Complement in immune thrombocytopenia (ITP): The role of complement in refractory ITP.

Immune thrombocytopenia (ITP) is a disorder characterized by low platelets due to increased clearance and decreased platelet production. While ITP has been characterized as an acquired disorder of the adaptive immune system, the resulting platelet autoantibodies provide ancillary links to the innate immune system via antibody interaction with the complement system. Most autoantibodies in patients with ITP are of the IgG1 subclass, which can be potent activators of the classical complement pathway.

SARS-CoV-2 vaccination and ITP in patients with de novo or preexisting ITP.

Cases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination.

Corticosteroid overuse in adults with immune thrombocytopenia: Cause for concern.

Corticosteroids remain a crucial component of first-line therapy for immune thrombocytopenia (ITP) due to low cost, high initial response rates, and acceptable short-term tolerability. However, extended and recurrent use of corticosteroids is associated with substantial toxicity. Survey studies indicate that >95% of patients with ITP treated with corticosteroids report adverse effects, more than one-third of whom require reduction or discontinuation of treatment.

Understanding Immune Thrombocytopenia: Looking Out of the Box.

The pathogenesis of immune thrombocytopenia (ITP) is increasingly being elucidated, and its etiology is becoming more frequently identified, leading to a diagnostic shift from primary to secondary ITP. The overlap between autoimmunity, immunodeficiency, and cancer is evident, implying more interdisciplinarity in daily care. This mini-review is based on an expert meeting on ITP organized by the Intercontinental Cooperative ITP Study Group and presents the challenges of hematologists in understanding and investigating "out of the box" concepts associated with ITP.

Tapering thrombopoietin receptor agonists in primary immune thrombocytopenia: Expert consensus based on the RAND/UCLA modified Delphi panel method.

Background: Thrombopoietin receptor agonists (TPO-RAs) are used to treat primary immune thrombocytopenia (ITP). Some patients have discontinued treatment while maintaining a hemostatic platelet count.

Objectives: To develop expert consensus on when it is appropriate to consider tapering TPO-RAs in ITP, how to taper patients off therapy, how to monitor patients after discontinuation, and how to restart therapy.

Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, characterized by a low platelet count (<100 × 10 /L) in the absence of other causes associated with thrombocytopenia. In most patients, IgG autoantibodies directed against platelet receptors can be detected. They accelerate platelet clearance and destruction, inhibit platelet production, and impair platelet function, resulting in increased risk of bleeding and impaired quality of life.

A Retrospective Study of the Combination of Rituximab, Cyclophosphamide and Dexamethasone for the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia.

The combination of rituximab, cyclophosphamide, and dexamethasone (RCD) is highly effective in the treatment of warm autoimmune hemolytic anemia (WAIHA) associated with chronic lymphocytic leukemia (CLL). We treated a cohort of patients with relapsed/refractory WAIHA, without CLL, with RCD. The primary objective was to evaluate the overall response (OR) of RCD therapy.

Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer.

Background: Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain.

Methods: In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks.

Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer.

Background: Protein disulfide isomerase (PDI) is a thiol isomerase secreted by vascular cells that is required for thrombus formation. Quercetin flavonoids inhibit PDI activity and block platelet accumulation and fibrin generation at the site of a vascular injury in mouse models, but the clinical effect of targeting extracellular PDI in humans has not been studied.

Methods: We conducted a multicenter phase II trial of sequential dosing cohorts to evaluate the efficacy of targeting PDI with isoquercetin to reduce hypercoagulability in cancer patients at high risk for thrombosis.

Cancer prognosis in patients with venous thromboembolism (VTE) and patients with clinical and laboratory biomarkers predictive of VTE risk.

Venous thromboembolism (VTE) is a well-documented complication of cancer and its treatment. While VTE contributes significant morbidity and some thrombotic mortality to cancer patients, a growing body of clinical and experimental data supports the finding that VTE is an important prognostic marker for cancer progression and mortality. This would suggest that hemostatic activation is an expression of an aggressive tumor phenotype.

Ethnic and racial difference in Helicobacter pylori infection in patients with immune thrombocytopenia treated at a major urban medical center.

Immune thrombocytopenia (ITP) is an autoimmune disorder with a complex immunopathology and pathogenesis characterized by thrombocytopenia and bleeding manifestations. The disorder is separated into primary (idiopathic) ITP and secondary ITP, when associated with other immune or lymphoproliferative disorders and certain chronic infections. Helicobacter pylori (H.

Clinical Predictors of Early Mortality in Colorectal Cancer Patients Undergoing Chemotherapy: Results From a Global Prospective Cohort Study.

Background: Early mortality is a major problem in colorectal cancer (CRC). We have shown that Khorana Score is predictive of early mortality in other cancers. Here, we evaluated the value of this score and other prognostic variables in predicting early mortality in CRC.

Predictors of Venous Thromboembolism and Early Mortality in Lung Cancer: Results from a Global Prospective Study (CANTARISK).

Background: Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). Venous thromboembolism is associated with increased risk for early mortality. However, there have been no studies performing a comprehensive assessment of risk factors for VTE or early mortality in lung cancer patients undergoing systemic chemotherapy in a global real-world setting.

Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemia is an acquired autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens causing shortened erythrocyte survival. The disorders can present as a primary disorder (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immune modulation with corticosteroids and other agents.

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia.

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×10/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues.

Immune modulation for autoimmune disorders: evolution of therapeutics.

Autoimmune disorders result from either congenital or acquired defects in central or peripheral immune tolerance. A genetic propensity may underlay the development of most such disorders, but an external trigger may be required for the eventual development of the autoimmune disease. The development of pharmacologic agents to treat such disorders by inducing self-tolerance has progressed over the last 60 years.

Incidental venous thromboembolic events in cancer patients: what we know in 2016.

Cancer patients are at high risk of venous thromboembolism (VTE). Previous reports on the epidemiology and incident of thrombotic complications in cancer patients are based upon documented symptomatic events. However, the frequent use of contrast enhanced computerized tomography for cancer staging has documented a high incidence of unsuspected venous thrombosis (DVT), pulmonary embolism (PE) and abdominal visceral thrombosis in cancer patients.

Life-threatening delayed hyperhemolytic transfusion reaction in a patient with sickle cell disease: effective treatment with eculizumab followed by rituximab.

Background: Hyperhemolysis in sickle cell disease is a rare and potentially life-threatening complication of transfusion.

Study Design And Methods: In this article we report a case of delayed hemolytic transfusion reaction with resultant hyperhemolysis triggered by an anti-IH autoantibody with alloantibody behavior.

Results: The anti-IH was reactive at room temperature as well as 37 °C, but only weakly reactive with autologous red blood cells.

Management of immune-mediated cytopenias in pregnancy.

Immune-mediated cytopenias are a well-described complication of pregnancy. Appropriate recognition and treatment are important in order to limit maternal and fetal morbidity and mortality. First line treatment options are fairly well-established for these entities.

Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014.

Purpose: To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.

Methods: PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts.

Approach to the management of incidental venous thromboembolic events in patients with cancer.

Venous thromboembolism (VTE) is a frequent clinical complication of cancer and its treatment. Although much of the epidemiologic data regarding this complication have been based on symptomatic events, the use of multidetector row CT scanner technology has led to increased identification of VTE on scans ordered primarily for staging or restaging of malignancy. These incidentally discovered VTEs are variously referred to in the literature as incidental, asymptomatic, unexpected, or unsuspected VTE.

Thrombocytopenia in cancer patients.

Thrombocytopenia is a frequent complication of cancer and its treatment. The causes of thrombocytopenia in cancer patients can be diverse and multifactorial. Systemic chemotherapy is the most frequent cause of thrombocytopenia.