Immune Thrombocytopaenic Purpura Research Articles

Immune Thrombocytopenic Purpura in Pregnancy: A Case Report in a Health Institution in Benin City, Nigeria

In comparison with reports among Caucasians, immune thrombocytopaenic purpura (ITP) is thought to be uncommon in native black Africans and persons of African ancestry worldwide. The uncommon presentation of these instances provides the information required for the collection of data for prospective research and as a foundation for improving illness management techniques aimed at promoting feto-maternal health. This paper offers a retrospective review of a 32-year-old woman who was diagnosed with ITP in her first trimester of pregnancy following a two-day history of nasal bleeding. Four years prior to her presentation, the patient had similar bleeding event, but was undiagnosed; however, it was managed by unorthodox means, with resolution of symptoms. Thereafter, she had recurrent episodes at this index presentation and a year earlier. For the treatment of this condition, corticosteroids such as oral prednisolone, intravenous methylprednisolone and dexamethasone were used in curtailing the bleeding episodes, despite the recurrence. The effectiveness of these medications was striking. She gave birth to a live female neonate through spontaneous vaginal delivery, and overall, the outcome was excellent in both the mother and neonate.

Budesonide bests COVID-19.

Immune thrombocytopaenic purpura (ITP) is often a diagnosis of exclusion with presentations ranging widely from asymptomatic patients to those with life-threatening bleeding. Secondary ITP following vaccination is relatively uncommon and underdiagnosed as majority of patients remain asymptomatic. Cases of severe thrombocytopaenia associated with SARS-CoV-2 messenger RNA (ribonucleic acid) vaccinations have been described previously, mostly as isolated occurrences, and typically occurring following the first dose. Here we present a case of severe ITP associated with the second dose of the Pfizer-BioNTech/BNT16B2b2 mRNA vaccine and provide a review of the current literature.

Complex Multivessel Percutaneous Coronary Intervention in a Patient With Severe Refractory Immune Thrombocytopaenic Purpura

Complex Multivessel Percutaneous Coronary Intervention in a Patient With Severe Refractory Immune Thrombocytopaenic Purpura

Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab

Anti-PD-1 antibodies (anti-PD-1) have clinical activity in a number of malignancies. All clinical trials have excluded patients with significant preexisting autoimmune disorders (ADs) and only one has included patients with immune-related adverse events (irAEs) with ipilimumab. We sought to explore the safety and efficacy of anti-PD-1 in such patients. Patients with advanced melanoma and preexisting ADs and/or major immune-related adverse events (irAEs) with ipilimumab (requiring systemic immunosuppression) that were treated with anti-PD-1 between 1 July 2012 and 30 September 2015 were retrospectively identified. One hundred and nineteen patients from 13 academic tertiary referral centers were treated with anti-PD-1. In patients with preexisting AD (N = 52), the response rate was 33%. 20 (38%) patients had a flare of AD requiring immunosuppression, including 7/13 with rheumatoid arthritis, 3/3 with polymyalgia rheumatica, 2/2 with Sjogren's syndrome, 2/2 with immune thrombocytopaenic purpura and 3/8 with psoriasis. No patients with gastrointestinal (N = 6) or neurological disorders (N = 5) flared. Only 2 (4%) patients discontinued treatment due to flare, but 15 (29%) developed other irAEs and 4 (8%) discontinued treatment. In patients with prior ipilimumab irAEs requiring immunosuppression (N = 67) the response rate was 40%. Two (3%) patients had a recurrence of the same ipilimumab irAEs, but 23 (34%) developed new irAEs (14, 21% grade 3-4) and 8 (12%) discontinued treatment. There were no treatment-related deaths. In melanoma patients with preexisting ADs or major irAEs with ipilimumab, anti-PD-1 induced relatively frequent immune toxicities, but these were often mild, easily managed and did not necessitate discontinuation of therapy, and a significant proportion of patients achieved clinical responses. The results support that anti-PD-1 can be administered safely and can achieve clinical benefit in patients with preexisting ADs or prior major irAEs with ipilimumab.

Danazol: an effective option in acquired amegakaryocytic thrombocytopaenic purpura.

Acquired amegakaryocytic thrombocytopaenic purpura (AATP) is a rare haematological condition characterised by isolated thrombocytopaenia with normal other cell lines. It is often initially misdiagnosed as immune thrombocytopaenic purpura but has characteristic bone marrow findings of reduced megakaryocyte numbers. The optimal treatment of AATP is not clearly defined but revolves around immunosuppressive therapies. We report a case of successful treatment of AATP with danazol, an antioestrogenic medication. We also review the aetiologies and pathogenesis of the disorder and suggest that danazol should be considered as an effective alternative to potent immunosuppression in AATP.

Immune thrombocytopaenic purpura: an autoimmune cross-link between infections and vaccines.

Immune thrombocytopaenic purpura (ITP) is an autoimmune systemic disease detectable by the presence of low blood platelets count (<10(5)/µl) and the production of autoantibodies against glycoproteins expressed on the platelet surface. The clinical course is often acute, and life-threatening events may occur especially in children, with 52% of paediatric patients recovering either spontaneously or after treatment. A chronic ITP evolution is observed in 64% of adults, of whom 12% will develop an overlapping autoimmune disease. Several microbial agents such as CagA-positive Helicobacter pylori or Candida albicans and a number of viruses including CMV, EBV or HIV can potentially trigger ITP through molecular mimicry. Moreover, ITP improves after treatment of the underlying infection. Similarly, vaccines such as MMR may prompt ITP (IRR 5.48, 1.61-18.64, p < 0.006). Early recognition of the underlying microbial trigger and the removal of modifiable aetiopathogenetic factors should be integrated as a complementary treatment strategy in all patients who do not readily improve with standard ITP care.

The Paradoxical Beneficial Effect on Thrombocytopenia in Refractory Immune Thrombocytopaenic Purpura by Leishmaniasis

The phenomenon of platelet recovery in untreated patients with severe chronic refractory immune thrombocytopenic purpura (ITP) has never been described. A 44 year old lady presented with pyrexia. The blood count was Hb 9.8 g/l WBC 6.5 × 109/l Platelets 125 × 109/l. A bone marrow aspirate revealed macrophage hyperplasia with heavy infiltration by Leishman Donovani. The patient had a twenty year history of severe ITP responsive only to high doses of prednisolone. She had undergone two splenectomies and failed to respond to the sequential administration of dapsone, azathiaprine and cyclosporine. The minimum daily dose of prednisolone required to maintain the platelet count was 30 mg and she was on this maintenance dose for most of the duration of the disease. Intensive treatment with liposomal amphotericin and sodium stibogluconate failed to clear the parasites and for the rest of her life (14 months) she remained a carrier of leishmania requiring maintainance monthly doses of Leishmaniacides. During this period the platelet count remained normal even though the steroids were tapered to zero. The normalisation of the platelet count without steroids was unexpected and had never been observed before in her case. It was noted that she maintained a normal platelet count spontaneously even though she had developed transfusion dependent anaemia. Moreover, by then she had developed severe neutropenia partially corrected with granulocyte colony stimulating factor. Both cytopenic effects were a consequence of the ongoing sepsis. The patient eventually succumbed to renal failure secondary to a diabetic nephropathy. Kala-azar in normal subjects characteristically causes thrombocytopenia partly because of hypersplenism and partly because of consumption by the diffuse macrophage hyperplasia within the reticuloendothelial system. Also, in HIV infection where ITP is common, visceral leishmaniasis has been shown to worsen the thrombocytopenia. The main reason for thrombocytopenia in ITP is macrophage mediated phagocytosis of the antibody coated platelets. Two highly effective therapeutic agents are directed against this macrophage activity. Intravenous immunoglobulin saturates the macrophage receptor sites, thereby sparing the sensitised platelets by competitive inhibition [1]. Anti–D transiently diverts macrophages from destruction of platelets by focusing their activity against the sensitised erythrocytes [2]. Using the similar paradigm of these immunemodulatory agents, I postulate that the continual saturation of macrophages with the Leishmania parasites likewise had a platelet sparing effect. This observation may be of interest for pharmaceutical companies in their drug development research.

Potential usefulness of thrombopoietin receptor agonists in haemophiliacs with thrombocytopaenia due to chronic liver disease

New thrombopoietin receptor agonists (TPO-RA) eltrombopag and romiplostin were initially used for refractory immune thrombocytopaenic purpura, but more recently reported experience shows that they may also be applied to patients with thrombocytopaenia secondary to hepatitis C virus (HCV)-related chronic liver disease (CLD) in certain clinical situations; in haemophilic patients these drugs are always part of a therapeutic approach involving other haemostatic resources required to cover the joint congenital and acquired bleeding diathesis found in these patients. Platelet count elevation before invasive procedures or surgery or prior to and during antiviral therapy involving interferon are the main clinical applications of these drugs; they might also be useful in cases with advanced CLD and severe thrombocytopaenia in order to prevent recurrent bleeding episodes (namely articular and muscular in haemophilic individuals) or reduce bleeding risk in patients with multiple haemorrhagic risk factors. Long-term prophylactic treatment with factor concentrates in such cases is mandatory. There have been some reports of portal or splanchnic thromboses in patients on TPO-RA with CLD, especially in cases undergoing invasive procedures who reach platelet counts at least 200×10/l and often with additional risk factors for thrombosis. For this reason, and although haemophilic patients have an important protection against thrombosis, platelet counts should ideally be maintained between 50 and 100×10/l with dose adjustments carried out as required and initial doses of eltrombopag in patients with moderate or severe CLD, especially in prolonged treatments, should be reduced to 25 g once daily. These new drugs can be a useful adjuvant tool in patients with thrombocytopaenia secondary to CLD.

An unusual haematological presentation of the immune reconstitution inflammatory syndrome

We describe the case of a newly diagnosed HIV-1-positive man who was noted to have asymptomatic HIV-related idiopathic (immune) thrombocytopaenic purpura. On commencing antiretroviral therapy we believe he experienced an uncommon immune reconstitution phenomenon resulting in the rapid worsening of his thrombocytopenia, requiring steroid therapy which stabilized his platelet levels.

Managment of immune thrombocytopaenia in children: a review

To provide an overview of the various treatment options available in the rational management of ITP in children. Published original research findings and reviews. On-line searches for published data on immune thrombocytopaenia, idiopathic thrombocytopaenia, thrombocytopaenic purpura. Abstracts of selected articles were read and analysed to determine their relevance to this article. All relevant articles were read in full and necessary contribution extracted for this review. Immune thrombocytopaenic purpura is a common disorder affecting children and adults. Ongoing research into the pathogenesis is providing the basis for future treatment options. Greater consensus as to appropriate treatment strategies is needed to improve outcomes.

Immune reconstitution syndrome and the thyroid

Reconstitution Graves' disease occurs in three settings. First, bone marrow transplantation from a donor with Graves' disease may cause this disease to appear in the recipient, as a result of adoptive immunity, although disordered immunoregulation secondary to graft-versus-host disease may also play a role. Second, alemtuzumab treatment for multiple sclerosis leads to the development of Graves' disease in up to a third of patients during the phase of naive T-cell expansion, which follows therapeutic lymphocyte depletion. Other reconstitution autoimmune phenomena, including immune thrombocytopaenic purpura, are also recognised after alemtuzumab administration. Finally, reconstitution Graves' disease may occur during a similar phase of CD4(+) T-cell expansion, which follows highly active antiretroviral therapy for human immunodeficiency virus infection. Again, this complication is part of a broader spectrum of immunoregulatory disturbances, which can arise after immune reconstitution. The mechanisms responsible for reconstitution Graves' disease are at present unclear, but may include a relative bias towards a Th2-mediated immune response and reduced competition for autoreactive lymphocytes to expand during the time when recovery from lymphopenia commences.

Romiplostim

In August 2008, romiplostim (Nplate; Amgen), a thrombopoietin receptor agonist, was approved by the US FDA for the treatment of thrombocytopaenia in patients with chronic immune thrombocytopaenic purpura who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.

Platelet‐associated IgG for the diagnosis of immune thrombocytopaenic purpura during peginterferon α and ribavirin treatment for chronic hepatitis C

Platelet‐associated IgG for the diagnosis of immune thrombocytopaenic purpura during peginterferon α and ribavirin treatment for chronic hepatitis C

Immunology

Immunology

Redimune® NF Liquid, a ready-to-use, high-concentration intravenous immunoglobulin therapy preparation, is safe and typically well tolerated in the routine clinical management of a broad range of conditions

In clinical practice, intravenous immunoglobulin therapy (IVIG) is used in the management of a wide variety of medical conditions. Observational studies examining IVIG use in routine clinical practice are therefore an important means of validating findings from more strictly randomized controlled trials of patients with specific conditions. In this observational study, we examined the tolerability of a high-concentration (12%) ready-to-use liquid IVIG (Redimune NF Liquid) when used in the standard management of a diverse range of conditions (including primary immunodeficiency diseases, neurology conditions, oncology conditions and immune thrombocytopaenic purpura). IVIG regimen and dose were selected by the physician based on the summary of product characteristics. During the study, 193 infusions were administered to 51 patients in 153 infusion cycles (per infusion cycle: one to five infusions; mean dose, 347.6 mg/kg; mean duration, 202.4 min). The mean maximum infusion rate per cycle was 2.9 mg/kg/min, demonstrating that the infusion rate was often higher than that recommended in the summary of product characteristics. Redimune NF Liquid was well tolerated: there were 36 adverse reactions (at least probably associated with IVIG) in 10 patients (19.6% of sample, 0.24 per infusion cycle, 0.19 per infusion). The most common adverse reaction was headache (50% of reactions), followed by chills (13.8%). Most reactions (69%) were mild and there were no serious or unexpected reactions. In conclusion, in routine clinical practice involving patients with many different conditions, Redimune NF Liquid was well tolerated by the majority of patients.

GS02 LATERAL LAPAROSCOPIC SPLENECTOMY: THE AUCKLAND CITY HOSPITAL EXPERIENCE

Purpose To review the experience with laparoscopic splenectomy, to determine it’s efficacy for treating immune thrombocytopaenic purpura (ITP) and to highlight key technical issues with the operation.Methodology All splenectomies performed between 1992 and 2005 were identified from the Otago Surgical Audit and the clinical notes reviewed, including the laboratory records for follow‐up data related to the haematologic cases.Results There were 289 splenectomies performed over the 13 year period. The indications were trauma (111, 38%), haematologic disease (93, 32%), incidental (40, 14%) splenic malignancy (39, 13%), and other (8, 3%). Of the 68 patients with ITP, 49 (72%) had a lateral laparoscopic splenectomy (LLS) with no conversions, a 5% complication rate and one mortality. Based on platelet counts and the requirement for maintenance steroids there was a complete response in 44 (68%) patients at &gt;6 months, a partial response in 16 (24%) and no response in 5 (8%) patients. A short video presentation will highlight the key steps for the safe and efficient performance of the LLS, including patient and port positioning, the use of ultrasonic dissection, splenic pedicle stapling, and morcellation. The indications for hand‐port assisted laparoscopic and open splenectomy will be discussed.Conclusions The LLS is the preferred approach to splenectomy for all but massive splenomegaly and can be performed safely with careful attention to key technical issues.

Laparoscopic splenectomy is a better treatment for adult ITP than steroids — it should be used earlier in patient management. Conclusions of a ten-year follow-up study

Laparoscopic splenectomy (LS) has rapidly become the preferred surgical treatment for immune thrombocytopaenic purpura (ITP). The aim of this study was to assess the long-term outcome of laparoscopic splenectomy for adult ITP performed in a single unit. Between 1992 and 2002, 55 patients underwent LS for ITP refractory to medical therapy. These were performed by one surgeon. Long-term outcome data was obtained by case note review and telephone-based questionnaire. Complete remission was defined as a sustained platelet count of >100 x 10(9)/L without further requirement for medical therapy. Follow-up information was obtained for 40 (73%) out of 55 patients. Overall, 35 (88%) of 40 patients were in complete remission at five-year median follow-up. Five (13%) patients required continued steroid therapy despite LS. Seven (18%) patients reported bleeding problems, in particular bruising. Thirty-five (88%) of 40 patients considered their operation a success. Of these, 16 (46%) patients wished that the operation had been performed earlier in the course of their disease. This ten-year experience demonstrates that LS is safe, effective, and yields excellent long-term results for adult ITP, equivalent to results after open splenectomy. Patients' views suggest that laparoscopic splenectomy should be considered sooner in the management of adult ITP, reducing the duration and morbidity of medical treatment.

The pathogenesis of immune thrombocytopaenic purpura

Immune thrombocytopaenic purpura (ITP) is an autoimmune bleeding disease that is rarely fatal. However, in many adults treatment is unsatisfactory, with as much morbidity from the immunosuppressive effects of treatment as from bleeding. Identifying the underlying disease process should help us to identify more targeted therapies and improve not only the treatment but also the quality of life of patients with this disorder.

Treatment of Refractory Chronic Immune Thrombocytopaenic Purpura (ITP) with Rituximab: Report of a Cases Series.

Purpose: To describe the response rates and time to treatment failure in patients with chronic refractory ITP treated with Rituximab.Methods: Fourteen consecutive patients with chronic refractory ITP, who didn't achieve a response to first- and second-line treatments (including splenectomy), were recruited between November 2001 and May 2004. Rituximab was administered at 375 mg/m2 iv weekly' 4 and all patients were pre-medicated with Diphenhydramine (30 mg single dose) and Hydrocortisone (100 mg IV single dose). The first response assessment was performed at week 4, using the following criteria: complete response, platelet count > 100 x 109/L; partial response, platelet count > 50 x 109/L; minimal response, platelet count persisted below 50 x 109/L but without bleeding or need for platelet transfusion; and no response if the platelet count did not change, or the patients required platelet transfusion or remained symptomatic. The response was considered sustained if it persisted for at least 6 months.Results: The age range was 17–70 years; the baseline platelet count range was 3–37 x 109/L. Five patients achieved a complete response, four patients a partial response, four a minimal response and one no response. The time to response was from 4–32 weeks and 10 patients showed a sustained response. No patients with a response showed bleeding and no patients required the use of other drugs.Conclusions: These results suggest that Rituximab should have a significant therapeutic effect and an acceptable safety profile in patients with refractory chronic ITP. However, there is a lack of randomized, prospective studies to demonstrate the therapeutic benefit of this treatment.

Protein C inhibitor and serum amyloid A in immune thrombocytopaenic purpura.

In immune thrombocytopaenic purpura (ITP), phagocytic cells prematurely destroy platelets opsonized by anti-platelet auto-antibodies, while residual platelets rescued from these autoimmune attacks are hyperfunctioning. The exact pathobiological basis of this phenomenon is unknown. Protein C inhibitor (PCI), a platelet alpha-granule pro-coagulant molecule, is released on activation of platelets. Serum amyloid A (SAA; an acute phase protein), however, inhibits platelet aggregation and modulates platelet adhesion. We aimed to assess circulating soluble plasma PCI and SAA concentrations in 17 patients with newly diagnosed ITP and ten healthy volunteers. Plasma PCI concentrations tended to be higher in ITP patients, despite absolute thrombocytopaenia, than in normal controls. SAA levels were significantly higher in ITP patients compared with the control group. We conclude that secretion of the alpha-granule PCI content of platelets could result from platelet activation, and that PCI may be the link between platelet microparticles and haemostatically active ITP platelets. Increased concentrations of SAA and PCI may interfere with the disordered and compensatory pro-coagulant mechanisms of ITP.