Autoimmune Cytopenias

The authors of this February review in EBioMedicine note that treatment for immune thrombocytopenia (ITP) is shifting away from immune suppression and toward use of newer therapeutic agents such as thrombopoietin receptor agonists, which "have transformed ITP care…have high efficacy, are well tolerated, and improve patients' quality of life." The authors outline newer targeted therapies in ITP, including inhibitors of the neonatal Fc receptor inhibitors, Bruton tyrosine kinase, and the complement pathway. Mechanisms underlying ITP and new approaches to ITP care are discussed.

In this review in Open Access Emergency Medicine, emergency department (ED) healthcare providers from Miami, Florida, discuss current literature and guidelines relevant to the care of both pediatric and adult patients with immune thrombocytopenia who present to the ED. They highlight the epidemiology, clinical presentation, diagnosis (including tests to avoid or defer in the ED), and treatment of this blood disorder; and briefly outline management of ITP in pregnant patients and patients with COVID-19.

In this review article, published in Blood in late November 2021, researchers used 4 large data sources to ultimately evaluate the impact of SARS-CoV-2 vaccination in 109 patients with pre-existing immune thrombocytopenia (ITP). One key finding was that splenectomy and past use of 5 or more therapies were predictive of higher risk of worsening thrombocytopenia following receipt of the SARS-CoV-2 vaccine in patients with ITP. While concluding that vaccination against COVID-19 is "generally safe" in the setting of ITP, they advised that "thrombocytopenia exacerbation may occur and requires monitoring."

In mid March 2021, Sobi, a North American affiliate of the international biopharmaceutical company Swedish Orphan Biovitrum AB, announced it had partnered with the Platelet Disorder Support Association, a leading immune thrombocytopenia (ITP) advocacy organization, to launch the mobile app florio ITP for patients living with ITP. The app, developed with input from ITP patients and healthcare professionals, enables people with ITP to organize, track, and record their health and treatment information. iOS (Apple) and Android mobile phone users can download florio ITP free of charge.

On its website, the American Society of Hematology (ASH) offers answers to FAQs regarding the use of anticoagulation therapy in patients with COVID-19, based on guidelines developed by a multidisciplinary, international expert panel convened by ASH. These guidelines were published in Blood Advances on November 2, 2021; they will be updated by ASH, in collaboration with the guideline panel, as new data on which to make evidence-based recommendations become available.

This 2021 resource for adult patients with immune thrombocytopenia (ITP), is available as a PDF from the Platelet Disorder Support Association. It provides concise background information about ITP, answers may common questions of concern, and offers helpful resources. (Its development was supported by an educational donation from argenx.)

As the authors of this October 2021 review point out, these rare anemias, often caused by autoimmune destruction of red cells, can be characterized by both intravascular and extravascular hemolysis, with IgG mediating warm antibody–induced hemolysis and IgM mediating cold antibody–induced hemolysis. Immunosuppression and other treatments for autoimmune hemolytic anemias are discussed.

This recent literature review by researchers from Montefiore Medical Center/Albert Einstein College of Medicine in New York City notes that immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) are the most common hematologic autoimmune disorders seen in patients with SARS-CoV-2 infection, and that vaccine-induced thrombocytopenia is a unique autoimmune hematologic cytopenia associated with vaccination against SARS-CoV-2. The authors highlight current literature on the association between SARS-CoV-2 infection and vaccination with autoimmune cytopenias, as well as the clinical course of autoimmune cytopenias in patients with COVID-19.

In this case-based review, the authors describe the diagnosis and management of a 47-year-old male patient in generally good oral and periodontal health who presented with a nonbleeding bluish lesion on the back of his tongue, who 1 day later developed ecchymotic-type lesions on the mucous membranes of his cheeks and upper lip; a bleeding lesion at the apex of the tongue; gingivorrhagia; and petechiae on his back, scalp, lower limbs, and feet. Clinical deterioration was rapid and required immediate hospitalization. He was diagnosed with idiopathic thrombocytopenic purpura (ITP) following oral, dermatologic, and hematologic evaluations and recovered several days after treatment with hydrocortisone.

This YouTube state-of-the science video from August 25, 2020, from the Foundation for Women & Girls With Blood Disorders, was presented by Terry Gernsheimer, MD, Professor of Medicine and Hematology at the University of Washington Seattle Cancer Care Alliance. It was moderated by Gowthami M. Arepally, MD, a professor of medicine in the division of hematology at Duke University Medical Center. Evidence-based recommendations and guidelines covering the management of immune thrombocytopenia (ITP), updated by American Society of Hematology (ASH) in 2019, are reviewed in the context of concerns relevant to female patents with ITP, including reproductive health and pregnancy.

An international multicenter team from Iran, the US, and Canada conducted a systematic review of the medical literature to evaluate cases of vaccine-induced immune thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following vaccination against COVID-19. A total of 19 of 49 patients (39%) with CVST died from complications of CVST and VITT.

In a multicenter prospective cohort study published in the New England Journal of Medicine, a team of investigators evaluated patients with suspected vaccine-induced immune thromobocytopenia and thrombosis (VITT). Patients with a low platelet count and intracranial hemorrhage had the highest VITT-associated mortality, with 73% mortality among patients with intracranial hemorrhage and platelet counts < 30,000/mm³.

In this systematic review, investigators hypothesize that thrombopoietin receptor agonists (TPO-RAs) “influence platelet function, global and secondary hemostasis, and/or fibrinolysis.” After evaluating 12 observational studies comprising 305 patients, they report “[t]here were indications that TPO-RA treatment enhanced platelet function, with respect to platelet-monocyte aggregates, soluble P-selectin, GPVI [glycoprotein VI] expression, and adhesion under flow.”

This review from StatPearls (available on the National Center for Biotechnology Information online bookshelf), updated in late June, provides comprehensive information and clinical pearls related to the autoimmune condition known as Evans syndrome. As the authors explain, patients with Evans syndrome present with two or more cytopenias; these are commonly warm autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), with or without immune neutropenia.

This mini-review highlights discussions from the sixth annual meeting on ITP organized by the Intercontinental Cooperative ITP Study Group and held in September 2019 in Locarno, Switzerland. At the 2019 meeting, the authors explain, “scientists and clinicians of pediatric and adult hematology, oncology, immunology, and genetics shared their ideas, experiences, and research findings to critically assess open questions and launch future joint projects” to investigate “out of the box” concepts associated with ITP.

The International ITP Alliance was formed in 2016 by support organizations around the world, to give patients with immune thrombocytopenia a greater voice and promote public awareness of this autoimmune bleeding disorder. This year’s celebration in late September marks its sixth annual global event. The website provides an ITP Awareness Toolkit to help people spread information about ITP on Facebook, Twitter, and other social media. It also offers links to ITP information and resources; patient support organizations, by country; and resources related to COVID-19.

The FWGBD’s mission is to support education and awareness among women, adolescent girls, and their healthcare providers regarding female bleeding disorders, given the challenges that such disorders can pose during the menstrual cycle and at various stages of the female reproductive life cycle (eg, pregnancy, childbirth, menopause). The FWGBD’s website offers particularly comprehensive resources on ITP, including expert interviews, videos, webinars, Q&A, and COVID-19 resources for providers treating patients with ITP.

In this review, researchers from Dijon, France, highlight recent advances in the understanding of ITP pathogenesis that have broadened and deepened the opportunities for therapeutic intervention. Beyond describing multiple potentially promising pathways and targets now under investigation, they caution that “[T]ogether with this therapeutic progress, new questions have arisen, such as the place of each drug in the algorithm of ITP management, the safety of their long-term use and the possibility of synergistic combination. Moreover, the various response rates to all these therapies highlight the crucial need for biomarkers to tailor the treatment to patients and optimize their management.”

The authors of this study state that iWISh “focused on perceptions of 1,507 patients and 472 physicians from 13 countries regarding the diagnostic pathway, frequency and severity of signs and symptoms, and treatment use” related to ITP.

This January 2021 consensus statement was written by clinicians with an interest in coagulation disorders or ITP and was reviewed by members of the UK ITP forum. The ITP Support Association is a UK charity.

The Platelet Disorder Support Association (PDSA) was patient-founded in 1998 for patients with immune thrombocytopenia (ITP) and other platelet disorders. Resources of interest to healthcare providers include a newsroom; the updated international consensus report on management of primary ITP (Provan et al, Nov. 2019); and more than a dozen patient education pamphlets covering a wide range of topics—including the role and function of platelets in ITP, the female lifecycle and ITP, FAQs and lifestyle tips related to ITP, and information about health insurance assistance programs for patients with ITP. The PDSA website also provides up-to-date information about the ITP Natural History Study Patient Registry; the COVID-19 and ITP Research Survey; and relevant medical meetings, including the “ITP Conference 2021,” a virtual event that will occur on July 31 and August 1, 2021.

The Castleman Disease Collaborative Network is a patient advocacy organization founded in 2012 to advance research and treatment. Patients can read patient education materials; donate tissue samples; and enter their medical data into the ACCLERATE patient registry, to inform clinical research (after data de-identification). Resources for clinicians include access to recent studies, treatment toolkits and guidelines, and information about CDCN-funded research. In AIM 2021 (“All-in Movement” 2021), the CDCN Scientific Advisory Board will crowdsource and prioritize questions and ideas from Castleman’s disease community to guide future clinical trials.

These evidence-based guidelines on management of ITP were developed by a multidisciplinary panel formed by ASH in 2015 to evaluate 2011 ITP guidelines and formulate recommendations based on available evidence and recommendations through May 2017. ASH will maintain currency of the guidelines by ongoing review and surveillance.

This review article summarizes current knowledge about this complex disease, highlights research into targeted treatment, and discusses how characteristics of AIHA may vary in older adults, depending on their immunological status.

This review article explores putative mechanisms by which infection and inflammation can trigger and drive hemolysis in cold agglutinin disease, or CAD, and secondary cold agglutinin syndrome, or CAS, as well as recent advances in understanding the pathogenesis of these disorders. Novel targeted treatments such as complement-directed therapies are discussed.

In this multicenter review and consensus opinion, clinicians from the US and UK shed new light on the possible etiology of immune-mediated cytopenias, and offer management strategies for patients with inherited metabolic disorders who develop single or multilineage cytopenias following hematopoietic stem cell transplantation.