Support of children and adults with immune thrombocytopenia (ITP) and continuation of the national and international research activities through the Intercontinental Cooperative ITP Study Group (ICIS)  (www.itpbasel.ch)

Characteristics of the bleeding disorder immune thrombocytopenia (ITP)

Over the past 50 years, international clinical and laboratory research have focused on the immune system, leading to major achievements in medicine. These advancements span not only the broad field of autoimmunity but also hematology, oncology, and immunodeficiency. Our research group is dedicated to study the autoimmune bleeding disorder known as ‚ITP.‘ ITP has been a key area of research for many decades at the University Children’s Hospital Basel and we continue to work on a wide range of ongoing projects. ITP is a complex autoimmune disorder that affects both megakaryocytes and platelets. These cells become a target by the own immune system and are cleared prematurely resulting in thrombocytopenia (platelet count of <100×10⁹/L).  The etiology of ITP unknown.

As platelets are important for maintaining integrity of blood vessels, thrombocytopenia is associated with an increased bleeding risk, ranging from skin bleeds to life-threatening bleeding, such as intracranial hemorrhage. Unfortunately, bleeding can occur spontaneously, i.e. without any trauma or injury. The prediction of bleeding severity appears to depend besides thrombocytopenia on many other factors, such as age, concomitant infectious diseases, comorbidities, other endogenous factors, and last but not least exogenous factors, such as drugs. On an individual basis, prediction of bleeding is limited, although severe bleeding is usually seen in patients with a platelet count of less than 20×10⁹/L and more often in elderly patients. Children, adolescents and adults who are suffering from this disease are not only at a daily risk for bleeding, but also exposed to fear from bleeding that reduces their quality of life significantly. Additionally, it has been realized in recent times that also other symptoms and complications are associated with ITP, e.g. fatigue,cognitive impairment and an increased risk for thrombosis.

ITP is biologically related to disturbances of both parts of the immune system, the innate and the adaptive immune system. ITP represents a model disorder for autoimmunity, because blood -as the target organ-is easily accessible and analyzed in the laboratory. In addition, the platelet enhancing  effect of many drugs can be monitored accurately within days and at low costs. This is not the case in many other autoimmune diseases, e.g. multiple sclerosis or rheumatic arthritis.

The management of ITP involves several endpoints: termination of bleeding, prevention from bleeding, improving quality of life, and curing ITP. Drug treatment is the mainstay of therapy. Splenectomy, introduced in ITP in 1916, although still successful is gradually pushed back by the advent of various drugs with different efficacy. In the 50ies of last century oral and intravenous corticosteroids were introduced, followed by intravenous immunoglobulins (antibodies) in the 80ies, and then at the turn of the centurymany drugs were developed that target platelet production (thrombopoietin-receptor agonists) and specific pathways of the immune system (monoclonal antibodies against B-lymphocytes). New drugs in development or already on the market  include monoclonal antibodies  against plasma cells, Bruton’s tyrosine-kinase inhibitors, syk inhibitors, complement inhibitors, neonatal Fc receptor inhibitors and  others.

International organizations and communities for basic and clinical ITP research

The intercontinental cooperative ITP study group (ICIS) was founded 1997 by a group of hematologists who were concerned about the fact that many medical activities and decisions were based on opinion of experts, but not on knowledge gained in clinical trials. This lack of evidence became obvious, when the first practice guidelines of the American Society of Hematology have been developed and published in 1996 (George J et al. Blood 1996).

ICIS was involved in early observations of beneficial effects of intravenous immunoglobulins on platelets in children and adults with ITP, first observed by Imbach P et al. (Lancet 1981), followed by a strong development of immunoglobulin products worldwide. After the commercialization of immunoglobulins, a research grant allowed ICIS to establish an international network of scientists and physicians involved in all aspects of ITP, and to organize every 3-4 years international expert meetings in Switzerland. ICIS is the first platform that bring pediatricians and adult hematologists together. Please visit www.itpbasel.ch for ICIS and its activities.

There is much clinical and scientific work ahead to better understand ITP and to help patients with this bleeding disorder. Future projects include a better knowledge of the pathophysiology and pathogenesis of ITP, predictability of the clinical course, particularly of the severity of bleedings and therisk of chronic disease, and to evaluate new treatments for therapy-refractory ITP, but also for all other forms of ITP, and to develop new strategies to avoid chronicity. This activity will be realized with our active participation in various clinical trials and registries, drug development programs and guideline developments.

For a successful continuation of our scientific work, ICIS needs support. Therefore, fundraising became an important part of ICIS. Three generations of physicians and scientists are working together and continue to further develop the international network and collaboration of ICIS and to deepen its achievements.

Short summary of the projects of ICIS

In 1997, ICIS Registry I was started as an international registry for children with newly diagnosed ITP. The aim was to collect clinical data of the natural history of ITP and the treatment of the disease. This registry was closed in 2000. Then, ICIS Registry II was opened (2002-2004) with the aim to study bleeding locations in the body and bleeding severity and its treatment. The results of registry I and II were discussed at the international expert-meeting 2006 in Switzerland and lead to an adaption of the terminology, definition and outcome of ITP for children and adults – after an agreement of an international working group (Rodeghiero F. et al. Blood 2009, 113: 2326). In parallel the Splenectomy Registry was opened in 1998 with the aim to study splenectomy in children regarding surgery, pre-, peri- and postoperative management and outcome of this procedure. In 2003, the Pediatric and Adult Registry on chronic ITP was opened to further collect clinical data and blood samples of children and adults with ITP. This registry was closed in December 2023. There are plans to initiate new registries.

Aims of research in children and adults with ITP and of activities of ICIS

ICIS continues to be active in clinical and basic research of ITP. As financial resources are limited, investigator-driven research must be coordinated. Therefore, collaborations with other groups involved in research of ITP are ongoing. ICIS will carefully select new projects that are feasible and will hopefully have an advancing effect of gaining knowledge in ITP.

Because ICIS is also traditionally involved in education and knowledge dissemination, the traditional expert meetings in Switzerland will continue, as they are popular and are able to give new impulses on clinical and basic research.

Financial aspects and active cooperation

University rules demand certain independence although cooperation and discussion with commercial and financial institutions are very welcome and necessary. As an example, at past expert meetings representatives of supporting companies were invited as audience and for contacts with experts.

The support of academic groups represents a challenge in recent years, and donations are becoming difficult to find for specific research. ICIS plans to expand this search into new ways for support by interested groups, including private persons, academic societies, competitive funds, industry, and others.

We are happy to receive suggestions and announcements of support and are happy to take questions.

Thank you and best regards,

Paul Imbach, Thomas Kühne und Alexandra Schifferli