The most common AE was headache, followed by nausea, vomiting, dizziness, unusual taste in the mouth, abdominal pain, mood changes, and increased appetite. The most common time point to report AEs was during the to hour time period.
Headache was reported during the to hour time period by 14 out of 16 children Nausea only reported in combination with headache was reported by 6 children on regimen A and 2 on regimen B.
Two children 5-year-old male and year-old female; both randomized to regimen A developed allergic reactions upon receiving IVIG. In both cases, their reactions resolved with medical therapy; the first patient received IV diphenhydramine and acetaminophen, while the second patient received IV hydrocortisone and IV diphenhydramine.
At baseline, 31 out of 32 children had a normal Hb level. The 5 children with a positive baseline Coombs test result showed no overall difference in Hb drop compared with the other children. We must however acknowledge that by excluding previous nonresponders to IVIG, we may have selected for patients who would show a better response to IVIG. Although we found a significant intergroup difference in PCs at the hour time point, we did not find a difference at either earlier end of therapy or 8 hours or later time points 72 hours; 1 week or 3 weeks.
In the setting of an actual life-threatening hemorrhage, IV corticosteroids and IVIG would likely be continued and could potentially boost further PCs at times 24, 48, and 72 hours after the initiation of combined therapy.
We found a trend for older children to show a less brisk increment in PC. Additional findings in our study include a statistically significant drop 8. KIT scores at study enrollment were comparable to what has been reported for children with acute ITP in the past, which tend to be in the range of 65 to Our study did have limitations. It involved a relatively small number of children and unequal randomization 18 vs It was only after post-hoc adjustment for differences in patient age that we saw a statistical significance.
Also, we excluded newly diagnosed children within 24 hours of presentation and children with life-threatening bleeding. Potentially, children who initially present with life-threatening bleeds may represent a group that might respond differently to treatment. Consequently, our study is supportive of the use of combination therapy in situations of life-threatening bleeds in children with primary ITP, where it is crucial to increase the PC as quickly as possible. In such situations, we would still advocate strongly for administering a large platelet transfusion and other adjunctive hemostatic therapies eg, recombinant factor VIIa and IV tranexamic acid Funding for this study was provided through an investigator-initiated peer-reviewed grant submitted to the Bayer-Talecris-Canadian Blood Services Partnership fund.
Contribution: M. Silva, M. Steele, and V. Sign In or Create an Account. Sign In. Skip Nav Destination Content Menu. Close Key Points. Article Navigation. Manuel Carcao , Manuel Carcao. This Site.
Google Scholar. Mariana Silva , Mariana Silva. Michele David , Michele David. Robert J. Klaassen , Robert J. Victoria Price , Victoria Price. Cindy Wakefield , Cindy Wakefield. Lussia Kim , Lussia Kim. Derek Stephens , Derek Stephens. Side effects include irritability, stomach irritation, weight gain, difficulty sleeping, mood changes and acne. IVIg works quickly — within 24 to 48 hours — but its effect typically only lasts several days to a couple weeks. If initial treatments are not effective, the following treatments can be tried: Rituximab "Rituxan" — An antibody specifically directed against the type of immune system cells that can produce antibodies against platelets.
This therapy may require up to four weekly infusions. The response to treatment is usually seen in four to six weeks after the first infusion, although it can take longer. PDSA will do everything we can to assist you. It is used to treat immune deficiency and many other conditions on-label and off-label. Different companies manufacture IVIG and each brand has slightly different features and side effect profiles.
IVIG is given intravenously for a period of several hours. There are two different dosage options:. The higher-dose, shorter-term administration leads to a more rapid rise in platelet count, but higher toxicities. The most common side effects of IVIG include: headache, fever, chills, nausea or vomiting, muscle pain or chest pain. Molecular mimicry may play a role in the development of cross-reactive platelet auto-antibodies as certain viral and bacterial pathogens such as human immunodeficiency virus HIV , hepatitis C virus HCV , varicella-zoster virus VZV and Helicobacter pylori H.
Interestingly, it has been shown that some peptides from these viral proteins are recognized by anti-platelet antibodies in vitro due to the similarities between the sequences of these viral proteins and platelet GPs Although the absence of these bacterial and viral infections leads to remission in most patients with ITP, there is still a high variation in response rates in patients infected with H.
In addition, anti-platelet antibodies can mediate complement-dependent cytotoxicity, inhibit megakaryocyte function, and induce desialylation-induced platelet destruction 74 - It has been shown that the destruction of platelets in ITP patients results in a shorter life span compared to healthy humans as confirmed by different groups using Chromium labeled platelets or Indium labelled platelets 79 - This may be a result of an activated mononuclear phagocyte system in ITP patients.
Noteworthy, the theory of increased platelet destruction in the spleen was also supported by the effectiveness of splenectomy in raising platelet counts in patients with ITP 81 , 84 - Besides the platelet destruction in the circulation, mechanisms leading to inadequate platelet production in the bone marrow due to an immune response against megakaryocytes is also involved in the pathogenesis of ITP 87 - While the immune mechanisms of insufficient platelet production in ITP remain not very well-known, there are some indications in some studies.
It has been shown that megakaryopoiesis is strongly affected in ITP as evidenced by an increase in the proportion of premature megakaryocytes and impaired development, which can be characterized by a decrease in the granularity, ploidy, cytoplasmic vacuolization and nuclear condensation, leading to significant reduction in platelet production 86 , 88 , Additionally, it has been shown that inappropriate levels of TPO contribute to inadequate platelet production in ITP 53 , 95 , TPO, the main growth factor of megakaryocytes, is predominantly and constitutively synthesized in the liver to regulate thrombopoiesis via binding and activation of its receptor, cMPL, on the megakaryocyte and platelet 97 , Thus, the higher number of platelets released into the circulation, the lower TPO level required to stimulate the megakaryocytes to produce more platelets Therefore, levels of TPO increase in the serum as an automatic compensatory response to thrombocytopenia, which has been observed by several studies 95 , - However, this is not the case in ITP as despite the low number of platelets in the circulation, the TPO concentration is not elevated and, instead, remains within the range of healthy individuals, which is not enough to bind to cMPL on megakaryocytes to increase platelet production in the bone marrow 53 , 96 , - Moreover, studies using electron microscopy showed that megakaryocytes from patients with ITP frequently undergo apoptosis , , which may further contribute to the insufficient platelet production in these patients.
Finally, ITP has been found to present a skewed cytokine profile While an increase in platelet destruction and a decrease in platelet production are central aspects in the pathophysiology of ITP, patients with ITP vary with the degree of these two processes with several abnormalities and multiple components of the immune system involved 58 - 62 , Therefore, this complexity and variations have led to different approaches and opened different ways for the design of specific immunotherapies to treat patients with ITP based on a case-by-case basis.
ITP is a disorder that occurs in both adults and children with considerable differences between these two populations For instance, the incidence rate of primary ITP is approximately 1. Most children undergo spontaneous remission and rarely experience active bleeding, although most of these patients still experience skin bruising and bleeding 5 , 6 , 18 , Therefore, current treatment protocols and practice guidelines for ITP are considered and developed in relationship with the clinically relevant differences between children and adult patients 5 , 6 , 23 , Thus, considering the nature of the disease and symptoms, it has been shown that adults with ITP often undergo pharmacological therapy and splenectomy more than children 5 , 6 , The manufacturing processes of IVIg include several steps such as precipitation, chromatography techniques and viral inactivation steps to purify the products, maximize tolerability and efficacy, and to minimize side effects , While the serum IgG is the dominant fraction in all the prepared IVIg, IVIg also contains small amounts of other proteins and components such as albumin, IgA, IgE, IgM, sugars, salts, solvents and buffers, which vary from batch to batch depending on the preparation and manufacturing processes 34 , These variabilities may contribute to tolerability complications and side effects post infusion 34 , Therefore, these variables should be carefully considered in relation to the clinical and physiologic conditions of the recipient.
In general, IVIg is considered safe and well tolerated with minimal mild and transient side effects most commonly; headache, fever, chills and nausea and rare serious adverse events AEs such as thrombosis and hemolysis 6 , 31 , 36 , see below. IVIg has been used for more than 40 years to treat ITP, initially used to treat primary immunodeficient patients and then later approved to be used to treat several autoimmune diseases and other conditions, including ITP - In ITP, IVIg is generally considered an effective and safe treatment option as high-quality evidences showed its favorable immunomodulatory effects , Although the mechanisms of actions of IVIg are complex and still unclear, there are several mechanisms that have been proposed and extrapolated discussed in further detail below ; but most of these mechanisms are extrapolated based on animal models.
Nevertheless, in humans, it has been revealed that IVIg plays a role in increasing the platelet lifespan in vivo by reducing the splenic clearance of platelets , via Fc-dependent mechanism 6 , Later studies confirmed the effectiveness of IVIg in the treatment of ITP in adult populations, with a comparable clinical response rate, leading to the widespread use of IVIg as an immunomodulatory therapy 6 , - Although not currently used to treat ITP, this product shows promise to replace intravenous IVIg administration in the future and further studies will show if this therapeutic approach has efficacy in adult ITP Even though the current IVIg products have a good safety profile and have been shown to be effective treatment for patients with ITP, there are challenges associated with product production, access and availability.
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