and total IVIG dose administered. Reports of IVIG-associated hemolysis for 10 years (2003-2012) for four participating IG manufacturers were identified using a uniform case definition (Standardized MedDRA Query "Hemolytic disorders," Broad Scope, Version 16.0) and analyzed. IVIG-associated hemolysis appears to occur predominantly at dose levels exceeding 0.5 g/kg, with 72% of cases with known dose information having dose levels between 1 and 2.5, and can affect patients at any age, without a clear gender preference. No association was found between hemagglutinin exposure and development of hemolysis, nor between dose levels and odds of receiving a transfusion to treat hemolysis. Patients with blood group AB may be at higher risk of hemolysis than those with group A or B. Data examined confirm that IVIG-associated hemolysis predominantly occurs following infusion of high IVIG doses, and can affect patients at every age of both genders. While presence of hemagglutinins appears to play a major role in pathogenesis of hemolytic disorders, high hemagglutinin titers of IVIG products themselves seem to be of less relevance, indicating that the pathomechanism of IVIG-associated hemolysis may be related to the presence, but not the absolute amount, of hemagglutinins. Patients with hemolysis had additional hemolytic risks such as multiple comorbidities and medication use. IG-treated patients with multiple risks should be closely monitored for hemolysis.

Enhanced Anti-Diabetogenic Effect of Intravenous Immune Globulin Modified by Ferrous Ion Exposure

The aim of this study was to investigate the immunomodulatory capacity of native and Fe(II)-exposed intravenous immune globulin (IVIg) in multiple low dose streptozotocin-induced diabetes and to delineate the mechanisms of their influence on immune cell functions. Optimal doses (200–600mg/kg) of IVIg prevented the development of hyperglycemia, glycosuria and attenuated mononuclear cell infiltration in pancreatic islets. Fe(II) exposure of IVIg decreased their optimal therapeutic dose to 100mg/kg which significantly decreased the serum levels of proinflammatory cytokines compared to the same dose of native IVIg. This was accompanied by lower numbers of TNF-α, IFN-γ and IL-17 producing CD4+ T cells and increased frequencies of CD4+IL-10+ and CD4+IL-4+ T cells in the pancreatic lymph nodes and islets on day 16 after diabetes induction. Ferrous ion-exposed IVIg enhanced the bias towards Th2 response while the regulatory Foxp3+ T cells were not affected.

Corticosteroids Plus Intravenous Immune Globulin (IVIg) Versus Corticosteroids Alone In The Treatment Of Newly Diagnosed Primary Immune Thrombocytopenia In Adults: A Retrospective Study

Background Primary immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by the immunologic destruction of platelets defined as a peripheral platelet count &lt; 100 x109/L in the absence of other causes or disorders that may be associated with thrombocytopenia. Corticosteroids are generally utilized as the initial agent of choice in the first-line treatment for newly diagnosed ITP in non-emergent situations. There is limited evidence available to help guide the use of intravenous immune globulin (IVIg) in the management of newly diagnosed ITP except in cases of emergent bleeding. It is unknown whether the addition of IVIg to corticosteroids leads to improved short-term or long-term outcomes. We conducted a retrospective study to investigate whether the addition of IVIg to corticosteroid therapy improved time to response and duration of response in the treatment of adults with newly diagnosed primary ITP. Methods Patients 18 years of age or older who were hospitalized with newly diagnosed primary ITP with an initial platelet count ≤30 x 109/L were identified from charts dating January 2000 until January 2010. Excluded patients included those with a history of previously treated ITP, HIV, hepatitis C, cirrhosis, active pregnancy, active infection requiring concurrent antibiotic therapy, concomitant malignancy requiring chemotherapy, active rheumatologic disease, and recent use of medications associated with drug-induced ITP. Data collected included rates of bleeding, initial and serial platelet counts, and dose and formulation of steroid and IVIg used. Endpoints of interest were time to achieve partial response (PR; defined as a platelet count ≥30 x 109/L), time to achieve complete response (CR; defined as platelet count ≥100 x 109/L), duration of PR, and duration of CR. Chi-square tests were used to determine statistical differences between categorical variables; continuous variables were compared using the Mann-Whitney test. Time-to-event analyses were performed using Kaplan-Meier log-rank tests. P-values &lt;0.05 were considered statistically significant. Results Fifty patients were identified of whom 29 (58%) were female and 21 (42%) were male. The median age of patients was 56 (range 19-96). Four patients (8%) presented with Grade III or IV bleeding. Twenty-two patients (44%) were given IVIg in the first three days of treatment concomitantly with steroids, and the remainder of patients (56%) was given steroids only. Ninety-one percent (20/22) of patients in the IVIg + steroids group achieved a PR, while 93% (26/28) of patients achieved a PR in the steroids alone group (p=0.80). Seventy-eight percent (17/22) of patients in the IVIg + steroids group achieved a CR, whereas 79% (22/28) of patients achieved a CR in the steroids alone group (p=0.78). Of those who achieved PR, the median time to achieve PR was 2 days versus 3 days in the IVIg + steroids group and steroids alone group, respectively (p=0.56). The median time to achieve CR was 10 days versus 22 days, respectively, with a trend toward statistical significance (p=0.11). Median duration of PR was not significant between the IVIG + steroids and steroids alone groups (median duration 646 days versus 893 days, respectively; p=0.83). Median duration of CR was not reached for the IVIg + steroids group and was 394 days in the steroids alone group (p=0.44). Discussion Patients diagnosed with acute primary ITP are typically treated with steroids, but no clear guidelines exist regarding who would benefit from the addition of IVIg. While the data suggests a trend towards a shorter time to achieving PR and CR as well as a trend toward longer duration of response in patients who received IVIg in addition to steroids, the differences are not significant in our cohort, probably due to small sample size. Rates of achievement of PR and CR were not different between the two groups. In an era focused on providing cost conscious health care, the lack of benefit from the addition of IVIg to corticosteroids could be a potential cost-saving measure. Further data in a larger retrospective study may improve the ability to discern a statistically significant difference between these two groups and further validation is needed through a prospective study. Disclosures: No relevant conflicts of interest to declare.

Romiplostim: A Bridge To Splenectomy In Three Patients With Refractory Immune Thrombocytopenia (ITP)

Background Ten to thirty percent of patients with immune thrombocytopenia (ITP) do not respond to initial therapy. Options for such patients include Rituximab, TPO-mimetic agents and splenectomy. We report on three patients with refractory ITP and significant thrombocytopenia who received romiplostim as a bridge to splenectomy. Methods Three patients with isolated ITP or Evans syndrome did not respond to steroids, intravenous immune-globulin (IVIG) or Rituximab. Romiplostim was given to increase the platelet count prior to laparoscopic splenectomy. Before surgery the bone marrow was evaluated and patients were vaccinated. We reviewed their baseline clinical characteristics, and clinical course. Results Patient 1: 51 y/o M presented with fatigue and melena. Laboratory data showed hemoglobin (Hgb) of 7.9 g/dl, platelet (plt) count of &lt; 2,000/uL, LDH of 997 U/L, reticulocyte count of 7.5 % and positive direct Coombs test. Prednisone and IVIG were started with improvement in Hgb but plt count remained &lt; 2000/uL. Rituximab was started on day 7 with no response in plt count after 4 doses. Weekly romiplostim was started on day 37 with no response after 3 doses and then pt was lost to follow up. He presented two months later with plt count of &lt; 2,000/uL and was treated with IVIG with transient response and restarted on Romiplostim. Plt count reached to 93,000/uL with a dose of 6 mcg/kg of romiplostim. He was maintained on romiplostim for a total of 19 doses and then underwent laparoscopic splenectomy. Platelet counts pre-op were 294,000/uL, post-op rose to 1,261,000/uL but normalized afterwards and he has been off all treatment for more than two years (figure 1). Patient 2: 28 y/o F presented with bruising and plt count of 12,000/uL. She was treated with 5 days of dexamethasone with transient improvement in plt count to 50,000/uL which rapidly dropped to &lt; 2,000/uL. Despite daily prednisone and IVIG, plt count continued to be &lt; 2000/uL and weekly rituximab was started on day 7. On day 14, plt count continued to be &lt;10,000/uL and weekly romiplostim was initiated at 1 mcg/kg and increased weekly for four weeks when the plt count reached 61,000/uL after receiving 4 mcg/kg. Patient then underwent laparoscopic splenectomy. Post-op platelet count increased to 1,053,000/uL which returned to normal afterwards and remained so off all treatment at nine months follow up after splenectomy. Patient 3: 66 y/o M with coronary artery disease and long standing ITP was on prednisone 10-20 mg/day with plt count of 10-20,000/uL. Because of side effects of steroids, he was treated with danazol and rituximab (6 weeks) with no response in plt count. Cardiac catheterization prior to splenectomy could not be done because of thrombocytopenia. Romiplostim was then started at dose of 1 mcg/kg and advanced weekly to 3 mcg/kg with improvement in counts to 60,000/uL with peak of 200,000/uL. Cardiac catheterization was normal and he underwent successful laparoscopic splenectomy. Plt count before splenectomy was 73,000/uL and increased to 513,000/uL post-op. The plt count decreased to 120,000/uL and has remained stable for more than two years without further treatment. Conclusions Rituximab and TPO-mimetic agents are increasingly used for treatment of relapsed, refractory ITP as an alternative to splenectomy. Rituximab has a significant relapse rate. TPO-mimetic agents are expensive, require lifelong use, and are associated with rebound thrombocytopenia in those who stop treatment. Long-term use has also been associated with reversible bone marrow fibrosis and thromboembolism. Laparoscopic splenectomy is a safe procedure that is ideally done after a platelet response to high dose steroids and/or IVIG to reduce bleeding risk. Two of our patients were refractory to Rituximab. One received Rituximab concurrently with Romiplostim. All 3 patients did not want long term treatment with a TPO agent and had low platelet counts that were an impediment to surgery. We found that a short course of Romiplostim increased the platelet counts enough to enable surgery. All 3 patients achieved sustained remissions requiring no further treatment. No rebound thrombocytopenia was observed after stopping Romiplostim and none of the patients had bleeding or thrombotic complications. This case series suggests that a short course of Romiplostim can be used safely and effectively as a bridge to splenectomy for patients with refractory ITP. Disclosures: No relevant conflicts of interest to declare.