Active clinical trials for "Hemolysis"

During open cardiac surgery, cardiopulmonary bypass (CPB) is used to temporarily replace the function of the heart and lungs. Renal ischemia resulting in acute kidney injury is common after cardiac surgery. The renal oxygenation is impaired during CPB, but the oxygenation may be improved by increasing the CPB blood flow. In this randomized study, two CPB flow rates will be compared regarding renal outcome (biomarkers and renal oxygenation/renal blood flow), as well as markers of inflammation and hemolysis. Additionally, urine oxygen tension will be measured during CPB and the early intensive care phase and compared to renal oxygenation. Regional oxygen saturation assessed with near infrared spectroscopy from the brain and kidneys will be monitored during and after surgery.

Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease (incidence <1/100,000 population) responsible for the destruction of red blood cells by the host immune system, notably through the action of autoantibodies. Apart from complications related to anemia, the occurrence of venous thromboembolism (VTE) in this population is frequent, estimated at 20-27%. The risk of VTE is highest during the period of hemolysis, especially during the first 3 months after the diagnosis of AIHA. This risk is 7.5 [4.7; 12.0] times greater than in the general population. No clinical predictive factor for VTE was identified and the usual factors (cancer, previous VTE, bed rest >3 days, surgery, age >70 years, heart or respiratory failure, myocardial infarction, stroke, obesity, hormone replacement therapy) were not considered. Several biological risk factors have been suggested (depth of anemia, bilirubin level, leukocyte count, antiphospholipid antibodies) but have not been confirmed in other studies. AIHA is therefore a risk factor for VTE in its own right, and the National Diagnostic and Care Protocol (NDCP) recommends the implementation of VTE prevention during acute hemolysis (Grade C). However, the value of this prophylaxis has never been prospectively evaluated and its duration is empirical. In practice, low-molecular-weight heparin (LMWH) is generally used during "flare-ups" of AIHA (diagnosis and relapse) in hospitalized patients, but is rarely continued beyond the hospital phase when VTE also occurs in ambulatory patients. Thus, we hypothesize that prolonged preventive anticoagulation during the 12-week risk period following diagnosis or relapse of AIHA could decrease the incidence of VTE. In orthopedic surgery, this strategy has been proven to decrease VTE from 50% to 10-15%. In certain high-risk medical situations, prolonged prophylaxis with apixaban has been shown to decrease the occurrence of VTE from 10.2% to 4.2% in solid cancers4 and from 4-11% to 2% in myeloma.

This is a multicenter, single arm, open-label, extension study to evaluate the long-term safety, tolerability, and efficacy of iptacopan in participants with aHUS.

Anemia is a lack of red blood cells (RBCs) in the circulation. Because RBCs carry the oxygen your body needs to function, anemia can affect one's ability to stay awake, alert, and perform physical activities. Anemia may happen for several reasons, including increased RBC destruction. Anemia often occurs in people who have been in bed for long periods (e.g., if they are very sick) or have decreased mobility (anemia of immobility). Interestingly, astronauts who have left Earth and traveled in space also return anemic. In fact, 5 decades of NASA data showed that astronauts' anemia was more severe the longer they were in space. In another study, astronauts aboard the International Space Station were shown to destroy 54% more of their RBCs in space. RBC destruction may be the culprit of space anemia as well as anemia of immobility on Earth. The ANEMIA Study proposes to measure key aspects of RBC destruction in astronauts in space. These measures will test critical hypotheses on the effects of spaceflight on red blood cells.

Temporary mechanical circulatory support devices are increasingly used for short-term support in patients with decompensated cardiogenic shock. Recently, a new axial flow pump has become widely available with the Impella System. The Impella has been FDA approved for short term usage. Hemolysis, however, has been a common complication that has increased morbidity and mortality in this patient population. It is hypothesized that a major source of hemolysis in this patient population is shear stress experienced by red blood cells (RBC) as they travel through the pump device. In addition to causing RBC loss and potential anemia, the hemolysis has multiple other downstream consequences including creation of a pro-thrombotic environment leading to clot formation and potential device failure and secondary end organ dysfunction (renal and liver failure). Due to the significant effects of hemolysis in this population, a great deal of interest has been recently focused on addressing this problem, but as of yet no durable solutions exist. Pentoxifylline improves red blood cell deformability and reduces blood viscosity. It is hypothesized here that administering Pentoxifylline to patients in CS who require temporary MCS will decrease the amount of shear stress related hemolysis through the improved deformability and durability of RBCs. We propose to perform a double-blinded randomized controlled trial in patients who undergo an axillary Impella 5.0 insertion for acute decompensated heart failure. There will be a control group who receives a placebo and the treatment group who receives pentoxifylline. Labs will be drawn to monitor hemolysis which is our current standard protocol for the life of the device to determine the efficacy of pentoxifylline in decreasing hemolysis in this patient population.

The purpose of this study is to assess the effectiveness of nipocalimab when compared to placebo in decreasing the risk of fetal anemia (a condition in which a baby's red blood cell volume falls below normal levels while the baby is developing in the womb) with live neonates in pregnant participants at risk for severe hemolytic disease of the fetus and newborn.

The goal of this observational study is to characterize the diagnostic and therapeutic management of autoimmune cytopenias including autoimmune hemolytic anemia, immune thrombocytopenia, and chronic idiopathic/autoimmune neutropenia. The main aims to answer are: evaluation of traditional and novel diagnostic tools including immunohematology, cytokine essays, bone marrow studies, molecular findings, and fecal microbiome. evaluation of type and sequence of the therapies administered, the response rates, and the adverse events. evaluation of clinical and laboratory (immunologic, molecular, and morphologic) predictors of outcome. evolution of autoimmune cytopenias into myelodysplastic syndromes. a subgroup of patients with myelodysplastic syndromes will be included to evaluate the presence of immunologic events, autoimmune activation, and red cell metabolism. Participants will receive a clinical/laboratory diagnostic workup as per current clinical practice. Furthermore They will be sampled at baseline (peripheral blood and feces for microbiome) and followed up for at least 3 years to evaluate their clinical course, therapeutic management and outcome.

This is a Phase II, open-label study designed to determine if intravenously administered NM8074 results in remission from TMA in treatment-naïve aHUS patients.

Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disorder characterized by the destruction of red blood cells through warm or cold antibodies. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. Bruton's tyrosine kinase (BTK) plays a crucial role in the signaling pathway of B-cell receptor (BCR), and has been found to be a major source of pathogenic signal transduction for various lymphoproliferative malignancies. The activity of BTK is related to the occurrence and progression of various B-cell lymphomas. Currently, BTK inhibitors are widely used in the treatment of B-cell lymphomas, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), and other B-cell lymphomas, showing significant efficacy. BTK affects the production of messenger molecules and regulates the BCR signaling pathway, causing B cells to transform into self-reactive B cells, which can trigger autoimmune diseases. Current research has shown that BTK activity increases in several autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) . Therefore, BTK inhibitors (BTKi) are important for the treatment of autoimmune diseases. Ibrutinib, one kind of BTKi, has been proven to treat secondary autoimmune hemolytic anemia (AIHA) in CLL and control CLL progression, and is an effective drug for treating lymphoma-associated AIHA . One kind of second-generation selective BTKi, acalabrutinib, can also reduce the incidence of AIHA in relapsed or refractory CLL patients. Currently, phase-II clinical studies exploring the treatment of AIHA using Ibrutinib, acalabrutinib, and rilzabrutinib, another BTKi, are underway. Zanubrutinib (BGB-3111, Brukinsa®, BeiGene) is a second-generation irreversible BTKi developed by Chinese company BeiGene. Compared to Ibrutinib, zanubrutinib has shown stronger effective activity and higher selectivity towards BTK, and weaker effects on other targets such as TEC, EGFR, and Src families, with low off-target side effects. Its efficacy, durability, oral absorption, and targeting are better than those of Ibrutinib. Zanubrutinib is approved for the treatment of various B-cell lymphomas, and clinical trials have shown excellent efficacy and tolerability in CLL and WM patients. In previously treated CLL patients, zanubrutinib exhibits better efficacy and safety than Ibrutinib. Currently, phase II clinical studies of zanubrutinib in ITP, antiphospholipid syndrome, IgG4-related immune diseases, and active proliferative lupus nephritis are underway. The therapeutic effect of zanubrutinib on refractory warm autoimmune hemolytic anemia, is worth exploring through exploratory research.

Acute microcirculatory perfusion disturbances is common in critical illness and associated with increased morbidity and mortality. Recent findings by our group showed that microcirculatory perfusion is disturbed during cardiac surgery with cardiopulmonary bypass (CPB) and remain disturbed up to 72 (seventy two) hours after surgery. A cardiopulmonary bypass is a machine which takes over heart and lung function, during the procedure. The disturbed microcirculation is associated with organ dysfunction induced by cardiac surgery using CPB, which is frequently seen (up to forty two percent, 42%) and results in a six-fold increase in mortality rate. The underlying cause of disturbed microcirculation is a higher endothelial permeability and vascular leakage and are a consequence of systemic inflammation, hemodilution (dilution of blood), hypothermia and hemolysis (breakdown of red blood cells). To gain the knowledge regarding disturbed microcirculation the investigators previously showed that hemodilution attributes to this disturbed perfusion. Hemodilution lowers colloid oncotic pressure (COP). Also, COP is affected by free hemoglobin, which increases with hemolysis and attributes to a disturbed microcirculation following CPB. This is interesting, as to the best of our knowledge, the effect of minimizing hemodilution and hemolysis during cardiac surgery on the microcirculatory perfusion has never been investigated, but could be the key factor in reducing organ dysfunction.