Acute Idiopathic Thrombocytopenia Research Articles

Comparing the Outcomes of IVIg with Combination of IVIg and Methylprednisolone in Children with Acute Idiopathic Thrombocytopenia; a Bayesian Logistic Approach

Background This study aimed to evaluate the effectiveness of Intravenous immunoglobulin (IVIg) and combination of IVIg and Methylprednisolone for childhood Idiopathic (autoimmune) Thrombocytopenia (ITP) treatment; in addition investigate the related factors to develop chronic form of under 15 years ITP. Materials and Methods This retrospective study conducted on 88 ITP patients that treated with IVIg or combination of IVIg and Methylpredinosolon. Children were treated with IVIg 2 mg/kg/d or combination of IVIg 2 mg/kg/d and Methylpredinosolon20 mg/kg/dfor maximum 5 days. The numbers of patients with a platelet count > 50,000/μl, after treatment initiation, were the primary outcome. Odds Ratio (OR) as well as 95% Bayesian Credible interval (Crl), were estimated using a Bayesian Logistic regression model. Results The median age of subjects was 3.5+ 4.42 years (Interquartile: 2 8.5). About 13% of patients were discharged from hospitalization in day 2 and day 3. The ITP of 23% of children were progressed to chronic form. The following factors were significantly associated with the development of chronic ITP, combination of IVIg and Methylprednisolone [OR: 3.24, 95% Crl: [1.06 11.11]), and day 2 and 3 of discharge from hospitalization (OR: 7.72, 95% Crl: (1.14 67.16)]. Conclusion The current results, suggest that the both IVIg and combination of IVIg are equally effective in providing a platelet level > 50,000/μl early. In addition patients how received combination drug were more likely to develop to chronic ITP. Therefore, we suggest that this route must be preferentially used in decision making for treatment childhood ITP.

Recommendations for the use of immunoglobulin therapy for immunomodulation and antibody replacement.

Polyvalent immunoglobin, derived from pooled human plasma, can be administered via the intravenous, subcutaneous or intramuscularroute. Therapy is standard of care in the treatment of a number of immune-mediated pathologies across disciplines. By volume, the majorityis used in neurology (~40%). In primary immunodeficiencies, therapy reconstitutes humoral immunity at replacement doses (0.4 - 0.6 g/kg/month), decreasing infections, and is usually lifelong. However, high doses, usually 2 g/kg total dose over five days, are required forimmunomodulation in autoimmune and inflammatory indications. A high-quality evidence base supports use in primary antibody failure,Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, acute idiopathic thrombocytopenia, Kawasaki disease andimmunobullous diseases. Low-quality evidence shows benefit in many other uncommon autoimmune and immunodeficient conditions.In South Africa, use of immunoglobulin therapy is restricted and, given the cost involved, will likely remain so. Therefore, the incrementalbenefit over other forms of immunosuppression, particularly corticosteroids, must be assessed carefully on a case-by-case basis. In mostcases, therapy will be second-line or 'rescue' and motivation will be required. This short review aims to provide clinicians with the necessaryunderstanding of the therapy, general considerations for use, and evidence base and quality thereof for well-established indications.

749 Human Immunoglobuline Role in Treatment of Idiopathic Thrombocytopenic Purpura

IntroductionIdiopathic thrombocytopenic purpura is a disorder, in which immune system destroys platelets, which are necessary for blood clotting. ITP persons have a very low platelet count. ITP appears when the...

Some unsettled questions in childhood thrombocytopenia caused by immunologic platelet destruction (acute and chronic ITP)

The cause of idiopathic thrombocytopenia (ITP) is largely unknown, although the underlying pathophysology is an autoimmune process. Anti-idiotypic antibodies and their role on regulatory T-cells might play an important role in the switch from acute to chronic ITP. The exact interaction remains to be elucidated. The effects of the dysregulated immune system and of the autoimmune process on thrombocytopoiesis and megakaryopiesis are ill defined. Therapy of acute and chronic ITP is directed to the risk of bleeding.

Platelet count, previous infection and FCGR2B genotype predict development of chronic disease in newly diagnosed idiopathic thrombocytopenia in childhood: results of a prospective study

About 25-30% of children with acute idiopathic thrombocytopenia (ITP) develop chronic disease. It is not well known which patient characteristics influence the course of the ITP. A prospective study in 60 children with newly diagnosed ITP was performed. The aim of the study was to identify patient characteristics at the onset of thrombocytopenia that predicts the progression to chronic ITP. Clinical data and blood samples were collected at several time points during the first 6 months of the disease. Variables predicting chronic disease, as calculated in a multivariate logistic regression analysis, were a platelet count >10 x 10(9)/l at the onset [odds ratio (OR) 1.1, 95% confidence interval (CI) 1.01-1.14], the absence of infection shortly before the onset of the disease (OR 4.8, CI 1.16-19.57) and FGR2B-232I/T genotype (OR 7.9, CI 0.96-65.27). The latter may point at an immune-modulating role of Fc gamma RIIb in ITP. Although only three patients had serious bleeds, 35 patients received immune-modulating treatment for low platelet counts only. Seventeen patients were treated with intravenous immunoglobulin (IVIG) and 18 patients received corticosteroids. Patient variables did not differ between these treatment groups. However, patients receiving IVIG had significantly lower risk for chronic disease.

The Human Platelet Alloantigen 5 Polymorphism as a Risk for the Development of Acute Idiopathic Thrombocytopenia Purpura

The Human Platelet Alloantigen 5 Polymorphism as a Risk for the Development of Acute Idiopathic Thrombocytopenia Purpura -

Type I autoimmune hepatitis is primarily a disease of later life.

Previous studies of type I autoimmune hepatitis (AIH) have been based on selected populations attending specialist liver units. We describe 41 patients with type I AIH from a stable population in South Wales sequentially diagnosed over an 11-year period. All were Caucasian; 32 women, nine men; median follow-up 4 years. All cases conformed with International AIH Group criteria. Median age at diagnosis was 62 years. At presentation, only five patients were under 40 years old, 23 were over 60. This was very different from the classical age distribution. The commonest presentation was acute icteric hepatitis (29/41); median duration of illness 3 months. Co-existing acute arthralgia was common (10/41), as were other autoimmune diseases. Liver biopsy revealed piecemeal necrosis or interface hepatitis in 30; others showed non-diagnostic acute hepatitis. Fourteen also had cirrhosis. Median AsT fell from 508 (73-2385) to 32 (13-607) U/I after immunosuppression, representing complete remission in 28, partial remission in eight, and two treatment failures. Three patients were not treated, because of either quiescent disease or spontaneous remission. To date, there have been eight deaths (median age 64, range 37-86); five due to liver failure, one to variceal haemorrhage, one to acute myocardial infarction and one to upper gastrointestinal haemorrhage caused by acute idiopathic thrombocytopenia. Contrary to previous descriptions, type 1 AIH is a disease of later life in this stable, unselected population; peak incidence was in the seventh decade, and few cases occurred before the fifth decade. Presentation was usually as painless acute icteric hepatitis. Immunosuppression was effective and safe in most cases; 5-year survival rates were 61% (> 60 years at diagnosis), 66% (< 60) and 64% (overall).

Characterization of autoantibodies against the platelet glycoprotein antigens IIb/IIIa in childhood idiopathic thrombocytopenia purpura.

The majority of children with idiopathic thrombocytopenia (ITP) have an acute self-limiting course and no diagnostic test has been identified which will predict the course of thrombocytopenia and detect those with the chronic autoimmune form. The detection of autoantibodies directed against the platelet glycoprotein complex IIB/IIIa, may identify patients with chronic ITP. Serum anti-GP IIb/IIIa antibodies were assessed by the indirect MAIPA assay in 54 children with immune thrompocytopenia at initial presentation along with an additional 7 children previously diagnosed with chronic ITP, to determine if there was a difference in antibody positivity between acute and chronic ITP patients, and whether the identification of antibodies could be used as a predictive test at diagnosis. There was no significant difference in the percentage of antibodies detected in children classified with acute ITP (27/40-68%) compared to children with chronic ITP (13/21-62%, P > 0.05). Patients with acute ITP had significantly lower mean platelet counts at diagnosis compared to the chronic ITP group (16,225/mm3 vs 32,250/mm3, P < 0.05), though there was no significant difference in the bleeding manifestations between the acute and chronic ITP groups. Serum anti-GP IIb/IIIa antibodies are detected in a high percentage of children with ITP and autoantibodies appear to be involved in the pathogenesis of both acute and chronic ITP. The detection of anti-GP IIb/IIIa antibodies at diagnosis, however, does not appear to be a useful prognostic test in childhood ITP.

Treatment of acute idiopathic thrombocytopenia of childhood with intravenous infusions of gammaglobulin

Gammaglobulin treatment was given at a dose of 1 gm/kg/day intravenously in 29 patients with acute idiopathic thrombocytopenic purpura: 15 previously untreated, 10 resistant to steroids, and four who were steroid dependent. The average platelet increase in 24 hours was greater than 50,000/microliter; the average peak platelet count was 194,000/microliter. Eighteen of 25 patients required only one infusion; 10 of these 18 never required any additional (maintenance) therapy. Outcome in previously untreated and steroid-resistant patients was identical; however, previously untreated patients required only 1.8 gm/kg total dose of gammaglobulin, whereas steroid-resistant patients received 3.9 gm/kg. Only one steroid-dependent child of the 29 patients still requires maintenance therapy, at 6-week intervals. Toxicity was minimal. Cost was minimized by not admitting patients and by giving treatment in one visit, rather than five.

Studies on Platelets: II. The Effect of Transfusion of Platelet-Rich Polycythemic Blood on the Platelets and Hemostatic Function in “Idiopathic” and “Secondary” Thrombocytopenic Purpura

Abstract1. Direct transfusions of platelet-rich polycythemic blood, using the multiple syringe technic and siliconized apparatus, were performed in 14 cases of "idiopathic" ("megakaryocytic") and 8 of "secondary" ("amegakaryocytic") thrombocytopenia. Effects on platelet number and function, and on hemorrhagic manifestations were studied.2. Platelets disappeared very rapidly from the circulation (one-half to twelve hours) in the 12 patients with acute idiopathic thrombocytopenia and in 1 patient with chronic thrombocytopenia with a low platelet count. They disappeared more slowly (twenty-four hours) in the other case of chronic idiopathic thrombocytopenia in which there was a higher platelet count. Essentially similar platelet disappearance curves were obtained in 2 patients, before and after unsuccessful splenectomy. In the patients with secondary thrombocytopenia, the survival of platelets in the circulation was much longer (average forty-eight to ninety-six hours).3. Behavior of clot retraction and prothrombin activity of serum paralleled closely that of the platelet count. The bleeding time and capillary fragility usually remained improved for twenty-four to forty-eight hours after the platelet count had fallen to the initial level. Likewise, the hemorrhagic manifestations were improved in every case for many hours after the platelet level had returned to its original value. Similar, but less marked beneficial effects on the hemorrhagic manifestations were also obtained with transfusions of fresh blood from donors with normal platelet counts, provided fresh blood was used and precautions taken to prevent excessive loss of platelets.4. Remissions were observed in 2 patients with idiopathic thrombocytopenia following direct transfusion of polycythemic blood. In both cases, the injected platelets disappeared promptly from the circulation but within twenty-four hours the platelet count began to rise and a long-sustained remission became established. This finding suggests the possibility that polycythemic blood may contain a stimulatory principle which can determine or accelerate a spontaneous remission.5. Conclusions. The prompt disappearance of injected platelets from the circulation of patients with "idiopathic" thrombocytopenia suggests a humoral destructive mechanism, which is not present in the "secondary" or "amegakaryocytic" cases. This destructive mechanism does not appear to originate in the spleen. Our observations do not exclude an inhibitory effect upon platelet production from the megakaryocytes of the bone marrow. Polycythemic blood may contain a platelet stimulatory factor.