Long-Term Efficacy and Safety of Danicopan as Add-On Therapy to Ravulizumab or Eculizumab in PNH With Significant EVH.

Complement C5 inhibitor treatment with ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH) improves outcomes and survival. Some patients remain anemic due to clinically significant extravascular hemolysis (cs-EVH: hemoglobin [Hgb] ≤9.5 g/dL and absolute reticulocyte count [ARC] ≥120×109/L).

Long-term effectiveness of eculizumab: Data from the International PNH Registry.

Objectives: Data from the International PNH Registry (NCT01374360) were used to estimate the overall survival and first occurrence of thromboembolic events/major adverse vascular events (TEs/MAVEs) for eculizumab-treated patients with paroxysmal nocturnal hemoglobinuria (PNH) compared with a contemporaneous untreated cohort.

Methods: Patients enrolled in the Registry from March 16, 2007, to February 14, 2022, were included. Treated patients received eculizumab for >35 days; untreated patients did not receive eculizumab at any time.

Risk factors for thromboembolic events in patients with paroxysmal nocturnal hemoglobinuria (PNH): a nested case-control study in the International PNH Registry.

The objective of this analysis was to identify risk factors for thromboembolic events (TE) in patients with paroxysmal nocturnal hemoglobinuria (PNH) who were not treated with C5 inhibitors. Patients with PNH and a history of ≥ 1 TE at enrollment in the International PNH Registry (NCT01374360; registration date, January 2011) were each matched with up to 5 patients without TE. Multivariable analysis was performed with the following variables: percentage glycosylphosphatidylinositol (GPI)-negative cells, high disease activity (HDA), non-TE major adverse vascular event history, and recent anticoagulation.

Therapeutic plasma exchange in alloimmune platelet refractoriness.

Patients with alloimmune platelet refractoriness can present complex clinical conundrums. Herein we describe a case of platelet refractoriness in the setting of combined HLA and HPA alloimmunization in a patient with acute myeloid leukemia and life-threatening bleeding. We discuss causative antibodies and compare prevailing therapeutic modalities.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. In the Ninth Edition, the JCA Special Issue Writing Committee has incorporated systematic review and evidence-based approaches in the grading of evidence and categorization of apheresis indications to make recommendations on the use of apheresis in a wide variety of diseases and conditions. This edition has largely maintained the general layout and concept of a fact sheet introduced in the Fourth Edition (2007).

Renal Thrombotic Microangiopathy: A Review.

Thrombotic microangiopathy (TMA), a pathological lesion observed in a wide spectrum of diseases, is triggered by endothelial injury and/or dysfunction. Although TMA lesions are often accompanied by clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ injury, renal-limited forms of TMA are not infrequently encountered in clinical practice. The presence of renal-limited manifestations can be diagnostically challenging, often delaying the initiation of targeted therapy.

Clinical and laboratory predictors of fetal and neonatal alloimmune thrombocytopenia.

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of intracranial hemorrhage (ICH) in thrombocytopenic term infants. We investigated clinical and laboratory predictors of severe FNAIT in a tertiary care referral center.

Study Design And Methods: Retrospective cohort study over a 30-year period.

Complement-Amplifying Conditions in Atypical Hemolytic Uremic Syndrome: A Canadian Case Series.

Rationale: Thrombotic microangiopathies (TMAs) are systemic disorders that often affect the kidneys and encompass a heterogeneous group of conditions, including atypical hemolytic uremic syndrome (aHUS). The complement pathway is thought to play a crucial role in the pathogenesis of aHUS, and a favorable response can be obtained through complement C5 inhibition. There is emerging evidence to suggest that the same is also true for several other forms of TMA.

Predictors of relapse and preventative strategies in immune thrombotic thrombocytopenic purpura.

Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune blood disorder, which presents with microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis and is caused by severe deficiency of ADAMTS13. iTTP may result in both acute and chronic complications and is rapidly fatal without expedient treatment. Life-time risk of relapse is approximately 40%.

Blood-brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood-brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later.

Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review.

Purpose Of Review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing -induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS).